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<title>bioRxiv Channel: Academia Sinica</title>
<link>https://biorxiv.org</link>
<description>
This feed contains articles for bioRxiv Channel "Academia Sinica"
</description>

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<prism:publicationName>bioRxiv</prism:publicationName>
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<title>bioRxiv</title>
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<link>https://biorxiv.org</link>
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<item rdf:about="https://biorxiv.org/content/10.1101/005702v1?rss=1">
<title>
<![CDATA[
High-throughput functional annotation of influenza A virus genome at single-nucleotide resolution 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/005702v1?rss=1</link>
<description><![CDATA[
A novel genome-wide genetics platform is presented in this study, which permits functional interrogation of all point mutations across a viral genome in parallel. Here we generated the first fitness profile of individual point mutations across the influenza virus genome. Critical residues on the viral genome were systematically identified, which provided a collection of subdomain data informative for structure-function studies and for effective rational drug and vaccine design. Our data was consistent with known, well-characterized structural features. In addition, we have achieved a validation rate of 68% for severely attenuated mutations and 94% for neutral mutations. The approach described in this study is applicable to other viral or microbial genomes where a means of genetic manipulation is available.
]]></description>
<dc:creator>Nicholas C. Wu</dc:creator>
<dc:creator>Arthur P. Young</dc:creator>
<dc:creator>Laith Q. Al-Mawsawi</dc:creator>
<dc:creator>C. Anders Olson</dc:creator>
<dc:creator>Jun Feng</dc:creator>
<dc:creator>Hangfei Qi</dc:creator>
<dc:creator>Shu-Hwa Chen</dc:creator>
<dc:creator>I-Hsuan Lu</dc:creator>
<dc:creator>Chung-Yen Lin</dc:creator>
<dc:creator>Robert G. Chin</dc:creator>
<dc:creator>Harding H. Luan</dc:creator>
<dc:creator>Nguyen Nguyen</dc:creator>
<dc:creator>Stanley F. Nelson</dc:creator>
<dc:creator>Xinmin Li</dc:creator>
<dc:creator>Ting-Ting Wu</dc:creator>
<dc:creator>Ren Sun</dc:creator>
<dc:creator></dc:creator>
<dc:date>2014-05-31</dc:date>
<dc:identifier>doi:10.1101/005702</dc:identifier>
<dc:title><![CDATA[High-throughput functional annotation of influenza A virus genome at single-nucleotide resolution]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2014-05-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/007617v1?rss=1">
<title>
<![CDATA[
The impacts of historical barriers on floristic patterns of plant groups with different dispersal abilities in the Ryukyu Archipelago, Japan 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/007617v1?rss=1</link>
<description><![CDATA[
The effects of historical barriers in biogeographical patterns are expected to persist differently depending on dispersal abilities of organisms. We tested two hypotheses that plant groups with different dispersal abilities display different floristic patterns, and that historical barriers can explain floristic differentiation patterns in plants with low dispersal ability but not in plants with higher dispersal ability, in the seed plant flora of the Ryukyu Archipelago. This area is biogeographically interesting because several similar floristic differentiation patterns have been proposed, all of which are primarily explained by two historical barriers, the Tokara Tectonic Strait (Tokara Gap) and the Kerama Gap, which arose during the formation of the islands. We calculated floristic dissimilarity distance among 26 islands based on data sets for three dispersal-ability classes. Clustering analyses based on the floristic dissimilarity distance generated similar floristic patterns regardless of dispersal-ability class. We propose that because the landscape resistance is so strong that migration of plants is severely restricted regardless of their dispersal abilities, the similar floristic differentiation patterns are generated. Multivariate regression analyses using Mantels randomization test indicated that floristic differentiations among islands were explained by the both effects of the historical barriers and geographic distance in all dispersal-ability classes. Significance of the historical barriers is not determined by the plant dispersal abilities but presumably by the spatial distribution of the islands, stochastic dispersals, and time since the formation of the barriers.
]]></description>
<dc:creator>Koh Nakamura</dc:creator>
<dc:creator>Rempei Suwa</dc:creator>
<dc:creator>Tetsuo Denda</dc:creator>
<dc:creator>Masatsugu Yokota</dc:creator>
<dc:creator></dc:creator>
<dc:date>2014-08-01</dc:date>
<dc:identifier>doi:10.1101/007617</dc:identifier>
<dc:title><![CDATA[The impacts of historical barriers on floristic patterns of plant groups with different dispersal abilities in the Ryukyu Archipelago, Japan]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2014-08-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/007625v1?rss=1">
<title>
<![CDATA[
The architectural stratification and woody species diversity in subtropical evergreen broadleaf forests along a latitudinal thermal gradient of the Ryukyu Archipelago, Japan 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/007625v1?rss=1</link>
<description><![CDATA[
In order to compare stand structure and woody species diversity of subtropical evergreen broadleaf forests along a latitudinal thermal gradient of the Ryukyu Archipelago, tree censuses in a 750 m2 plot in Okinawa Island and a 400 m2 plot in Ishigaki Island were performed. The number of layers increased along a latitudinal thermal gradient from four in the forest of Okinawa Island to five in the forest of Ishigaki Island. The values of Shannons index H' and Pielous index J' tended to increase from the top layer downward in the forest of Okinawa Island, whereas in the forest of Ishigaki Island, these values tended to increase from the bottom layer upward. High woody species diversity depended on small-sized trees in the Okinawa forest, whereas it depended on large-sized trees in the Ishigaki forest. The woody species diversity is higher in the Okinawa forest (H' = 4.83 bit) than in the Ishigaki forest (H' = 4.36 bit). According to successively decreasing height of layers from the top downward, the value of H' increased continuously from the top layer downward in the Okinawa forest. This increasing trend was different from the Ishigaki forest, where the value of H' increased up to the second layer and then decreased downward. In the Okinawa forest, the expected number of species increased continuously from the top toward the bottom layer, i.e. the bottom layer contained the highest potential number of species (65). However, in the Ishigaki forest, it increased from the top to the fourth layer and then decreased to the bottom layer, i.e. the fourth layer contained the highest potential number of species (90). The floristic composition in the Okinawa forest was different from that in the Ishigaki forest in terms of similarity index, though approximately half of the species were common between them. The highest degree of similarity in floristic composition was between the second and third layers in the Okinawa forest, whereas it was between the third and bottom layers in the Ishigaki forest. The degree of similarity in floristic composition among layers was higher in the Okinawa forest than in the Ishigaki forest. Except the top and the bottom layer respectively in the forests of Okinawa Island and Ishigaki Island, the spatial distribution of trees was random in each layer. The degree of overlapping in the spatial distribution of trees among layers in these two forests suggested that trees in the upper two layers in the Ishigaki forest can catch sufficient light, while light can not penetrate easily to the lower three layers in both of the forests. As a result, almost species in the lower layers might be shade-tolerant in both of the forests. For both of the forests, mean tree weight of each layer decreased from the top downward, whereas the corresponding tree density increased from the top downward. This trend resembled the mean weight-density trajectory of self-thinning plant populations.
]]></description>
<dc:creator>Sm Feroz</dc:creator>
<dc:creator>Rempei Suwa</dc:creator>
<dc:creator>Koh Nakamura</dc:creator>
<dc:creator>Akio Hagihara</dc:creator>
<dc:creator>Masatsugu Yokota</dc:creator>
<dc:creator></dc:creator>
<dc:date>2014-08-03</dc:date>
<dc:identifier>doi:10.1101/007625</dc:identifier>
<dc:title><![CDATA[The architectural stratification and woody species diversity in subtropical evergreen broadleaf forests along a latitudinal thermal gradient of the Ryukyu Archipelago, Japan]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2014-08-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/051276v1?rss=1">
<title>
<![CDATA[
The genetic basis of natural variation in C. elegans telomere length 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/051276v1?rss=1</link>
<description><![CDATA[
Telomeres are involved in the maintenance of chromosomes and the prevention of genome instability. Despite this central importance, significant variation in telomere length has been observed in a variety of organisms. The genetic determinants of telomere-length variation and their effects on organismal fitness are largely unexplored. Here, we describe natural variation in telomere length across the Caenorhabditis elegans species. We identify a large-effect variant that contributes to differences in telomere length. The variant alters the conserved oligosaccharide/oligonucleotide-binding fold of POT-2, a homolog of a human telomere-capping shelterin complex subunit. Mutations within this domain likely reduce the ability of POT-2 to bind telomeric DNA, thereby increasing telomere length. We find that telomere-length variation does not correlate with offspring production or longevity in C. elegans wild isolates, suggesting that naturally long telomeres play a limited role in modifying fitness phenotypes in C. elegans.
]]></description>
<dc:creator>Daniel E Cook</dc:creator>
<dc:creator>Stefan Zdraljevic</dc:creator>
<dc:creator>Robyn E Tanny</dc:creator>
<dc:creator>Beomseok Seo</dc:creator>
<dc:creator>David Riccardi</dc:creator>
<dc:creator>Luke M Noble</dc:creator>
<dc:creator>Matthew V Rockman</dc:creator>
<dc:creator>Mark Alkema</dc:creator>
<dc:creator>Christian Braendle</dc:creator>
<dc:creator>Jan Kammenga</dc:creator>
<dc:creator>John Wang</dc:creator>
<dc:creator>Leonid Kruglyak</dc:creator>
<dc:creator>Marie-Anne Felix</dc:creator>
<dc:creator>Junho Lee</dc:creator>
<dc:creator>Erik Andersen</dc:creator>
<dc:creator></dc:creator>
<dc:date>2016-05-02</dc:date>
<dc:identifier>doi:10.1101/051276</dc:identifier>
<dc:title><![CDATA[The genetic basis of natural variation in C. elegans telomere length]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2016-05-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/053066v1?rss=1">
<title>
<![CDATA[
Antibiotic Stress Selects against Cooperation in a Pathogenic Bacterium 
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</title>
<link>https://biorxiv.org/content/10.1101/053066v1?rss=1</link>
<description><![CDATA[
Ecological antagonisms such as predation, parasitism, competition, and abiotic environmental stress play key roles in shaping population biology, in particular by inducing stress responses and selecting for tolerant or resistant phenotypes. Little is known, however, about their impact on social traits, such as the production of public goods. Evolutionary trade-off theory predicts that adaptation to stresses should lessen investments in costly helping behaviours when cooperation does not increase resistance or tolerance, but support for this prediction is scarce. We employed theory and experiments to investigate how ecological antagonism influences social dynamics and resistance evolution in the pathogenic bacterium Pseudomonas aeruginosa. We subjected two clones of bacterium to four doses of antibiotics and assessed growth and frequencies of public goods producing and non-producing genotypes. Our results show that abiotic stress selects against public goods production. Specifically, we found that non-producers of costly iron chelating molecules (siderophores) most rapidly increased in frequency under intermediate antibiotic pressure. Moreover, the dominance of non-producers in mixed cultures was associated with higher survival and resistance to antibiotics than in either producer or non-producer monocultures. Mathematical modelling explains this counterintuitive result, and shows how these qualitative patterns are predicted to generalise to many other systems. Our results shed light on the complex interactions between social traits and ecological antagonisms, and in particular the consequences for bacterial social evolution and antibiotic resistance.
]]></description>
<dc:creator>Marie Vasse</dc:creator>
<dc:creator>Robert Noble</dc:creator>
<dc:creator>Andrei R Akhmetzhanov</dc:creator>
<dc:creator>Clara Torres-Barceló</dc:creator>
<dc:creator>James Gurney</dc:creator>
<dc:creator>Simon Benateau</dc:creator>
<dc:creator>Claire Gougat-Barbera</dc:creator>
<dc:creator>Oliver Kaltz</dc:creator>
<dc:creator>Michael E Hochberg</dc:creator>
<dc:creator></dc:creator>
<dc:date>2016-05-12</dc:date>
<dc:identifier>doi:10.1101/053066</dc:identifier>
<dc:title><![CDATA[Antibiotic Stress Selects against Cooperation in a Pathogenic Bacterium]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2016-05-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/094953v1?rss=1">
<title>
<![CDATA[
Familial Mutations and Post-translational Modifications of UCH-L1 in Parkinson’s Disease and Neurodegenerative Disorders 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/094953v1?rss=1</link>
<description><![CDATA[
Parkinsons disease (PD) is one of the most common progressive neurodegenerative disorders in modern society. The disease involves many genetic risk factors as well as a sporadic pathogenesis that is age- and environment-dependent. Of particular interest is the formation of intra-neural fibrillar aggregates, namely Lewy bodies (LBs), the histological hallmark of PD, which results from aberrant protein homeostasis or misfolding that results in neurotoxicity. A better understanding of the molecular mechanism and composition of these cellular inclusions will help shed light on the progression of misfolding-associated neurodegenerative disorders. Ubiquitin carbonyl-terminal hydrolase L1 (UCH-L1) is found to co-aggregate with -synuclein (S), the major component of LBs. Several familial mutations of UCH-L1, namely p.Ile93Met (p.I93M), p.Glu7Ala (p.E7A), and p.Ser18Tyr (p.S18Y), are associated with PD and other neurodegenerative disorders. Here, we review recent progress and recapitulate the impact of PD-associated mutations of UCH-L1 in the context of their biological functions gleaned from biochemical and biophysical studies. Finally, we summarize the effect of these genetic mutations and post-translational modifications on the association of UCH-L1 and PD in terms of loss of cellular functions or gain of cellular toxicity.
]]></description>
<dc:creator>Lee, Y.-T. C.</dc:creator>
<dc:creator>Hsu, S.-T. D.</dc:creator>
<dc:date>2016-12-17</dc:date>
<dc:identifier>doi:10.1101/094953</dc:identifier>
<dc:title><![CDATA[Familial Mutations and Post-translational Modifications of UCH-L1 in Parkinson’s Disease and Neurodegenerative Disorders]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2016-12-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/112375v1?rss=1">
<title>
<![CDATA[
Allopatric divergence, local adaptation, and multiple Quaternary refugia in a long-lived tree (Quercus spinosa) from subtropical China 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/112375v1?rss=1</link>
<description><![CDATA[
O_LIThe complex geography and climatic changes occurring in subtropical China during the Tertiary and Quaternary might have provided substantial opportunities for allopatric speciation. To gain further insight into these processes, we reconstruct the evolutionary history of Quercus spinosa, a common evergreen tree species mainly distributed in this area.nC_LIO_LIForty-six populations were genotyped using four chloroplast DNA regions and 12 nuclear microsatellite loci to assess genetic structure and diversity, which was supplemented by divergence time and diversification rate analyses, environmental factor analysis, and ecological niche modeling of the species distributions in the past and at present.nC_LIO_LIThe genetic data consistently identified two lineages: the western Eastern Himalaya-Hengduan Mountains lineage and the eastern Central-Eastern China lineage, mostly maintained by populations environmental adaptation. These lineages diverged through climate/orogeny-induced vicariance during the Neogene and remained separated thereafter. Genetic data strongly supported the multiple refugia (per se, interglacial refugia) or refugia within refugia hypotheses to explain Q. spinosa phylogeography in subtropical China.nC_LIO_LIQ. spinosa population structure highlighted the importance of complex geography and climatic changes occurring in subtropical China during the Neogene in providing substantial opportunities for allopatric divergence.nC_LI
]]></description>
<dc:creator>Feng, L.</dc:creator>
<dc:creator>Zhang, Y.-P.</dc:creator>
<dc:creator>Chen, X.-D.</dc:creator>
<dc:creator>Yang, J.</dc:creator>
<dc:creator>Zhou, T.</dc:creator>
<dc:creator>Bai, G.-Q.</dc:creator>
<dc:creator>Yang, J.</dc:creator>
<dc:creator>Li, Z.-H.</dc:creator>
<dc:creator>Peng, C.-I.</dc:creator>
<dc:creator>Zhao, G.-F.</dc:creator>
<dc:date>2017-02-28</dc:date>
<dc:identifier>doi:10.1101/112375</dc:identifier>
<dc:title><![CDATA[Allopatric divergence, local adaptation, and multiple Quaternary refugia in a long-lived tree (Quercus spinosa) from subtropical China]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-02-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/116996v1?rss=1">
<title>
<![CDATA[
Molecular Basis Underlying Male Sterility In bHLH142 Overexpressing Rice 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/116996v1?rss=1</link>
<description><![CDATA[
Development of stable male sterility lines is essential for efficient hybrid seed production. We previously showed that knockout of bHLH142 in rice (Oryza sativa) causes pollen sterility by interrupting tapetal programmed cell death (PCD). In this study, we demonstrated that overexpression of bHLH142 (OE142) under the control of ubiquitin promoter also leads to male sterility in rice by triggering the premature onset of PCD. Protein of bHLH142 was found to accumulate specifically in the OE142 anthers. Overexpression of bHLH142 induced early expression of several key regulatory transcription factors in pollen development. In particular, the upregulation of EAT1 at the early stage of pollen development promoted premature PCD in the OE142 anthers, while its downregulation at the late stage impaired pollen development by suppressing genes involved in pollen wall biosynthesis, ROS scavenging and PCD. Collectively, these events led to male sterility in OE142. Analyses of related mutants further revealed the hierarchy of these pollen development regulatory genes. Thus, the findings of this study create a new method to generate genic male sterility in rice. Exploitation of this novel functionality of bHLH142 would confer a big advantage to hybrid seed production.nnHighlightOverexpression of bHLH142 leads to male sterility in transgenic rice due to early onset of tapetal PCD. This study creates a new method to generate male sterility in rice.
]]></description>
<dc:creator>Ko, S.-S.</dc:creator>
<dc:creator>Li, M.-J.</dc:creator>
<dc:creator>Lin, Y.-J.</dc:creator>
<dc:creator>Hsing, H.-X.</dc:creator>
<dc:creator>Yang, T.-T.</dc:creator>
<dc:creator>Chen, T.-K.</dc:creator>
<dc:creator>Jhong, C.-M.</dc:creator>
<dc:creator>Ku, M. S.-B.</dc:creator>
<dc:date>2017-03-15</dc:date>
<dc:identifier>doi:10.1101/116996</dc:identifier>
<dc:title><![CDATA[Molecular Basis Underlying Male Sterility In bHLH142 Overexpressing Rice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-03-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/120071v1?rss=1">
<title>
<![CDATA[
Trichoderma reesei Complete Genome Sequence, Repeat-Induced Point Mutation And Partitioning Of CAZyme Gene Clusters 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/120071v1?rss=1</link>
<description><![CDATA[
Trichoderma reesei (Ascomycota, Pezizomycotina) QM6a is a model fungus for a broad spectrum of physiological phenomena, including plant cell wall degradation, industrial production of enzymes, light responses, conidiation, sexual development, polyketide biosynthesis and plant-fungal interactions. The genomes of QM6a and its high-enzyme producing mutants have been sequenced by second-generation-sequencing methods and are publicly available from the Joint Genome Institute (JGI). While these genome sequences have offered useful information for genomic and transcriptomic studies, their limitations and especially their short read lengths make them poorly suited for some particular biological problems, including assembly, genome-wide determination of chromosome architecture and genetic modification or engineering. We integrated Pacific Biosciences and Illumina sequencing platforms for the highest-quality genome assembly yet achieved, revealing seven telomere-to-telomere chromosomes (34,922,528 bp; 10877 genes) with 1630 newly-predicted genes and >1.5 Mb of new sequences. Most new sequences are located on AT-rich blocks, including 7 centromeres, 14 subtelomeres and 2329 interspersed AT-rich blocks. The seven QM6a centromeres separately consist of 24 conserved repeats and 37 putative centromere-encoded genes. These findings open up a new perspective for future centromere and chromosome architecture studies. Next, we demonstrate that sexual crossing readily induced cytosine-to-thymine point mutations on both tandem and unlinked duplicated sequences. We also show by bioinformatic analysis that Trichoderma reesei has evolved a robust repeat-induced point mutation (RIP) system to accumulate AT-rich sequences, with longer AT-rich blocks having more RIP mutations. The widespread distribution of AT-rich blocks correlates genome-wide partitions with gene clusters, explaining why clustering of genes has been reported to not influence gene expression in Trichoderma reesei. Compartmentation of ancestral gene clusters by AT-rich blocks might promote flexibilities that are evolutionarily advantageous in this fungus soil habitats and other natural environments. Our analyses, together with the complete genome sequence, provide a better blueprint for biotechnological and industrial applications.
]]></description>
<dc:creator>Li, W.-C.</dc:creator>
<dc:creator>Huang, C.-H.</dc:creator>
<dc:creator>Chen, C.-L.</dc:creator>
<dc:creator>Chuang, Y.-C.</dc:creator>
<dc:creator>Tung, S.-Y.</dc:creator>
<dc:creator>Wang, T.-F.</dc:creator>
<dc:date>2017-03-24</dc:date>
<dc:identifier>doi:10.1101/120071</dc:identifier>
<dc:title><![CDATA[Trichoderma reesei Complete Genome Sequence, Repeat-Induced Point Mutation And Partitioning Of CAZyme Gene Clusters]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-03-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/120444v1?rss=1">
<title>
<![CDATA[
Three-dimensional actin-based protrusions of migrating neutrophils are intrinsically lamellar and facilitate direction changes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/120444v1?rss=1</link>
<description><![CDATA[
Leukocytes and other amoeboid cells change shape as they move, forming highly dynamic, actin-filled pseudopods. Although we understand much about the architecture and dynamics of thin lamellipodia made by slow-moving cells on flat surfaces, conventional light microscopy lacks the spatial and temporal resolution required to track complex pseudopods of cells moving in three dimensions. We therefore employed lattice light sheet microscopy to perform three-dimensional, time-lapse imaging of neutrophil-like HL-60 cells crawling through collagen matrices. To analyze three-dimensional pseudopods we: (i) developed fluorescent probe combinations that distinguish cortical actin from dynamic, pseudopod-forming actin networks, and (ii) adapted molecular visualization tools from structural biology to render and analyze complex cell surfaces. Surprisingly, three-dimensional pseudopods turn out to be composed of thin (<0.75 m), flat sheets that sometimes interleave to form rosettes. Their laminar nature is not templated by an external surface, but likely reflects a linear arrangement of regulatory molecules. Although we find that pseudopods are dispensable for three-dimensional locomotion, their elimination dramatically decreases the frequency of cell turning, and pseudopod dynamics increase when cells change direction, highlighting the important role pseudopods play in pathfinding.
]]></description>
<dc:creator>Fritz-Laylin, L. K.</dc:creator>
<dc:creator>Riel-Mehan, M.</dc:creator>
<dc:creator>Chen, B.-C.</dc:creator>
<dc:creator>Lord, S. J.</dc:creator>
<dc:creator>Goddard, T. D.</dc:creator>
<dc:creator>Ferrin, T. E.</dc:creator>
<dc:creator>Johnson, G.</dc:creator>
<dc:creator>Betzig, E.</dc:creator>
<dc:creator>Mullins, R. D.</dc:creator>
<dc:date>2017-03-24</dc:date>
<dc:identifier>doi:10.1101/120444</dc:identifier>
<dc:title><![CDATA[Three-dimensional actin-based protrusions of migrating neutrophils are intrinsically lamellar and facilitate direction changes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-03-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/123992v1?rss=1">
<title>
<![CDATA[
Regulatory Divergence In Wound-Responsive Gene Expression In Domesticated And Wild Tomato 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/123992v1?rss=1</link>
<description><![CDATA[
BackgroundThe evolution of cis- and trans-regulatory components of transcription is central to how stress response and tolerance differ across species. However, it remains largely unknown how divergence in TF binding specificity and cis-regulatory sites contribute to the divergence of stress-responsive gene expression between wild and domesticated species.nnResultsUsing tomato as model, we analyzed the transcriptional profile of wound-responsive genes in wild Solanum pennellii and domesticated S. lycopersicum. We found that extensive expression divergence of wound-responsive genes is associated with speciation. To assess the degree of trans-regulatory divergence between these two species, 342 and 267 putative cis-regulatory elements (pCREs) in S. lycopersicum and S. pennellii, respectively, were identified that were predictive of wound-induced gene expression. We found that 35-66% of pCREs were conserved across species, suggesting that the remaining proportion (34-65%) of pCREs are species specific. This finding indicates a substantially higher degree of trans-regulatory divergence between these two plant species, which diverged [~]3-7 million years ago, compared to that observed in mouse and human, which diverged [~]100 million years ago. In addition, differences in pCRE sites were significantly associated with differences in wound-responsive gene expression between wild and domesticated tomato orthologs, suggesting the presence of substantial cis-regulatory divergence.nnConclusionsOur study provides new insights into the mechanistic basis of how the transcriptional response to wounding is regulated and, importantly, the contribution of cis- and trans-regulatory components to variation in wound-responsive gene expression during species domestication.
]]></description>
<dc:creator>Liu, M.-J.</dc:creator>
<dc:creator>Sugimoto, K.</dc:creator>
<dc:creator>Uygun, S.</dc:creator>
<dc:creator>Panchy, N.</dc:creator>
<dc:creator>Campbell, M. S.</dc:creator>
<dc:creator>Yandell, M.</dc:creator>
<dc:creator>Howe, G. A.</dc:creator>
<dc:creator>Shiu, S.-H.</dc:creator>
<dc:date>2017-04-04</dc:date>
<dc:identifier>doi:10.1101/123992</dc:identifier>
<dc:title><![CDATA[Regulatory Divergence In Wound-Responsive Gene Expression In Domesticated And Wild Tomato]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-04-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/132712v1?rss=1">
<title>
<![CDATA[
The Genomic Landscape Of Tree Rot In Phellinus noxius And Its Hymenochaetales Members 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/132712v1?rss=1</link>
<description><![CDATA[
The order Hymenochaetales of white rot fungi contain some of the most aggressive wood decayers causing tree deaths around the world. Despite their ecological importance and the impact of diseases they cause, little is known about the evolution and transmission patterns of these pathogens. Here, we sequenced and undertook comparative genomics analyses of Hymenochaetales genomes using brown root rot fungus Phellinus noxius, wood-decomposing fungus Phellinus lamaensis, laminated root rot fungus Phellinus sulphurascens, and trunk pathogen Porodaedalea pini. Many gene families of lignin-degrading enzymes were identified from these fungi, reflecting their ability as white rot fungi. Comparing against distant fungi highlighted the expansion of 1,3-beta-glucan synthases in P. noxius, which may account for its fast-growing attribute. We identified 13 linkage groups conserved within Agaricomycetes, suggesting the evolution of stable karyotypes. We determined that P. noxius has a bipolar heterothallic mating system, with unusual highly expanded ~60 kb A locus as a result of accumulating gene transposition. We investigated the population genomics of 60 P. noxius isolates across multiple islands of the Asia Pacific region. Whole-genome sequencing showed this multinucleate species contains abundant poly-allelic single-nucleotide-polymorphisms (SNPs) with atypical allele frequencies. Different patterns of intra-isolate polymorphism reflect mono-/heterokaryotic states which are both prevalent in nature. We have shown two genetically separated lineages with one spanning across many islands despite the geographical barriers. Both populations possess extraordinary genetic diversity and show contrasting evolutionary scenarios. These results provide a framework to further investigate the genetic basis underlying the fitness and virulence of white rot fungi.
]]></description>
<dc:creator>Chung, C.-L.</dc:creator>
<dc:creator>Lee, J. T.</dc:creator>
<dc:creator>Akiba, M.</dc:creator>
<dc:creator>Lee, H.-H.</dc:creator>
<dc:creator>Kuo, T.-H.</dc:creator>
<dc:creator>Liu, D.</dc:creator>
<dc:creator>Ke, H.-M.</dc:creator>
<dc:creator>Yokoi, T.</dc:creator>
<dc:creator>Roa, M. B.</dc:creator>
<dc:creator>Lu, M. J.</dc:creator>
<dc:creator>Chang, Y.-Y.</dc:creator>
<dc:creator>Ann, P.-J.</dc:creator>
<dc:creator>Tsai, J.-N.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Tzean, S.-S.</dc:creator>
<dc:creator>Ota, Y.</dc:creator>
<dc:creator>Hattori, T.</dc:creator>
<dc:creator>Sahashi, N.</dc:creator>
<dc:creator>Liou, R.-F.</dc:creator>
<dc:creator>Kikuchi, T.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2017-05-07</dc:date>
<dc:identifier>doi:10.1101/132712</dc:identifier>
<dc:title><![CDATA[The Genomic Landscape Of Tree Rot In Phellinus noxius And Its Hymenochaetales Members]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-05-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/143107v1?rss=1">
<title>
<![CDATA[
Matryoshka: Ratiometric biosensors from a nested 1 cassette of green- and orange-emitting fluorescent proteins 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/143107v1?rss=1</link>
<description><![CDATA[
Sensitivity, dynamic and detection range as well as exclusion of expression and instrumental artifacts are critical for the quantitation of data obtained with fluorescent protein (FP)-based biosensors in vivo. Current biosensors designs are, in general, unable to simultaneously meet all these criteria. Here, we describe a generalizable platform to create dual-FP biosensors with large dynamic ranges by employing a single FP-cassette, named GO-(Green-Orange) Matryoshka. The cassette nests a stable reference FP (large Stokes shift LSSmOrange) within a reporter FP (circularly permuted green FP). GO-Matryoshka yields green and orange fluorescence upon blue excitation. As proof of concept, we converted existing, single-emission biosensors into a series of ratiometric calcium sensors (MatryoshCaMP6s) and ammonium transport activity sensors (AmTryoshka1;3). We additionally identified the internal acid-base equilibrium as a key determinant of the GCaMP dynamic range. Matryoshka technology promises flexibility in the design of a wide spectrum of ratiometric biosensors and expanded in vivo applications.
]]></description>
<dc:creator>Ast, C.</dc:creator>
<dc:creator>Foret, J.</dc:creator>
<dc:creator>Oltrogge, L.</dc:creator>
<dc:creator>De Michele, R.</dc:creator>
<dc:creator>Kleist, T.</dc:creator>
<dc:creator>Ho, C.-H.</dc:creator>
<dc:creator>Frommer, W.</dc:creator>
<dc:date>2017-06-06</dc:date>
<dc:identifier>doi:10.1101/143107</dc:identifier>
<dc:title><![CDATA[Matryoshka: Ratiometric biosensors from a nested 1 cassette of green- and orange-emitting fluorescent proteins]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-06-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/149989v1?rss=1">
<title>
<![CDATA[
Inferring synteny between genome assemblies: a systematic evaluation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/149989v1?rss=1</link>
<description><![CDATA[
Identification of synteny between genomes of closely related species is an important aspect of comparative genomics. However, it is unknown to what extent draft assemblies lead to errors in such analysis. To investigate this, we fragmented genome assemblies of model nematodes to various extents and conducted synteny identification and downstream analysis. We first show that synteny between species can be underestimated up to 40% and find disagreements between popular tools that infer synteny blocks. This inconsistency and further demonstration of erroneous gene ontology enrichment tests throws into question the robustness of previous synteny analysis when gold standard genome sequences remain limited. In addition, determining the true evolutionary relationship is compromised by assembly improvement using a reference guided approach with a closely related species. Annotation quality, however, has minimal effect on synteny if the assembled genome is highly contiguous. Our results highlight the need for gold standard genome assemblies for synteny identification and accurate downstream analysis.nnAuthor summaryGenome assemblies across all domains of life are currently produced routinely. Initial analysis of any new genome usually includes annotation and comparative genomics. Synteny provides a framework in which conservation of homologous genes and gene order is identified between genomes of different species. The availability of human and mouse genomes paved the way for algorithm development in large-scale synteny mapping, which eventually became an integral part of comparative genomics. Synteny analysis is regularly performed on assembled sequences that are fragmented, neglecting the fact that most methods were developed using complete genomes. Here, we systematically evaluate this interplay by inferring synteny in genome assemblies with different degrees of contiguation. As expected, our investigation reveals that assembly quality can drastically affect synteny analysis, from the initial synteny identification to downstream analysis. Importantly, we found that improving a fragmented assembly using synteny with the genome of a related species can be dangerous, as this a priori assumes a potentially false evolutionary relationship between the species. The results presented here re-emphasize the importance of gold standard genomes to the science community, and should be achieved given the current progress in sequencing technology.
]]></description>
<dc:creator>Liu, D.</dc:creator>
<dc:creator>Hunt, M.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2017-06-14</dc:date>
<dc:identifier>doi:10.1101/149989</dc:identifier>
<dc:title><![CDATA[Inferring synteny between genome assemblies: a systematic evaluation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-06-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/151662v1?rss=1">
<title>
<![CDATA[
Fibroblast Growth Factor Signaling Instructs Ensheathing Glia Wrapping of Drosophila Olfactory Glomeruli 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/151662v1?rss=1</link>
<description><![CDATA[
The formation of complex yet highly organized neural circuits requires interactions between neurons and glia. During the assembly of the Drosophila olfactory circuit, 50 olfactory receptor neuron (ORN) classes and 50 projection neuron (PN) classes form synaptic connections in 50 glomerular compartments in the antennal lobe, each of which represents a discrete olfactory information processing channel. Each compartment is separated from the adjacent compartments by membranous processes from ensheathing glia. Here we show that Thisbe, a fibroblast growth factor (FGF) released from olfactory neurons, particularly local interneurons, instructs ensheathing glia to wrap each glomerulus. The Heartless FGF receptor acts cell-autonomously in ensheathing glia to regulate process extension so as to insulate each neuropil compartment. Overexpressing Thisbe in ORNs or PNs causes over-wrapping of glomeruli to which their axons or dendrites target. Failure to establish the FGF-dependent glia structure disrupts precise ORN axon targeting and discrete glomerular formation.nnSignificance StatementThis research reports that reciprocal interactions between Drosophila olfactory neurons and ensheathing glia mediate the formation of neuronal compartments--groups of synapses that are packed into discrete structures called glomeruli that carry specific olfactory information. Ensheathing glia respond to a neuronal cue, the fibroblast growth factor (FGF) Thisbe, to pattern the boundaries of the nascent compartments. Neural compartments in turn require such glial barriers to separate themselves from neighboring compartments, so as to ensure the correct organization of the olfactory circuit. These findings highlight the importance of glia in the assembly and maintenance of neural circuits and the functions of FGF signaling in these processes.
]]></description>
<dc:creator>Wu, B.</dc:creator>
<dc:creator>Li, J.</dc:creator>
<dc:creator>Chou, Y.-H.</dc:creator>
<dc:creator>Luginbuhl, D.</dc:creator>
<dc:creator>Luo, L.</dc:creator>
<dc:date>2017-06-18</dc:date>
<dc:identifier>doi:10.1101/151662</dc:identifier>
<dc:title><![CDATA[Fibroblast Growth Factor Signaling Instructs Ensheathing Glia Wrapping of Drosophila Olfactory Glomeruli]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-06-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/163626v1?rss=1">
<title>
<![CDATA[
Comparative genomic analyses highlight the contribution of pseudogenized protein-coding genes to human lincRNAs 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/163626v1?rss=1</link>
<description><![CDATA[
BackgroundThe regulatory roles of long intergenic noncoding RNAs (lincRNAs) in humans have been revealed through the use of advanced sequencing technology. Recently, three possible scenarios of lincRNA origin have been proposed: de novo origination from intergenic regions, duplication from long noncoding RNA, and pseudogenization from protein. The first two scenarios are largely studied and supported, yet few studies focused on the evolution from pseudo genized protein-coding sequence to lincRNA. Due to the non-mutually exclusive nature that these three scenarios have, accompanied by the need of systematic investigation of lincRNA origination, we conduct a comparative genomics study to investigate the evolution of human lincRNAs.nnResultsCombining with syntenic analysis and stringent Blastn e-value cutoff, we found that the majority of lincRNAs are aligned to the intergenic regions of other species. Interestingly, 193 human lincRNAs could have protein-coding orthologs in at least two of nine vertebrates. Transposable elements in these conserved regions in human genome are much less than expectation. Moreover, 19% of these lincRNAs have overlaps with or are close to pseudogenes in the human genome.nnConclusionsWe suggest that a notable portion of lincRNAs could be derived from pseudogenized protein-coding genes. Furthermore, based on our computational analysis, we hypothesize that a subset of these lincRNAs could have potential to regulate their paralogs by functioning as competing endogenous RNAs. Our results provide evolutionary evidence of the relationship between human lincRNAs and protein-coding genes.
]]></description>
<dc:creator>Liu, W.-H.</dc:creator>
<dc:creator>Tsai, Z. T.-Y.</dc:creator>
<dc:creator>Tsai, H.-K.</dc:creator>
<dc:date>2017-07-17</dc:date>
<dc:identifier>doi:10.1101/163626</dc:identifier>
<dc:title><![CDATA[Comparative genomic analyses highlight the contribution of pseudogenized protein-coding genes to human lincRNAs]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-07-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/177931v1?rss=1">
<title>
<![CDATA[
SFMetaDB: A Comprehensive Annotation of Mouse RNA Splicing Factor RNA-Seq Datasets 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/177931v1?rss=1</link>
<description><![CDATA[
Although the number of RNA-Seq datasets deposited publicly has increased over the past few years, incomplete annotation of the associated metadata limits their potential use. Because of the importance of RNA splicing in diseases and biological processes, we constructed a database called SFMetaDB by curating datasets related with RNA splicing factors. Our effort focused on the RNA-Seq datasets in which splicing factors were knocked-down, knocked-out or over-expressed, leading to 75 datasets corresponding to 56 splicing factors. These datasets can be used in differential alternative splicing analysis for the identification of the potential targets of these splicing factors and other functional studies. Surprisingly, only [~]15% of all the splicing factors have been studied by loss- or gain-of-function experiments using RNA-Seq. In particular, splicing factors with domains from a few dominant Pfam domain families have not been studied. This suggests a significant gap that needs to be addressed to fully elucidate the splicing regulatory landscape. Indeed, there are already mouse models available for [~]20 of the unstudied splicing factors, and it can be a fruitful research direction to study these splicing factors in vitro and in vivo using RNA-Seq.nnDatabase URLhttp://sfmetadb.ece.tamu.edu/
]]></description>
<dc:creator>Li, J.</dc:creator>
<dc:creator>Tseng, C.-S.</dc:creator>
<dc:creator>Federico, A.</dc:creator>
<dc:creator>Ivankovic, F.</dc:creator>
<dc:creator>Huang, Y.-S.</dc:creator>
<dc:creator>Ciccodicola, A.</dc:creator>
<dc:creator>Swanson, M. S.</dc:creator>
<dc:creator>Yu, P.</dc:creator>
<dc:date>2017-08-18</dc:date>
<dc:identifier>doi:10.1101/177931</dc:identifier>
<dc:title><![CDATA[SFMetaDB: A Comprehensive Annotation of Mouse RNA Splicing Factor RNA-Seq Datasets]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-08-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/193474v1?rss=1">
<title>
<![CDATA[
Architecture of mammalian centriole distal appendages accommodates distinct blade and matrix functional elements 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/193474v1?rss=1</link>
<description><![CDATA[
Distal appendages (DAPs) are nanoscale, pinwheel-like structures protruding from the distal end of the centriole that mediate membrane docking during ciliogenesis, marking the cilia base around the ciliary gate. Here, we determined a superresolved multiplex of 16 centriole-distal-end components. Surprisingly, rather than pinwheels, intact DAPs exhibit a cone-shaped architecture with components filling the space between each pinwheel blade, a new structural element we termed the distal appendage matrix (DAM). Specifically, CEP83, CEP89, SCLT1, and CEP164 form the backbone of pinwheel blades, with CEP83 confined at the root and CEP164 extending to the tip near the membrane-docking site. By contrast, FBF1 marks the distal end of the DAM near the ciliary membrane. Strikingly, unlike CEP164 which is essential for ciliogenesis, FBF1 is required for ciliary gating of transmembrane proteins, revealing DAPs as an essential component of the ciliary gate. Our findings redefine both the structure and function of DAPs.
]]></description>
<dc:creator>Yang, T. T.</dc:creator>
<dc:creator>Chong, W. M.</dc:creator>
<dc:creator>Wang, W.-J.</dc:creator>
<dc:creator>Mazo, G.</dc:creator>
<dc:creator>Tanos, B.</dc:creator>
<dc:creator>Chen, Z.</dc:creator>
<dc:creator>Tran, M. N. T.</dc:creator>
<dc:creator>Chen, Y.-D.</dc:creator>
<dc:creator>Weng, R. R.</dc:creator>
<dc:creator>Huang, C.-E.</dc:creator>
<dc:creator>Jane, W.-N.</dc:creator>
<dc:creator>Tsou, M.-F. B.</dc:creator>
<dc:creator>Liao, J.-C.</dc:creator>
<dc:date>2017-09-25</dc:date>
<dc:identifier>doi:10.1101/193474</dc:identifier>
<dc:title><![CDATA[Architecture of mammalian centriole distal appendages accommodates distinct blade and matrix functional elements]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-09-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/195248v1?rss=1">
<title>
<![CDATA[
Response to Qian et al (2017): Daily and seasonal climate variations are both critical in the evolution of species’ elevational range size 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/195248v1?rss=1</link>
<description><![CDATA[
In their recent critique, Qian et al. (2017) claimed that the results of structural equation modeling analysis (SEM) in Chan et al. (2016) were flawed. Here, we show that the source of the difference in their re-analysis is that Qian et al. did not follow the standard, iterative process of SEM, which allows researchers to evaluate which model offers the best account of the data in both absolute and relative senses. Here, we provide step-by-step instructions to reproduce our published results. All of Qian et al.s concerns regarding SEM can be put to rest. Moreover, in our original paper we used three distinct statistical methods--hierarchical partitioning, SEM, and stationary bootstrap--to show that different temporal scales of environmental variability can differentially impact the elevational range size (ERS) of species. It is time to move on to probing the pressing issue of how and why climatic variability impacts ERS.
]]></description>
<dc:creator>Chan, W.-P.</dc:creator>
<dc:creator>Chen, I.-C.</dc:creator>
<dc:creator>Colwell, R. K.</dc:creator>
<dc:creator>Liu, W.-C.</dc:creator>
<dc:creator>Huang, C.-y.</dc:creator>
<dc:creator>Shen, S.-F.</dc:creator>
<dc:date>2017-09-30</dc:date>
<dc:identifier>doi:10.1101/195248</dc:identifier>
<dc:title><![CDATA[Response to Qian et al (2017): Daily and seasonal climate variations are both critical in the evolution of species’ elevational range size]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-09-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/196857v1?rss=1">
<title>
<![CDATA[
Adenylate kinase-4 modulates oxidative stress and stabilizes HIF-1α to drive lung cancer metastasis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/196857v1?rss=1</link>
<description><![CDATA[
Disrupting signaling axes that are essential for tumor metastasis may provide therapeutic opportunity to cure cancer. We previously identified adenylate kinase 4 (AK4) as a biomarker of metastasis in lung cancer. Here we analyze AK4-associated metabolic gene signature and reveal HIF-1 is transcriptionally activated and associated with poor prognosis in lung adenocarcinoma patients. Overexpression of AK4 shifts metabolism towards aerobic glycolysis and elevates intracellular reactive oxygen species (ROS), which stabilizes and exaggerates HIF1- protein expression and concurrently drives epithelial-to-mesenchymal transition (EMT) in hypoxia. Furthermore, overexpression of AK4 reduces hypoxic necrosis in tumors and promotes liver metastasis in vivo. Connectivity map analysis of AK4 gene signature identifies Withaferin-A as a potential compound to inhibit AK4-HIF-1 signaling axis, which then shows promising anti-metastatic potency in an orthotopic xenograft model of lung cancer. Our findings offer an alternative strategy to impair lung cancer metastasis via targeting AK4-HIF-1 axis.
]]></description>
<dc:creator>Jan, Y.-H.</dc:creator>
<dc:creator>Lai, T.-C.</dc:creator>
<dc:creator>Yang, C.-J.</dc:creator>
<dc:creator>Lin, Y.-F.</dc:creator>
<dc:creator>Huang, M.-S.</dc:creator>
<dc:creator>Hsiao, M.</dc:creator>
<dc:date>2017-10-01</dc:date>
<dc:identifier>doi:10.1101/196857</dc:identifier>
<dc:title><![CDATA[Adenylate kinase-4 modulates oxidative stress and stabilizes HIF-1α to drive lung cancer metastasis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-10-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2019.12.12.874008v1?rss=1">
<title>
<![CDATA[
Landscape structured by physical settings and benthic polychaete and avifauna habitat uses in a mangrove-vegetated estuary 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2019.12.12.874008v1?rss=1</link>
<description><![CDATA[
Mangrove expansion monopolizes estuarine landscapes by diminishing habitat diversity and hence biodiversity. Physical landcover types, including mangrove vegetation, influence polychaete and avifauna habitat uses. The connections between the physical to biota-associated landscapes warrant investigation. We determine how to best describe the landscape in a mangrove-vegetated wetland according to the physical, polychaete and bird domains and identify what physical attributes would affect the biota-associated landscapes. Differences among the physical and biota-associated landscapes were evaluated using multivariate ordination analyses. Six physical landcover types were aligned along elevation, inundation and sedimentary gradients. The polychaete-associated landscape was structured by three landcover types, mainly mangroves and tidal flats with intermediate and high inundation. Deposit-feeding spionid and nereid, carnivorous goniadid and suspension-feeding sabellid polychaetes depended on the different landcover types. Shorebirds occurred distinctively in tidal flats with large, open surface areas. Egrets characterized tidal flats and mangroves, and foliage and ground gleaners characterized mangroves. Open tidal flats are crucial to polychaetes, which are the main prey of shorebirds and are also important to egret foraging. Our results suggest that effective management strategies for conserving these migratory birds require the maintenance of open tidal flats in the landscape.
]]></description>
<dc:creator>Shih, S.-S.</dc:creator>
<dc:creator>Ding, T.-S.</dc:creator>
<dc:creator>Chen, C.-P.</dc:creator>
<dc:creator>Huang, S.-C.</dc:creator>
<dc:creator>Hsieh, H.-L.</dc:creator>
<dc:date>2019-12-12</dc:date>
<dc:identifier>doi:10.1101/2019.12.12.874008</dc:identifier>
<dc:title><![CDATA[Landscape structured by physical settings and benthic polychaete and avifauna habitat uses in a mangrove-vegetated estuary]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-12-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2019.12.20.883736v1?rss=1">
<title>
<![CDATA[
A genomic view of coral-associated Prosthecochloris and a companion sulfate-reducing bacterium 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2019.12.20.883736v1?rss=1</link>
<description><![CDATA[
Endolithic microbial symbionts in the coral skeleton may play a pivotal role in maintaining coral health. However, compared to aerobic microorganisms, research on the roles of endolithic anaerobic microorganisms and microbe-microbe interactions in the coral skeleton are still in their infancy. In our previous study, we showed that a group of coral-associated Prosthecochloris (CAP), a genus of anaerobic green sulfur bacteria, was dominant in the skeleton of the coral Isopora palifera. Though CAP is diverse, the 16S rRNA phylogeny presents it as a distinct clade separate from other free-living Prosthecochloris. In this study, we build on previous research and further characterize the genomic and metabolic traits of CAP by recovering two new near-complete CAP genomes--Candidatus Prosthecochloris isoporaea and Candidatus Prosthecochloris sp. N1--from coral Isopora palifera endolithic cultures. Genomic analysis revealed that these two CAP genomes have high genomic similarities compared with other Prosthecochloris and harbor several CAP-unique genes. Interestingly, different CAP species harbor various pigment synthesis and sulfur metabolism genes, indicating that individual CAPs can adapt to a diversity of coral microenvironments. A novel near-complete SRB genome--Candidatus Halodesulfovibrio lyudaonia--was also recovered from the same culture. The fact that CAP and various sulfate-reducing bacteria (SRB) co-exist in coral endolithic cultures and coral skeleton highlights the importance of SRB in the coral endolithic community. Based on functional genomic analysis of Ca. P. sp. N1 and Ca. H. lyudaonia, we also propose a syntrophic relationship between the SRB and CAP in the coral skeleton.

ImportanceLittle is known about the ecological roles of endolithic microbes in the coral skeleton; one potential role is as a nutrient source for their coral hosts. Here, we identified a close ecological relationship between CAP and SRB. Recovering novel near-complete CAP and SRB genomes from endolithic cultures in this study enabled us to understand the genomic and metabolic features of anaerobic endolithic bacteria in coral skeletons. These results demonstrate that CAP members with similar functions in carbon, sulfur, and nitrogen metabolisms harbor different light-harvesting components, suggesting that CAP in the skeleton adapts to niches with different light intensities. Our study highlights the potential ecological roles of CAP and SRB in coral skeletons and paves the way for future investigations into how coral endolithic communities will respond to environmental changes.
]]></description>
<dc:creator>Chen, Y.-H.</dc:creator>
<dc:creator>Yang, S.-H.</dc:creator>
<dc:creator>Tandon, K.</dc:creator>
<dc:creator>Lu, C.-Y.</dc:creator>
<dc:creator>Chen, H.-J.</dc:creator>
<dc:creator>Shih, C.-J.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:date>2019-12-20</dc:date>
<dc:identifier>doi:10.1101/2019.12.20.883736</dc:identifier>
<dc:title><![CDATA[A genomic view of coral-associated Prosthecochloris and a companion sulfate-reducing bacterium]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-12-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2019.12.20.884429v1?rss=1">
<title>
<![CDATA[
Bmal1 integrates mitochondrial metabolism and macrophage activation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2019.12.20.884429v1?rss=1</link>
<description><![CDATA[
Metabolic pathways and inflammatory processes are under circadian regulation. While rhythmic immune cell recruitment is known to impact infection outcomes, whether the circadian clock modulates immunometabolism remains unclear. We find the molecular clock Bmal1 is induced by inflammatory stimulants, including Ifn-{gamma}/lipopolysaccharide (M1) and tumor conditioned medium, to maintain mitochondrial metabolism under these metabolically stressed conditions in mouse macrophages. Upon M1 stimulation, myeloid-specific Bmal1 knockout (M-BKO) renders macrophages unable to sustain mitochondrial function, enhancing succinate dehydrogenase (SDH)-mediated mitochondrial ROS production and Hif-1-dependent metabolic reprogramming and inflammatory damage. In tumor-associated macrophages, the aberrant Hif-1 activation and metabolic dysregulation by M-BKO contribute to an immunosuppressive tumor microenvironment. Consequently, M-BKO increases melanoma tumor burden, while administrating an SDH inhibitor dimethyl malonate suppresses tumor growth. Therefore, Bmal1 functions as a metabolic checkpoint integrating macrophage mitochondrial metabolism, redox homeostasis and effector functions. This Bmal1-Hif-1 regulatory loop may provide therapeutic opportunities for inflammatory diseases and immunotherapy.
]]></description>
<dc:creator>Lee, C.-H.</dc:creator>
<dc:creator>Alexander, R.</dc:creator>
<dc:creator>Liou, Y.-H.</dc:creator>
<dc:creator>Knudsen, N.</dc:creator>
<dc:creator>Starost, K.</dc:creator>
<dc:creator>Xu, C.</dc:creator>
<dc:creator>Hyde, A.</dc:creator>
<dc:creator>Liu, S.</dc:creator>
<dc:creator>Jacobi, D.</dc:creator>
<dc:creator>Liao, N.-S.</dc:creator>
<dc:date>2019-12-20</dc:date>
<dc:identifier>doi:10.1101/2019.12.20.884429</dc:identifier>
<dc:title><![CDATA[Bmal1 integrates mitochondrial metabolism and macrophage activation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-12-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2019.12.23.887638v1?rss=1">
<title>
<![CDATA[
Plasma membrane damage removal by F-actin-mediated shedding from repurposed filopodia 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2019.12.23.887638v1?rss=1</link>
<description><![CDATA[
Repairing plasma membrane damage is vital to eukaryotic cell survival. Membrane shedding is thought to be key to this repair process, but a detailed view of how the process occurs is still missing. Here we used electron cryotomography to image the ultrastructural details of plasma membrane wound healing. We found that filopodia-like protrusions are built at damage sites, accompanied by retraction of neighboring filopodia, and that these repurposed protrusions act as scaffolds for membrane shedding. This suggests a new role for filopodia as reservoirs of membrane and actin for plasma membrane damage repair. Damage-induced shedding was dependent on F-actin dynamics and Myo1a, as well as Vps4B, an important component of the ESCRT machinery. Thus we find that damage shedding is more complex than current models of simple vesiculation from flat membrane domains. Rather, we observe structural similarities between damage-mediated shedding and constitutive shedding from enterocytes that argue for conservation of a general membrane shedding mechanism.
]]></description>
<dc:creator>Mageswaran, S. K.</dc:creator>
<dc:creator>Yang, W. Y.</dc:creator>
<dc:creator>Chakrabarty, Y.</dc:creator>
<dc:creator>Oikonomou, C. M.</dc:creator>
<dc:creator>Jensen, G. J.</dc:creator>
<dc:date>2019-12-24</dc:date>
<dc:identifier>doi:10.1101/2019.12.23.887638</dc:identifier>
<dc:title><![CDATA[Plasma membrane damage removal by F-actin-mediated shedding from repurposed filopodia]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-12-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.01.06.896746v1?rss=1">
<title>
<![CDATA[
Long-term warming weakens stabilizing effects of biodiversity in aquatic ecosystems 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.01.06.896746v1?rss=1</link>
<description><![CDATA[
Despite the consensus that warming will affect biodiversity, alter physicochemical environments, and disrupt biological interactions, the relative importance of these key processes and how they interact to determine overall ecosystem function is poorly understood. Here, we analyze long-term (16[~]39 years) time series data from ten aquatic ecosystems and use convergent cross mapping (CCM) to quantify the hidden causal network linking species diversity, ecosystem function, and physicochemical factors. We observe that aquatic ecosystems subject to stronger warming exhibit decreased stability (larger fluctuations in phytoplankton biomass). We further show that this effect can be attributed to a weakening of stabilizing causal pathways between biodiversity, nutrient cycling, and phytoplankton biomass. Thus, rather than thinking in terms of separate factors, a more holistic view, that causally links biodiversity and the other ecosystem components, is required to understand and predict climate impacts on the temporal stability of aquatic ecosystems.
]]></description>
<dc:creator>Chang, C.-W.</dc:creator>
<dc:creator>Ye, H.</dc:creator>
<dc:creator>Miki, T.</dc:creator>
<dc:creator>Deyle, E. R.</dc:creator>
<dc:creator>Souissi, S.</dc:creator>
<dc:creator>Anneville, O.</dc:creator>
<dc:creator>Adrian, R.</dc:creator>
<dc:creator>Chiang, Y.-R.</dc:creator>
<dc:creator>Ichise, S.</dc:creator>
<dc:creator>Kumagai, M.</dc:creator>
<dc:creator>Matsuzaki, S.-i. S.</dc:creator>
<dc:creator>Shiah, F.-K.</dc:creator>
<dc:creator>Wu, J.-T.</dc:creator>
<dc:creator>Hsieh, C.-h.</dc:creator>
<dc:creator>Sugihara, G.</dc:creator>
<dc:date>2020-01-07</dc:date>
<dc:identifier>doi:10.1101/2020.01.06.896746</dc:identifier>
<dc:title><![CDATA[Long-term warming weakens stabilizing effects of biodiversity in aquatic ecosystems]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-01-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.01.10.901983v1?rss=1">
<title>
<![CDATA[
Genomic rearrangements generate hypervariable mini-chromosomes in host-specific lineages of the blast fungus 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.01.10.901983v1?rss=1</link>
<description><![CDATA[
Supernumerary mini-chromosomes-a unique type of genomic structural variation-have been implicated in the emergence of virulence traits in plant pathogenic fungi. However, the mechanisms that facilitate the emergence and maintenance of mini-chromosomes across fungi remain poorly understood. In the blast fungus Magnaporthe oryzae, mini-chromosomes have been first described in the early 1990s but, until very recently, have been overlooked in genomic studies. Here we investigated structural variation in four isolates of the blast fungus M. oryzae from different grass hosts and analyzed the sequences of mini-chromosomes in the rice, foxtail millet and goosegrass isolates. The mini-chromosomes of these isolates turned out to be highly diverse with distinct sequence composition. They are enriched in repetitive elements and have lower gene density than core-chromosomes. We identified several virulence-related genes in the mini-chromosome of the rice isolate, including the polyketide synthase Ace1 and the effector gene AVR-Pik. Macrosynteny analyses around these loci revealed structural rearrangements, including inter-chromosomal translocations between core- and mini-chromosomes. Our findings provide evidence that mini-chromosomes independently emerge from structural rearrangements of core-chromosomes and might contribute to adaptive evolution of the blast fungus.

Author summaryThe genomes of plant pathogens often exhibit an architecture that facilitates high rates of dynamic rearrangements and genetic diversification in virulence associated regions. These regions, which tend to be gene sparse and repeat rich, are thought to serve as a cradle for adaptive evolution. Supernumerary chromosomes, i.e. chromosomes that are only present in some but not all individuals of a species, are a special type of structural variation that have been observed in plants, animals, and fungi. Here we identified and studied supernumerary mini-chromosomes in the blast fungus Magnaporthe oryzae, a pathogen that causes some of the most destructive plant diseases. We found that rice, foxtail millet and goosegrass isolates of this pathogen contain mini-chromosomes with distinct sequence composition. All mini-chromosomes are rich in repetitive genetic elements and have lower gene densities than core-chromosomes. Further, we identified virulence-related genes on the mini-chromosome of the rice isolate. We observed large-scale genomic rearrangements around these loci, indicative of a role of mini-chromosomes in facilitating genome dynamics. Taken together, our results indicate that mini-chromosomes facilitate genome rearrangements and possibly adaptive evolution of the blast fungus.
]]></description>
<dc:creator>Langner, T.</dc:creator>
<dc:creator>Harant, A.</dc:creator>
<dc:creator>Gomez-Luciano, L. B.</dc:creator>
<dc:creator>Shrestha, R. K.</dc:creator>
<dc:creator>Win, J.</dc:creator>
<dc:creator>Kamoun, S.</dc:creator>
<dc:date>2020-01-11</dc:date>
<dc:identifier>doi:10.1101/2020.01.10.901983</dc:identifier>
<dc:title><![CDATA[Genomic rearrangements generate hypervariable mini-chromosomes in host-specific lineages of the blast fungus]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-01-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.01.19.911685v1?rss=1">
<title>
<![CDATA[
On the origin and evolution of RNA editing in metazoans 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.01.19.911685v1?rss=1</link>
<description><![CDATA[
Extensive adenosine-to-inosine (A-to-I) editing of nuclear-transcribed RNAs is the hallmark of metazoan transcriptional regulation, and is fundamental to numerous biochemical processes. Here we explore the origin and evolution of this regulatory innovation, by quantifying its prevalence in 22 species that represent all major transitions in metazoan evolution. We provide substantial evidence that extensive RNA editing emerged in the common ancestor of extant metazoans. We find the frequency of RNA editing varies across taxa in a manner independent of metazoan complexity. Nevertheless, cis-acting features that guide A-to-I editing are under strong constraint across all metazoans. RNA editing seems to preserve an ancient mechanism for suppressing the more recently evolved repetitive elements, and is generally nonadaptive in protein-coding regions across metazoans, except for Drosophila and cephalopods. Interestingly, RNA editing preferentially target genes involved in neurotransmission, cellular communication and cytoskeleton, and recodes identical amino acid positions in several conserved genes across diverse taxa, emphasizing broad roles of RNA editing in cellular functions during metazoan evolution that have been previously underappreciated.
]]></description>
<dc:creator>Li, Q.</dc:creator>
<dc:creator>Zhang, P.</dc:creator>
<dc:creator>Li, J.</dc:creator>
<dc:creator>Yu, H.</dc:creator>
<dc:creator>Zhan, X.</dc:creator>
<dc:creator>Zhu, Y.</dc:creator>
<dc:creator>Guo, Q.</dc:creator>
<dc:creator>Tan, H.</dc:creator>
<dc:creator>Lundholm, N.</dc:creator>
<dc:creator>Garcia, L.</dc:creator>
<dc:creator>Martin, M. D.</dc:creator>
<dc:creator>Subirats, M. A.</dc:creator>
<dc:creator>Su, Y.-H.</dc:creator>
<dc:creator>Ruiz-Trillo, I.</dc:creator>
<dc:creator>Martindale, M. Q.</dc:creator>
<dc:creator>Yu, J.-K.</dc:creator>
<dc:creator>Gilbert, M. T. P.</dc:creator>
<dc:creator>Zhang, G.</dc:creator>
<dc:date>2020-01-19</dc:date>
<dc:identifier>doi:10.1101/2020.01.19.911685</dc:identifier>
<dc:title><![CDATA[On the origin and evolution of RNA editing in metazoans]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-01-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.01.23.916718v1?rss=1">
<title>
<![CDATA[
Dietary supplementation with PUFAs rescues the eggshell defects caused by seipin mutations in C. elegans 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.01.23.916718v1?rss=1</link>
<description><![CDATA[
SEIPIN, an ER membrane protein, plays critical roles in lipid droplet (LD) formation and lipid storage. Dysfunction of SEIPIN causes a variety of human diseases, including lipodystrophy, neuropathies, and male and female infertility. However, the cellular and molecular mechanisms of SEIPIN in causing these diseases are poorly understood. To address such mechanisms, we investigated the functional roles of R01B10.6 (seip-1), the sole SEIPIN1 ortholog in C. elegans, using CRISPR/Cas9 gene editing, and transcriptional assays. SEIP-1::mScarlet is widely expressed throughout development in C. elegans. Three full gene deletion mutants, generated by CRISPR/Cas9, displayed penetrant embryonic lethality. EM imaging and the visualization of reporter genes revealed that the lipid-rich permeability barrier, the innermost layer of the C. elegans embryonic eggshell, was defective or missing. Intriguingly, depletion of SEIP-1 revealed a perturbed gene expression pattern for fatty acid biosynthesis enzymes, in agreement with the disrupted permeability barrier formation phenotype of the embryos. Lastly, dietary supplementation of PUFAs rescued the embryonic lethality and defective permeability barrier in the deletion mutants. In sum, our study suggests that SEIP-1 may maternally regulate LD biogenesis and maintain lipid homeostasis to orchestrate the formation of the lipid-rich permeability barrier, which is crucial for eggshell formation and embryogenesis.
]]></description>
<dc:creator>Bai, X.</dc:creator>
<dc:creator>Huang, L.-J.</dc:creator>
<dc:creator>Chen, S.-W.</dc:creator>
<dc:creator>Nebenfuehr, B.</dc:creator>
<dc:creator>Wysolmerski, B.</dc:creator>
<dc:creator>Wu, J.-C.</dc:creator>
<dc:creator>Olson, S. K.</dc:creator>
<dc:creator>Golden, A.</dc:creator>
<dc:creator>Wang, C.-W.</dc:creator>
<dc:date>2020-01-23</dc:date>
<dc:identifier>doi:10.1101/2020.01.23.916718</dc:identifier>
<dc:title><![CDATA[Dietary supplementation with PUFAs rescues the eggshell defects caused by seipin mutations in C. elegans]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-01-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.01.31.928135v1?rss=1">
<title>
<![CDATA[
Species boundaries and molecular markers for classification among 16SrI phytoplasmas informed by genome analysis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.01.31.928135v1?rss=1</link>
<description><![CDATA[
Phytoplasmas are plant-pathogenic bacteria that impact agriculture worldwide. The commonly adopted classification system for phytoplasmas is based on the restriction fragment length polymorphism (RFLP) analysis of their 16S rRNA genes. With the increased availability of phytoplasma genome sequences, the classification system can now be refined. This work examined 11 strains in the 16SrI group within the genus  Candidatus Phytoplasma and investigated the possible species boundaries. We confirmed that the RFLP classification method is problematic due to intragenomic variation of the 16S rRNA genes and uneven weighing of different nucleotide positions. Importantly, our results based on the molecular phylogeny, differentiations in chromosomal segments and gene content, and divergence in homologous sequences, all supported that these strains may be classified into multiple operational taxonomic units (OTUs) equivalent to species. Strains assigned to the same OTU share >97% genome-wide average nucleotide identity (ANI) and >78% of their protein-coding genes. In comparison, strains assigned to different OTUs share <94% ANI and <75% of their genes. Reduction in homologous recombination between OTUs is one possible explanation for the discontinuity in genome similarities, and these findings supported the proposal that 95% ANI could serve as a cutoff for distinguishing species in bacteria. Additionally, critical examination of these results and the raw sequencing reads led to the identification of one genome that was presumably mis-assembled by combining two sequencing libraries built from phytoplasmas belonging to different OTUs. This finding provided a cautionary tale for working on uncultivated bacteria. Based on the new understanding of phytoplasma divergence and the current genome availability, we developed five molecular markers that could be used for multilocus sequence analysis (MLSA). By selecting markers that are short yet highly informative, and are distributed evenly across the chromosome, these markers provided a cost-effective system that is robust against recombination. Finally, examination of the effector gene distribution further confirmed the rapid gains and losses of these genes, as well as the involvement of potential mobile units (PMUs) in their molecular evolution. Future improvements on the taxon sampling of phytoplasma genomes will allow further expansions of similar analysis, and thus contribute to phytoplasma taxonomy and diagnostics.
]]></description>
<dc:creator>Cho, S.-T.</dc:creator>
<dc:creator>Kung, H.-J.</dc:creator>
<dc:creator>Huang, W.</dc:creator>
<dc:creator>Hogenhout, S. A.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:date>2020-01-31</dc:date>
<dc:identifier>doi:10.1101/2020.01.31.928135</dc:identifier>
<dc:title><![CDATA[Species boundaries and molecular markers for classification among 16SrI phytoplasmas informed by genome analysis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-01-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.02.01.930198v1?rss=1">
<title>
<![CDATA[
Reciprocal transplant experiment in lakes with disparate trophic states show resolution dependent partial functional redundancy 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.02.01.930198v1?rss=1</link>
<description><![CDATA[
Microbial communities are considered to be functionally redundant, but few studies have tested this hypothesis empirically. In this study, we performed an in situ reciprocal transplant experiment on the surface and bottom waters of two lakes with disparate trophic states and tracked changes in their microbial community and functional attributes for 6 weeks using high-throughput sequencing and functional approaches. The communities from both lakes were resistant to changes in composition after the reciprocal transplant, but their functions tended to become similar to the incubating lakes functional profiles. A significant linear positive relationship was observed between the microbial community and functional attributes, though with varying scales of similarity, suggesting partial functional redundancy. Furthermore, the entropy-based L-divergence measure quantified the scale of partial functional redundancy in the lakes surface and bottom waters. This study establishes and quantifies the scale of partial functional redundancy in the freshwater ecosystem through empirical investigation.
]]></description>
<dc:creator>Tandon, K.</dc:creator>
<dc:creator>Wan, M.-T.</dc:creator>
<dc:creator>Yang, C.-C.</dc:creator>
<dc:creator>Yang, S.-H.</dc:creator>
<dc:creator>Baatar, B.</dc:creator>
<dc:creator>Chiu, C.-Y.</dc:creator>
<dc:creator>Tsai, J.-W.</dc:creator>
<dc:creator>Liu, W.-C.</dc:creator>
<dc:creator>Ng, C. S.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:date>2020-02-02</dc:date>
<dc:identifier>doi:10.1101/2020.02.01.930198</dc:identifier>
<dc:title><![CDATA[Reciprocal transplant experiment in lakes with disparate trophic states show resolution dependent partial functional redundancy]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-02-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.02.03.933127v1?rss=1">
<title>
<![CDATA[
EM-net: Deep learning for electron microscopy image segmentation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.02.03.933127v1?rss=1</link>
<description><![CDATA[
Recent high-throughput electron microscopy techniques such as focused ion-beam scanning electron microscopy (FIB-SEM) provide thousands of serial sections which assist the biologists in studying sub-cellular structures at high resolution and large volume. Low contrast of such images hinder image segmentation and 3D visualisation of these datasets. With recent advances in computer vision and deep learning, such datasets can be segmented and reconstructed in 3D with greater ease and speed than with previous approaches. However, these methods still rely on thousands of ground-truth samples for training and electron microscopy datasets require significant amounts of time for carefully curated manual annotations. We address these bottlenecks with EM-net, a scalable deep convolutional neural network for EM image segmentation. We have evaluated EM-net using two datasets, one of which belongs to an ongoing competition on EM stack segmentation since 2012. We show that EM-net variants achieve better performances than current deep learning methods using small- and medium-sized ground-truth datasets. We also show that the ensemble of top EM-net base classifiers outperforms other methods across a wide variety of evaluation metrics.
]]></description>
<dc:creator>Khadangi, A.</dc:creator>
<dc:creator>Boudier, T.</dc:creator>
<dc:creator>Rajagopal, V.</dc:creator>
<dc:date>2020-02-04</dc:date>
<dc:identifier>doi:10.1101/2020.02.03.933127</dc:identifier>
<dc:title><![CDATA[EM-net: Deep learning for electron microscopy image segmentation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-02-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.02.06.936781v1?rss=1">
<title>
<![CDATA[
Directed effective connectivity and synaptic weights of invitro neuronal cultures revealed from high-density multielectrode array recordings 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.02.06.936781v1?rss=1</link>
<description><![CDATA[
Studying connectivity of neuronal cultures can provide insights for understanding brain networks but it is challenging to reveal neuronal connectivity from measurements. We apply a novel method that uses a theoretical relation between the time-lagged cross-covariance and the equal-time cross-covariance to reveal directed effective connectivity and synaptic weights of cortical neuron cultures at different days in vitro from multielectrode array recordings. Using a stochastic leaky-integrate-and-fire model, we show that the simulated spiking activity of the reconstructed networks can well capture the measured network bursts. The neuronal networks are found to be highly nonrandom with an over-representation of bidirectionally connections as compared to a random network of the same connection probability, with the fraction of inhibitory nodes comparable to the measured fractions of inhibitory neurons in various cortical regions in monkey, and have small-world topology with basic network measures comparable to those of the nematode C. elegans chemical synaptic network. Our analyses further reveal that (i) the excitatory and inhibitory incoming degrees have bimodal distributions the excitatory and inhibitory incoming degrees have bimodal distributions, which are that distributions that have been indicated to be optimal against both random failures and attacks in undirected networks; (ii) the distribution of the physical length of excitatory incoming links has two peaks indicating that excitatory signal is transmitted at two spatial scales, one localized to nearest nodes and the other spatially extended to nodes millimeters away, and the shortest links are mostly excitatory towards excitatory nodes and have larger synaptic weights on average; (iii) the average incoming and outgoing synaptic strength is non-Gaussian with long tails and, in particular, the distribution of outgoing synaptic strength of excitatory nodes with excitatory incoming synaptic strength is lognormal, similar to the measured excitatory postsynaptic potential in rat cortex.

Author summaryTo understand how the brain processes signal and carries out its function, it is useful to know the connectivity of the underlying neuronal circuits. For large-scale neuronal networks, it is difficult to measure connectivity directly using electron microscopy techniques and methods that can estimate connectivity from electrophysiological recordings are thus highly desirable. Existing methods focus mainly on estimating functional connectivity, which is defined by statistical dependencies between neuronal activities but the relevant direct casual interactions are captured by effective connectivity. Here we apply a novel covariance-relation based method to estimate the directed effective connectivity and synaptic weights of cortical neuron cultures from recordings of multielectrode array of over 4000 electrodes taken at different days in vitro. The neuronal networks are found to be nonrandom, small-world, excitation/inhibition balanced as measured in monkey cortex, and with feeder hubs. Our analyses further suggest some form of specialisation of nodes in receiving excitatory and inhibitory signals and the transmission of excitatory signals at two spatial scales, one localized to nearest nodes and the other spatially extended to nodes millimeters away, and reveal that the distributions of the average incoming and outgoing synaptic strength are skewed with long tails.
]]></description>
<dc:creator>Sun, C.</dc:creator>
<dc:creator>Lin, K. C.</dc:creator>
<dc:creator>Huang, Y.-T.</dc:creator>
<dc:creator>Ching, E. S. C.</dc:creator>
<dc:creator>Lai, P.-Y.</dc:creator>
<dc:creator>Chan, C. K.</dc:creator>
<dc:date>2020-02-06</dc:date>
<dc:identifier>doi:10.1101/2020.02.06.936781</dc:identifier>
<dc:title><![CDATA[Directed effective connectivity and synaptic weights of invitro neuronal cultures revealed from high-density multielectrode array recordings]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-02-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.02.07.938399v1?rss=1">
<title>
<![CDATA[
Comparative transcriptomics across nematode life cycles reveal gene expression conservation and correlated evolution in adjacent developmental stages 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.02.07.938399v1?rss=1</link>
<description><![CDATA[
Nematodes are highly abundant animals with diverse habitats and lifestyles. Some are free-living while others parasitize animals or plants, and among the latter, infection abilities change across developmental stages to infect hosts and complete life cycles. Although parasitism has independently arisen multiple times over evolutionary history, common pressures of parasitism--such as adapting to the host environment, evading and subverting the host immune system, and changing environments across life cycles--have led phenotypes and developmental stages among parasites to converge. To determine the relationship between transcriptome evolution and morphological divergences among nematodes, we compared 48 transcriptomes of different developmental stages across eight nematode species. The transcriptomes were clustered broadly into embryo, larva, and adult stages, suggesting that gene expression is conserved to some extent across the entire nematode life cycle. Such patterns were partly accounted for by tissue-specific genes--such as those in oocytes and the hypodermis--being expressed at different proportions. Although nematodes typically have 3-5 larval stages, the transcriptomes for these stages were found to be highly correlated within each species, suggesting high similarity among larval stages across species. For the Caenorhabditis elegans-C. briggsae and Strongyloides stercoralis-S. venezuelensis comparisons, we found that around 50% of genes were expressed at multiple stages, whereas half of their orthologues were also expressed in multiple but different stages. Such frequent changes in expression have resulted in concerted transcriptome evolution across adjacent stages, thus generating species-specific transcriptomes over the course of nematode evolution. Our study provides a first insight into the evolution of nematode transcriptomes beyond embryonic development.
]]></description>
<dc:creator>Lu, M. R.</dc:creator>
<dc:creator>Lai, C.-K.</dc:creator>
<dc:creator>Liao, B.-Y.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2020-02-07</dc:date>
<dc:identifier>doi:10.1101/2020.02.07.938399</dc:identifier>
<dc:title><![CDATA[Comparative transcriptomics across nematode life cycles reveal gene expression conservation and correlated evolution in adjacent developmental stages]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-02-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.02.13.946657v1?rss=1">
<title>
<![CDATA[
Alteration of Power Law Scaling of Spontaneous Brain Activity in Schizophrenia 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.02.13.946657v1?rss=1</link>
<description><![CDATA[
Nonlinear dynamical analysis has been used to quantify the complexity of brain signal at temporal scales. Power law scaling is a well-validated method in physics that has been used to describe the complex nature of a system across different time scales. In this research, we investigated the change of power-law characteristics in a large-scale resting-state fMRI data of schizophrenia (N = 200) and healthy participants (N = 200) derived from Taiwan Aging and Mental Illness cohort. Fourier transform was used to determine the power spectral density (PSD) of resting-state fMRI signal. We estimated the power law scaling of PSD of resting-state fMRI signal by determining the slope of the regression line fitting to the log-log plot of PSD. The power law scaling represents the dynamical properties of resting-state fMRI signal ranging from noisy oscillation (e.g., white noise) to complex fluctuations (e.g., slope approaches -1). Linear regression model was used to assess the statistical difference in power law scaling between schizophrenia and healthy participants. The significant differences in power law scaling were found in six brain regions. Schizophrenia patients has significantly more positive power law scaling (i.e., frequency components become more homogenous) at four brain regions: left precuneus, left medial dorsal nucleus, right inferior frontal gyrus, and right middle temporal gyrus, compared with healthy participants. Additionally, schizophrenia exhibited less positive power law scaling (i.e., frequency components are more dominant at lower frequency range) in bilateral putamen. Significant correlations of power law scaling with the severity of psychosis were found in these identified brain areas in schizophrenia. These findings suggest that schizophrenia has abnormal brain signal complexity toward random patterns, which is linked to psychotic symptoms. The power law scaling analysis may serve as a novel functional brain imaging marker for evaluating patients with mental illness.
]]></description>
<dc:creator>Lee, Y.-J.</dc:creator>
<dc:creator>Huang, S.-Y.</dc:creator>
<dc:creator>Lin, C.-P.</dc:creator>
<dc:creator>Tsai, S.-J.</dc:creator>
<dc:creator>Yang, A. C.</dc:creator>
<dc:date>2020-02-13</dc:date>
<dc:identifier>doi:10.1101/2020.02.13.946657</dc:identifier>
<dc:title><![CDATA[Alteration of Power Law Scaling of Spontaneous Brain Activity in Schizophrenia]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-02-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.02.13.947093v1?rss=1">
<title>
<![CDATA[
A universal subcuticular bacterial symbiont of a coral predator, the crown-of-thorns starfish 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.02.13.947093v1?rss=1</link>
<description><![CDATA[
BackgroundPopulation outbreaks of the crown-of-thorns starfish (Acanthaster planci sensu lato; COTS), a primary predator of reef-building corals in the Indo-Pacific Ocean, are major concerns in coral reef management. While biological and ecological knowledge of COTS has been accumulating since the 1960s, little is known about its associated bacteria. The aim of this study was to provide fundamental information on dominant COTS-associated bacteria through a multifaceted molecular approach.

MethodsA total of 205 COTS individuals from 17 locations throughout the Indo-Pacific Ocean were examined for the presence of COTS-associated bacteria. We conducted 16S rRNA metabarcoding of COTS to determine the bacterial profiles of different parts of the body, and generated a full-length 16S rRNA gene sequence from a single dominant bacterium, which we designated COTS27. We performed phylogenetic analysis to determine the taxonomy, screening of COTS27 across the Indo-Pacific, FISH to visualize it within the COTS tissues, and reconstruction of the chromosome from the hologenome sequence data.

ResultsWe discovered that a single bacterium exists at high densities in the subcuticular space in COTS forming a biofilm-like structure between the cuticle and the epidermis. COTS27 belongs to a clade that presumably represents a distinct order (so-called marine spirochetes) in the phylum Spirochaetes and is universally present in COTS throughout the Indo-Pacific Ocean. The reconstructed genome of COTS27 includes some genetic traits that are probably linked to adaptation to marine environments and evolution as an extracellular endosymbiont in subcuticular spaces.

ConclusionsCOTS27 can be found in three allopatrically speciated COTS species, ranging from northern Red Sea to the Pacific, implying that symbiotic relationship arose before the speciation (approximately 2 million years ago). The universal association of COTS27 with COTS and nearly mono-specific association at least with the Indo-Pacific COTS potentially provides a useful model system for studying symbiont-host interactions in marine invertebrates.
]]></description>
<dc:creator>Wada, N.</dc:creator>
<dc:creator>Yuasa, H.</dc:creator>
<dc:creator>Kajitani, R.</dc:creator>
<dc:creator>Gotoh, Y.</dc:creator>
<dc:creator>Ogura, Y.</dc:creator>
<dc:creator>Yoshimura, D.</dc:creator>
<dc:creator>Toyoda, A.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:creator>Higashimura, Y.</dc:creator>
<dc:creator>Sweatman, H.</dc:creator>
<dc:creator>Forsman, Z. H.</dc:creator>
<dc:creator>Bronstein, O.</dc:creator>
<dc:creator>Eyal, G.</dc:creator>
<dc:creator>Thongtham, N.</dc:creator>
<dc:creator>Itoh, T.</dc:creator>
<dc:creator>Hayashi, T.</dc:creator>
<dc:creator>Yasuda, N.</dc:creator>
<dc:date>2020-02-14</dc:date>
<dc:identifier>doi:10.1101/2020.02.13.947093</dc:identifier>
<dc:title><![CDATA[A universal subcuticular bacterial symbiont of a coral predator, the crown-of-thorns starfish]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-02-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.02.18.953554v1?rss=1">
<title>
<![CDATA[
G protein-Coupled Receptor Distribution Impacts the Effectiveness of Signal Transmission. 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.02.18.953554v1?rss=1</link>
<description><![CDATA[
Numbers of activated receptor dictate efficacy of neurotransmitter stimulation. Many PLC coupled receptors activated by ligands elicit canonical downstream Gq/11 pathway to induce endogenous Ca2+ gated chloride channels. The coupling from receptors to effectors was analyzed in Xenopus oocytes expressing genetically modified angiotensin receptor type 1 receptor (AT1R). The latency between ATII binding and Ca2+-induced Cl- current surge was inversely correlated. AT1R activation triggered a chain of chemical reactions, of which the products were playing messengers for subsequent events. Messenger accumulation must rate-limit the agonism. For accurate quantification the speed of ATII triggered the i Cl-. The T-form AT1R-IRK1 fusion exhibits faster induction compared to the M-form. The latency of the recorded none vanished i Cl-, marking the lowest genuine calcium activation, took place at earlier time point by the timer time. The evoked i Cl- however reached similar maximal amplitudes. This kinetic effect raises the possibility to use temporal coding to complement amplitude coding (analogous to FM versus AM radio transmission) for receptor-agonist pairs.
]]></description>
<dc:creator>Chou, M.-Y.</dc:creator>
<dc:creator>Hu, Y.-Y.</dc:creator>
<dc:creator>Chuang, H.-h.</dc:creator>
<dc:date>2020-02-18</dc:date>
<dc:identifier>doi:10.1101/2020.02.18.953554</dc:identifier>
<dc:title><![CDATA[G protein-Coupled Receptor Distribution Impacts the Effectiveness of Signal Transmission.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-02-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.02.24.962415v1?rss=1">
<title>
<![CDATA[
Basal leakage in oscillation: coupled transcriptional and translational control using feed-forward loops 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.02.24.962415v1?rss=1</link>
<description><![CDATA[
The circadian clock is a complex system that plays many important roles in most organisms. Previously, many mathematical models have been used to sharpen our understanding of the Arabidopsis clock. However, these models are mostly dependent on transcriptional regulation, and the importance of post-translational regulation is still rarely discussed from theoretical aspects. In this study, we built a series of simplified oscillators with different regulations to study the importance of post-translational regulation (specifically, 26S proteasome degradation) in the clock system. We found that a simple transcriptional-based oscillator can already generate sustained oscillation, but the oscillation can be easily destroyed in the presence of transcriptional leakage. Coupling post-translational control with transcriptional-based oscillator in a feed-forward loop will greatly improve the robustness of the oscillator in the presence of basal leakage. Using these general models, we were able to replicate the increased variability observed in the E3 ligase mutant for both plant and mammalian clocks. With this insight, we also predict a plausible regulator of several E3 ligase genes in the plants clock. Thus, our results provide insights into and the plausible importance in coupling transcription and post-translation controls in the clock system.

Author summaryFor circadian clocks, several current models had successfully captured the essential dynamic behavior of the clock system mainly with transcriptional regulation. Previous studies have shown that the 26s (1, 2) proteasome degradation controls are important in maintaining the stability of circadian rhythms. However, how the loss-of-function or over-expression mutant of this targeted degradations lead to unstable oscillation is still unclear. In this work, we investigate the importance of coupled transcriptional and post-translational feedback loop in the circadian oscillator. With general models our study indicate that the unstable behavior of degradation mutants could be caused by the increase in the basal level of the clock genes. We found that coupling a non-linear degradation control into this transcriptional based oscillator using feed-forward loop improves the robustness of the oscillator. Using this finding, we further predict some plausible regulators of Arabidopsiss E3 ligase protein such as COP1 and SINAT5. Hence, our results provide insights on the importance of coupling transcription and post-translation controls in the clock system.
]]></description>
<dc:creator>Hsu, C.-P.</dc:creator>
<dc:creator>Joanito, I.</dc:creator>
<dc:creator>Sanders, C.-C.</dc:creator>
<dc:creator>Chu, J.-W.</dc:creator>
<dc:creator>Wu, S.-H.</dc:creator>
<dc:date>2020-02-24</dc:date>
<dc:identifier>doi:10.1101/2020.02.24.962415</dc:identifier>
<dc:title><![CDATA[Basal leakage in oscillation: coupled transcriptional and translational control using feed-forward loops]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-02-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.02.28.970210v1?rss=1">
<title>
<![CDATA[
Parkin coordinates mitochondrial lipid remodeling to execute mitophagy 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.02.28.970210v1?rss=1</link>
<description><![CDATA[
Mitochondrial failure caused by Parkin mutations contributes to Parkinsons disease. Parkin binds, ubiquitinates, and targets impaired mitochondria for autophagic destruction. Robust mitophagy involves peri-nuclear concentration of Parkin-tagged mitochondria, followed by dissemination of juxtanuclear mitochondrial aggregates, and efficient sequestration of individualized mitochondria by autophagosomes. Here, we report that the execution of complex mitophagic events requires active mitochondrial lipid remodeling. Parkin recruits phospholipase D2 to the depolarized mitochondria and generate phosphatidic acid (PA). Mitochondrial PA is subsequently converted to diacylglycerol (DAG) by Lipin-1 phosphatase-a process that further requires mitochondrial ubiquitination and ubiquitin-binding autophagic receptors, NDP52 and Optineurin. We show that Optineurin transports, via Golgi-derived vesicles, a PA-binding factor EndoB1 to ubiquitinated mitochondria, thereby facilitating DAG production. Mitochondrial DAG activates both F-actin assembly to drive mitochondrial individualization, and autophagosome biogenesis to efficiently restrict impaired mitochondria. Thus Parkin, autophagic receptors and the Golgi complex orchestrate mitochondrial lipid remodeling to execute robust mitophagy.
]]></description>
<dc:creator>Lin, C.-C.</dc:creator>
<dc:creator>Yan, J.</dc:creator>
<dc:creator>Kapur, M. D.</dc:creator>
<dc:creator>Norris, K. L.</dc:creator>
<dc:creator>Hsieh, C.-W.</dc:creator>
<dc:creator>Lai, C.-H.</dc:creator>
<dc:creator>Vitale, N.</dc:creator>
<dc:creator>Lim, K.-L.</dc:creator>
<dc:creator>Guan, Z.</dc:creator>
<dc:creator>Chi, J.-T.</dc:creator>
<dc:creator>Yang, W.-Y.</dc:creator>
<dc:creator>Yao, T.-P.</dc:creator>
<dc:date>2020-02-28</dc:date>
<dc:identifier>doi:10.1101/2020.02.28.970210</dc:identifier>
<dc:title><![CDATA[Parkin coordinates mitochondrial lipid remodeling to execute mitophagy]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-02-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.03.06.980706v1?rss=1">
<title>
<![CDATA[
PIP3 depletion rescues myoblast fusion defects in human rhabdomyosarcoma cells 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.03.06.980706v1?rss=1</link>
<description><![CDATA[
Myoblast fusion is required for myotube formation during myogenesis, and defects in myoblast differentiation and fusion have been implicated in a number of diseases, including human rhabdomyosarcoma. While the transcriptional regulation of the myogenic program has been studied extensively, the mechanisms controlling myoblast fusion remain largely unknown. This study identified and characterized the dynamics of a distinct class of blebs, termed bubbling blebs, which are smaller than those that participate in migration. The formation of these bubbling blebs occurred during differentiation and decreased alongside a decline in phosphatidylinositol-(3,4,5)-trisphosphate (PIP3) at the plasma membrane before myoblast fusion. In a human rhabdomyosarcoma-derived (RD) cell line that exhibits strong blebbing dynamics and myoblast fusion defects, PIP3 was constitutively abundant on the membrane during myogenesis. Targeting phosphatase and tensin homolog (PTEN) to the plasma membrane reduced PIP3 levels, inhibited bubbling blebs, and rescued myoblast fusion defects in RD cells. These findings highlight the differential distribution and crucial role of PIP3 during myoblast fusion and reveal a novel mechanism underlying myogenesis defects in human rhabdomyosarcoma.

Summary StatementThis study reveals a novel mechanism underlying myogenesis defects in human rhabdomyosarcoma cells involving PIP3, whose depletion with PTEN rescues myoblast fusion defects.
]]></description>
<dc:creator>Lian, Y.-L.</dc:creator>
<dc:creator>Chen, K.-W.</dc:creator>
<dc:creator>Chou, Y.-T.</dc:creator>
<dc:creator>Ke, T.-L.</dc:creator>
<dc:creator>Chen, B.-C.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Chen, L.</dc:creator>
<dc:date>2020-03-07</dc:date>
<dc:identifier>doi:10.1101/2020.03.06.980706</dc:identifier>
<dc:title><![CDATA[PIP3 depletion rescues myoblast fusion defects in human rhabdomyosarcoma cells]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-03-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.03.12.988089v1?rss=1">
<title>
<![CDATA[
Standardization and Harmonization of Distributed Multi-National Proteotype Analysis supporting Precision Medicine Studies 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.03.12.988089v1?rss=1</link>
<description><![CDATA[
Cancer has no borders: Generation and analysis of molecular data across multiple centers worldwide is necessary to gain statistically significant clinical insights for the benefit of patients. Here we conceived and standardized a proteotype data generation and analysis workflow enabling distributed data generation and evaluated the quantitative data generated across laboratories of the international Cancer Moonshot consortium. Using harmonized mass spectrometry (MS) instrument platforms and standardized data acquisition procedures, we demonstrated robust, sensitive, and reproducible data generation across eleven sites in nine countries on seven consecutive days in a 24/7 operation mode. The data presented from the high-resolution MS1-based quantitative data-independent acquisition (HRMS1-DIA) workflow shows that coordinated proteotype data acquisition is feasible from clinical specimens using such standardized strategies. This work paves the way for the distributed multi-omic digitization of large clinical specimen cohorts across multiple sites as a prerequisite for turning molecular precision medicine into reality.
]]></description>
<dc:creator>Xuan, Y.</dc:creator>
<dc:creator>Bateman, N. W.</dc:creator>
<dc:creator>Gallien, S.</dc:creator>
<dc:creator>Goetze, S.</dc:creator>
<dc:creator>Zhou, Y.</dc:creator>
<dc:creator>Navarro, P.</dc:creator>
<dc:creator>Hu, M.</dc:creator>
<dc:creator>Parikh, N.</dc:creator>
<dc:creator>Hood, B. L.</dc:creator>
<dc:creator>Conrads, K. A.</dc:creator>
<dc:creator>Loosse, C.</dc:creator>
<dc:creator>Kitata, R. B.</dc:creator>
<dc:creator>Piersma, S. R.</dc:creator>
<dc:creator>Chiasserini, D.</dc:creator>
<dc:creator>Zhu, H.</dc:creator>
<dc:creator>Hou, G.</dc:creator>
<dc:creator>Tahir, M.</dc:creator>
<dc:creator>Macklin, A.</dc:creator>
<dc:creator>Khoo, A.</dc:creator>
<dc:creator>Sun, X.</dc:creator>
<dc:creator>Crossett, B.</dc:creator>
<dc:creator>Sickmann, A.</dc:creator>
<dc:creator>Chen, Y.-J.</dc:creator>
<dc:creator>Jimenez, C. R.</dc:creator>
<dc:creator>Zhou, H.</dc:creator>
<dc:creator>Liu, S.</dc:creator>
<dc:creator>Larsen, M. R.</dc:creator>
<dc:creator>Kislinger, T.</dc:creator>
<dc:creator>Chen, Z.</dc:creator>
<dc:creator>Parker, B. L.</dc:creator>
<dc:creator>Cordwell, S. J.</dc:creator>
<dc:creator>Wollscheid, B.</dc:creator>
<dc:creator>Conrads, T. P.</dc:creator>
<dc:date>2020-03-12</dc:date>
<dc:identifier>doi:10.1101/2020.03.12.988089</dc:identifier>
<dc:title><![CDATA[Standardization and Harmonization of Distributed Multi-National Proteotype Analysis supporting Precision Medicine Studies]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-03-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.03.16.994426v1?rss=1">
<title>
<![CDATA[
TPX2 activation by GM130 controls astral microtubule formation and spindle orientation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.03.16.994426v1?rss=1</link>
<description><![CDATA[
Spindle orientation is important in multiple developmental processes as it determines cell fate and function. The correct orientation of the mitotic spindle depends on the assembly of a proper astral microtubule network. Here, we report that the spindle assembly factor TPX2 regulates the astral microtubule network. TPX2 in the spindle pole area is activated by GM130 on mitotic Golgi membranes to promote astral microtubule growth. GM130 relieves TPX2 inhibition by competing for importin  binding. During mitosis, phosphorylation of importin  at Serine 62 by Cdk1 switches its substrate preference from TPX2 to GM130, thereby enabling competition-based activation. Importin  S62A impedes local TPX2 activation and compromises astral microtubule formation, ultimately resulting in misoriented spindles. Blocking the GM130-importin -TPX2 pathway impairs astral microtubule growth. Our results reveal a novel role for TPX2 in the organization of astral microtubules. Furthermore, we show that the substrate preference of the important mitotic modulator importin  is regulated by Cdk1 phosphorylation.
]]></description>
<dc:creator>Guo, H.</dc:creator>
<dc:creator>Wei, J.-H.</dc:creator>
<dc:creator>Seemann, J.</dc:creator>
<dc:date>2020-03-17</dc:date>
<dc:identifier>doi:10.1101/2020.03.16.994426</dc:identifier>
<dc:title><![CDATA[TPX2 activation by GM130 controls astral microtubule formation and spindle orientation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-03-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.03.18.997080v1?rss=1">
<title>
<![CDATA[
Activation of JUN in fibroblasts promotes pro-fibrotic programme and modulates protective immunity 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.03.18.997080v1?rss=1</link>
<description><![CDATA[
In pulmonary fibrosis, the transcription factor JUN is highly expressed in the fibrotic foci. Its induction in adult mice drives lung fibrosis, which is abrogated by administration of anti-CD47. Here, we use high-dimensional mass cytometry to profile protein expression and the secretome of individual fibroblasts and leukocytes from pulmonary fibrosis patients. We show that JUN is activated in fibroblasts derived from fibrotic lungs which also demonstrated increased CD47 and PD-L1 expression. Using ATAC-seq and ChIP-seq, we found that activation of JUN in fibroblasts rendered enhancers of CD47 and PD-L1 accessible, an observation that reporter assays corroborated. Meanwhile we detected increased IL-6 signaling which amplified both JUN-mediated CD47-enhancer activity and protein expression in fibrotic lung fibroblasts. Using an in vivo mouse model of fibrosis, we found two distinct mechanisms by which blocking IL-6, CD47, and PD-L1 reversed fibrosis--increased phagocytosis of profibrotic fibroblasts and elimination of suppressive effects on adaptive immunity. Our results identify specific immune mechanisms that promote the fibrotic process and suggest a complementary therapeutic approach that could be used alongside conventional anti-fibrotics for pulmonary fibrosis diseases.
]]></description>
<dc:creator>Cui, L.</dc:creator>
<dc:creator>Chen, S.-Y.</dc:creator>
<dc:creator>Lerbs, T.</dc:creator>
<dc:creator>Lee, J.-W.</dc:creator>
<dc:creator>Domizi, P.</dc:creator>
<dc:creator>Gordon, S.</dc:creator>
<dc:creator>Kim, Y.-h.</dc:creator>
<dc:creator>Nolan, G. P.</dc:creator>
<dc:creator>Betancur, P.</dc:creator>
<dc:creator>Wernig, G.</dc:creator>
<dc:date>2020-03-20</dc:date>
<dc:identifier>doi:10.1101/2020.03.18.997080</dc:identifier>
<dc:title><![CDATA[Activation of JUN in fibroblasts promotes pro-fibrotic programme and modulates protective immunity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-03-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.03.26.009159v1?rss=1">
<title>
<![CDATA[
Medicago truncatula Yellow Stripe-Like7 encodes a peptide transporter required for symbiotic nitrogen fixation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.03.26.009159v1?rss=1</link>
<description><![CDATA[
Yellow Stripe-Like (YSL) proteins are a family of plant transporters typically involved in transition metal homeostasis. The substrate of three of the four YSL clades (clades I, II, and IV) are metal complexes with non-proteinogenic amino acid nicotianamine or its derivatives. No such transport capabilities have been shown for any member of the remaining clade (clade III), which is able to translocate short peptides across the membranes instead. The connection between clade III YSL members and metal homeostasis might have been masked by the functional redundancy characteristic of this family. This might have been circumvented in legumes through neofunctionalization of YSLs to ensure a steady supply of transition metals for symbiotic nitrogen fixation in root nodules. To test this possibility, Medicago truncatula clade III transporter MtYSL7 has been studied both when the plant was fertilized with ammonium nitrate or when nitrogen had to be provided by endosymbiotic rhizobia within the root nodules. MtYSL7 is a plasma membrane protein expressed in the vasculature and in the nodule cortex. This protein is able to transport short peptides into the cytosol, although none with known metal homeostasis roles. Reducing MtYSL7 expression levels resulted in diminished nitrogen fixation rates. In addition, nodules of mutant lines lacking YSL7 accumulated more copper and iron, the later the likely result of increased expression in roots of iron uptake and delivery genes. The available data is indicative of a role of MtYSL7, and likely other clade III YSLs, in transition metal homeostasis.

ONE SENTENCE SUMMARYMedicago truncatula YSL7 is a peptide transporter required for symbiotic nitrogen fixation in legume nodules, likely controlling transition metal allocation to these organs.
]]></description>
<dc:creator>Castro-Rodriguez, R.</dc:creator>
<dc:creator>Reguera, M.</dc:creator>
<dc:creator>Escudero, V.</dc:creator>
<dc:creator>Gil-Diez, P.</dc:creator>
<dc:creator>Quintana, J.</dc:creator>
<dc:creator>Prieto, R. I.</dc:creator>
<dc:creator>Kumar, R. K.</dc:creator>
<dc:creator>Brear, E.</dc:creator>
<dc:creator>Grillet, L.</dc:creator>
<dc:creator>Wen, J.</dc:creator>
<dc:creator>Mysore, K. S.</dc:creator>
<dc:creator>Walker, E. L.</dc:creator>
<dc:creator>Smith, P. M.</dc:creator>
<dc:creator>Imperial, J.</dc:creator>
<dc:creator>Gonzalez-Guerrero, M.</dc:creator>
<dc:date>2020-03-27</dc:date>
<dc:identifier>doi:10.1101/2020.03.26.009159</dc:identifier>
<dc:title><![CDATA[Medicago truncatula Yellow Stripe-Like7 encodes a peptide transporter required for symbiotic nitrogen fixation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-03-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.03.27.012625v1?rss=1">
<title>
<![CDATA[
Redirected tropisms of extracellular vesicles and exomeres yield distinct biodistribution profiles 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.03.27.012625v1?rss=1</link>
<description><![CDATA[
Extracellular particles (EP) including extracellular vesicles (EVs) and exomeres have been shown to play significant roles in diseases and therapeutic applications. However, their spatiotemporal dynamics in vivo have remained largely unresolved in detail due to the lack of a suitable method. We therefore created a bioluminescence resonance energy transfer (BRET)-based reporter, PalmGRET, to enable pan-EP labelling ranging from exomeres (< 50 nm) to small (< 200 nm) and medium and large (> 200 nm) EVs. PalmGRET emits robust, sustained signals and allows the visualization, tracking and quantification of the EPs from whole-animal to nanoscopic resolutions under different imaging modalities, including bioluminescence, BRET and fluorescence. Using PalmGRET, we show that EPs released by lung metastatic hepatocellular carcinoma (HCC) exhibit lung tropism with varying distributions to other major organs in immunocompetent mice. We further demonstrate that gene knockdown of lung-tropic membrane proteins, solute carrier organic anion transporter family member 2A1 (Slco2a1), alanine aminopeptidase (Cd13) and chloride intracellular channel (Clic1) decreases HCC-EP distribution to the lungs and yields distinct biodistribution profiles. We anticipate that EP-specific imaging, quantitative assays and detailed in vivo characterization to be a starting point for more accurate and comprehensive in vivo models of EP biology and therapeutic design.
]]></description>
<dc:creator>Wu, A. Y.-T.</dc:creator>
<dc:creator>Sung, Y.-C.</dc:creator>
<dc:creator>Chou, S. T.-Y.</dc:creator>
<dc:creator>Guo, V.</dc:creator>
<dc:creator>Chien, J. C.-Y.</dc:creator>
<dc:creator>Ko, J. J.-S.</dc:creator>
<dc:creator>Yang, A. L.</dc:creator>
<dc:creator>Chuang, J.-C.</dc:creator>
<dc:creator>Huang, H.-C.</dc:creator>
<dc:creator>Wu, Y.</dc:creator>
<dc:creator>Ho, M.-R.</dc:creator>
<dc:creator>Ericsson, M.</dc:creator>
<dc:creator>Lin, W.-W.</dc:creator>
<dc:creator>Cheung, C. H. Y.</dc:creator>
<dc:creator>Juan, H.-F.</dc:creator>
<dc:creator>Ueda, K.</dc:creator>
<dc:creator>Chen, Y.</dc:creator>
<dc:creator>Lai, C. P.-K.</dc:creator>
<dc:date>2020-03-28</dc:date>
<dc:identifier>doi:10.1101/2020.03.27.012625</dc:identifier>
<dc:title><![CDATA[Redirected tropisms of extracellular vesicles and exomeres yield distinct biodistribution profiles]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-03-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.03.30.015271v1?rss=1">
<title>
<![CDATA[
A multiplexed bioluminescent reporter for sensitive and non-invasive tracking of DNA double strand break repair dynamics in vitro and in vivo 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.03.30.015271v1?rss=1</link>
<description><![CDATA[
Tracking DNA double strand break (DSB) repair is paramount for the understanding and therapeutic development of various diseases including cancers. Herein, we describe a multiplexed bioluminescent repair reporter (BLRR) for non-invasive monitoring of DSB repair pathways in living cells and animals. The BLRR approach employs secreted Gaussia and Vargula luciferases to simultaneously detect homology-directed repair (HDR) and non-homologous end joining (NHEJ), respectively. BLRR data are consistent with next-generation sequencing results for reporting HDR (R2 = 0.9722) and NHEJ (R2 = 0.919) events. Moreover, BLRR analysis allows longitudinal tracking of HDR and NHEJ activities in cells, and enables detection of DSB repairs in xenografted tumours in vivo. Using the BLRR system, we observed a significant difference in the efficiency of CRISPR/Cas9-mediated editing with guide RNAs only 1-10 bp apart. Moreover, BLRR analysis detected altered dynamics for DSB repair induced by small-molecule modulators. Finally, we discovered HDR-suppressing functions of anticancer cardiac glycosides in human glioblastomas and glioma cancer stem-like cells via inhibition of DNA repair protein RAD51 homolog 1 (RAD51). The BLRR method provides a highly sensitive platform to simultaneously and longitudinally track HDR and NHEJ dynamics that is sufficiently versatile for elucidating the physiology and therapeutic development of DSB repair.
]]></description>
<dc:creator>Chien, J. C.</dc:creator>
<dc:creator>Tabet, E.</dc:creator>
<dc:creator>Pinkham, K.</dc:creator>
<dc:creator>da Hora, C. C.</dc:creator>
<dc:creator>Chang, J. C.</dc:creator>
<dc:creator>Lin, S.</dc:creator>
<dc:creator>Badr, C. E.</dc:creator>
<dc:creator>Lai, C. P.</dc:creator>
<dc:date>2020-03-31</dc:date>
<dc:identifier>doi:10.1101/2020.03.30.015271</dc:identifier>
<dc:title><![CDATA[A multiplexed bioluminescent reporter for sensitive and non-invasive tracking of DNA double strand break repair dynamics in vitro and in vivo]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-03-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.04.12.038554v1?rss=1">
<title>
<![CDATA[
The origin and underlying driving forces of the SARS-CoV-2 outbreak 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.04.12.038554v1?rss=1</link>
<description><![CDATA[
The spread of SARS-CoV-2 since December 2019 has become a pandemic and impacted many aspects of human society. Here, we analyzed genetic variation of SARS-CoV-2 and its related coronavirus and found the evidence of intergenomic recombination. After correction for mutational bias, analysis of 137 SARS-CoV-2 genomes as of 2/23/2020 revealed the excess of low frequency mutations on both synonymous and nonsynonymous sites which is consistent with recent origin of the virus. In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China was two time higher than those derived from the rest of the world. In addition, in network analysis, haplotypes collected from Wuhan city were at interior and have more mutational connections, both of which are consistent with the observation that the outbreak of cov-19 was originated from China.

SUMMARYIn contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated.
]]></description>
<dc:creator>Chaw, S.-M.</dc:creator>
<dc:creator>Tai, J.-H.</dc:creator>
<dc:creator>Chen, S.-L.</dc:creator>
<dc:creator>Hsieh, C.-H.</dc:creator>
<dc:creator>Chang, S.-Y.</dc:creator>
<dc:creator>Yeh, S.-H.</dc:creator>
<dc:creator>Yang, W.-S.</dc:creator>
<dc:creator>Chen, P.-J.</dc:creator>
<dc:creator>Wang, H.-Y.</dc:creator>
<dc:date>2020-04-14</dc:date>
<dc:identifier>doi:10.1101/2020.04.12.038554</dc:identifier>
<dc:title><![CDATA[The origin and underlying driving forces of the SARS-CoV-2 outbreak]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-04-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.04.13.038844v1?rss=1">
<title>
<![CDATA[
Mitochondrial ROS1 increases mitochondrial fission and respiration in oral squamous cancer carcinoma 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.04.13.038844v1?rss=1</link>
<description><![CDATA[
Increased ROS1 oncogene expression has been implicated in the invasiveness of human oral squamous cell carcinoma (OSCC). The cellular distribution of ROS1 has long been assumed at the plasma membrane. However, a previous work reported a differential cellular distribution of mutant ROS1 derived from chromosomal translocation, resulting in increased carcinogenesis. We thus hypothesized that cellular distribution of up-regulated ROS1 in OSCC may correlate with invasiveness. We found that ROS1 can localize to mitochondria in the highly invasive OSCC and identified a mitochondria-targeting signal sequence in ROS1. We also demonstrated that ROS1 targeting to mitochondria is required for mitochondrial fission phenotype in the highly invasive OSCC cells. OSCC cells expressing high levels of ROS1 consumed more oxygen and had increased levels of cellular ATP levels. Our results also revealed that ROS1 regulates mitochondrial biogenesis and cellular metabolic plasticity. Together, these findings demonstrate that ROS1 targeting to mitochondria enhances OSCC invasion through regulating mitochondrial morphogenesis and cellular respiratory.

Summary StatementThis study discovers a new role for the ROS1 in mitochondrial fission and metabolic activities.
]]></description>
<dc:creator>Chang, Y.-J.</dc:creator>
<dc:creator>Chen, K.-W.</dc:creator>
<dc:creator>Chen, L.</dc:creator>
<dc:date>2020-04-13</dc:date>
<dc:identifier>doi:10.1101/2020.04.13.038844</dc:identifier>
<dc:title><![CDATA[Mitochondrial ROS1 increases mitochondrial fission and respiration in oral squamous cancer carcinoma]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-04-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.04.22.055863v1?rss=1">
<title>
<![CDATA[
Genomic, geographic and temporal distributions of SARS-CoV-2 mutations 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.04.22.055863v1?rss=1</link>
<description><![CDATA[
The COVID-19 pandemic is the most significant public health issue in recent history. Its causal agent, SARS-CoV-2, has evolved rapidly since its first emergence in December 2019. Mutations in the viral genome have critical impacts on the adaptation of viral strains to the local environment, and may alter the characteristics of viral transmission, disease manifestation, and the efficacy of treatment and vaccination. Using the complete sequences of 1,932 SARS-CoV-2 genomes, we examined the genomic, geographic and temporal distributions of aged, new, and frequent mutations of SARS-CoV-2, and identified six phylogenetic clusters of the strains, which also exhibit a geographic preference in different continents. Mutations in the form of single nucleotide variations (SNVs) provide a direct interpretation for the six phylogenetic clusters. Linkage disequilibrium, haplotype structure, evolutionary process, global distribution of mutations unveiled a sketch of the mutational history. Additionally, we found a positive correlation between the average mutation count and case fatality, and this correlation had strengthened with time, suggesting an important role of SNVs on disease outcomes. This study suggests that SNVs may become an important consideration in virus detection, clinical treatment, drug design, and vaccine development to avoid target shifting, and that continued isolation and sequencing is a crucial component in the fight against this pandemic.

Significance StatementMutation is the driving force of evolution for viruses like SARS-CoV-2, the causal agent of COVID-19. In this study, we discovered that the genome of SARS-CoV-2 is changing rapidly from the originally isolated form. These mutations have been spreading around the world and caused more than 2.5 million of infected cases and 170 thousands of deaths. We found that fourteen frequent mutations identified in this study can characterize the six main clusters of SARS-CoV-2 strains. In addition, we found the mutation burden is positively correlated with the fatality of COVID-19 patients. Understanding mutations in the SARS-CoV-2 genome will provide useful insight for the design of treatment and vaccination.
]]></description>
<dc:creator>Yang, H.-C.</dc:creator>
<dc:creator>Chen, C.-h.</dc:creator>
<dc:creator>Wang, J.-H.</dc:creator>
<dc:creator>Liao, H.-C.</dc:creator>
<dc:creator>Yang, C.-T.</dc:creator>
<dc:creator>Chen, C.-W.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Kao, C.-H.</dc:creator>
<dc:creator>Liao, J. C.</dc:creator>
<dc:date>2020-04-24</dc:date>
<dc:identifier>doi:10.1101/2020.04.22.055863</dc:identifier>
<dc:title><![CDATA[Genomic, geographic and temporal distributions of SARS-CoV-2 mutations]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-04-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.04.29.068361v1?rss=1">
<title>
<![CDATA[
Molecular basis for the ATPase-powered substrate translocation by the Lon AAA+ protease 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.04.29.068361v1?rss=1</link>
<description><![CDATA[
The Lon AAA+ (adenosine triphosphatases associated with diverse cellular activities) protease (LonA) converts ATP-fuelled conformational changes into sufficient mechanical force to drive translocation of the substrate into a hexameric proteolytic chamber. To understand the structural basis for the substrate translocation process, we have determined the cryo-electron microscopy (cryo-EM) structure of Meiothermus taiwanensis LonA (MtaLonA) at 3.6 [A] resolution in a substrate-engaged state. Substrate interactions are mediated by the dual pore-loops of the ATPase domains, organized in spiral staircase arrangement from four consecutive protomers in different ATP-binding and hydrolysis states; a closed AAA+ ring is nevertheless maintained by two disengaged ADP-bound protomers transiting between the lowest and highest position. The structure reveals a processive rotary translocation mechanism mediated by LonA-specific nucleotide-dependent allosteric coordination among the ATPase domains, which is induced by substrate binding.
]]></description>
<dc:creator>Zhang, K.</dc:creator>
<dc:creator>Li, S.</dc:creator>
<dc:creator>Hsieh, K.-Y.</dc:creator>
<dc:creator>Su, S.-C.</dc:creator>
<dc:creator>Pintilie, G. D.</dc:creator>
<dc:creator>Chiu, W.</dc:creator>
<dc:creator>Chang, C.-I.</dc:creator>
<dc:date>2020-04-30</dc:date>
<dc:identifier>doi:10.1101/2020.04.29.068361</dc:identifier>
<dc:title><![CDATA[Molecular basis for the ATPase-powered substrate translocation by the Lon AAA+ protease]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-04-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.04.30.069955v1?rss=1">
<title>
<![CDATA[
Epigenetic therapy remodels the immune synaptic cytoskeleton to potentiate cancer susceptibility to γδ T cells 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.04.30.069955v1?rss=1</link>
<description><![CDATA[
{gamma}{delta} T cells are a distinct subgroup of T cells that bridge the innate and adaptive immune systems and can attack cancer or virus-infected cells in an MHC-unrestricted manner. Despite its antitumor ability in both autologous and allogeneic settings, earlier trials of adoptive {gamma}{delta} T cell transfer in solid tumors had limited success due to limitations in cell expansion and the lack of a strategy to modulate tumor lytic interactions between {gamma}{delta} T and cancer cells. Here, we show through quantitative surface proteomics and gene enrichment analyses that DNA methyltransferase inhibitors (DNMTis) upregulate multiple surface molecules related to {gamma}{delta} T cell activation in cancer cells. DNMTi treatment of human lung cancer potentiates tumor lysis by ex vivo-expanded {gamma}{delta} T cells using a clinical-grade expansion protocol developed by our team to enrich for the V{delta}1 subset while preserving their antitumor effector functions. Mechanistically, DNMTis enhance immune synapse formation and stabilize the synaptic cleft to facilitate {gamma}{delta} T-mediated tumor lysis. Through integrated analysis of RNA-seq, DNA methylation, and ATAC-seq, we demonstrate that depletion of DNMTs induces coordinated pattern alterations of immune synaptic-cytoskeletal networks at the cancer side of the immune synapse. In addition, single-cell mass cytometry reveals enrichment of polyfunctional {gamma}{delta} T subsets by DNMTis. Combined DNMTi and adoptive {gamma}{delta} T transfer in a mouse lung cancer model offers a significant survival benefit. Consistently, the DNMTi-associated cytoskeleton signature identifies a subset of lung cancer patients with improved survival. Our results demonstrate that epigenetic mechanisms are crucial for cytoskeletal remodeling in cancer to potentiate immune attack and support a combinatorial strategy of DNMTis and {gamma}{delta} T cell-based immunotherapy in lung cancer management.

One Sentence SummaryDNA methyltransferase inhibitors potentiate the killing of lung cancer by {gamma}{delta} T cells through remodeling cytoskeletal-immune synaptic networks.
]]></description>
<dc:creator>Weng, R. R.</dc:creator>
<dc:creator>Lu, H.-H.</dc:creator>
<dc:creator>Lin, C.-T.</dc:creator>
<dc:creator>Fan, C.-C.</dc:creator>
<dc:creator>Lin, R.-S.</dc:creator>
<dc:creator>Huang, T.-C.</dc:creator>
<dc:creator>Lin, S.-Y.</dc:creator>
<dc:creator>Huang, Y.-J.</dc:creator>
<dc:creator>Juan, Y.-H.</dc:creator>
<dc:creator>Wu, Y.-C.</dc:creator>
<dc:creator>Hung, Z.-C.</dc:creator>
<dc:creator>Liu, C.</dc:creator>
<dc:creator>Lin, X.-H.</dc:creator>
<dc:creator>Hsieh, W.-C.</dc:creator>
<dc:creator>Chiu, T.-Y.</dc:creator>
<dc:creator>Liao, J.-C.</dc:creator>
<dc:creator>Chiu, Y.-L.</dc:creator>
<dc:creator>Chen, S.-Y.</dc:creator>
<dc:creator>Yu, C.-J.</dc:creator>
<dc:creator>Tsai, H.-C.</dc:creator>
<dc:date>2020-05-02</dc:date>
<dc:identifier>doi:10.1101/2020.04.30.069955</dc:identifier>
<dc:title><![CDATA[Epigenetic therapy remodels the immune synaptic cytoskeleton to potentiate cancer susceptibility to γδ T cells]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-05-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.05.03.075325v1?rss=1">
<title>
<![CDATA[
Antagonistic Effects of Intraspecific Cooperation and Interspecific Competition on Thermal Performance 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.05.03.075325v1?rss=1</link>
<description><![CDATA[
Understanding how climate-mediated biotic interactions shape thermal niche width is critical in an era of global change. Yet, most previous work on thermal niches has ignored detailed mechanistic information about the relationship between temperature and organismal performance, which can be described by a thermal performance curve. Here, we develop a model that predicts the width of thermal performance curves will be narrower in the presence of interspecific competitors, causing a species optimal breeding temperature to diverge from that of a competitor. We test this prediction in the Asian burying beetle Nicrophorus nepalensis, confirming that the divergence in actual and optimal breeding temperatures is the result of competition with blowflies. However, we further show that intraspecific cooperation enables beetles to outcompete blowflies by recovering their optimal breeding temperature. Ultimately, linking direct (abiotic factors) and indirect effects (biotic interactions) on niche width will be critical for understanding species-specific responses to climate change.
]]></description>
<dc:creator>Tsai, H.-Y.</dc:creator>
<dc:creator>Rubenstein, D. R.</dc:creator>
<dc:creator>Chen, B.-F.</dc:creator>
<dc:creator>Liu, M.</dc:creator>
<dc:creator>Chan, S.-F.</dc:creator>
<dc:creator>Chen, D.-P.</dc:creator>
<dc:creator>Sun, S.-J.</dc:creator>
<dc:creator>Yuan, T.-N.</dc:creator>
<dc:creator>Shen, S.-F.</dc:creator>
<dc:date>2020-05-04</dc:date>
<dc:identifier>doi:10.1101/2020.05.03.075325</dc:identifier>
<dc:title><![CDATA[Antagonistic Effects of Intraspecific Cooperation and Interspecific Competition on Thermal Performance]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-05-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.05.06.079921v1?rss=1">
<title>
<![CDATA[
Mycena genomes resolve the evolution of fungal bioluminescence 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.05.06.079921v1?rss=1</link>
<description><![CDATA[
Mushroom-forming fungi in the order Agaricales represent an independent origin of bioluminescence in the tree of life, yet the diversity, evolutionary history, and timing of the origin of fungal luciferases remain elusive. We sequenced the genomes and transcriptomes of five bonnet mushroom species (Mycena spp.), a diverse lineage comprising the majority of bioluminescent fungi. Two species with haploid genome assemblies [~]150Mb are amongst the largest in Agaricales, and we found that a variety of repeats between Mycena species were differentially mediated by DNA methylation. We show that bioluminescence evolved in the last common ancestor of mycenoid and the marasmioid clade of Agaricales and was maintained through at least 160 million years of evolution. Analyses of synteny across genomes of bioluminescent species resolved how the luciferase cluster was derived by duplication and translocation, frequently rearranged and lost in most Mycena species, but conserved in the Armillaria lineage. Luciferase cluster members were co-expressed across developmental stages, with highest expression in fruiting body caps and stipes, suggesting fruiting-related adaptive functions. Our results contribute to understanding a de novo origin of bioluminescence and the corresponding gene cluster in a diverse group of enigmatic fungal species.

SignificanceWe present the genomes of five new bonnet mushroom Mycena species, formerly the last fungal bioluminescent lineage lacking reference genomes. These genome-scale datasets allowed us to construct an evolutionary model pinpointing all possible changes in the luciferase cluster across all fungi and additional genes involved in bioluminescence. We show that luciferase clusters were differentially lost in different fungal lineages and in particular a substantial loss was observed in the Mycena lineage. This can be attributed to genome regions of Mycena underwent different evolutionary dynamics. Our findings offer insights into the evolution of how a gene cluster that emerged 160 million years ago and was frequently lost or maintained due to differences in genome plasticity.
]]></description>
<dc:creator>Ke, H.-M.</dc:creator>
<dc:creator>Lee, H.-H.</dc:creator>
<dc:creator>Lin, C.-Y. I.</dc:creator>
<dc:creator>Liu, Y.-C.</dc:creator>
<dc:creator>Lu, M. R.</dc:creator>
<dc:creator>Hsieh, J.-W. A.</dc:creator>
<dc:creator>Chang, C.-C.</dc:creator>
<dc:creator>Wu, P.-H.</dc:creator>
<dc:creator>Lu, M. J.</dc:creator>
<dc:creator>Li, J.-Y.</dc:creator>
<dc:creator>Shang, G.</dc:creator>
<dc:creator>Lu, R. J.-H.</dc:creator>
<dc:creator>Nagy, L. G.</dc:creator>
<dc:creator>Chen, P.-Y.</dc:creator>
<dc:creator>Kao, H.-W.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2020-05-07</dc:date>
<dc:identifier>doi:10.1101/2020.05.06.079921</dc:identifier>
<dc:title><![CDATA[Mycena genomes resolve the evolution of fungal bioluminescence]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-05-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.05.12.090068v1?rss=1">
<title>
<![CDATA[
Cell-extracellular matrix interactions in the fluidic phase direct the topology and polarity of self-organized epithelial structures 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.05.12.090068v1?rss=1</link>
<description><![CDATA[
In vivo, cells are surrounded by extracellular matrix (ECM). To build organs from single cells, it is generally believed that ECM serves as scaffolds to coordinate cell positioning and differentiation. Nevertheless, how cells utilize cell-ECM interactions for the spatiotemporal coordination to different ECM at the tissue scale is not fully understood. Here, using in vitro assay with engineered MDCK cells expressing H2B-mCherry (nucleus) and gp135/Podocalyxin-GFP (apical marker), we show in multi-dimensions that such coordination for epithelial morphogenesis can be determined by cell-soluble ECM interaction in the fluidic phase. The coordination depends on the native topology of ECM components such as sheet-like basement membrane (BM) and type I collagen (COL) fibers: scaffold formed by BM (COL) facilitates a close-ended (open-ended) coordination that leads to the formation of lobular (tubular) epithelium. Further, cells form apicobasal polarity throughout the entire lobule/tubule without a complete coverage of ECM at the basal side, and time-lapse two-photon scanning imaging reveals the polarization occurring early and maintained through the lobular expansion. During polarization, gp135-GFP was converged to the apical surface collectively in the lobular/tubular structures, suggesting possible intercellular communications. Under suspension culture, the polarization was impaired with multi-lumen formation in the tubules, implying the importance of ECM biomechanical microenvironment. Our results suggest a biophysical mechanism for cells to form polarity and coordinate positioning at tissue scale, and in engineering epithelium through cell-soluble ECM interaction and self-assembly.
]]></description>
<dc:creator>Ouyang, M.</dc:creator>
<dc:creator>Yu, J.-Y.</dc:creator>
<dc:creator>Chen, Y.</dc:creator>
<dc:creator>Deng, L.</dc:creator>
<dc:creator>Guo, C.-L.</dc:creator>
<dc:date>2020-05-14</dc:date>
<dc:identifier>doi:10.1101/2020.05.12.090068</dc:identifier>
<dc:title><![CDATA[Cell-extracellular matrix interactions in the fluidic phase direct the topology and polarity of self-organized epithelial structures]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-05-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.05.21.109280v1?rss=1">
<title>
<![CDATA[
A previously uncharacterized gene in SARS-CoV-2 illuminates the functional dynamics and evolutionary origins of the COVID-19 pandemic 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.05.21.109280v1?rss=1</link>
<description><![CDATA[
Understanding the emergence of novel viruses requires an accurate and comprehensive annotation of their genomes. Overlapping genes (OLGs) are common in viruses and have been associated with pandemics, but are still widely overlooked. We identify and characterize ORF3d, a novel OLG in SARS-CoV-2 that is also present in Guangxi pangolin-CoVs but not other closely related pangolin-CoVs or bat-CoVs. We then document evidence of ORF3d translation, characterize its protein sequence, and conduct an evolutionary analysis at three levels: between taxa (21 members of Severe acute respiratory syndrome-related coronavirus), between human hosts (3978 SARS-CoV-2 consensus sequences), and within human hosts (401 deeply sequenced SARS-CoV-2 samples). ORF3d has been independently identified and shown to elicit a strong antibody response in COVID-19 patients. However, it has been misclassified as the unrelated gene ORF3b, leading to confusion. Our results liken ORF3d to other accessory genes in emerging viruses and highlight the importance of OLGs.
]]></description>
<dc:creator>Nelson, C. W.</dc:creator>
<dc:creator>Ardern, Z.</dc:creator>
<dc:creator>Goldberg, T. L.</dc:creator>
<dc:creator>Meng, C.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:creator>Ludwig, C.</dc:creator>
<dc:creator>Kolokotronis, S.-O.</dc:creator>
<dc:creator>Wei, X.</dc:creator>
<dc:date>2020-05-22</dc:date>
<dc:identifier>doi:10.1101/2020.05.21.109280</dc:identifier>
<dc:title><![CDATA[A previously uncharacterized gene in SARS-CoV-2 illuminates the functional dynamics and evolutionary origins of the COVID-19 pandemic]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-05-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.05.21.109777v1?rss=1">
<title>
<![CDATA[
pH-Dependent Transcriptional Profile Changes in Iron-Deficient Arabidopsis Roots 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.05.21.109777v1?rss=1</link>
<description><![CDATA[
Iron is an essential element for plants and abundantly present in most mineral soils. The mobility of iron is, however, dependent on the redox potential and hydrogen activity (pH) of the soil, factors that may limit its availability to plants in particular at alkaline pHs. Iron deficiency triggers pronounced changes in the transcriptional profile of plants, inducing processes that aid in the acquisition, uptake, and translocation of iron. How ambient pH impact the transcriptional iron deficiency response has not yet been elucidated in detail. Here, we provide an RNA-seq data set that catalogs global gene expression changes of iron-deficient plants grown at either optimal (5.5) or high (7.0) pH. A suite of 857 genes changed significantly and more than twofold in expression; only 54 genes of this suite were also differentially expressed between iron-deficient and iron-sufficient plants grown at pH 5.5. Among the high pH-responsive genes, 186 were earlier shown to be responsive to short-term transfer to low pH, 91 genes of this subset were anti-directionally regulated by high and low pH. The latter subset contained genes involved in cell wall organization, auxin homeostasis, and potential hubs of yet undefined signaling circuits. Growing iron-deficient plants at high pH also modulated the transcriptional iron deficiency response observed at pH 5.5 by compromising the enzymatic reduction of ferric chelates and favoring the production of iron-mobilizing coumarins. It is concluded that ambient pH is an important determinant of global gene expression which tunes iron acquisition to the prevailing edaphic conditions.
]]></description>
<dc:creator>Tsai, H.-H.</dc:creator>
<dc:creator>Schmidt, W.</dc:creator>
<dc:date>2020-05-22</dc:date>
<dc:identifier>doi:10.1101/2020.05.21.109777</dc:identifier>
<dc:title><![CDATA[pH-Dependent Transcriptional Profile Changes in Iron-Deficient Arabidopsis Roots]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-05-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.05.26.112193v1?rss=1">
<title>
<![CDATA[
An updated staging system for cephalochordate development: one table suits them all 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.05.26.112193v1?rss=1</link>
<description><![CDATA[
Chordates are divided into three subphyla: Vertebrata, Tunicata and Cephalochordata. Phylogenetically, the Cephalochordata, more commonly known as lancelets or amphioxus, constitute the sister group of Vertebrata and Tunicata. Lancelets are small, benthic, marine filter feeders, and their roughly three dozen described species are divided into three genera: Branchiostoma, Epigonichthys and Asymmetron. Due to their phylogenetic position and their stereotypical chordate morphology and genome architecture, lancelets are key models for understanding the evolutionary history of chordates. Lancelets have thus been studied by generations of scientists, with the first descriptions of adult anatomy and developmental morphology dating back to the 19th century. Today, several different lancelet species are used as laboratory models, predominantly for developmental, molecular and genomic studies. Surprisingly, however, a universal staging system and an unambiguous nomenclature for developing lancelets have not yet been adopted by the scientific community.

In this work, we characterized the development of the European amphioxus (Branchiostoma lanceolatum) using confocal microscopy and compiled a streamlined developmental staging system, from fertilization through larval life, including an unambiguous stage nomenclature. By tracing growth curves of the European amphioxus reared at different temperatures, we were able to show that our staging system permitted an easy conversion of any developmental time into a specific stage name. Furthermore, comparisons of embryos and larvae from the European lancelet (B. lanceolatum), the Florida lancelet (B. floridae), the Chinese lancelet (B. belcheri), the Japanese lancelet (B. japonicum) and the Bahamas lancelet (Asymmetron lucayanum) demonstrated that our staging system could readily be applied to other lancelet species.

Although the detailed staging description was carried out on developing B. lanceolatum, the comparisons with other lancelet species thus strongly suggested that both staging and nomenclature are applicable to all extant lancelets. We conclude that this description of embryonic and larval development will be of great use for the scientific community and that it should be adopted as the new standard for defining and naming developing lancelets. More generally, we anticipate that this work will facilitate future studies comparing representatives from different chordate lineages.
]]></description>
<dc:creator>Carvalho, J. E.</dc:creator>
<dc:creator>Lahaye, F.</dc:creator>
<dc:creator>Yong, L. W.</dc:creator>
<dc:creator>Croce, J. C.</dc:creator>
<dc:creator>Escriva, H.</dc:creator>
<dc:creator>Yu, J.-K.</dc:creator>
<dc:creator>Schubert, M.</dc:creator>
<dc:date>2020-05-26</dc:date>
<dc:identifier>doi:10.1101/2020.05.26.112193</dc:identifier>
<dc:title><![CDATA[An updated staging system for cephalochordate development: one table suits them all]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-05-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.05.26.116020v1?rss=1">
<title>
<![CDATA[
Simeprevir suppresses SARS-CoV-2 replication and synergizes with remdesivir 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.05.26.116020v1?rss=1</link>
<description><![CDATA[
The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global threat to human health. Using a multidisciplinary approach, we identified and validated the hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. Simeprevir potently reduces SARS-CoV-2 viral load by multiple orders of magnitude and synergizes with remdesivir in vitro. Mechanistically, we showed that simeprevir inhibits the main protease (Mpro) and unexpectedly the RNA-dependent RNA polymerase (RdRp). Our results thus reveal the viral protein targets of simeprevir, and provide preclinical rationale for the combination of simeprevir and remdesivir for the pharmacological management of COVID-19 patients.

One Sentence SummaryDiscovery of simeprevir as a potent suppressor of SARS-CoV-2 viral replication that synergizes with remdesivir.
]]></description>
<dc:creator>Lo, H. S.</dc:creator>
<dc:creator>Hui, K. P. Y.</dc:creator>
<dc:creator>Lai, H.-M.</dc:creator>
<dc:creator>Khan, K. S.</dc:creator>
<dc:creator>Kaur, S.</dc:creator>
<dc:creator>Li, Z.</dc:creator>
<dc:creator>Chan, A. K. N.</dc:creator>
<dc:creator>Cheung, H. H.-Y.</dc:creator>
<dc:creator>Ng, K. C.</dc:creator>
<dc:creator>Ho, J. C. W.</dc:creator>
<dc:creator>Che, Y. W.</dc:creator>
<dc:creator>Ma, B.</dc:creator>
<dc:creator>Cheung, P. M.-H.</dc:creator>
<dc:creator>Shin, D.</dc:creator>
<dc:creator>Wang, K.</dc:creator>
<dc:creator>Wu, K.-P.</dc:creator>
<dc:creator>Dikic, I.</dc:creator>
<dc:creator>Liang, P.-H.</dc:creator>
<dc:creator>Zuo, Z.</dc:creator>
<dc:creator>Chan, F. K. L.</dc:creator>
<dc:creator>Hui, D. S. C.</dc:creator>
<dc:creator>Mok, V. C. T.</dc:creator>
<dc:creator>Wong, K.-B.</dc:creator>
<dc:creator>Ko, H.</dc:creator>
<dc:creator>Aik, W. S.</dc:creator>
<dc:creator>Chan, M. C. W.</dc:creator>
<dc:creator>Ng, W.-L.</dc:creator>
<dc:date>2020-05-26</dc:date>
<dc:identifier>doi:10.1101/2020.05.26.116020</dc:identifier>
<dc:title><![CDATA[Simeprevir suppresses SARS-CoV-2 replication and synergizes with remdesivir]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-05-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.05.30.125062v1?rss=1">
<title>
<![CDATA[
Dynamin-2 regulates synaptic podosome maturation to facilitate neuromuscular junction development 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.05.30.125062v1?rss=1</link>
<description><![CDATA[
Neuromuscular junctions (NMJs) govern rapid and efficient neuronal communication with muscle cells, which relies on the proper architecture of specialized postsynaptic compartments. However, the intrinsic mechanism in muscle cells contributing to elaborate NMJ development has been unclear. In this study, we reveal that the GTPase dynamin-2 (Dyn2), best-known for catalyzing synaptic vesicle endocytosis at the presynaptic membrane, is also involved in postsynaptic morphogenesis. We demonstrate that Dyn2 is enriched in the postsynaptic membrane of muscle cells and is involved in the maturation of neurotransmitter receptor clusters via its actin bundling ability. Dyn2 functions as a molecular girdle to regulate synaptic podosome turnover and promote morphogenesis of the postsynaptic apparatus. In Drosophila NMJs, Dyn2 is required to organize the postsynaptic actin cytoskeleton and to mediate its electrophysiological activities. Mechanistically, the actin binding, self-assembly, GTP hydrolysis ability, and Y597 phosphorylation of Dyn2 all regulate its actin bundling activity. Together, our study uncovers a role for Dyn2 in cytoskeleton remodeling and organization at the postsynaptic membrane of NMJs.
]]></description>
<dc:creator>Lin, S.-S.</dc:creator>
<dc:creator>Hsieh, T.-L.</dc:creator>
<dc:creator>Liou, G.-G.</dc:creator>
<dc:creator>Li, T.-N.</dc:creator>
<dc:creator>Lin, H.-C.</dc:creator>
<dc:creator>Chang, C.-W.</dc:creator>
<dc:creator>Wu, H.-Y.</dc:creator>
<dc:creator>Yao, C.-K.</dc:creator>
<dc:creator>Liu, Y.-W.</dc:creator>
<dc:date>2020-05-31</dc:date>
<dc:identifier>doi:10.1101/2020.05.30.125062</dc:identifier>
<dc:title><![CDATA[Dynamin-2 regulates synaptic podosome maturation to facilitate neuromuscular junction development]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-05-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.06.12.148387v1?rss=1">
<title>
<![CDATA[
Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.06.12.148387v1?rss=1</link>
<description><![CDATA[
The COVID-19 pandemic has had unprecedented health and economic impact, but currently there are no approved therapies. We have isolated an antibody, EY6A, from a late-stage COVID-19 patient and show it neutralises SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds tightly (KD of 2 nM) the receptor binding domain (RBD) of the viral Spike glycoprotein and a 2.6[A] crystal structure of an RBD/EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues of this epitope are key to stabilising the pre-fusion Spike. Cryo-EM analyses of the pre-fusion Spike incubated with EY6A Fab reveal a complex of the intact trimer with three Fabs bound and two further multimeric forms comprising destabilized Spike attached to Fab. EY6A binds what is probably a major neutralising epitope, making it a candidate therapeutic for COVID-19.
]]></description>
<dc:creator>Zhou, D.</dc:creator>
<dc:creator>Duyvesteyn, H. M. E.</dc:creator>
<dc:creator>Chen, C.-P.</dc:creator>
<dc:creator>Huang, C.-G.</dc:creator>
<dc:creator>Chen, T.-H.</dc:creator>
<dc:creator>Shih, S.-R.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Cheng, C.-Y.</dc:creator>
<dc:creator>Cheng, S.-H.</dc:creator>
<dc:creator>Huang, Y.-C.</dc:creator>
<dc:creator>Lin, T.-Y.</dc:creator>
<dc:creator>Ma, C.</dc:creator>
<dc:creator>Huo, J.</dc:creator>
<dc:creator>Carrique, L.</dc:creator>
<dc:creator>Malinauskas, T.</dc:creator>
<dc:creator>Ruza, R. R.</dc:creator>
<dc:creator>Shah, P.</dc:creator>
<dc:creator>Tan, T. K.</dc:creator>
<dc:creator>Rijal, P.</dc:creator>
<dc:creator>Donat, R. F.</dc:creator>
<dc:creator>Godwin, K.</dc:creator>
<dc:creator>Buttigieg, K.</dc:creator>
<dc:creator>Tree, J.</dc:creator>
<dc:creator>Radecke, J.</dc:creator>
<dc:creator>Paterson, N. G.</dc:creator>
<dc:creator>Supasa, P.</dc:creator>
<dc:creator>Mongkolsapaya, J.</dc:creator>
<dc:creator>Screaton, G. R.</dc:creator>
<dc:creator>Carroll, M. W.</dc:creator>
<dc:creator>Jaramillo, J. G.</dc:creator>
<dc:creator>Knight, M.</dc:creator>
<dc:creator>James, W. S.</dc:creator>
<dc:creator>Owens, R. J.</dc:creator>
<dc:creator>Naismith, J. H.</dc:creator>
<dc:creator>Townsend, A.</dc:creator>
<dc:creator>Fry, E. E.</dc:creator>
<dc:creator>Zhao, Y.</dc:creator>
<dc:creator>Ren, J.</dc:creator>
<dc:creator>Stuart, D. I.</dc:creator>
<dc:creator>Huang, K.-Y. A.</dc:creator>
<dc:date>2020-06-13</dc:date>
<dc:identifier>doi:10.1101/2020.06.12.148387</dc:identifier>
<dc:title><![CDATA[Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-06-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.06.22.164400v1?rss=1">
<title>
<![CDATA[
Flower initiates a positive feedback loop upon PIP2 enrichment at periactive zones to control bulk endocytosis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.06.22.164400v1?rss=1</link>
<description><![CDATA[
Synaptic vesicle (SV) endocytosis is coupled to exocytosis to maintain SV pool size and thus neurotransmitter release. Intense stimulation induces activity-dependent bulk endocytosis (ADBE) to recapture large quantities of SV constituents in large endosomes from which SVs reform. How these consecutive processes are spatiotemporally coordinated remains unknown. Here, we show that the Flower Ca2+ channel-dependent phosphatidylinositol 4,5-bisphosphate (PIP2) compartmentalization governs such control. Strong stimuli trigger PIP2 microdomain formation at periactive zones. Upon exocytosis Flower translocates from SVs to periactive zones, where it increases PIP2 levels via Ca2+ influxes. Remarkably, PIP2 directly enhances Flower channel activity, thereby establishing a positive feedback loop for PIP2 microdomain compartmentalization. The PIP2 microdomains drive ADBE and SV reformation from bulk endosomes. PIP2 further sorts Flower to bulk endosomes, thereby terminating endocytosis. Hence, we propose that the interplay between Flower and PIP2 is the crucial spatiotemporal cue that couples exocytosis to ADBE and subsequent SV reformation.
]]></description>
<dc:creator>Yao, C.-K.</dc:creator>
<dc:creator>Li, T.-N.</dc:creator>
<dc:creator>Chen, Y.-J.</dc:creator>
<dc:creator>Wang, Y.-T.</dc:creator>
<dc:creator>Lin, H.-C.</dc:creator>
<dc:date>2020-06-22</dc:date>
<dc:identifier>doi:10.1101/2020.06.22.164400</dc:identifier>
<dc:title><![CDATA[Flower initiates a positive feedback loop upon PIP2 enrichment at periactive zones to control bulk endocytosis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-06-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.07.03.182949v1?rss=1">
<title>
<![CDATA[
Three Dimensional Multi-gene Expression Maps Reveal Cell Fate Changes Associated with Laterality Reversal of Zebrafish Habenula 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.07.03.182949v1?rss=1</link>
<description><![CDATA[
ABSTRACTThe conserved bilateral habenular nuclei (HA) in vertebrate diencephalon develop into compartmentalized structures containing neurons derived from different cell lineages. Despite extensive studies demonstrated that zebrafish larval HA display distinct left-right (L-R) asymmetry in gene expression and connectivity, the spatial gene expression domains were mainly obtained from two-dimensional (2D) snapshots of colorimetric RNA in situ hybridization staining which could not properly reflect different HA neuronal lineages constructed in three-dimension (3D). Combing the tyramide-based fluorescent mRNA in situ hybridization, confocal microscopy and customized imaging processing procedures, we have created spatial distribution maps of four genes for 4 day old zebrafish and in sibling fish whose L-R asymmetry was spontaneously reversed. 3D volumetric analyses showed that ratios of cpd2, lov, ron and nrp1a expression in L-R reversed HA were reversed according to the parapineal positions. However, the quantitative changes of gene expression in reversed larval brains do not mirror the gene expression level in the obverse larval brains. There were a total 87.78% increase of lov+nrp1a+ and a total 12.45% decrease of lov+ron+ double-positive neurons when the L-R asymmetry of HA was reversed. Thus, our volumetric analyses of the 3D maps indicate that changes of HA neuronal cell fates are associated with the reversal of HA laterality. These changes likely account for the behavior changes associated with HA laterality alterations.Competing Interest StatementThe authors have declared no competing interest.View Full Text
]]></description>
<dc:creator>Wang, G.-T.</dc:creator>
<dc:creator>Pan, H.-Y.</dc:creator>
<dc:creator>Lang, W.-H.</dc:creator>
<dc:creator>Yu, Y.-D.</dc:creator>
<dc:creator>Hsieh, C.-H.</dc:creator>
<dc:creator>Kuan, Y.-S.</dc:creator>
<dc:date>2020-07-05</dc:date>
<dc:identifier>doi:10.1101/2020.07.03.182949</dc:identifier>
<dc:title><![CDATA[Three Dimensional Multi-gene Expression Maps Reveal Cell Fate Changes Associated with Laterality Reversal of Zebrafish Habenula]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-07-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.07.10.196477v1?rss=1">
<title>
<![CDATA[
The Peroxiredoxin 6 gene plays a critical role in the homeostatic regulation of fear response 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.07.10.196477v1?rss=1</link>
<description><![CDATA[
Peroxiredoxin 6 (PRDX6) is a multifunctional enzyme implicated in redox regulation and expressed in many organs including the brain. It is known to participate in many psychiatric functions, but its role in fear memory is unknown. The present study demonstrates that PRDX6 plays a critical role in the regulation of fear response. Using Prdx6 knockout (Prdx6-/-) mice, we identified that PRDX6 acts as a suppressor in fear memory formation. Lack of Prdx6 leads to the faster fear acquisition and enhanced contextual fear response. This phenomenon was confirmed by the fact that injection of lentivirus-carried human PRDX6-V5 into the hippocampus of Prdx6-/- mice restored the enhanced fear response to the wild-type level. In the hippocampus of Prdx6-/- mice, calcium-dependent PLA2 level was increased, which may compensate for the lack of aiPLA2 function to maintain normal synaptic membranes. On the other hand, reactive oxygen species (ROS) levels did not change, indicating loss of peroxidase function did not affect the regulation of fear response.
]]></description>
<dc:creator>Sarayut Phasuk</dc:creator>
<dc:creator>Tanita Pairojana</dc:creator>
<dc:creator>Pavithra Suresh</dc:creator>
<dc:creator>Shun-Ping Huang</dc:creator>
<dc:creator>Narawut Pakaprot</dc:creator>
<dc:creator>Supin Chompoopong</dc:creator>
<dc:creator>Chee-Hing Yang</dc:creator>
<dc:creator>Hsueh-Kai Chang</dc:creator>
<dc:creator>Chien-Chang Chen</dc:creator>
<dc:creator>Ingrid Liu</dc:creator>
<dc:date>2020-07-10</dc:date>
<dc:identifier>doi:10.1101/2020.07.10.196477</dc:identifier>
<dc:title><![CDATA[The Peroxiredoxin 6 gene plays a critical role in the homeostatic regulation of fear response]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-07-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.07.10.196634v1?rss=1">
<title>
<![CDATA[
ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.07.10.196634v1?rss=1</link>
<description><![CDATA[
Accumulating evidence has shown transcranial low-intensity ultrasound can be potentially a non-invasive neural modulation tool to treat brain diseases. However, the underlying mechanism remains elusive, because the majority of studies on animal models applying rather high-intensity ultrasound that cannot be safely used in humans. Here we showed low-intensity ultrasound was able to activate neurons in the mouse brain and repeated ultrasound stimulation resulted in adult neurogenesis in specific brain regions. In vitro calcium imaging studies showed that a specific ultrasound stimulation mode, which combined with both ultrasound-induced pressure and acoustic streaming mechanotransduction, is required to activate cultured cortical neurons. ASIC1a and the tether-mode mechanotransduction were involved in the low-intensity ultrasound-mediated mechanotransduction and cultured neuron activation, which was inhibited by ASIC1a blockade and cytoskeleton-modified agents. In contrast, the inhibition of mechanical sensitive channels involved in bilayer-model mechanotransduction like Piezo or TRP proteins did not affect the ultrasound-mediated neuronal activation.

SIGNIFICANCECNS neurons have no sensory function, protected by the skull. For this reason, brain neuromodulation by ultrasound were either done at a high intensity or through auditory nerves. We demonstrate in this study CNS neurons react to ultrasound stimulation at an intensity (5 mW/cm2) far lower than typical therapeutic ultrasound (>30 mW/cm2). Using micropipette ultrasound in calcium imaging, we show the reactions of CNS neurons to ultrasound is through ASIC1a channels, pointing to the molecular basis for direct ultrasound neuromodulation at low intensity. Furthermore, we also show evidence of neurogenesis with the same ultrasound stimulation, suggesting potential therapeutic translation.
]]></description>
<dc:creator>Jormay Lim</dc:creator>
<dc:creator>Ya-Cherng Chu</dc:creator>
<dc:creator>Chen-Ming Hao</dc:creator>
<dc:creator>Wei-Hao Liao</dc:creator>
<dc:creator>Shao-Shien Lin</dc:creator>
<dc:creator>Sherry Hsu</dc:creator>
<dc:creator>Hsiao-Hsin Tai</dc:creator>
<dc:creator>Ya-Chih Chien</dc:creator>
<dc:creator>Dar-Ming Lai</dc:creator>
<dc:creator>Wen-Shiang Chen</dc:creator>
<dc:creator>Chih-Cheng Chen</dc:creator>
<dc:creator>Jaw-Lin Wang</dc:creator>
<dc:date>2020-07-10</dc:date>
<dc:identifier>doi:10.1101/2020.07.10.196634</dc:identifier>
<dc:title><![CDATA[ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-07-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.07.15.203836v1?rss=1">
<title>
<![CDATA[
EM-stellar: benchmarking deep learning for electron microscopy image segmentation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.07.15.203836v1?rss=1</link>
<description><![CDATA[
The inherent low contrast of electron microscopy (EM) datasets presents a significant challenge for rapid segmentation of cellular ultrastructures from EM data. This challenge is particularly prominent when working with high resolution big-datasets that are now acquired using electron tomography and serial block-face imaging techniques. Deep learning (DL) methods offer an exciting opportunity to automate the segmentation process by learning from manual annotations of a small sample of EM data. While many DL methods are being rapidly adopted to segment EM data no benchmark analysis has been conducted on these methods to date. We present EM-stellar, a Jupyter Notebook platform that is hosted on google Colab that can be used to benchmark the performance of a range of state-of-the-art DL methods on user-provided datasets. Using EM-Stellar we show that the performance of any DL method is dependent on the properties of the images being segmented. It also follows that no single DL method performs consistently across all performance evaluation metrics.
]]></description>
<dc:creator>Khadangi, A.</dc:creator>
<dc:creator>Boudier, T.</dc:creator>
<dc:creator>Rajagopal, V.</dc:creator>
<dc:date>2020-07-15</dc:date>
<dc:identifier>doi:10.1101/2020.07.15.203836</dc:identifier>
<dc:title><![CDATA[EM-stellar: benchmarking deep learning for electron microscopy image segmentation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-07-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.07.24.219121v1?rss=1">
<title>
<![CDATA[
Neurodegeneration induces a developmental RNA processing program by calpain-mediated MBNL2 degradation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.07.24.219121v1?rss=1</link>
<description><![CDATA[
The Muscleblind-like (MBNL) protein family plays an important role in regulating developmental RNA processing transition. Loss of MBNL2 function has been implicated in the neurodegeneration of myotonic dystrophy type 1 (DM1). However, the causal mechanism of neurodegeneration-induced MBNL2 loss of function remains elusive. Here, we show that neurodegenerative conditions including NMDAR-mediated excitotoxicity and dysregulated calcium homeostasis triggered nuclear translocation of calpain-2 resulting in MBNL2 degradation and reversion of MBNL2-regulated RNA processing to developmental patterns. The developmental stage featured nucleus-enriched distribution of calpain-2 and low expression of MBNL2. Increased MBNL2 expression during development is required for promoting developmental RNA processing transition and neuronal maturation. Knockdown of calpain-2 expression inhibited neurodegeneration-induced MBNL2 reduction and dysregulated RNA processing. Neurodegenerative disease mouse models including DM1 and Alzheimers disease showed nuclear translocation of calpain-2 associated with MBNL2 degradation and reversion of MBNL2-regulated RNA processing to the developmental pattern. Our results identify a novel regulatory mechanism for MBNL2 downregulation and suggest that reduced MBNL2 expression accompanied by the re-induction of a developmental RNA processing program may be a common feature of neurodegeneration.
]]></description>
<dc:creator>Wang, L.-H.</dc:creator>
<dc:creator>Lin, Y.-M.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Chern, Y.</dc:creator>
<dc:creator>Wang, G.-S.</dc:creator>
<dc:date>2020-07-25</dc:date>
<dc:identifier>doi:10.1101/2020.07.24.219121</dc:identifier>
<dc:title><![CDATA[Neurodegeneration induces a developmental RNA processing program by calpain-mediated MBNL2 degradation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-07-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.07.28.225250v1?rss=1">
<title>
<![CDATA[
ZmMTOPVIB is essential for double-strand break formation and bipolar spindle assembly in maize meiosis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.07.28.225250v1?rss=1</link>
<description><![CDATA[
The programmed formation of DNA double-strand breaks (DSBs) during early meiosis is catalyzed by SPO11, a conserved ortholog to the A subunit of an archaeal topoisomerase VI (TopoVI) which functions as a hetero-tetramer comprising two A and two B subunits. An essential role of the meiotic TopoVI B subunit (TopVIB) in DSB formation has been reported in mouse, Arabidopsis and rice. Very recently, rice MTopVIB was revealed to have an unexpected role in meiotic bipolar spindle assembly, highlighting multiple functions of MTopVIB during rice meiosis. In this work, the meiotic TopVIB in maize (ZmMTOPVIB) was characterized. The ZmmtopVIB mutant plants exhibited normal vegetative growth but male and female sterility. DSB formation is abolished in mutant meiocytes. Despite normal assembly of axial elements, synapsis was severely affected and homologous pairing was disrupted in mutants. Importantly, we showed that bipolar spindle assembly was also affected in ZmmtopVIB, resulting in triad and polyad formation. Overall, our results demonstrate that ZmMTOPVIB plays critical roles in DSB formation and homologous recombination. In addition, the newly-discovered function of MTOPVIB in bipolar spindle assembly is likely conserved across different monocots.

One-sentence summaryThe dual roles of MTOPVIB in regulating meiotic DSB formation and bipolar spindle assembly are evolutionarily conserved in monocot plants.
]]></description>
<dc:creator>Jing, J.</dc:creator>
<dc:creator>Zhang, T.</dc:creator>
<dc:creator>He, Y.</dc:creator>
<dc:creator>Kao, Y.-H.</dc:creator>
<dc:creator>Huang, T.-H.</dc:creator>
<dc:creator>Wang, C.-J. R.</dc:creator>
<dc:date>2020-07-28</dc:date>
<dc:identifier>doi:10.1101/2020.07.28.225250</dc:identifier>
<dc:title><![CDATA[ZmMTOPVIB is essential for double-strand break formation and bipolar spindle assembly in maize meiosis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-07-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.07.31.230235v1?rss=1">
<title>
<![CDATA[
Species-specific phototaxis of coral larvae causes variation in vertical positioning during dispersal 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.07.31.230235v1?rss=1</link>
<description><![CDATA[
Controlling vertical positioning is a key factor limiting the distance coral larvae can travel, as oceanic currents are faster closer to surface. Currently, the vertical position of coral larvae is assumed to be determined by buoyant, lipid-rich gametes. However, here we show that some, but not all, coral species can control vertical positioning by phototaxis. We first examined the effect of light on the vertical positioning of larvae from five different coral species in the laboratory. We found that larvae from P. verrucosa, but not from other coral species, show phototaxis towards light and accumulate near the surface. This behavior was consistent at any age and at any time during the day. In field experiments, using P. verrucosa larvae at three different depths (1, 7 and 15 m), the accumulation of larvae in the top half of transparent chambers was observed at all depths. However, such behavior failed to occur in dark chambers. We conclude that larvae from P. verrucosa, but not all coral species, accumulate close to the seawater surface as a result of actively swimming towards sunlight. This finding provides a new hypothesis that phototactic behavior is a key factor in regulating vertical positioning for the dispersal of coral larvae.
]]></description>
<dc:creator>Mulla, A. J.</dc:creator>
<dc:creator>Lin, C.-H.</dc:creator>
<dc:creator>Takahashi, S.</dc:creator>
<dc:creator>Nozawa, Y.</dc:creator>
<dc:date>2020-08-02</dc:date>
<dc:identifier>doi:10.1101/2020.07.31.230235</dc:identifier>
<dc:title><![CDATA[Species-specific phototaxis of coral larvae causes variation in vertical positioning during dispersal]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-08-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.08.13.249342v1?rss=1">
<title>
<![CDATA[
A Statistical Framework for QTL Hotspot Detection 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.08.13.249342v1?rss=1</link>
<description><![CDATA[
Quantitative trait loci (QTL) hotspots (genomic locations enriched in QTL) are a common and notable feature when collecting many QTL for various traits in many areas of biological studies. The QTL hotspots are important and attractive since they are highly informative and may harbor genes for the quantitative traits. So far, the current statistical methods for QTL hotspot detection use either the individual-level data from the genetical genomics experiments or the summarized data from public QTL databases to proceed with the detection analysis. These detection methods attempt to address some of the concerns, including the correlation structure among traits, the magnitude of LOD scores within a hotspot and computational cost, that arise during the process of QTL hotspot detection. In this article, we describe a statistical framework that can handle both types of data as well as address all the concerns at a time for QTL hotspot detection. Our statistical framework directly operates on the QTL matrix and hence has a very cheap computation cost, and is deployed to take advantage of the QTL mapping results for assisting the detection analysis. Two special devices, trait grouping and top {gamma}n, profile, are introduced into the framework. The trait grouping attempts to group the closely linked or pleiotropic traits together to take care of the true linkages and cope with the underestimation of hotspot thresholds due to non-genetic correlations (arising from ignoring the correlation structure among traits), so as to have the ability to obtain much stricter thresholds and dismiss spurious hotspots. The top {gamma}n, profile is designed to outline the LOD-score pattern of a hotspot across the different hotspot architectures, so that it can serve to identify and characterize the types of QTL hotspots with varying sizes and LOD score distributions. Real examples, numerical analysis and simulation study are performed to validate our statistical framework, investigate the detection properties, and also compare with the current methods in QTL hotspot detection. The results demonstrate that the proposed statistical framework can effectively accommodate the correlation structure among traits, identify the types of hotspots and still keep the notable features of easy implementation and fast computation for practical QTL hotspot detection.
]]></description>
<dc:creator>Kao, C.-H.</dc:creator>
<dc:creator>Wu, P.-Y.</dc:creator>
<dc:creator>Yang, M.-H.</dc:creator>
<dc:date>2020-08-14</dc:date>
<dc:identifier>doi:10.1101/2020.08.13.249342</dc:identifier>
<dc:title><![CDATA[A Statistical Framework for QTL Hotspot Detection]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-08-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.08.20.258905v1?rss=1">
<title>
<![CDATA[
Segmentation boosting with compensation methods in optical coherence tomography angiography images 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.08.20.258905v1?rss=1</link>
<description><![CDATA[
Optical coherence tomography angiography is a noninvasive imaging modality to establish the diagnosis of retinal vascular diseases. However, angiography images are significantly interfered if patients jitter or blink. In this study, a novel retinal image analysis method to accurately detect blood vessels and compensate the effect of interference was proposed. We call this the patch U-Net compensation (PUC) system, which is based on the famous U-Net. Several techniques, including a better training mechanism, direction criteria, area criteria, gap criteria, and probability map criteria, have been proposed to improve its accuracy. Simulations show that the proposed PUC achieves much better performance than state-of-art methods.
]]></description>
<dc:creator>Lee, Y.-C.</dc:creator>
<dc:creator>Ding, J.-J.</dc:creator>
<dc:creator>Yeung, L.</dc:creator>
<dc:creator>Lee, T.-W.</dc:creator>
<dc:creator>Chang, C.-J.</dc:creator>
<dc:creator>Lin, Y.-T.</dc:creator>
<dc:creator>Chang, R. Y.</dc:creator>
<dc:date>2020-08-20</dc:date>
<dc:identifier>doi:10.1101/2020.08.20.258905</dc:identifier>
<dc:title><![CDATA[Segmentation boosting with compensation methods in optical coherence tomography angiography images]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-08-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.08.23.258699v1?rss=1">
<title>
<![CDATA[
Hyperpolyploidization of hepatocyte initiates preneoplastic lesion formation in the liver 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.08.23.258699v1?rss=1</link>
<description><![CDATA[
Hepatocellular carcinoma (HCC) is the most predominant primary malignancy in the liver. Genotoxic and genetic models have revealed that HCC cells are derived from hepatocytes, but where the critical region for tumor foci emergence is and how this transformation occurs are still unclear. Here, hyperpolyploidization of hepatocytes around the centrilobular (CL) region was demonstrated to be closely linked with the development of HCC cells after diethylnitrosamine treatment. We identified the CL region as a dominant lobule for accumulation of hyperpolyploid hepatocytes and preneoplastic tumor foci formation. We also demonstrated that upregulation of Aurkb plays a critical role in promoting hyperpolyploidization. Increase of AURKB phosphorylation was detected on the midbody during cytokinesis, causing abscission failure and hyperpolyploidization. Pharmacological inhibition of AURKB dramatically reduced nucleus size and tumor foci number surrounding the CL region in diethylnitrosamine-treated liver. Our work reveals an intimate molecular link between pathological hyperpolyploidy of CL hepatocytes and transformation into HCC cells.
]]></description>
<dc:creator>Chao, H.-W.</dc:creator>
<dc:creator>Lin, H.</dc:creator>
<dc:creator>Huang, Y.-S.</dc:creator>
<dc:creator>Fustin, J.-M.</dc:creator>
<dc:creator>Doi, M.</dc:creator>
<dc:creator>Chen, H.</dc:creator>
<dc:creator>Lai, H.-H.</dc:creator>
<dc:creator>Lin, S.-H.</dc:creator>
<dc:creator>Lee, Y.-L.</dc:creator>
<dc:creator>King, P.-C.</dc:creator>
<dc:creator>Hou, H.-S.</dc:creator>
<dc:creator>Chen, H.-W.</dc:creator>
<dc:creator>Young, P.-Y.</dc:creator>
<dc:date>2020-08-24</dc:date>
<dc:identifier>doi:10.1101/2020.08.23.258699</dc:identifier>
<dc:title><![CDATA[Hyperpolyploidization of hepatocyte initiates preneoplastic lesion formation in the liver]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-08-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.08.28.267526v1?rss=1">
<title>
<![CDATA[
Plasmablast-derived antibody response to acute SARS-CoV-2 infection in humans 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.08.28.267526v1?rss=1</link>
<description><![CDATA[
Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 13.0% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) and over half of anti-nucleocapsid (19 of 35) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-RBD, three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. At last, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.
]]></description>
<dc:creator>Huang, K.-Y. A.</dc:creator>
<dc:creator>Tan, T.</dc:creator>
<dc:creator>Chen, T.-H.</dc:creator>
<dc:creator>Huang, C.-G.</dc:creator>
<dc:creator>Harvey, R.</dc:creator>
<dc:creator>Hussain, S.</dc:creator>
<dc:creator>Chen, C.-P.</dc:creator>
<dc:creator>Harding, A.</dc:creator>
<dc:creator>Gilbert-Jaramillo, J.</dc:creator>
<dc:creator>Liu, X.</dc:creator>
<dc:creator>Knight, M.</dc:creator>
<dc:creator>Schimanski, L.</dc:creator>
<dc:creator>Shih, S.-R.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Cheng, C.-Y.</dc:creator>
<dc:creator>Cheng, S.-H.</dc:creator>
<dc:creator>Huang, Y.-C.</dc:creator>
<dc:creator>Lin, T.-Y.</dc:creator>
<dc:creator>Rahikainen, R.</dc:creator>
<dc:creator>Howarth, M.</dc:creator>
<dc:creator>Jan, J.-T.</dc:creator>
<dc:creator>Ma, C.</dc:creator>
<dc:creator>James, W. S.</dc:creator>
<dc:creator>Daniels, R.</dc:creator>
<dc:creator>McCauley, J.</dc:creator>
<dc:creator>Rijal, P.</dc:creator>
<dc:creator>Townsend, A.</dc:creator>
<dc:date>2020-08-28</dc:date>
<dc:identifier>doi:10.1101/2020.08.28.267526</dc:identifier>
<dc:title><![CDATA[Plasmablast-derived antibody response to acute SARS-CoV-2 infection in humans]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-08-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.09.01.278473v1?rss=1">
<title>
<![CDATA[
A Human Multi-Lineage Hepatic Organoid Model for Liver Fibrosis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.09.01.278473v1?rss=1</link>
<description><![CDATA[
BackgroundTo characterize fibrogenic mechanisms, genome engineering and a human hepatic organoid system was used to produce an in vitro model for human liver fibrosis.

Methods and resultsHuman hepatic organoids that were engineered to express the most common causative mutation for Autosomal Recessive Polycystic Kidney Disease (ARPKD) developed the key features of ARPKD liver pathology (abnormal bile ducts and hepatic fibrosis) in only 21 days. Second harmonic generation microscopy confirmed that the ARPKD mutation increased collagen abundance and thick collagen fiber production in hepatic organoids; and we demonstrated that these changes mirrored that occurring in ARPKD liver tissue. Transcriptomic and other analyses indicated that the ARPKD mutation generates cholangiocytes with increased TGF{beta}-associated pathway activation, which are actively involved in collagen fiber generation. The abnormal cholangiocytes promote the expansion of collagen-producing myofibroblasts with markedly increased PDGFR{beta} protein expression and an activated STAT3 signaling pathway. Moreover, the transcriptome of ARPKD organoid myofibroblasts resembled that of myofibroblasts in liver tissue obtained from patients with commonly occurring acquired forms of liver fibrosis. The involvement of the PDGFRB pathway was confirmed by the anti-fibrotic effect observed when ARPKD organoids were treated with PDGFRB inhibitors.

ConclusionsBesides providing mechanistic insight into the pathogenesis of congenital (and possibly acquired) forms of liver fibrosis, ARPKD organoids could also be used to test the anti-fibrotic efficacy of potential anti-fibrotic therapies.
]]></description>
<dc:creator>GUAN, Y.</dc:creator>
<dc:creator>Enejder, A.</dc:creator>
<dc:creator>Wang, M.</dc:creator>
<dc:creator>Fang, Z.</dc:creator>
<dc:creator>Cui, L.</dc:creator>
<dc:creator>Chen, S.-Y.</dc:creator>
<dc:creator>Wang, J.</dc:creator>
<dc:creator>Tan, Y.</dc:creator>
<dc:creator>Wu, M.</dc:creator>
<dc:creator>Chen, X.</dc:creator>
<dc:creator>Johansson, P. K.</dc:creator>
<dc:creator>Osman, I.</dc:creator>
<dc:creator>Kunimoto, K.</dc:creator>
<dc:creator>Russo, P.</dc:creator>
<dc:creator>Heilshorn, S. C.</dc:creator>
<dc:creator>Peltz, G.</dc:creator>
<dc:date>2020-09-02</dc:date>
<dc:identifier>doi:10.1101/2020.09.01.278473</dc:identifier>
<dc:title><![CDATA[A Human Multi-Lineage Hepatic Organoid Model for Liver Fibrosis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-09-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.09.03.281089v1?rss=1">
<title>
<![CDATA[
Genomic analyses of two Italian oyster mushroom Pleurotus pulmonarius strains 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.09.03.281089v1?rss=1</link>
<description><![CDATA[
Pleurotus mushrooms are among the most cultivated fungi in the world and are highly valuable for food, medicine and biotechnology industries. Furthermore, Pleurotus species are carnivorous fungi; they can rapidly paralyze and kill nematodes when nutrient-deprived. The predator-prey interactions between Pleurotus and nematodes are still widely unexplored. Moreover, the molecular mechanisms and the genes involved in the carnivorous behavior of Pleurotus mushrooms remain a mystery. We are attempting to understand the interactions between Pleurotus mushrooms and their nematode prey through genetic and genomic analyses. Two single spores (ss2 and ss5) isolated from a fruiting body of Pleurotus pulmonarius exhibited significant differences in growth and toxicity against nematodes. Thus, using PacBio long reads, we assembled and annotated two high-quality genomes for these two isolates of Pleurotus pulmonarius. Each of these assemblies contains 23 scaffolds, including 6 (ss2) and 8 (ss5) telomere-to-telomere scaffolds, and they are among the most complete assembled genomes of the Pleurotus species. Comparative analyses identified the genomic differences between the two P. pulmonarius strains. In sum, this work provides a genomic resource that will be invaluable for better understanding the Italian oyster mushroom P. pulmonarius.
]]></description>
<dc:creator>Vidal-Diez de Ulzurrun, G.</dc:creator>
<dc:creator>Lee, Y.-Y.</dc:creator>
<dc:creator>Stajich, J. E.</dc:creator>
<dc:creator>Schwarz, E. M.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:date>2020-09-03</dc:date>
<dc:identifier>doi:10.1101/2020.09.03.281089</dc:identifier>
<dc:title><![CDATA[Genomic analyses of two Italian oyster mushroom Pleurotus pulmonarius strains]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-09-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.09.03.281683v1?rss=1">
<title>
<![CDATA[
Genome sequence of the oyster mushroom Pleurotus ostreatus strain PC9 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.09.03.281683v1?rss=1</link>
<description><![CDATA[
The oyster mushroom Pleurotus ostreatus is a basidiomycete commonly found in the rotten wood and it is one of the most cultivated edible mushrooms globally. P. ostreatus is also a carnivorous fungus, which can paralyze and kill nematodes within minutes. However, the molecular mechanisms of the predator-prey interactions between P. ostreatus and nematodes remain unclear. PC9 and PC15 are two model strains of P. ostreatus and the genomes of both strains have been sequenced and deposited at the Joint Genome Institute (JGI). These two monokaryotic strains exhibit dramatic differences in growth, but because PC9 grows more robustly in laboratory conditions, it has become the strain of choice for many studies. Despite the fact that PC9 is the common strain for investigation, its genome is fragmentary and incomplete relative to that of PC15. To overcome this problem, we used PacBio long reads and Illumina sequencing to assemble and polish a more integrated genome for PC9. Our PC9 genome assembly, distributed across 17 scaffolds, is highly contiguous and includes six telomere-to-telomere scaffolds, dramatically improving the genome quality. We believe that our PC9 genome resource will be useful to the fungal research community investigating various aspects of P. ostreatus biology.
]]></description>
<dc:creator>Lee, Y.-Y.</dc:creator>
<dc:creator>Vidal-Diez de Ulzurrun, G.</dc:creator>
<dc:creator>Schwarz, E. M.</dc:creator>
<dc:creator>Stajich, J. E.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:date>2020-09-04</dc:date>
<dc:identifier>doi:10.1101/2020.09.03.281683</dc:identifier>
<dc:title><![CDATA[Genome sequence of the oyster mushroom Pleurotus ostreatus strain PC9]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-09-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.09.15.298422v1?rss=1">
<title>
<![CDATA[
Forward genetic screens identified mutants with defects in trap morphogenesis in the nematode-trapping fungus Arthrobotrys oligospora 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.09.15.298422v1?rss=1</link>
<description><![CDATA[
Nematode-trapping fungi (NTF) are carnivorous fungi that prey on nematodes under nutrient-poor conditions via specialized hyphae that function as traps. The molecular mechanisms involved in the interactions between nematode-trapping fungi and their nematode prey are largely unknown. In this study, we conducted forward genetic screens to identify potential genes and pathways that are involved in trap morphogenesis and predation in the NTF Arthrobotrys oligospora. Using Ethyl methanesulfonate and UV as the mutagens, we generated 5552 randomly-mutagenized A. oligospora strains and identified 15 mutants with strong defects in trap morphogenesis. Whole genome sequencing and bioinformatic analyses revealed mutations in genes with roles in signaling, transcription or membrane transport that may contribute to the defects of trap morphogenesis in these mutants. We further conducted functional analyses on a candidate gene, YBP-1, and demonstrate that mutation of that gene was causative of the phenotypes observed in one of the mutants. The methods established in this study might provide helpful insights for establishing forward genetic screening methods for other non-model fungal species.
]]></description>
<dc:creator>Huang, T.-Y.</dc:creator>
<dc:creator>Lee, Y.-Y.</dc:creator>
<dc:creator>Vidal-Diez de Ulzurrun, G.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:date>2020-09-16</dc:date>
<dc:identifier>doi:10.1101/2020.09.15.298422</dc:identifier>
<dc:title><![CDATA[Forward genetic screens identified mutants with defects in trap morphogenesis in the nematode-trapping fungus Arthrobotrys oligospora]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-09-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.09.16.299149v1?rss=1">
<title>
<![CDATA[
A self-assembled protein nanoparticle serving as a one-shot vaccine carrier 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.09.16.299149v1?rss=1</link>
<description><![CDATA[
In this paper, we are exploring the role of an amphipathic helical peptide in mediating the self-assembly of a fusion protein into a protein nanoparticle and the application of the nanoparticle as a one-shot vaccine carrier. Out of several candidates, an amphipathic helical peptide derived from M2 protein of type A influenza virus is found to stimulate high antigenicity when fused to a fluorescent protein genetically. This fusion protein was found to form protein nanoparticle spontaneously when expressed and purified protein stimulates long-lasting antibody responses in single immunization. Through modeling peptide structure and nanoparticle assembly, we have improved this vaccine carrier in complex stability. The revised vaccine carrier is able to stimulate constant antibody titer to a heterologous antigen for at least six months in single immunization. The immune response against a heterologous antigen can be boosted further by additional immunization in spite of high immune responses to carrier protein.
]]></description>
<dc:creator>Kan, M.-C.</dc:creator>
<dc:creator>Wong, T.-T.</dc:creator>
<dc:creator>Liou, G.-G.</dc:creator>
<dc:date>2020-09-18</dc:date>
<dc:identifier>doi:10.1101/2020.09.16.299149</dc:identifier>
<dc:title><![CDATA[A self-assembled protein nanoparticle serving as a one-shot vaccine carrier]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-09-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.09.21.306498v1?rss=1">
<title>
<![CDATA[
Ultra-sensitive measurement of brain penetration mechanics and blood vessel rupture with microscale probes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.09.21.306498v1?rss=1</link>
<description><![CDATA[
Microscale electrodes, on the order of 10-100 m, are rapidly becoming critical tools for neuroscience and brain-machine interfaces (BMIs) for their high channel counts and spatial resolution, yet the mechanical details of how probes at this scale insert into brain tissue are largely unknown. Here, we performed quantitative measurements of the force and compression mechanics together with real-time microscopy for in vivo insertion of a systematic series of microelectrode probes as a function of diameter (7.5-100 m and rectangular Neuropixels) and tip geometry (flat, angled, and electrochemically sharpened). Results elucidated the role of tip geometry, surface forces, and mechanical scaling with diameter. Surprisingly, the insertion force post-pia penetration was constant with distance and did not depend on tip shape. Real-time microscopy revealed that at small enough lengthscales (<25 m), blood vessel rupture and bleeding during implantation could be entirely avoided. This appears to occur via vessel displacement, avoiding capture on the probe surface which led to elongation and tearing for larger probes. We propose a new, three-zone model to account for the probe size dependence of bleeding, and provide mechanistic guidance for probe design.

Significance StatementMicroscale neural probes are central to next-generation brain-machine interfaces, yet how they physically penetrate living brain remains poorly quantified. Using a high-sensitivity force sensor integrated with real-time microscopy, we measured in vivo force-displacement and visualized vascular responses for microwires (7.5-100 m) and Neuropixels. We find that once the brains protective pia membrane is breached, insertion force remains essentially constant with depth, while pia puncture force and pre-penetration compression scale linearly with probe diameter. Real-time imaging reveals a sub-25 m regime in which blood vessels are displaced rather than ruptured. These results motivate a three-zone model of vessel capture versus displacement and provide actionable mechanical design rules for low-trauma, high-density neural interfaces.
]]></description>
<dc:creator>Obaid, A.</dc:creator>
<dc:creator>Wu, Y.-W.</dc:creator>
<dc:creator>Hanna, M.-E.</dc:creator>
<dc:creator>Jaidar, O.</dc:creator>
<dc:creator>Nix, W.</dc:creator>
<dc:creator>Ding, J. B.</dc:creator>
<dc:creator>Melosh, N.</dc:creator>
<dc:date>2020-09-22</dc:date>
<dc:identifier>doi:10.1101/2020.09.21.306498</dc:identifier>
<dc:title><![CDATA[Ultra-sensitive measurement of brain penetration mechanics and blood vessel rupture with microscale probes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-09-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.09.26.314641v1?rss=1">
<title>
<![CDATA[
GAMYB modulates bHLH142 and is homeostatically regulated by TDR during rice anther tapetal and pollen development 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.09.26.314641v1?rss=1</link>
<description><![CDATA[
GAMYB, UDT1, TIP2/bHLH142, TDR, and EAT1/DTD are important transcription factors (TFs) that play a crucial role during rice pollen development. This study demonstrates that bHLH142 acts downstream of UDT1 and GAMYB and works as a "hub" in these two pollen pathways. We show that GAMYB modulates bHLH142 expression through specific binding to the MYB motif of bHLH142 promoter during early stage of pollen development; while TDR acts as a transcriptional repressor of the GAMYB modulation of bHLH142 by binding to the E-box close to the MYB motif on the promoter. The up- and down-regulation of TFs highlights the importance that a tight, precise, and coordinated regulation among these TFs is essential for normal pollen development. Most notably, this study illustrates the regulatory pathways of GAMYB and UDT1 that rely on bHLH142 in a direct and an indirect manner, respectively, and function in different tissues with distinct biological functions during pollen development. This study advances our understanding of the molecular mechanisms of rice pollen development.

HighlightGAMYB can directly modulate the transactivation of the bHLH142, but the modulation is repressed by TDR to keep the homeostasis of bHLH142 gene expression to ensure normal pollen development.
]]></description>
<dc:creator>Ko, S.-S.</dc:creator>
<dc:creator>Li, M.-J.</dc:creator>
<dc:creator>Ho, Y.-C.</dc:creator>
<dc:creator>Yu, C.-P.</dc:creator>
<dc:creator>Yang, T.-T.</dc:creator>
<dc:creator>Lin, Y.-J.</dc:creator>
<dc:creator>Hsing, H.-C.</dc:creator>
<dc:creator>Chen, T.-K.</dc:creator>
<dc:creator>Jhong, C.-M.</dc:creator>
<dc:creator>Li, W.-H.</dc:creator>
<dc:creator>Ku, M. S.-B.</dc:creator>
<dc:date>2020-09-26</dc:date>
<dc:identifier>doi:10.1101/2020.09.26.314641</dc:identifier>
<dc:title><![CDATA[GAMYB modulates bHLH142 and is homeostatically regulated by TDR during rice anther tapetal and pollen development]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-09-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.09.30.319996v1?rss=1">
<title>
<![CDATA[
ezGeno: An Automatic Model Selection Package for Genomic Data Analysis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.09.30.319996v1?rss=1</link>
<description><![CDATA[
To facilitate the process of tailor-making a deep neural network for exploring the dynamics of genomic DNA, we have developed a hands-on package called ezGeno that automates the search process of various parameters and network structure. ezGeno considers three different sets of search spaces, namely, the number of filters, dilation factors, and the connectivity between different layers. ezGeno can be applied to any kind of 1D genomic input such as genomic sequences, histone modifications, DNase feature data and so on. Combinations of multiple abovementioned 1D features are also applicable. Specifically, for the task of predicting TF binding using genomic sequences as the input, ezGeno can consistently return the best performing set of parameters and network structure, as well as highlight the important segments within the original sequences. For the task of predicting tissue-specific enhancer activity using both sequence and DNase feature data as the input, ezGeno also regularly outperforms the hand-designed models. In this study, we demonstrate that ezGeno is superior in efficiency and accuracy when compared to AutoKeras, a general open-source AutoML package. The average AUC of ezGeno is also consistently higher than the result of using a one-layer DeepBind model. With the flexibility of ezGeno, we expect that this package can provide future researchers not only support of model design in their analysis of genomic studies but also more insights into the regulatory landscape.

AvailabilityThe ezGeno package can be freely accessed at https://github.com/ailabstw/ezGeno.

ContactDr. Chien-Yu Chen, chienyuchen@ntu.edu.tw
]]></description>
<dc:creator>Lin, J.-L.</dc:creator>
<dc:creator>Hsieh, T.-T.</dc:creator>
<dc:creator>Tung, Y.-A.</dc:creator>
<dc:creator>Chen, X.-J.</dc:creator>
<dc:creator>Hsiao, Y.-C.</dc:creator>
<dc:creator>Yang, C.-L.</dc:creator>
<dc:creator>Liu, T.-L.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:date>2020-10-02</dc:date>
<dc:identifier>doi:10.1101/2020.09.30.319996</dc:identifier>
<dc:title><![CDATA[ezGeno: An Automatic Model Selection Package for Genomic Data Analysis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.10.02.323238v1?rss=1">
<title>
<![CDATA[
South Asian patient population genetics reveal strong founder effects and high rates of homozygosity - new resources for precision medicine 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.10.02.323238v1?rss=1</link>
<description><![CDATA[
Population-scale genetic studies can identify drug targets and allow disease risk to be predicted with resulting benefit for management of individual health risks and system-wide allocation of health care delivery resources. Although population-scale projects are underway in many parts of the world, genetic variation between population groups means that additional projects are warranted. South Asia has a population whose genetics is the least characterized of any of the worlds major populations. Here we describe GenomeAsia studies that characterize population structure in South Asia and that create tools for economical and accurate genotyping at population-scale. Prior work on population structure characterized isolated population groups, the relevance of which to large-scale studies of disease genetics is unclear. For our studies we used whole genome sequence information from 4,807 individuals recruited in the health care delivery systems of Pakistan, India and Bangladesh to ensure relevance to population-scale studies of disease genetics. We combined this with WGS data from 927 individuals from isolated South Asian population groups, and developed a custom SNP array (called SARGAM) that is optimized for future human genetic studies in South Asia. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of homozygosity that approach 100 times that seen in outbred populations. We describe founder effects that increase the power to associate functional variants with disease processes and that make South Asia a uniquely powerful place for population-scale genetic studies.
]]></description>
<dc:creator>Wall, J.</dc:creator>
<dc:creator>Sathirapongsasuti, J. F.</dc:creator>
<dc:creator>Gupta, R.</dc:creator>
<dc:creator>Barik, A.</dc:creator>
<dc:creator>Rai, R. K.</dc:creator>
<dc:creator>Rasheed, A.</dc:creator>
<dc:creator>Radha, V.</dc:creator>
<dc:creator>Belsare, S.</dc:creator>
<dc:creator>Menon, R.</dc:creator>
<dc:creator>Phalke, S.</dc:creator>
<dc:creator>Mittal, A.</dc:creator>
<dc:creator>Fang, J.</dc:creator>
<dc:creator>Tanneeru, D.</dc:creator>
<dc:creator>Robinson, J.</dc:creator>
<dc:creator>Chaudhary, R.</dc:creator>
<dc:creator>Fuchsberger, C.</dc:creator>
<dc:creator>Forer, L.</dc:creator>
<dc:creator>Schoenherr, S.</dc:creator>
<dc:creator>Bei, Q.</dc:creator>
<dc:creator>Bhangale, T.</dc:creator>
<dc:creator>Tom, J.</dc:creator>
<dc:creator>Gadde, S. G. K.</dc:creator>
<dc:creator>V, P. B.</dc:creator>
<dc:creator>Naik, N. K.</dc:creator>
<dc:creator>Wang, M.</dc:creator>
<dc:creator>Kwok, P.-Y.</dc:creator>
<dc:creator>Khera, A. V.</dc:creator>
<dc:creator>Lakshmi, B. R.</dc:creator>
<dc:creator>Butterworth, A.</dc:creator>
<dc:creator>Danesh, J.</dc:creator>
<dc:creator>Seshagiri, S.</dc:creator>
<dc:creator>Kathiresan, S.</dc:creator>
<dc:creator>Ghosh, A.</dc:creator>
<dc:creator>Mohan, V.</dc:creator>
<dc:creator>Chowdhury, A.</dc:creator>
<dc:creator>Saleheen, D.</dc:creator>
<dc:creator>Stawiski, E.</dc:creator>
<dc:creator>Peterson, A. S.</dc:creator>
<dc:date>2020-10-02</dc:date>
<dc:identifier>doi:10.1101/2020.10.02.323238</dc:identifier>
<dc:title><![CDATA[South Asian patient population genetics reveal strong founder effects and high rates of homozygosity - new resources for precision medicine]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.10.07.329094v1?rss=1">
<title>
<![CDATA[
Genetic and metabolite biomarkers reveal actinobacteria-mediated estrogen biodegradation in urban estuarine sediment 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.10.07.329094v1?rss=1</link>
<description><![CDATA[
Steroidal estrogens are often accumulated in urban estuarine sediments worldwide at microgram per gram levels. These aromatic steroids have been classified as endocrine disruptors with an EC50 at sub-nanomolar concentrations and classified as Group 1 carcinogens by the World Health Organization. Microbial degradation is a naturally occurring mechanism that mineralizes estrogens in the biosphere; however, the corresponding genes in estrogen-degrading actinobacteria remain unidentified. In this study, we identified a gene cluster encoding several putative estrogen-degrading genes in actinobacterium Rhodococcus sp. strain B50. Among them, the oecB and oecC genes involved in estrogenic A-ring cleavage were identified through gene-disruption experiments. We also detected the accumulation of two extracellular estrogenic metabolites, including pyridinestrone acid (PEA) and 3a-H-4(3-propanoate)-7a{beta}-methylhexahydro-1,5-indanedione (HIP), in the estrone-fed strain B50 cultures. Since actinobacterial oecC and proteobacterial oecC shared less than 40% sequence identity, oecC could serve as a specific biomarker to differentiate the contribution of actinobacteria and proteobacteria in environmental estrogen degradation. Therefore, oecC and the extracellular metabolites PEA and HIP were used as biomarkers to investigate estrogen biodegradation in an urban estuarine sediment. Interestingly, our data suggested that actinobacteria, rather than alpha-proteobacteria function in sewage treatment plants, are actively degrading estrogens in the urban estuarine sediment.

Graphical Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/329094v1_ufig1.gif" ALT="Figure 1">
View larger version (93K):
org.highwire.dtl.DTLVardef@17e1e23org.highwire.dtl.DTLVardef@ecc60borg.highwire.dtl.DTLVardef@be03d4org.highwire.dtl.DTLVardef@ed81d6_HPS_FORMAT_FIGEXP  M_FIG C_FIG HighlightsO_LIIsolation of an estrogen-degrading actinobacterium Rhodococcus sp. strain B50 and establishment of a strain B50 genetic manipulation system.
C_LIO_LIStrain B50 exhibits a two-fold estrogen degradation rate of that of estrogen-degrading alpha-proteobacteria under the same cultivation conditions.
C_LIO_LIFunctional characterization of two oxygenase genes, oecB and oecC, involved in estrogenic A-ring cleavage in actinobacteria.
C_LIO_LIIdentification of two extracellular estrogenic metabolites, PEA and HIP, in the estrone-fed strain B50 cultures.
C_LIO_LIDetection of actinobacterial oecC sequences as well as PEA and HIP in the estrone-spiked urban estuarine sediments.
C_LI
]]></description>
<dc:creator>Hsiao, T.-H.</dc:creator>
<dc:creator>Chen, Y.-L.</dc:creator>
<dc:creator>Meng, M.</dc:creator>
<dc:creator>Chuang, M.-R.</dc:creator>
<dc:creator>Horinouchi, M.</dc:creator>
<dc:creator>Hayashi, T.</dc:creator>
<dc:creator>Wang, P.-H.</dc:creator>
<dc:creator>Chiang, Y.-R.</dc:creator>
<dc:date>2020-10-07</dc:date>
<dc:identifier>doi:10.1101/2020.10.07.329094</dc:identifier>
<dc:title><![CDATA[Genetic and metabolite biomarkers reveal actinobacteria-mediated estrogen biodegradation in urban estuarine sediment]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-10-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.10.21.349712v1?rss=1">
<title>
<![CDATA[
Two-photon microscopy at >500 volumes/second 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.10.21.349712v1?rss=1</link>
<description><![CDATA[
We demonstrate a multi-focal multi-photon volumetric microscopy via combination of 32-beam parallel lateral-scanning, a 70-kHz axial-scanning acoustic lens, and a 32-channel photodetector, enabling unprecedented data rate (2-10 GHz) and >500-volumes/second imaging speed over ~200x200x200-m3.
]]></description>
<dc:creator>Tsai, Y.-H.</dc:creator>
<dc:creator>Liu, C.-W.</dc:creator>
<dc:creator>Lin, W.-K.</dc:creator>
<dc:creator>Wang, C.-S.</dc:creator>
<dc:creator>Chiang, C.-H.</dc:creator>
<dc:creator>Singh, V. R.</dc:creator>
<dc:creator>So, P. T. C.</dc:creator>
<dc:creator>Chou, C.-F.</dc:creator>
<dc:creator>Chu, S.-W.</dc:creator>
<dc:date>2020-10-22</dc:date>
<dc:identifier>doi:10.1101/2020.10.21.349712</dc:identifier>
<dc:title><![CDATA[Two-photon microscopy at >500 volumes/second]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-10-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.10.25.334201v1?rss=1">
<title>
<![CDATA[
A novel equilibrative nucleoside transporter 1 inhibitor alleviates Tau-mediated neurodegeneration 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.10.25.334201v1?rss=1</link>
<description><![CDATA[
Tau hyperphosphorylation favors the formation of neurofibrillary tangles and triggers the gradual loss of neuronal functions in tauopathies, including Alzheimers disease. Herein, we demonstrated that chronic treatment with an inhibitor (J4) of equilibrative nucleoside transporter 1 (ENT1), which plays a critical role in controlling adenosine homeostasis and purine metabolism in the brain, exerted beneficial effects in a mouse model of tauopathy (Thy-Tau22, Tau22). Chronic treatment with J4 improved spatial memory deficits, mitochondrial dysfunction, synaptic plasticity impairment, and gliosis. Immunofluorescence assays showed that J4 not only reduced Tau hyperphosphorylation but also normalized the reduction in mitochondrial mass and suppressed the abnormal activation of AMP-activated protein kinase (AMPK), a pathogenic feature that is also observed in the brains of patients with tauopathies. Given that AMPK is an important energy sensor, our findings suggest that energy dysfunction is associated with tauopathy and that J4 may exert its protective effect by improving energy homeostasis. Bulk RNA-seq analysis revealed that J4 also mitigated immune signature associated with Tau pathology including C1q upregulation and A1 astrocyte markers. Collectively, our findings suggest that identifying strategies for normalizing energy and neuroimmune dysfunctions in tauopathies through adenosinergic signaling modulation may pave the way for the development of treatments for Alzheimers disease.
]]></description>
<dc:creator>Chang, C.-P.</dc:creator>
<dc:creator>Chang, Y.-G.</dc:creator>
<dc:creator>Chuang, P.-Y.</dc:creator>
<dc:creator>Nguyen, A. T. N.</dc:creator>
<dc:creator>Chou, F.-Y.</dc:creator>
<dc:creator>Cheng, S.-J.</dc:creator>
<dc:creator>Chen, H.-M.</dc:creator>
<dc:creator>Jin, L.-W.</dc:creator>
<dc:creator>Carvalho, K.</dc:creator>
<dc:creator>Huin, V.</dc:creator>
<dc:creator>Buee, L.</dc:creator>
<dc:creator>Blum, D.</dc:creator>
<dc:creator>Liao, Y.-F.</dc:creator>
<dc:creator>Lin, C.-J.</dc:creator>
<dc:creator>Chern, Y.</dc:creator>
<dc:date>2020-10-26</dc:date>
<dc:identifier>doi:10.1101/2020.10.25.334201</dc:identifier>
<dc:title><![CDATA[A novel equilibrative nucleoside transporter 1 inhibitor alleviates Tau-mediated neurodegeneration]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-10-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.10.28.359398v1?rss=1">
<title>
<![CDATA[
IFN-{lambda}4 may contribute to HCV persistence by increasing ER stress and enhancing IRF1 signaling 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.10.28.359398v1?rss=1</link>
<description><![CDATA[
Chronic hepatitis C virus (HCV) infection and cirrhosis are major risk factors for developing hepatocellular carcinoma (HCC). Genetic polymorphisms in the IFNL3/IFNL4 locus have been associated both with impaired clearance of HCV and protection from liver fibrosis, an early stage of cirrhosis. Here, we aimed to address the genetic and functional relationships between IFNL3/IFNL4 polymorphisms, HCV-related cirrhosis, and HCC risk. We evaluated associations between IFNL4 genotype, defined as the presence of rs368234815-dG or rs12979860-T alleles, with cirrhosis and HCC risk in patients with chronic HCV - 2,931 from Taiwan and 3,566 from Japan. We detected associations between IFNL4 genotype and decreased risk of cirrhosis (OR=0.66, 95%CI=0.46-0.93, P=0.018, in Taiwan), but increased risk of HCC (OR=1.28, 95%CI=1.07-1.52, P=0.0058, in Japan). In-vitro, IFN-{lambda}4 expression increased ER stress, and enhanced positive regulation of IFN responses via IRF1 induction, which mediated antiproliferative effects in hepatic cells. Our data present novel IFN-{lambda}4-associated pathways that may be contributing to HCV persistence and development of HCC.
]]></description>
<dc:creator>Onabajo, O. O.</dc:creator>
<dc:creator>Wang, F.</dc:creator>
<dc:creator>Lee, M.-H.</dc:creator>
<dc:creator>Florez-Vargas, O.</dc:creator>
<dc:creator>Obajemu, A.</dc:creator>
<dc:creator>Castro, M. A. A.</dc:creator>
<dc:creator>Tanikawa, C.</dc:creator>
<dc:creator>Vargas, J.</dc:creator>
<dc:creator>Liao, S.-F.</dc:creator>
<dc:creator>Song, C.</dc:creator>
<dc:creator>Huang, Y.-H.</dc:creator>
<dc:creator>Shen, C.-Y.</dc:creator>
<dc:creator>Banday, A. R.</dc:creator>
<dc:creator>O'Brien, T. R.</dc:creator>
<dc:creator>Hu, Z.</dc:creator>
<dc:creator>Matsuda, K.</dc:creator>
<dc:creator>Robertson, A. G.</dc:creator>
<dc:creator>Prokunina-Olsson, L.</dc:creator>
<dc:date>2020-10-29</dc:date>
<dc:identifier>doi:10.1101/2020.10.28.359398</dc:identifier>
<dc:title><![CDATA[IFN-{lambda}4 may contribute to HCV persistence by increasing ER stress and enhancing IRF1 signaling]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-10-29</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.11.03.367383v1?rss=1">
<title>
<![CDATA[
Feedback inhibition of AMT1 NH4+-transporters mediated by CIPK15 kinase 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.11.03.367383v1?rss=1</link>
<description><![CDATA[
Ammonium (NH4+), a key nitrogen form, becomes toxic when it accumulates to high levels. Ammonium transporters (AMTs) are the key transporters responsible for NH4+ uptake. AMT activity is under allosteric feedback control, mediated by phosphorylation of a threonine in the cytosolic C-terminus (CCT). However, the kinases responsible for the NH4+-triggered phosphorylation remain unknown. In this study, a functional screen identified protein kinase CBL-Interacting Protein Kinase15 (CIPK15) as a negative regulator of AMT1;1 activity. CIPK15 was able to interact with several AMT1 paralogs at the plasma membrane. Analysis of AmTryoshka, an NH4+ transporter activity sensor for AMT1;3 in yeast, and a two-electrode-voltage-clamp (TEVC) of AMT1;1 in Xenopus oocytes showed that CIPK15 inhibits AMT activity. CIPK15 transcript levels increased when seedlings were exposed to elevated NH4+ levels. Notably, cipk15 knockout mutants showed higher 15NH4+ uptake and accumulated higher amounts of NH4+ compared to the wild-type. Consistently, cipk15 was hypersensitive to both NH4+ and methylammonium but not nitrate (NO3-). Taken together, our data indicate that feedback inhibition of AMT1 activity is mediated by the protein kinase CIPK15 via phosphorylation of residues in the CCT to reduce NH4+-accumulation.
]]></description>
<dc:creator>Chen, H.-Y.</dc:creator>
<dc:creator>Chen, Y.-N.</dc:creator>
<dc:creator>Wang, H.-Y.</dc:creator>
<dc:creator>Liu, Z.-T.</dc:creator>
<dc:creator>Frommer, W. B.</dc:creator>
<dc:creator>Ho, C.-H.</dc:creator>
<dc:date>2020-11-04</dc:date>
<dc:identifier>doi:10.1101/2020.11.03.367383</dc:identifier>
<dc:title><![CDATA[Feedback inhibition of AMT1 NH4+-transporters mediated by CIPK15 kinase]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-11-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.11.10.375717v1?rss=1">
<title>
<![CDATA[
accuEnhancer: Accurate enhancer prediction by integration of multiple cell type data with deep learning 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.11.10.375717v1?rss=1</link>
<description><![CDATA[
Enhancers are one class of the regulatory elements that have been shown to act as key components to assist promoters in modulating the gene expression in living cells. At present, the number of enhancers as well as their activities in different cell types are still largely unclear. Previous studies have shown that enhancer activities are associated with various functional data, such as histone modifications, sequence motifs, and chromatin accessibilities. In this study, we utilized DNase data to build a deep learning model for predicting the H3K27ac peaks as the active enhancers in a target cell type. We propose joint training of multiple cell types to boost the model performance in predicting the enhancer activities of an unstudied cell type. The results demonstrated that by incorporating more datasets across different cell types, the complex regulatory patterns could be captured by deep learning models and the prediction accuracy can be largely improved. The analyses conducted in this study demonstrated that the cell type-specific enhancer activity can be predicted by joint learning of multiple cell type data using only DNase data and the primitive sequences as the input features. This reveals the importance of cross-cell type learning, and the constructed model can be applied to investigate potential active enhancers of a novel cell type which does not have the H3K27ac modification data yet.

AvailabilityThe accuEnhancer package can be freely accessed at: https://github.com/callsobing/accuEnhancer
]]></description>
<dc:creator>Tung, Y.-A.</dc:creator>
<dc:creator>Yang, W.-T.</dc:creator>
<dc:creator>Hsieh, T.-T.</dc:creator>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Wu, J.-T.</dc:creator>
<dc:creator>Oyang, Y.-J.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:date>2020-11-11</dc:date>
<dc:identifier>doi:10.1101/2020.11.10.375717</dc:identifier>
<dc:title><![CDATA[accuEnhancer: Accurate enhancer prediction by integration of multiple cell type data with deep learning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-11-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.11.17.386672v1?rss=1">
<title>
<![CDATA[
The histone deacetylase HDA15 interacts with MAC3A and MAC3B to regulate intron retention of ABA-responsive genes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.11.17.386672v1?rss=1</link>
<description><![CDATA[
Histone deacetylases (HDAs) play an important role in transcriptional regulation involved in multiple biological processes. In this study, we investigate the function of HDA15 in abscisic acid (ABA) responses. Immunopurification coupled with mass spectrometry-based proteomics was used to identify the HDA15 interacting proteins. We found that HDA15 can interact with the core subunits of MOS4-Associated Complex (MAC), MAC3A and MAC3B. In addition, ABA enhances the interaction of HDA15 with MAC3B. hda15 and mac3a/mac3b mutants are ABA-insensitive in seed germination and hyposensitive to salinity. RNA sequencing (RNA-seq) analysis demonstrate that HDA15 and MAC3A/MAC3B not only affect the expression of ABA-related genes, but also regulate ABA-responsive intron retention (IR). Furthermore, HDA15 and MAC3A/MAC3B reduce the histone acetylation level of the genomic regions near ABA-responsive IRs. Our studies uncovered the role of histone deacetylation in ABA-mediated splicing regulation and identified that HDA15-MAC3A/MAC3B acts as an important regulation module to mediate splicing of introns in ABA responses.

One Sentence SummaryHDA15 and MAC3A/MAC3B coregulate intron retention and reduce the histone acetylation level of the genomic regions near ABA-responsive retained introns.
]]></description>
<dc:creator>Tu, Y.-T.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Huang, Y.-S.</dc:creator>
<dc:creator>Yen, M.-R.</dc:creator>
<dc:creator>Hsieh, J.-W. A.</dc:creator>
<dc:creator>Chen, P.-Y.</dc:creator>
<dc:creator>Wu, K.</dc:creator>
<dc:date>2020-11-17</dc:date>
<dc:identifier>doi:10.1101/2020.11.17.386672</dc:identifier>
<dc:title><![CDATA[The histone deacetylase HDA15 interacts with MAC3A and MAC3B to regulate intron retention of ABA-responsive genes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-11-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.11.19.389437v1?rss=1">
<title>
<![CDATA[
Differential Hsp90-dependent gene expression is strain-specific and common among yeast strains 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.11.19.389437v1?rss=1</link>
<description><![CDATA[
Enhanced phenotypic diversity increases the likelihood of a population surviving catastrophic conditions. It has been suggested that Hsp90, an essential molecular chaperone in eukaryotes, can suppress (i.e., buffer) or enhance (i.e., potentiate) the effects of genetic variation, enabling organisms to adjust their levels of phenotypic diversity in response to environmental cues. Many Hsp90-interacting proteins are involved in signaling transduction pathways and transcriptional regulation. However, it remains unclear if Hsp90-dependent differential gene expression is common in natural populations. By examining the gene expression profiles of five diverse yeast strains, we identified many genes exhibiting Hsp90-dependent strain-specific differential expression. We employed an analysis pipeline to identify transcription factors (TFs) potentially contributing to variable expression. We found that upon Hsp90 inhibition or heat stress, activities or abundances of Hsp90-dependent TFs varied among strains, resulting in differential strain-specific expression of their target genes, which consequently led to phenotypic diversity. We provide evidence that individual populations can readily display specific Hsp90-dependent gene expression, suggesting that the evolutionary impacts of Hsp90 are widespread in nature.

HighlightsO_LIHsp90-dependent gene expression varies among different yeast strains.
C_LIO_LIHsp90 differentially influences transcriptional activity or protein abundances of transcription factors among yeast strains.
C_LIO_LIDifferential strain-specific gene expression is correlated with phenotypic variations upon Hsp90 inhibition.
C_LIO_LIHsp90-mediated strain-specific regulation manifests under environmental stress.
C_LI
]]></description>
<dc:creator>Hung, P.-H.</dc:creator>
<dc:creator>Liao, C.-W.</dc:creator>
<dc:creator>Ko, F.-H.</dc:creator>
<dc:creator>Tsai, H.-K.</dc:creator>
<dc:creator>Leu, J.-Y.</dc:creator>
<dc:date>2020-11-20</dc:date>
<dc:identifier>doi:10.1101/2020.11.19.389437</dc:identifier>
<dc:title><![CDATA[Differential Hsp90-dependent gene expression is strain-specific and common among yeast strains]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-11-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.11.24.396713v1?rss=1">
<title>
<![CDATA[
Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.11.24.396713v1?rss=1</link>
<description><![CDATA[
Determining the conformation of chromatin in cells at the nucleosome level and its relationship to cellular processes has been a central challenge in biology. We show that in quiescent yeast, widespread transcriptional repression coincides with the local compaction of chromatin fibers into structures that are less condensed and more heteromorphic than canonical 30-nanometer forms. Acetylation or substitution of H4 tail residues decompacts fibers and leads to global transcriptional de-repression. Fiber decompaction also increases the rate of loop extrusion by condensin. These findings establish a role for H4 tail-dependent local chromatin fiber folding in regulating transcription and loop extrusion in cells. They also demonstrate the physiological relevance of canonical chromatin fiber folding mechanisms even in the absence of regular 30-nanometer structures.
]]></description>
<dc:creator>Swygert, S. G.</dc:creator>
<dc:creator>Lin, D.</dc:creator>
<dc:creator>Portillo-Ledesma, S.</dc:creator>
<dc:creator>Lin, P.-Y.</dc:creator>
<dc:creator>Hunt, D. R.</dc:creator>
<dc:creator>Kao, C.-F.</dc:creator>
<dc:creator>Schlick, T.</dc:creator>
<dc:creator>Noble, W. S.</dc:creator>
<dc:creator>Tsukiyama, T.</dc:creator>
<dc:date>2020-11-24</dc:date>
<dc:identifier>doi:10.1101/2020.11.24.396713</dc:identifier>
<dc:title><![CDATA[Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-11-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.11.25.398784v1?rss=1">
<title>
<![CDATA[
phiC31 integrase for recombination mediated single copy insertion and genome manipulation in C. elegans 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.11.25.398784v1?rss=1</link>
<description><![CDATA[
C. elegans benefits from a large set of tools for genome manipulation. Yet, the insertion of large DNA constructs and the generation of inversions is still challenging. Here, we adapted the phiC31 integrase system for C. elegans. We generated an integrated phiC31 integrase expressing strain flanked by attP sites that also serves as a landing pad for integration of transgenes by recombination mediated cassette exchange (RCME). This strain is unc-119(-) so RMCE integrants can be produced simply by injection of a plasmid carrying attB sites flanking unc-119(+) and the gene(s) of interest. Additionally, phiC31 integrase is removed concomitantly with integration, eliminating the need to outcross away the integrase. Integrations are relatively easy to obtain for insert sizes up to ~15 kb. Taking advantage of this integration method we establish a dual color fluorescent operon reporter system to study post-transcriptional regulation of mRNA. Last we show that large chromosomal segments can be inverted using phiC31 integrase. Thus the phiC31 integrase system should be a useful addition to the C. elegans toolkit.
]]></description>
<dc:creator>Yang, F.-J.</dc:creator>
<dc:creator>Chen, C.-N.</dc:creator>
<dc:creator>Chang, T.</dc:creator>
<dc:creator>Cheng, T.-W.</dc:creator>
<dc:creator>Chang, N.-C.</dc:creator>
<dc:creator>Kao, C.-Y.</dc:creator>
<dc:creator>Lee, C.-C.</dc:creator>
<dc:creator>Huang, Y.-C.</dc:creator>
<dc:creator>Chan, S.-P.</dc:creator>
<dc:creator>Wang, J.</dc:creator>
<dc:date>2020-11-25</dc:date>
<dc:identifier>doi:10.1101/2020.11.25.398784</dc:identifier>
<dc:title><![CDATA[phiC31 integrase for recombination mediated single copy insertion and genome manipulation in C. elegans]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-11-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.11.27.399857v1?rss=1">
<title>
<![CDATA[
Profiling Germline Adaptive Immune Receptor Repertoire with gAIRR Suite 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.11.27.399857v1?rss=1</link>
<description><![CDATA[
Genetic profiling of germline adaptive immune receptor repertoire (AIRR), including T cell receptor (TR) and immunoglobulin (IG), is imaginably relevant to numerous immune-related conditions, but currently insurmountable due to high genetic complexity. Our gAIRR Suite comprises three modules. gAIRR-seq, a probe capture-based targeted sequencing pipeline, profiles AIRR from individual DNA samples. gAIRR-call and gAIRR-annotate call alleles from gAIRR-seq reads and annotate whole-genome assemblies respectively. We gAIRR-seqed TRV and TRJ of seven Genome in a Bottle (GIAB) DNA samples with 100% accuracy, and discovered novel alleles. We also gAIRR-seqed and gAIRR-called a subject from both the peripheral blood mononuclear cells (PBMC) and oral mucosal cells. The calling results from these two cell types have a high concordance (99% for all known AIRR alleles). We gAIRR-annotated 36 genomes to cumulatively unearth 325 novel TRV alleles and 29 novel TRJ alleles. We could further profile the flanking sequences, including the recombination signal sequence (RSS). We validated two structural variants for HG002. We uncovered substantial conflicts of AIRR genes in references GRCh37 and GRCh38. The gAIRR Suite can potentially benefit future genetic study and clinical applications of various immune-related phenotypes.
]]></description>
<dc:creator>Lin, M.-J.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Chen, N.-C.</dc:creator>
<dc:creator>Luo, A. C.-L.</dc:creator>
<dc:creator>Lai, S.-K.</dc:creator>
<dc:creator>Hsu, C.-L.</dc:creator>
<dc:creator>Hsu, J. S.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Yang, W.-S.</dc:creator>
<dc:creator>Chen, P.-L.</dc:creator>
<dc:date>2020-11-27</dc:date>
<dc:identifier>doi:10.1101/2020.11.27.399857</dc:identifier>
<dc:title><![CDATA[Profiling Germline Adaptive Immune Receptor Repertoire with gAIRR Suite]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-11-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.11.30.399154v1?rss=1">
<title>
<![CDATA[
A Novel SARS-CoV-2 Multitope Protein/Peptide Vaccine Candidate is Highly Immunogenic and Prevents Lung Infection in an Adeno Associated Virus Human Angiotensin-Converting Enzyme 2 (AAV hACE2) Mouse Model 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.11.30.399154v1?rss=1</link>
<description><![CDATA[
A novel multitope protein-peptide vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and disease is described in this report. The initial development and characterization experiments are presented along with proof-of-concept studies for the vaccine candidate UB-612. UB-612 consists of eight components rationally designed for induction of potently neutralizing antibodies and broad T cell responses against SARS-CoV-2: the S1-RBD-sFc fusion protein, six synthetic peptides (one universal peptide and five SARS-CoV-2-derived peptides), a proprietary CpG TLR-9 agonist at low concentration as an excipient, and aluminum phosphate adjuvant. Through immunogenicity studies in Guinea pigs and rats, we optimized the design of protein/peptide immunogens and selected an adjuvant system, yielding a vaccine that provides excellent S1-RBD binding and high neutralizing antibody responses, robust cellular responses, and a Th1-oriented response at low doses. In challenge studies, UB- 612 vaccination reduced viral load and prevented development of disease in mouse and non-human primate challenge models. With a Phase 1 trial completed, a Phase 2 trial ongoing in Taiwan, and additional trials planned to support global authorizations, UB-612 is a highly promising and differentiated vaccine candidate for prevention of SARS-CoV-2 infection and COVID-19 disease.

Author SummarySARS-CoV-2 virus, the causative agent of Coronavirus Disease 2019 (COVID-19), has spread globally since its origin in 2019, causing an unprecedented public health crisis that has resulted in greater than 4.7 million deaths worldwide. Many vaccines are under development to limit disease spread and reduce the number of cases, but additional candidates that promote a robust immune response are needed. Here, we describe a multitope protein-peptide vaccine platform that is unique among COVID-19 vaccines. The advantages of our approach are induction of both high levels of neutralizing antibodies as well as a Th/CTL response in the vaccinated host, which mimics the immune response that occurs after natural infection with SARS-CoV-2. We demonstrate that our vaccine is immunogenic and effective in preventing disease in several animal models, including AAV- hACE-2 transduced mice, and both rhesus and cynomolgus macaques. Importantly, no immunopathology was observed in the lungs of immunized animals, therefore showing that antibody-dependent enhancement (ADE) does not occur. Our study provides an additional, novel vaccine candidate for advancement in clinical trials to treat and prevent SARS-CoV-2 infection and COVID-19 disease.
]]></description>
<dc:creator>Guirakhoo, F.</dc:creator>
<dc:creator>Kuo, L.</dc:creator>
<dc:creator>Peng, J.</dc:creator>
<dc:creator>Huang, J. H.</dc:creator>
<dc:creator>Kuo, B.</dc:creator>
<dc:creator>Lin, F.</dc:creator>
<dc:creator>Liu, K.</dc:creator>
<dc:creator>Liu, Z.</dc:creator>
<dc:creator>Wu, G.</dc:creator>
<dc:creator>Ding, S.</dc:creator>
<dc:creator>Hou, L.-L.</dc:creator>
<dc:creator>Cheng, J.</dc:creator>
<dc:creator>Yang, V.</dc:creator>
<dc:creator>Jiang, H.</dc:creator>
<dc:creator>Wang, J.</dc:creator>
<dc:creator>Chen, T.</dc:creator>
<dc:creator>Xia, W.</dc:creator>
<dc:creator>Lin, E.</dc:creator>
<dc:creator>Hung, C. H.</dc:creator>
<dc:creator>Chen, K.</dc:creator>
<dc:creator>Shih, Z.</dc:creator>
<dc:creator>Lin, Y.</dc:creator>
<dc:creator>Schurter, B. T.</dc:creator>
<dc:creator>Hu, M. M.</dc:creator>
<dc:creator>Heppner, G.</dc:creator>
<dc:creator>Malherbe, D. C.</dc:creator>
<dc:creator>Bukreyev, A.</dc:creator>
<dc:creator>Hellerstein, M.</dc:creator>
<dc:creator>Monath, T.</dc:creator>
<dc:creator>Wang, C. Y.</dc:creator>
<dc:date>2020-11-30</dc:date>
<dc:identifier>doi:10.1101/2020.11.30.399154</dc:identifier>
<dc:title><![CDATA[A Novel SARS-CoV-2 Multitope Protein/Peptide Vaccine Candidate is Highly Immunogenic and Prevents Lung Infection in an Adeno Associated Virus Human Angiotensin-Converting Enzyme 2 (AAV hACE2) Mouse Model]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-11-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.11.30.404376v1?rss=1">
<title>
<![CDATA[
Comparative Analysis of Embryo Proper and Suspensor Transcriptomes in Plant Embryos With Different Morphologies 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.11.30.404376v1?rss=1</link>
<description><![CDATA[
An important question is what genes govern the differentiation of plant embryos into suspensor and embryo-proper regions following fertilization and division of the zygote. We compared embryo proper and suspensor transcriptomes of four plants that vary in embryo morphology within the suspensor region. We determined that genes encoding enzymes in several metabolic pathways leading to the formation of hormones, such as gibberellic acid, and other metabolites are up-regulated in giant Scarlet Runner Bean and Common Bean suspensors. Genes involved in transport and Golgi body organization are up-regulated within the suspensors of these plants as well - strengthening the view that giant specialized suspensors serve as a hormone factory and a conduit for transferring substances to the developing embryo proper. By contrast, genes controlling transcriptional regulation, development, and cell division are up-regulated primarily within the embryo proper. Transcriptomes from less specialized soybean and Arabidopsis suspensors demonstrated that fewer genes encoding metabolic enzymes and hormones are up-regulated. Genes active in the embryo proper, however, are functionally similar to those active in Scarlet Runner Bean and Common Bean embryo proper regions. We uncovered a set of suspensor- and embryo-proper-specific transcription factors (TFs) that are shared by all embryos irrespective of morphology, suggesting that they are involved in early differentiation processes common to all plants. ChIP-Seq experiments with Scarlet Runner Bean and soybean WOX9, an up-regulated suspensor TF, gained entry into a regulatory network important for suspensor development irrespective of morphology.

SignificanceHow plant embryos are differentiated into embryo proper and suspensor regions following fertilization is a major unanswered question. The suspensor is unique because it can vary in morphology in different plant species. We hypothesized that regulatory genes controlling the specification of embryo proper and suspensor regions should be shared by all plants irrespective of embryo morphology. We compared embryo proper and suspensor transcriptomes of plants with distinct suspensor morphologies. Scarlet Runner Bean and Common Bean have highly specialized giant suspensor regions, whereas soybean and Arabidopsis suspensors are smaller and less specialized. We uncovered a small set of embryo-proper- and suspensor-specific transcription factors shared by all embryos irrespective of morphology, suggesting that they play an important role in early embryo differentiation.
]]></description>
<dc:creator>Goldberg, R.</dc:creator>
<dc:creator>Chen, M.</dc:creator>
<dc:creator>Lin, J.-Y.</dc:creator>
<dc:creator>Wu, X.</dc:creator>
<dc:creator>Apuya, N. R.</dc:creator>
<dc:creator>Henry, K. F.</dc:creator>
<dc:creator>Le, B. H.</dc:creator>
<dc:creator>Bui, A. Q.</dc:creator>
<dc:creator>Pelletier, J. M.</dc:creator>
<dc:creator>Cokus, S.</dc:creator>
<dc:creator>Pellegrini, M.</dc:creator>
<dc:creator>Harada, J. J.</dc:creator>
<dc:date>2020-12-01</dc:date>
<dc:identifier>doi:10.1101/2020.11.30.404376</dc:identifier>
<dc:title><![CDATA[Comparative Analysis of Embryo Proper and Suspensor Transcriptomes in Plant Embryos With Different Morphologies]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-12-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.12.03.409763v1?rss=1">
<title>
<![CDATA[
SARS-CoV-2 D614 and G614 spike variants impair neuronal synapses and exhibit differential fusion ability 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.12.03.409763v1?rss=1</link>
<description><![CDATA[
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Coronavirus disease 2019 (COVID-19) exhibits two major variants based on mutations of its spike protein, i.e., the D614 prototype and G614 variant. Although neurological symptoms have been frequently reported in patients, it is still unclear whether SARS-CoV-2 impairs neuronal activity or function. Here, we show that expression of both D614 and G614 spike proteins is sufficient to induce phenotypes of impaired neuronal morphology, including defective dendritic spines and shortened dendritic length. Using spike protein-specific monoclonal antibodies, we found that D614 and G614 spike proteins show differential S1/S2 cleavage and cell fusion efficiency. Our findings provide an explanation for higher transmission of the G614 variant and the neurological manifestations observed in COVID-19 patients.
]]></description>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Chou, Y.-C.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:date>2020-12-03</dc:date>
<dc:identifier>doi:10.1101/2020.12.03.409763</dc:identifier>
<dc:title><![CDATA[SARS-CoV-2 D614 and G614 spike variants impair neuronal synapses and exhibit differential fusion ability]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-12-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.12.08.407247v1?rss=1">
<title>
<![CDATA[
Intrinsic disorder codes for leaps of protein expression 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.12.08.407247v1?rss=1</link>
<description><![CDATA[
Serine(S)/threonine(T)-glutamine(Q) cluster domains (SCDs), polyglutamine (polyQ) tracts and polyglutamine/asparagine (polyQ/N) tracts are Q-rich motifs found in many proteins. SCDs often are intrinsically disordered regions that mediate protein phosphorylation and protein-protein interactions. PolyQ and polyQ/N tracts are structurally flexible sequences that trigger protein aggregation. We report that due to their high percentages of STQ or STQN amino acid content, four SCDs and three prion-causing Q/N-rich motifs of yeast proteins possess autonomous protein expression-enhancing activities. Since these Q-rich motifs can endow proteins with structural and functional plasticity, we suggest that they represent useful toolkits for evolutionary novelty. Comparative Gene Ontology (GO) analyses of the near-complete proteomes of 27 representative model eukaryotes reveal that Q-rich motifs prevail in proteins involved in specialized biological processes, including Saccharomyces cerevisiae RNA-mediated transposition and pseudohyphal growth, Candida albicans filamentous growth, ciliate peptidyl-glutamic acid modification and microtubule-based movement, Tetrahymena thermophila xylan catabolism and meiosis, Dictyostelium discoideum development and sexual cycles, Plasmodium falciparum infection, and the nervous systems of Drosophila melanogaster, Mus musculus and Homo sapiens. We also show that Q-rich-motif proteins are expanded massively in ten ciliates with reassigned TAAQ and TAGQ codons. Notably, the usage frequency of CAGQ is much lower in ciliates with reassigned TAAQ and TAGQ codons than in organisms with expanded and unstable Q runs (e.g., D. melanogaster and H. sapiens), indicating that the use of noncanonical stop codons in ciliates may have coevolved with codon usage biases to avoid triplet repeat disorders mediated by CAG/GTC replication slippage.
]]></description>
<dc:creator>Chuang, C.-N.</dc:creator>
<dc:creator>Woo, T.-T.</dc:creator>
<dc:creator>Tsai, S.-Y.</dc:creator>
<dc:creator>Chen, C.-L.</dc:creator>
<dc:creator>Li, W.-C.</dc:creator>
<dc:creator>Liu, H.-C.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:creator>Wang, T.-F.</dc:creator>
<dc:date>2020-12-08</dc:date>
<dc:identifier>doi:10.1101/2020.12.08.407247</dc:identifier>
<dc:title><![CDATA[Intrinsic disorder codes for leaps of protein expression]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-12-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.12.17.423354v1?rss=1">
<title>
<![CDATA[
Molecular insights into substrate recognition and discrimination by the N-terminal domain of Lon AAA+ protease 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.12.17.423354v1?rss=1</link>
<description><![CDATA[
The Lon AAA+ proteases (LonA) is a ubiquitous ATP-dependent proteolytic machine, which selectively degrades damaged proteins or native proteins carrying exposed motifs (degrons). Here we characterize the structural basis for substrate recognition and discrimination by the N-terminal domain (NTD) of LonA. The results reveal that the six NTDs are attached to the hexameric LonA chamber by flexible linkers such that the formers tumble independently of the latter. Further spectral analyses show that the NTD selectively interacts with unfolded proteins, protein aggregates, and degron-tagged proteins by two hydrophobic patches of its N-lobe, but not intrinsically disordered substrate, -casein. Moreover, the NTD selectively binds to protein substrates when they are thermally induced to adopt unfolded conformations. Collectively, our findings demonstrate that NTDs enable LonA to perform protein quality control to selectively degrade proteins in damaged states and suggest that substrate discrimination and selective degradation by LonA are mediated by multiple NTD interactions.

Impact StatementThe N-terminal domains enable Lon protease to discriminate and capture selected protein species for degradation by exposed hydrophobic patches and flexible linkages to the hexameric core complex.
]]></description>
<dc:creator>Tzeng, S.-R.</dc:creator>
<dc:creator>Tseng, Y.-C.</dc:creator>
<dc:creator>Lin, C.-C.</dc:creator>
<dc:creator>Hsu, C.-Y.</dc:creator>
<dc:creator>Huang, S.-J.</dc:creator>
<dc:creator>Kuo, Y.-T.</dc:creator>
<dc:creator>Chang, C.-I.</dc:creator>
<dc:date>2020-12-18</dc:date>
<dc:identifier>doi:10.1101/2020.12.17.423354</dc:identifier>
<dc:title><![CDATA[Molecular insights into substrate recognition and discrimination by the N-terminal domain of Lon AAA+ protease]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-12-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.12.17.423359v1?rss=1">
<title>
<![CDATA[
AI4AMP: Sequence-based antimicrobial peptides predictor using physicochemical properties-based encoding method and deep learning 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.12.17.423359v1?rss=1</link>
<description><![CDATA[
MotivationAntimicrobial peptides (AMPs) are innate immune components that have aroused a great deal of interest among drug developers recently, as they may become a substitution for antibiotics. However, AMPs discovery through traditional wet-lab research is expensive and inefficient. Thus, we developed AI4AMP, a user-friendly web-server that provides an accurate prediction of the antimicrobial activity of a given protein sequence, to accelerate the process of AMP discovery.

ResultsOur results show that our prediction model is superior to the existing AMP predictors.

AvailabilityAI4AMP is freely accessible at http://symbiosis.iis.sinica.edu.tw/PC_6/

Contactcylin@iis.sinica.edu.tw
]]></description>
<dc:creator>Lin, T.-T.</dc:creator>
<dc:creator>Yang, L.-Y.</dc:creator>
<dc:creator>Lu, I.-H.</dc:creator>
<dc:creator>Cheng, W.-C.</dc:creator>
<dc:creator>Hsu, Z.-R.</dc:creator>
<dc:creator>Chen, S.-H.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:date>2020-12-18</dc:date>
<dc:identifier>doi:10.1101/2020.12.17.423359</dc:identifier>
<dc:title><![CDATA[AI4AMP: Sequence-based antimicrobial peptides predictor using physicochemical properties-based encoding method and deep learning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-12-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.12.18.423418v1?rss=1">
<title>
<![CDATA[
Human Surfactant Protein D Binds S1 and Receptor Binding Domain of Spike protein and acts as an entry inhibitor of SARS-CoV-2 Pseudotyped viral particles in vitro 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.12.18.423418v1?rss=1</link>
<description><![CDATA[
Human SP-D is a potent innate immune molecule whose presence at pulmonary mucosal surfaces allows immune surveillance role against pulmonary pathogens. Higher levels of serum SP-D have been reported in patients with severe acute respiratory syndrome coronavirus-1 (SARS-CoV). Studies have suggested the ability of human SP-D to recognise spike glycoprotein of SARS-CoV; its interaction with HCoV-229E strain leads to viral inhibition in human bronchial epithelial (16HBE) cells. Previous studies have reported that a recombinant fragment of human SP-D (rfhSP-D) composed of 8 Gly-X-Y repeats, neck and CRD region, can act against a range of viral pathogens including influenza A Virus and Respiratory Syncytial Virus in vitro, in vivo and ex vivo models. In this context, this study was aimed at examining the likely protective role of rfhSP-D against SARS-CoV-2 infection. rfhSP-D showed a dose-responsive binding to S1 spike protein of SARS-CoV-2 and its receptor binding domain. Importantly, rfhSP-D inhibited interaction of S1 protein with the HEK293T cells overexpressing Angiotensin Converting Enzyme 2. The protective role of rfhSP-D against SARS-CoV-2 infection as an entry inhibitor was further validated by the use of pseudotyped lentiviral particles expressing SARS-CoV-2 S1 protein; ~0.5 RLU fold reduction in viral entry was seen following rfhSP-D treatment (10 g/ml). The results highlight the therapeutic potential of rfhSP-D in SARS-CoV-2 infection and merits pre-clinical studies in murine models.
]]></description>
<dc:creator>Hsieh, M.-H.</dc:creator>
<dc:creator>Beirag, N.</dc:creator>
<dc:creator>Murugaiah, V.</dc:creator>
<dc:creator>Chou, Y.-C.</dc:creator>
<dc:creator>Kuo, W.-S.</dc:creator>
<dc:creator>Kao, H.-F.</dc:creator>
<dc:creator>Madan, T.</dc:creator>
<dc:creator>Kishore, U.</dc:creator>
<dc:creator>Wang, J.-Y.</dc:creator>
<dc:date>2020-12-18</dc:date>
<dc:identifier>doi:10.1101/2020.12.18.423418</dc:identifier>
<dc:title><![CDATA[Human Surfactant Protein D Binds S1 and Receptor Binding Domain of Spike protein and acts as an entry inhibitor of SARS-CoV-2 Pseudotyped viral particles in vitro]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-12-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.12.22.423783v1?rss=1">
<title>
<![CDATA[
Rare coding variants in 35 genes associate with circulating lipid levels: a multi-ancestry analysis of 170,000 exomes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.12.22.423783v1?rss=1</link>
<description><![CDATA[
Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency<1%) predicted damaging coding variation using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels. Ten of these: ALB, SRSF2, JAK2, CREB3L3, TMEM136, VARS, NR1H3, PLA2G12A, PPARG and STAB1 have not been implicated for lipid levels using rare coding variation in population-based samples. We prioritize 32 genes identified in array-based genome-wide association study (GWAS) loci based on gene-based associations, of which three: EVI5, SH2B3, and PLIN1, had no prior evidence of rare coding variant associations. Most of the associated genes showed evidence of association in multiple ancestries. Also, we observed an enrichment of gene-based associations for low-density lipoprotein cholesterol drug target genes, and for genes closest to GWAS index single nucleotide polymorphisms (SNP). Our results demonstrate that gene-based associations can be beneficial for drug target development and provide evidence that the gene closest to the array-based GWAS index SNP is often the functional gene for blood lipid levels.
]]></description>
<dc:creator>Hindy, G.</dc:creator>
<dc:creator>Dornbos, P.</dc:creator>
<dc:creator>Chaffin, M. D.</dc:creator>
<dc:creator>Liu, D. J.</dc:creator>
<dc:creator>Wang, M. X.</dc:creator>
<dc:creator>Aguilar-Salinas, C. A.</dc:creator>
<dc:creator>Antonacci-Fulton, L.</dc:creator>
<dc:creator>Ardissino, D.</dc:creator>
<dc:creator>Arnett, D. K.</dc:creator>
<dc:creator>Aslibekyan, S.</dc:creator>
<dc:creator>Atzmon, G.</dc:creator>
<dc:creator>Ballantyne, C. M.</dc:creator>
<dc:creator>Barajas-Olmos, F.</dc:creator>
<dc:creator>Barzilai, N.</dc:creator>
<dc:creator>Becker, L. C.</dc:creator>
<dc:creator>Bielak, L. F.</dc:creator>
<dc:creator>Bis, J. C.</dc:creator>
<dc:creator>Blangero, J.</dc:creator>
<dc:creator>Boerwinkle, E.</dc:creator>
<dc:creator>Bonnycastle, L. L.</dc:creator>
<dc:creator>Bottinger, E.</dc:creator>
<dc:creator>Bowden, D. W.</dc:creator>
<dc:creator>Bown, M. J.</dc:creator>
<dc:creator>Brody, J. A.</dc:creator>
<dc:creator>Broome, J. G.</dc:creator>
<dc:creator>Burtt, N. P.</dc:creator>
<dc:creator>Cade, B. E.</dc:creator>
<dc:creator>Centeno-Cruz, F.</dc:creator>
<dc:creator>Chan, E.</dc:creator>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Chen, Y.-D. I.</dc:creator>
<dc:creator>Cheng, C.-Y.</dc:creator>
<dc:creator>Choi, W. J.</dc:creator>
<dc:creator>Chowdhury, R.</dc:creator>
<dc:creator>Contreras-Cubas, C.</dc:creator>
<dc:creator>Cordova, E. J.</dc:creator>
<dc:creator>Correa, A.</dc:creator>
<dc:creator>Cupples, L. A.</dc:creator>
<dc:creator>Curran, J. E.</dc:creator>
<dc:creator>Danesh,</dc:creator>
<dc:date>2020-12-23</dc:date>
<dc:identifier>doi:10.1101/2020.12.22.423783</dc:identifier>
<dc:title><![CDATA[Rare coding variants in 35 genes associate with circulating lipid levels: a multi-ancestry analysis of 170,000 exomes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-12-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2020.12.31.424895v1?rss=1">
<title>
<![CDATA[
Population Differentiation of Rhodobacteraceae Along Coral Compartments 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2020.12.31.424895v1?rss=1</link>
<description><![CDATA[
Coral mucus, tissue and skeleton harbor compositionally different microbiota, but how these coral compartments shape the microbial evolution remains unexplored. Here, we focused on the Rhodobacteraceae, which represents a significant but variable proportion (5-50%) of the coral microbiota. We sequenced 234 genomes constituting two divergent populations inhabiting a prevalent coral species Platygyra acuta. One population diverged into two clades colonizing the mucus and skeleton respectively. We reconstructed the ancestral gene changing events that potentially drove the split, and found that the affected genes matched well with the distinct physicochemical features of the mucus and skeleton. Specifically, the mucus clade acquired functions involved in the utilization of coral osmolytes abundant in the mucus (e.g., methylamines, DMSP, taurine and L-proline), whereas the skeleton clade uniquely harbored traits that may promote adaptation to the low-energy and diurnally anoxic skeleton (e.g., sulfur oxidation and swimming motility). These between-clade genetic differences were largely supported by physiological assays. Expanded analyses by including relatives isolated from various marine environments suggest that the mucus and skeleton clades may have diversified in non-coral habitats, but they also consolidated a key role of distinct coral compartments in diversifying many of the above-mentioned traits. The second population varied only at a few dozen nucleotide sites across the whole genomes, and the Slatkin-Maddison test supported that dispersal limitation between coral compartments is another key mechanism driving microbial population differentiation. Collectively, our results suggest that different coral compartments represent ecologically distinct and microgeographically separate habitats that drive the evolution of the coral microbiota.
]]></description>
<dc:creator>Luo, H.</dc:creator>
<dc:creator>Luo, D.</dc:creator>
<dc:creator>Wang, X.</dc:creator>
<dc:creator>Feng, X.</dc:creator>
<dc:creator>Tian, M.</dc:creator>
<dc:creator>Wang, S.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:creator>Ang, P. O.</dc:creator>
<dc:creator>Yan, A.</dc:creator>
<dc:date>2021-01-05</dc:date>
<dc:identifier>doi:10.1101/2020.12.31.424895</dc:identifier>
<dc:title><![CDATA[Population Differentiation of Rhodobacteraceae Along Coral Compartments]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-01-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.01.06.425541v1?rss=1">
<title>
<![CDATA[
INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.01.06.425541v1?rss=1</link>
<description><![CDATA[
The immune synapse, a specialized interface formed between T lymphocytes and antigen-presenting cells (APCs) after antigen recognition, is essential for T cell activation and the adaptive immune response. It has been shown that this interface shares similarities with the primary cilium, a sensory organelle in eukaryotic cells, although roles of ciliary proteins on the immune synapse remain elusive. In this study, we find that inositol polyphosphate-5-phosphatase E (INPP5E), a cilium-enriched protein responsible for regulating phosphoinositide localization, accumulated at the immune synapse during antigen-specific conjugation or antibody capping, and formed a complex with CD3{zeta}, ZAP-70, and Lck. Silencing INPP5E in T-cells impaired polarized distribution of CD3{zeta} at the immune synapse, and correlated with a failure of PI(4,5)P2 clearance at the center of the synapse. Moreover, INPP5E silencing decreased proximal TCR signaling, including phosphorylation of CD3{zeta} and ZAP-70, and finally, attenuated IL-2 secretion. Our results suggest that INPP5E is a new player in phosphoinositide manipulation at the synapse, controlling the TCR signaling cascade.
]]></description>
<dc:creator>Chiu, T.-Y.</dc:creator>
<dc:creator>Yang, F.-H.</dc:creator>
<dc:creator>Chong, W. M.</dc:creator>
<dc:creator>Tsai, H.-C.</dc:creator>
<dc:creator>Wang, W.-J.</dc:creator>
<dc:creator>Liao, J.-C.</dc:creator>
<dc:date>2021-01-07</dc:date>
<dc:identifier>doi:10.1101/2021.01.06.425541</dc:identifier>
<dc:title><![CDATA[INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-01-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.01.07.425674v1?rss=1">
<title>
<![CDATA[
CpG-adjuvanted stable prefusion SARS-CoV-2 spike protein protected hamsters from SARS-CoV-2 challenge 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.01.07.425674v1?rss=1</link>
<description><![CDATA[
The COVID-19 pandemic presents an unprecedented challenge to global public health. Rapid development and deployment of safe and effective vaccines are imperative to control the pandemic. In the current study, we applied our adjuvanted stable prefusion SARS-CoV-2 spike (S-2P)-based vaccine, MVC-COV1901, to hamster models to demonstrate immunogenicity and protection from virus challenge. Golden Syrian hamsters immunized intramuscularly with two injections of 1 {micro}g or 5 {micro}g of S-2P adjuvanted with CpG 1018 and aluminum hydroxide (alum) were challenged intranasally with SARS-CoV-2. Prior to virus challenge, the vaccine induced high levels of neutralizing antibodies with 10,000-fold higher IgG level and an average of 50-fold higher pseudovirus neutralizing titers in either dose groups than vehicle or adjuvant control groups. Six days after infection, vaccinated hamsters did not display any weight loss associated with infection and had significantly reduced lung pathology and most importantly, lung viral load levels were reduced to lower than detection limit compared to unvaccinated animals. Vaccination with either 1 g or 5 g of adjuvanted S-2P produced comparable immunogenicity and protection from infection. This study builds upon our previous results to support the clinical development of MVC-COV1901 as a safe, highly immunogenic, and protective COVID-19 vaccine.
]]></description>
<dc:creator>Lien, C.-E.</dc:creator>
<dc:creator>Lin, Y.-J.</dc:creator>
<dc:creator>Kuo, T.-Y.</dc:creator>
<dc:creator>Campbell, J. D.</dc:creator>
<dc:creator>Traquina, P.</dc:creator>
<dc:creator>Lin, M.-Y.</dc:creator>
<dc:creator>Liu, L. T. C.</dc:creator>
<dc:creator>Chuang, Y.-S.</dc:creator>
<dc:creator>Ku, H.-Y.</dc:creator>
<dc:creator>Liao, C.-C.</dc:creator>
<dc:creator>Chen, Y.-H.</dc:creator>
<dc:creator>Jan, J.-T.</dc:creator>
<dc:creator>Sun, C.-P.</dc:creator>
<dc:creator>Lin, Y.-S.</dc:creator>
<dc:creator>Wu, P.-Y.</dc:creator>
<dc:creator>Wang, Y.-C.</dc:creator>
<dc:creator>Tao, M.-H.</dc:creator>
<dc:creator>Lin, Y.-L.</dc:creator>
<dc:date>2021-01-07</dc:date>
<dc:identifier>doi:10.1101/2021.01.07.425674</dc:identifier>
<dc:title><![CDATA[CpG-adjuvanted stable prefusion SARS-CoV-2 spike protein protected hamsters from SARS-CoV-2 challenge]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-01-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.01.13.426511v1?rss=1">
<title>
<![CDATA[
An integrative approach unveils a distal encounter site for rPTPε and phospho-Src complex formation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.01.13.426511v1?rss=1</link>
<description><![CDATA[
Protein tyrosine phosphatase: phospho-protein complex structure determination, which requires to understand how specificity is achieved at the protein level remains a significant challenge for protein crystallography and cryoEM due to the transient nature of binding interactions. Using rPTP{varepsilon}D1 and phospho-SrcKD as a model system, we established an integrative workflow involving protein crystallography, SAXS and pTyr-tailored MD simulations to reveal the complex formed between rPTP{varepsilon}D1 and phospho-SrcKD, revealing transient protein-protein interactions distal to the active site. To support our finding, we determined the associate rate between rPTP{varepsilon}D1 and phospho-SrcKD and showed that a single mutation on rPTP{varepsilon}D1 disrupts this transient interaction, resulting in the reduction of association rate and activity. Our simulations suggest that rPTP{varepsilon}D1 employs a binding mechanism involving conformational change prior to the engagement of cSrcKD. This integrative approach is applicable to other PTP: phospho-protein complex determination and is a general approach for elucidating transient protein surface interactions.
]]></description>
<dc:creator>EswarKumar, N.</dc:creator>
<dc:creator>Yang, C.-H.</dc:creator>
<dc:creator>Tewary, S.</dc:creator>
<dc:creator>Yeh, Y.-Q.</dc:creator>
<dc:creator>Yang, H.-C.</dc:creator>
<dc:creator>Ho, M.-C.</dc:creator>
<dc:date>2021-01-14</dc:date>
<dc:identifier>doi:10.1101/2021.01.13.426511</dc:identifier>
<dc:title><![CDATA[An integrative approach unveils a distal encounter site for rPTPε and phospho-Src complex formation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-01-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.02.04.429686v1?rss=1">
<title>
<![CDATA[
The prevalence, predominance, and metabolic potentials of Candidatus Prochlorobium terpiosii in the coral-killing sponge, Terpios hoshinota 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.02.04.429686v1?rss=1</link>
<description><![CDATA[
Terpios hoshinota is a ferocious, space-competing sponge that kills a variety of stony corals by overgrowth. Outbreaks of this species have led to intense coral reef damage and declines in living corals on the square kilometer scale in many geographical locations. Our large-scale 16S rRNA gene survey across three oceans revealed that the core microbiome of T. hoshinota included operational taxonomic units (OTUs) related to Prochloron, Endozoicomonas, Pseudospirillum, SAR116, Magnetospira, and Ruegeria. A Prochloron- related OTU was the most dominant cyanobacterium in T. hoshinota in the western Pacific Ocean, South China Sea, and Indian Ocean. The complete metagenome-assembled genome of the Prochloron-related cyanobacterium and our pigment analysis revealed that this bacterium had phycobiliproteins and phycobilins and lacked chlorophyll b, inconsistent with the iconic definition of Prochloron. Furthermore, the phylogenetic analyses based on 16S rRNA genes and 120 single-copy genes demonstrated that the bacterium was phylogenetically distinct to Prochloron, strongly suggesting that it should be a sister taxon to Prochloron; we therefore proposed this symbiotic cyanobacterium as a novel species under a new genus: Candidatus Paraprochloron terpiosii. With the recovery of the complete genome, we characterized the metabolic potentials of the novel cyanobacterium in carbon and nitrogen cycling and proposed a model for the interaction between Ca. Pp. terpiosi LD05 and T. hoshinota. In addition, comparative genomics analysis revealed that Ca. Paraprochloron and Prochloron showed distinct features in transporter systems and DNA replication.

ImportanceThe finding that one species predominates cyanobacteria in T. hoshinota from different geographic locations indicates that this sponge and Ca. Pp. terpiosi LD05 share a tight relationship. This study builds the foundation for T. hoshinotas microbiome and paves a way for understanding the ecosystem, invasion mechanism, and causes of outbreak of this coral-killing sponge. Also, the first Prochloron-related complete genome enables us to study this bacterium with molecular approaches in the future and broadens our knowledge of the evolution of symbiotic cyanobacteria.
]]></description>
<dc:creator>Chen, Y.-H.</dc:creator>
<dc:creator>Chen, H.-J.</dc:creator>
<dc:creator>Yang, C.-Y.</dc:creator>
<dc:creator>Shiu, J.-H.</dc:creator>
<dc:creator>Hoh, D. Z.</dc:creator>
<dc:creator>Chiang, P.-W.</dc:creator>
<dc:creator>Chow, W. S.</dc:creator>
<dc:creator>Chen, C. A.</dc:creator>
<dc:creator>Shih, T.-H.</dc:creator>
<dc:creator>Lin, S.-H.</dc:creator>
<dc:creator>Yang, C.-M.</dc:creator>
<dc:creator>Reimer, J. D.</dc:creator>
<dc:creator>Hirose, E.</dc:creator>
<dc:creator>Iskandar, B. H.</dc:creator>
<dc:creator>Huang, H.</dc:creator>
<dc:creator>Schupp, P. J.</dc:creator>
<dc:creator>Tan, C. H. J.</dc:creator>
<dc:creator>Yamashiro, H.</dc:creator>
<dc:creator>Liao, M.-H.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:date>2021-02-05</dc:date>
<dc:identifier>doi:10.1101/2021.02.04.429686</dc:identifier>
<dc:title><![CDATA[The prevalence, predominance, and metabolic potentials of Candidatus Prochlorobium terpiosii in the coral-killing sponge, Terpios hoshinota]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-02-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.02.15.430920v1?rss=1">
<title>
<![CDATA[
Parasite co-opts a ubiquitin receptor to induce a plethora of developmental changes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.02.15.430920v1?rss=1</link>
<description><![CDATA[
Obligate parasites can induce complex and substantial phenotypic changes in their hosts in ways that favour their transmission to other trophic levels. However, mechanisms underlying these changes remain largely unknown. Here, we demonstrate how SAP05 protein effectors from insect-vectored plant pathogenic phytoplasmas take control of several plant developmental processes to simultaneously prolong host lifespan and induce witchs broom-like proliferations of leaf and sterile shoots, organs colonized by phytoplasmas and vectors. SAP05 acts by mediating the concurrent degradation of SPL and GATA developmental regulators via a process that uniquely relies on hijacking the plant ubiquitin receptor RPN10 independently of substrate lysine ubiquitination. RPN10 is highly conserved among eukaryotes, but SAP05 does not bind insect vector RPN10. A two-amino-acid substitution within plant RPN10 generates a functional variant that is resistant to SAP05 activities. Therefore, one effector protein enables obligate parasitic phytoplasmas to induce a plethora of developmental phenotypes in their hosts.
]]></description>
<dc:creator>Huang, W.</dc:creator>
<dc:creator>MacLean, A.</dc:creator>
<dc:creator>Sugio, A.</dc:creator>
<dc:creator>Maqbool, A.</dc:creator>
<dc:creator>Busscher, M.</dc:creator>
<dc:creator>Cho, S.-T.</dc:creator>
<dc:creator>Kamoun, S.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:creator>Immink, R. G. H.</dc:creator>
<dc:creator>Hogenhout, S. A.</dc:creator>
<dc:date>2021-02-15</dc:date>
<dc:identifier>doi:10.1101/2021.02.15.430920</dc:identifier>
<dc:title><![CDATA[Parasite co-opts a ubiquitin receptor to induce a plethora of developmental changes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-02-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.02.16.431461v1?rss=1">
<title>
<![CDATA[
IRONMAN Tunes Responses to Iron Deficiency in Concert with Environmental pH 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.02.16.431461v1?rss=1</link>
<description><![CDATA[
Iron (Fe) is an essential mineral element which governs the composition of natural plant communities and limits crop yield in agricultural ecosystems due to its extremely low availability in most soils, particularly at alkaline pH. To extract sufficient Fe from the soil under such conditions, some plants including Arabidopsis thaliana secrete Fe-mobilizing phenylpropanoids, which mobilize sparingly soluble Fe hydroxides by reduction and chelation. We show here that ectopic expression of the IRONMAN peptides IMA1 and IMA2 improves growth on calcareous soil by inducing the biosynthesis and secretion of the catecholic coumarin fraxetin (7,8-dihydroxy-6-methoxycoumarin) through increased expression of MYB72 and SCOPOLETIN 8-HYDROXYLASE (S8H), a response which is strictly dependent on elevated environmental pH (pHe). By contrast, transcription of the cytochrome P450 family protein CYP82C4, catalyzing the subsequent hydroxylation of fraxetin to sideretin, which forms less stable complexes with iron, was strongly repressed under such conditions. Luciferase reporter assays in transiently transformed protoplasts showed that IMA1/IMA2 peptides are translated and modulate the expression of CYP82C4 and MYB72 by acting as transcriptional coactivators. It is concluded that IMA peptides regulate processes supporting Fe uptake at both acidic and elevated pH by controlling gene expression upstream of or in concert with a putative pHe signal to adapt the plant to the prevailing edaphic conditions. This regulatory pattern confers tolerance to calcareous soils by extending the pH range in which Fe can be efficiently absorbed from the soil. Altering the expression of IMA peptides provides a novel route for generating plants adapted to calcareous soils.

One sentence summaryEctopic expression of IRONMAN peptides improves growth under iron-limiting conditions by inducing responses to limited iron availability in accordance with the environmental pH.

The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantphysiol.org) is: Wolfgang Schmidt (wosh@gate.sinica.edu.tw).
]]></description>
<dc:creator>Schmidt, W.</dc:creator>
<dc:creator>Tsai, H.-H.</dc:creator>
<dc:creator>Gautam, C. K.</dc:creator>
<dc:date>2021-02-17</dc:date>
<dc:identifier>doi:10.1101/2021.02.16.431461</dc:identifier>
<dc:title><![CDATA[IRONMAN Tunes Responses to Iron Deficiency in Concert with Environmental pH]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-02-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.03.08.434228v1?rss=1">
<title>
<![CDATA[
Sialic acid-Dependent Binding and Viral Entry of SARS-CoV-2 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.03.08.434228v1?rss=1</link>
<description><![CDATA[
Emerging evidence suggests that host glycans influence infection by SARS-CoV-2. Here, we reveal that the receptor-binding domain (RBD) of the spike (S)-protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (SA), with preference for the oligosaccharide of monosialylated gangliosides. Gangliosides embedded within an artificial membrane also bind the RBD. The monomeric affinities (Kd = 100-200 M) of gangliosides for the RBD are similar to heparan sulfate, another negatively charged glycan ligand of the RBD proposed as a viral coreceptor. RBD binding and infection of SARS-CoV-2 pseudotyped lentivirus to ACE2-expressing cells is decreased upon depleting cell surface SA level using three approaches: sialyltransferase inhibition, genetic knock-out of SA biosynthesis, or neuraminidase treatment. These effects on RBD binding and pseudotyped viral entry are recapitulated with pharmacological or genetic disruption of glycolipid biosynthesis. Together, these results suggest that sialylated glycans, specifically glycolipids, facilitate viral entry of SARS-CoV-2.
]]></description>
<dc:creator>Nguyen, L.</dc:creator>
<dc:creator>McCord, K. A.</dc:creator>
<dc:creator>Bui, D. T.</dc:creator>
<dc:creator>Bouwman, K. A.</dc:creator>
<dc:creator>Kitova, E. N.</dc:creator>
<dc:creator>Kumawat, D.</dc:creator>
<dc:creator>Daskan, G. C.</dc:creator>
<dc:creator>Tomris, I.</dc:creator>
<dc:creator>Han, L.</dc:creator>
<dc:creator>Chopra, P.</dc:creator>
<dc:creator>Yang, T.-J.</dc:creator>
<dc:creator>Williows, S. D.</dc:creator>
<dc:creator>Lowary, T. L.</dc:creator>
<dc:creator>West, L. J.</dc:creator>
<dc:creator>Hsu, S.-T. D.</dc:creator>
<dc:creator>Tompkins, S. M.</dc:creator>
<dc:creator>Boons, G.-J.</dc:creator>
<dc:creator>Mason, A. L.</dc:creator>
<dc:creator>de Vries, R. P.</dc:creator>
<dc:creator>Macauley, M. S.</dc:creator>
<dc:creator>Klassen, J. S.</dc:creator>
<dc:date>2021-03-08</dc:date>
<dc:identifier>doi:10.1101/2021.03.08.434228</dc:identifier>
<dc:title><![CDATA[Sialic acid-Dependent Binding and Viral Entry of SARS-CoV-2]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-03-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.03.08.434500v1?rss=1">
<title>
<![CDATA[
Complete genome sequence of Xylella taiwanensis and comparative analysis of virulence gene content with Xylella fastidiosa 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.03.08.434500v1?rss=1</link>
<description><![CDATA[
The bacterial genus Xylella contains plant pathogens that are major threats to agriculture in America and Europe. Although extensive research was conducted to characterize different subspecies of Xylella fastidiosa (Xf), comparative analysis at above-species levels were lacking due to the unavailability of appropriate data sets. Recently, a bacterium that causes pear leaf scorch (PLS) in Taiwan was described as the second Xylella species (i.e., Xylella taiwanensis; Xt). In this work, we report the complete genome sequence of Xt type strain PLS229T. The genome-scale phylogeny provided strong support that Xf subspecies pauca (Xfp) is the basal lineage of this species and Xylella was derived from the paraphyletic genus Xanthomonas. Quantification of genomic divergence indicated that different Xf subspecies share [~]87-95% of their chromosomal segments, while the two Xylella species share only [~]66-70%. Analysis of overall gene content suggested that Xt is most similar to Xf subspecies sandyi (Xfs). Based on the existing knowledge of Xf virulence genes, the homolog distribution among 28 Xylella representatives was examined. Among the 11 functional categories, those involved in secretion and metabolism are the most conserved ones with no copy number variation. In contrast, several genes related to adhesins, hydrolytic enzymes, and toxin-antitoxin systems are highly variable in their copy numbers. Those virulence genes with high levels of conservation or variation may be promising candidates for future studies. In summary, the new genome sequence and analysis reported in this work contributed to the study of several important pathogens in the family Xanthomonadaceae.

Contribution to the FieldXylella fastidiosa is a plant-pathogenic bacterium with multiple subspecies that are major threats to agriculture in America and Europe. Although extensive research has been conducted, comparative analysis of this species with other bacteria is lacking due to the unavailability of known close relatives. In this work, we report the complete genome sequence of Xylella taiwanensis, a newly described species within the same genus. This new data set and our focused analysis helped to better understand the evolutionary relationships among different Xylella lineages and their genomic diversity. Moreover, detailed examination of their virulence genes identified those that are either highly conserved or variable, providing promising candidates for future studies to further investigate the molecular mechanisms of Xylella virulence.
]]></description>
<dc:creator>Weng, L.-W.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Su, C.-C.</dc:creator>
<dc:creator>Huang, C.-T.</dc:creator>
<dc:creator>Cho, S.-T.</dc:creator>
<dc:creator>Chen, A.-P.</dc:creator>
<dc:creator>Chou, S.-J.</dc:creator>
<dc:creator>Tsai, C.-W.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:date>2021-03-09</dc:date>
<dc:identifier>doi:10.1101/2021.03.08.434500</dc:identifier>
<dc:title><![CDATA[Complete genome sequence of Xylella taiwanensis and comparative analysis of virulence gene content with Xylella fastidiosa]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-03-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.03.09.434087v1?rss=1">
<title>
<![CDATA[
A New Protocol for Targeted insertion using CRISPR-Cas9, Oligo Single-Stranded DNA and Protoplast Regeneration 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.03.09.434087v1?rss=1</link>
<description><![CDATA[
Versatile genome editing can be facilitated by the insertion of DNA sequences into specific locations. Current protocols involving clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins rely on low efficiency homology-directed repair or non-homologous end joining with modified double-stranded DNA oligonucleotides as donors. Our simple protocol eliminates the need for expensive equipment, chemical and enzymatic donor DNA modification or plasmid construction by using polyethylene glycol-calcium to deliver non-modified single-stranded DNA oligonucleotides and CRISPR-Cas9 ribonucleoprotein into protoplasts. Plants regenerated via edited protoplasts achieved targeted insertion frequencies of up to 50.0% in Nicotiana benthamiana and 13.6% in rapid cycling Brassica oleracea without antibiotic selection. Using a 60-nt donor containing 27 nt in each homologous arm, 6 of 22 regenerated N. benthamiana plants showed targeted insertions, and one contained a precise insertion of a 6-bp HindIII site. The inserted sequences were transmitted to the next generation and invite the possibility of future exploration of versatile genome editing by targeted DNA insertion in plants.
]]></description>
<dc:creator>Hsu, C.-T.</dc:creator>
<dc:creator>Yuan, Y.-H.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Lin, S.</dc:creator>
<dc:creator>Cheng, Q.-W.</dc:creator>
<dc:creator>Wu, F.-H.</dc:creator>
<dc:creator>Sheen, J.</dc:creator>
<dc:creator>Shih, M.-C.</dc:creator>
<dc:creator>Lin, C.-S.</dc:creator>
<dc:date>2021-03-10</dc:date>
<dc:identifier>doi:10.1101/2021.03.09.434087</dc:identifier>
<dc:title><![CDATA[A New Protocol for Targeted insertion using CRISPR-Cas9, Oligo Single-Stranded DNA and Protoplast Regeneration]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-03-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.03.14.435332v1?rss=1">
<title>
<![CDATA[
Community Evaluation of Glycoproteomics Informatics Solutions Reveals High-Performance Search Strategies of Glycopeptide Data 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.03.14.435332v1?rss=1</link>
<description><![CDATA[
Glycoproteome profiling (glycoproteomics) is a powerful yet analytically challenging research tool. The complex tandem mass spectra generated from glycopeptide mixtures require sophisticated analysis pipelines for structural determination. Diverse software aiding the process have appeared, but their relative performance remains untested. Conducted through the HUPO Human Proteome Project - Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates the performance of informatics solutions for system-wide glycopeptide analysis. Mass spectrometry-based glycoproteomics datasets from human serum were shared with all teams. The relative team performance for N- and O-glycopeptide data analysis was comprehensively established and validated through orthogonal performance tests. Excitingly, several high-performance glycoproteomics informatics solutions were identified. While the study illustrated that significant informatics challenges remain, as indicated by a high discordance between annotated glycopeptides, lists of high-confidence (consensus) glycopeptides were compiled from the standardised team reports. Deep analysis of the performance data revealed key performance-associated search variables and led to recommendations for improved "high coverage" and "high accuracy" glycoproteomics search strategies. This study concludes that diverse software for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies, and specifies key variables that may guide future software developments and assist informatics decision-making in glycoproteomics.
]]></description>
<dc:creator>Kawahara, R.</dc:creator>
<dc:creator>Alagesan, K.</dc:creator>
<dc:creator>Bern, M.</dc:creator>
<dc:creator>Cao, W.</dc:creator>
<dc:creator>Chalkley, R. J.</dc:creator>
<dc:creator>Cheng, K.</dc:creator>
<dc:creator>Choo, M. S.</dc:creator>
<dc:creator>Edwards, N.</dc:creator>
<dc:creator>Goldman, R.</dc:creator>
<dc:creator>Hoffmann, M.</dc:creator>
<dc:creator>Hu, Y.</dc:creator>
<dc:creator>Huang, Y.</dc:creator>
<dc:creator>Kim, J. Y.</dc:creator>
<dc:creator>Kletter, D.</dc:creator>
<dc:creator>Liquet-Weiland, B.</dc:creator>
<dc:creator>Liu, M.</dc:creator>
<dc:creator>Mechref, Y.</dc:creator>
<dc:creator>Meng, B.</dc:creator>
<dc:creator>Neelamegham, S.</dc:creator>
<dc:creator>Nguyen-Khuong, T.</dc:creator>
<dc:creator>Nilsson, J.</dc:creator>
<dc:creator>Pap, A.</dc:creator>
<dc:creator>Park, G. W.</dc:creator>
<dc:creator>Parker, B. L.</dc:creator>
<dc:creator>Pegg, C. L.</dc:creator>
<dc:creator>Penninger, J. M.</dc:creator>
<dc:creator>Phung, T. K.</dc:creator>
<dc:creator>Pioch, M.</dc:creator>
<dc:creator>Rapp, E.</dc:creator>
<dc:creator>Sakalli, E.</dc:creator>
<dc:creator>Sanda, M.</dc:creator>
<dc:creator>Shulz, B. L.</dc:creator>
<dc:creator>Scott, N. E.</dc:creator>
<dc:creator>Sofronov, G.</dc:creator>
<dc:creator>Stadlmann, J.</dc:creator>
<dc:creator>Vakhrushev, S. Y.</dc:creator>
<dc:creator>Woo, C. M.</dc:creator>
<dc:creator>Wu, H.-Y.</dc:creator>
<dc:creator>Yang, P.</dc:creator>
<dc:creator>Ying, W.</dc:creator>
<dc:creator>Zhang, H.</dc:creator>
<dc:creator>Zhang, Y.</dc:creator>
<dc:creator>Zhao, J.</dc:creator>
<dc:creator>Zaia, J.</dc:creator>
<dc:creator>Haslam, S. M.</dc:creator>
<dc:creator>Palmisano, G.</dc:creator>
<dc:creator>Yoo, J. S</dc:creator>
<dc:date>2021-03-15</dc:date>
<dc:identifier>doi:10.1101/2021.03.14.435332</dc:identifier>
<dc:title><![CDATA[Community Evaluation of Glycoproteomics Informatics Solutions Reveals High-Performance Search Strategies of Glycopeptide Data]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-03-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.03.24.436723v1?rss=1">
<title>
<![CDATA[
Genetic differentiation of Xylella fastidiosa following the introduction into Taiwan 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.03.24.436723v1?rss=1</link>
<description><![CDATA[
The economically important plant pathogen Xylella fastidiosa has been reported in multiple regions of the globe during the last two decades, threatening a growing list of crops and industries. Xylella fastidiosa subspecies fastidiosa causes disease in grapevines (Pierces disease of grapevines, PD), a current problem in the United States (US), Spain, and Taiwan. We studied PD-causing subsp. fastidiosa populations and compared the genome sequences of 33 isolates found in Central Taiwan with 171 isolates from the US and two from Spain.

Phylogenetic relationships, haplotype network, and genetic diversity analyses confirm that subsp. fastidiosa was recently introduced into Taiwan from the Southeast US (i.e., the PD-I lineage in Georgia based on available data). Recent core genome recombination events were detected among introduced subsp. fastidiosa isolates in Taiwan and contributed to the development of genetic diversity, particularly in the Houli District of Taichung City in Central Taiwan. Unexpectedly, despite comprehensive sampling of all regions with high PD incidences in Taiwan, the genetic diversity observed include contributions through recombination from unknown donors, suggesting that higher diversity exists in the region. Nevertheless, no recombination event was detected between X. fastidiosa subsp. fastidiosa and the endemic sister species Xylella taiwanensis. In summary, this study improved our understanding of the genetic diversity of PD-causing subsp. fastidiosa after invasion to a new region.
]]></description>
<dc:creator>Castillo, A. I.</dc:creator>
<dc:creator>Tsai, C.-W.</dc:creator>
<dc:creator>Su, C.-C.</dc:creator>
<dc:creator>Weng, L.-W.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Cho, S.-T.</dc:creator>
<dc:creator>Almeida, R. P. P.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:date>2021-03-24</dc:date>
<dc:identifier>doi:10.1101/2021.03.24.436723</dc:identifier>
<dc:title><![CDATA[Genetic differentiation of Xylella fastidiosa following the introduction into Taiwan]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-03-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.03.24.436900v1?rss=1">
<title>
<![CDATA[
Integrated multi-omics investigations reveal the key role of synergistic microbial networks in removing plasticizer di-(2-ethylhexyl) phthalate from estuarine sediments 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.03.24.436900v1?rss=1</link>
<description><![CDATA[
Di-(2-ethylhexyl) phthalate (DEHP) is the most widely used plasticizer worldwide with an annual global production of over eight million tons. Because of its improper disposal, endocrine-disrupting DEHP often accumulates in estuarine sediments in industrialized countries at sub-millimolar levels, resulting in adverse effects on both ecosystems and human beings. The microbial degraders and biodegradation pathways of DEHP in O2-limited estuarine sediments remain elusive. Here, we employed an integrated meta-omics approach to identify the DEHP degradation pathway and major degraders in this ecosystem. Estuarine sediments were treated with DEHP or its derived metabolites, o-phthalic acid and benzoic acid. The rate of DEHP degradation in denitrifying mesocosms was two times slower than that of o-phthalic acid, suggesting that side-chain hydrolysis of DEHP is the rate-limiting step of anaerobic DEHP degradation. On the basis of microbial community structures, functional gene expression, and metabolite profile analysis, we proposed that DEHP biodegradation in estuarine sediments is mainly achieved through synergistic networks between denitrifying proteobacteria. Acidovorax and Sedimenticola are the major degraders of DEHP side-chains; the resulting o-phthalic acid is mainly degraded by Aestuariibacter through the UbiD-dependent benzoyl-CoA pathway. We isolated and characterized Acidovorax sp. strain 210-6 and its extracellular hydrolase, which hydrolyzes both alkyl side-chains of DEHP. Interestingly, genes encoding DEHP/MEHP hydrolase and phthaloyl-CoA decarboxylase--key enzymes for side-chain hydrolysis and o-phthalic acid degradation, respectively--are flanked by transposases in these proteobacterial genomes, indicating that DEHP degradation capacity is likely transferred horizontally in microbial communities.

ImportanceXenobiotic phthalate esters (PAE) have been produced on a considerably large scale for only 70 years. The occurrence of endocrine-disrupting di-(2-ethylhexyl) phthalate (DEHP) in environments has raised public concern, and estuarine sediments are major DEHP reservoirs. Our multi-omics analyses indicated that complete DEHP degradation in O2-limited estuarine sediments depends on synergistic microbial networks between diverse denitrifying proteobacteria and uncultured candidates. Our data also suggest that the side-chain hydrolysis of DEHP, rather than o-phthalic acid activation, is the rate-limiting step in DEHP biodegradation within O2-limited estuarine sediments. Therefore, deciphering the bacterial ecophysiology and related biochemical mechanisms can help facilitate the practice of bioremediation in O2-limited environments. Furthermore, the DEHP hydrolase genes of active DEHP degraders can be used as molecular markers to monitor environmental DEHP degradation. Finally, future studies on the directed evolution of identified DEHP/MEHP hydrolase would bring a more catalytically efficient DEHP/MEHP hydrolase into practice.
]]></description>
<dc:creator>Wei, S. T.-S.</dc:creator>
<dc:creator>Chen, Y.-L.</dc:creator>
<dc:creator>Wu, Y.-W.</dc:creator>
<dc:creator>Wu, T.-Y.</dc:creator>
<dc:creator>Lai, Y.-L.</dc:creator>
<dc:creator>Wang, P.-H.</dc:creator>
<dc:creator>Ismail, W.</dc:creator>
<dc:creator>Lee, T.-H.</dc:creator>
<dc:creator>Chiang, Y.-R.</dc:creator>
<dc:date>2021-03-25</dc:date>
<dc:identifier>doi:10.1101/2021.03.24.436900</dc:identifier>
<dc:title><![CDATA[Integrated multi-omics investigations reveal the key role of synergistic microbial networks in removing plasticizer di-(2-ethylhexyl) phthalate from estuarine sediments]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-03-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.03.25.436574v1?rss=1">
<title>
<![CDATA[
A viral toolbox for conditional and transneuronal gene expression in zebrafish 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.03.25.436574v1?rss=1</link>
<description><![CDATA[
The zebrafish is an important model in systems neuroscience but a key limitation is the lack of viral tools to dissect the structure and function of neuronal circuitry. We developed methods for efficient gene transfer and retrograde tracing in adult and larval zebrafish by herpes simplex viruses (HSV1). HSV1 can be combined with the Gal4/UAS system to target cell types with high spatial, temporal and molecular specificity. We also established methods for efficient transneuronal tracing by modified rabies viruses in zebrafish. We demonstrate that HSV1 and rabies viruses can be used to visualize and manipulate genetically or anatomically identified neurons within and across different brain areas of adult and larval zebrafish. An expandable library of viruses is provided to express fluorescent proteins, calcium indicators, optogenetic probes, toxins and other molecular tools. This toolbox creates new opportunities to interrogate neuronal circuits in zebrafish through combinations of genetic and viral approaches.
]]></description>
<dc:creator>Satou, C.</dc:creator>
<dc:creator>Neve, R. L.</dc:creator>
<dc:creator>Oyibo, H. K.</dc:creator>
<dc:creator>Arn Bouldoires, E.</dc:creator>
<dc:creator>Mori, T.</dc:creator>
<dc:creator>Higashijima, S.-i.</dc:creator>
<dc:creator>Keller, G. B.</dc:creator>
<dc:creator>Friedrich, R. W.</dc:creator>
<dc:date>2021-03-25</dc:date>
<dc:identifier>doi:10.1101/2021.03.25.436574</dc:identifier>
<dc:title><![CDATA[A viral toolbox for conditional and transneuronal gene expression in zebrafish]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-03-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.03.28.437426v1?rss=1">
<title>
<![CDATA[
COVID-19 dominant D614G mutation in the SARS-CoV-2 spike protein desensitizes its temperature-dependent denaturation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.03.28.437426v1?rss=1</link>
<description><![CDATA[
The D614G mutation in the spike protein of SARS-CoV-2 alters the fitness of the virus, making it the dominant form in the COVID-19 pandemic. Here we demonstrated by cryo-electron microscopy that the D614G mutation does not significantly perturb the structure of the spike protein, but multiple receptor binding domains are in an upward conformation poised for host receptor binding. The impact of the mutation lies in its ability to eliminate the unusual cold-induced unfolding characteristics, and to significantly increase the thermal stability under physiological pH. Our findings shed light on how the D614G mutation enhances the infectivity of SARS-CoV-2 through a stabilizing mutation, and suggest an approach for better design of spike-protein based conjugates for vaccine development.
]]></description>
<dc:creator>Yang, T.-J.</dc:creator>
<dc:creator>Yu, P.-Y.</dc:creator>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Kuo, C.-W.</dc:creator>
<dc:creator>Khoo, K.-H.</dc:creator>
<dc:creator>Hsu, S.-T. D.</dc:creator>
<dc:date>2021-03-29</dc:date>
<dc:identifier>doi:10.1101/2021.03.28.437426</dc:identifier>
<dc:title><![CDATA[COVID-19 dominant D614G mutation in the SARS-CoV-2 spike protein desensitizes its temperature-dependent denaturation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-03-29</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.03.30.437786v1?rss=1">
<title>
<![CDATA[
Multi-omics approach to identify bacterial polyynes and unveil their antifungal mechanism against Candida albicans 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.03.30.437786v1?rss=1</link>
<description><![CDATA[
Bacterial polyynes are highly active natural products with a broad-spectrum of antimicrobial activities. However, their detailed mechanism of action remains unclear. Through integrating comparative genomics, transcriptomics, functional genetics, and metabolomics analysis, we identified a unique polyyne resistance gene, masL (encoding acetyl-CoA acetyltransferase), from the biosynthesis gene cluster (BGC) dominant for the production of antifungal polyynes (massilin A, massilin B, collimonin C, and collimonin D) in Massilia sp. YMA4. Phylogenic and chemotaxonomic analyses characterized the core architecture of bacterial polyyne BGC. The crystallographic analysis of the MasL-collimonin C complex indicated that bacterial polyynes serve as a covalent inhibitor of acetyl-CoA acetyltransferase. Moreover, we confirmed that the bacterial polyynes disrupted cell membrane integrity and inhibited cell viability of Candida albicans by targeting ERG10 (homolog of MasL). Overall, understanding of the antifungal mechanism of bacterial polyynes presented herein will be useful for the development of polyynes for fungal infections.
]]></description>
<dc:creator>Lin, C.-C.</dc:creator>
<dc:creator>Hoo, S. Y.</dc:creator>
<dc:creator>Lin, C.</dc:creator>
<dc:creator>Huang, K.-F.</dc:creator>
<dc:creator>Ho, Y.-N.</dc:creator>
<dc:creator>Sun, C.-H.</dc:creator>
<dc:creator>Lee, H.-J.</dc:creator>
<dc:creator>Chen, P.-Y.</dc:creator>
<dc:creator>Shu, L.-J.</dc:creator>
<dc:creator>Wang, B.-W.</dc:creator>
<dc:creator>Hsu, W.-C.</dc:creator>
<dc:creator>Yang, Y.-L.</dc:creator>
<dc:date>2021-03-31</dc:date>
<dc:identifier>doi:10.1101/2021.03.30.437786</dc:identifier>
<dc:title><![CDATA[Multi-omics approach to identify bacterial polyynes and unveil their antifungal mechanism against Candida albicans]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-03-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.04.08.439008v1?rss=1">
<title>
<![CDATA[
A Positive Regulatory Feedback Loop Between 1 EKLF/ KLF1 and TAL1/SCL2 Sustaining the Erythropoiesis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.04.08.439008v1?rss=1</link>
<description><![CDATA[
The erythroid Kruppel-like factor EKLF/KLF1 is a hematopoietic transcription factor binding to CACCC DNA motif and participating in the regulation of erythroid differentiation. With combined use of microarray-based gene expression profiling and promoter-based ChIP-chip assay of E14.5 fetal liver cells from wild type (WT) and EKLF-knockout (Eklf-/-) mouse embryos, we have identified the pathways and direct target genes activated or repressed by EKLF. This genome-wide study together with molecular/cellular analysis of mouse erythroleukemic cells (MEL) indicate that among the downstream direct target genes of EKLF is Tal1/Scl. Tal1/Scl encodes another DNA-binding hematopoietic transcription factor TAL1/SCL known to be an Eklf activator and essential for definitive erythroid differentiation. Further identification of the authentic Tall gene promoter in combination with in vivo genomic footprinting approach and DNA reporter assay demonstrate that EKLF activates Tall gene through binding to a specific CACCC motif located in its promoter. These data establish the existence of a previously unknow positive regulatory feedback loop between two DNA-binding hematopoietic transcription factors that sustains the mammalian erythropoiesis.
]]></description>
<dc:creator>Hung, C.-H.</dc:creator>
<dc:creator>Huang, Y.-S.</dc:creator>
<dc:creator>Lee, T.-L.</dc:creator>
<dc:creator>Yang, K.-C.</dc:creator>
<dc:creator>Shyu, Y.-C.</dc:creator>
<dc:creator>Wen, S.-C.</dc:creator>
<dc:creator>Lu, M.-J.</dc:creator>
<dc:creator>Yuan, S.</dc:creator>
<dc:creator>Shen, C.-K. J.</dc:creator>
<dc:date>2021-04-08</dc:date>
<dc:identifier>doi:10.1101/2021.04.08.439008</dc:identifier>
<dc:title><![CDATA[A Positive Regulatory Feedback Loop Between 1 EKLF/ KLF1 and TAL1/SCL2 Sustaining the Erythropoiesis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-04-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.04.18.440359v1?rss=1">
<title>
<![CDATA[
Connecting MHC-I-binding motifs with HLA alleles via deep learning 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.04.18.440359v1?rss=1</link>
<description><![CDATA[
The selection of peptides presented by MHC molecules is crucial for antigen discovery. Previously, several predictors have shown impressive performance on binding affinity. However, the decisive MHC residues and their relation to the selection of binding peptides are still unrevealed. Here, we connected HLA alleles with binding motifs via our deep learning-based framework, MHCfovea. MHCfovea expanded the knowledge of MHC-I-binding motifs from 150 to 13,008 alleles. After clustering N-terminal and C-terminal sub-motifs on both observed and unobserved alleles, MHCfovea calculated the hyper-motifs and the corresponding allele signatures on the important positions to disclose the relation between binding motifs and MHC-I sequences. MHCfovea delivered 32 pairs of hyper-motifs and allele signatures (HLA-A: 13, HLA-B: 12, and HLA-C: 7). The paired hyper-motifs and allele signatures disclosed the critical polymorphic residues that determine the binding preference, which are believed to be valuable for antigen discovery and vaccine design when allele specificity is concerned.
]]></description>
<dc:creator>Lee, K.-H.</dc:creator>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Chen, T.-F.</dc:creator>
<dc:creator>Juan, H.-F.</dc:creator>
<dc:creator>Tsai, H.-K.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:date>2021-04-20</dc:date>
<dc:identifier>doi:10.1101/2021.04.18.440359</dc:identifier>
<dc:title><![CDATA[Connecting MHC-I-binding motifs with HLA alleles via deep learning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-04-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.04.22.440886v1?rss=1">
<title>
<![CDATA[
Identification of essential β-oxidation genes and corresponding metabolites for estrogen degradation by actinobacteria 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.04.22.440886v1?rss=1</link>
<description><![CDATA[
Steroidal estrogens (C18) are contaminants receiving increasing attention due to their endocrine-disrupting activities at sub-nanomolar concentrations. Although estrogens can be eliminated through photodegradation, microbial function is critical for removing estrogens from ecosystems devoid of sunlight exposure including activated sludge, soils, and aquatic sediments. Actinobacteria were found to be key estrogen degraders in manure-contaminated soils and estuarine sediments. Previously, we used the actinobacterium Rhodococcus sp. strain B50 as a model microorganism to identify two oxygenase genes, aedA and aedB, involved in the activation and subsequent cleavage of the estrogenic A-ring, respectively. However, genes responsible for the downstream degradation of estrogen A/B-rings remained completely unknown. In this study, we employed tiered comparative transcriptomics, gene disruption experiments, and mass spectrometry-based metabolite profile analysis to identify estrogen catabolic genes. We observed the up-regulation of thiolase-encoding aedF and aedK in the transcriptome of strain B50 grown with estrone. Consistently, two downstream estrogenic metabolites, 5-oxo-4-norestrogenic acid (C17) and 2,3,4-trinorestrogenic acid (C15), were accumulated in aedF- and aedK-disrupted strain B50 cultures. Disruption of fadD3 [3a-H-4(3-propanoate)-7a{beta}-methylhexahydro-1,5-indanedione (HIP)-coenzyme A ligase gene] in strain B50 resulted in apparent HIP accumulation in estrone-fed cultures, indicating the essential role of fadD3 in actinobacterial estrogen degradation. In addition, we detected a unique meta-cleavage product, 4,5-seco-estrogenic acid (C18), during actinobacterial estrogen degradation. Differentiating the estrogenic metabolite profile and degradation genes of actinobacteria and proteobacteria enables the cost-effective and time-saving identification of potential estrogen degraders in various ecosystems through liquid chromatography-mass spectrometry analysis and polymerase chain reaction-based functional assays.
]]></description>
<dc:creator>Hsiao, T.-H.</dc:creator>
<dc:creator>Lee, T.-H.</dc:creator>
<dc:creator>Chuang, M.-R.</dc:creator>
<dc:creator>Wang, P.-H.</dc:creator>
<dc:creator>Meng, M.</dc:creator>
<dc:creator>Horinouchi, M.</dc:creator>
<dc:creator>Hayashi, T.</dc:creator>
<dc:creator>Chen, Y.-L.</dc:creator>
<dc:creator>Chiang, Y.-R.</dc:creator>
<dc:date>2021-04-22</dc:date>
<dc:identifier>doi:10.1101/2021.04.22.440886</dc:identifier>
<dc:title><![CDATA[Identification of essential β-oxidation genes and corresponding metabolites for estrogen degradation by actinobacteria]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-04-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.04.25.441383v1?rss=1">
<title>
<![CDATA[
TIC236 gain-of-function mutations unveil the link between plastid division and plastid protein import 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.04.25.441383v1?rss=1</link>
<description><![CDATA[
The chloroplast translocons TOC75 and TIC236 are homologs of the bacterial translocation and assembly module (Tam) A and TamB involved in protein export. Here, we unveil a TIC236-allied component, the chloroplast outer membrane protein CRUMPLED LEAF (CRL), absence of which impairs plastid division and induces autoimmune responses in Arabidopsis thaliana. A forward genetic screen aimed at finding crl suppressors revealed multiple TIC236 gain-of-function mutations (TIC236GFs). Despite the low sequence identity between TIC236 and bacterial TamB, each mutated TIC236GF residue is conserved in TamB. Consistently, a tic236- knockdown mutant exhibited multiple lesion phenotypes similar to crl, indicating a shared functionality of CRL and TIC236. Ensuing reverse genetic analyses revealed genetic interaction between CRL and SP1, a RING-type ubiquitin E3 ligase, as well as with the plastid protease FTSH11, which function in TOC and TIC protein turnover, respectively. Loss of either SP1 or FTSH11 rescued crl mutant phenotypes to varying degrees due to increased translocon levels. Consistent with impaired plastid division exhibited by both crl and tic236-knockdown mutants, CRL interacts with the transit peptides of proteins essential in plastid division, and TIC236GF mutant proteins reinforce their import via increased TIC236 stability. Overall, our data shed new light on the links between plastid division, plant stress response and plastid protein import. We have also isolated and characterized the first GF mutants exhibiting increased protein import efficiency, which may inspire chloroplast engineering for agricultural advancement.
]]></description>
<dc:creator>Kim, C.</dc:creator>
<dc:creator>Fang, J.</dc:creator>
<dc:creator>Li, B.</dc:creator>
<dc:creator>Chen, L.-J.</dc:creator>
<dc:creator>Dogra, V.</dc:creator>
<dc:creator>Luo, S.</dc:creator>
<dc:creator>Wang, P.</dc:creator>
<dc:creator>Hwang, I.</dc:creator>
<dc:creator>Li, H.-m.</dc:creator>
<dc:date>2021-04-26</dc:date>
<dc:identifier>doi:10.1101/2021.04.25.441383</dc:identifier>
<dc:title><![CDATA[TIC236 gain-of-function mutations unveil the link between plastid division and plastid protein import]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-04-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.04.26.441548v1?rss=1">
<title>
<![CDATA[
Ancient gene duplications, rather than polyploidization, facilitate diversification of petal pigmentation patterns in Clarkia gracilis (Onagraceae) 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.04.26.441548v1?rss=1</link>
<description><![CDATA[
It has been suggested that gene duplication and polyploidization create opportunities for the evolution of novel characters. However, the connections between the effects of polyploidization and morphological novelties have rarely been examined. In this study, we investigated whether petal pigmentation patterning in an allotetraploid Clarkia gracilis has evolved as a result of polyploidization. C. gracilis is thought to be derived through a recent polyploidization event with two diploid species, C. amoena huntiana and an extinct species that is closely related to C. lassenensis. We reconstructed phylogenetic relationships of the R2R3-MYBs (the regulators of petal pigmentation) from two subspecies of C. gracilis and the two purported progenitors, C. a. huntiana and C. lassenensis. The gene tree reveals that these R2R3-MYB genes have arisen through duplications that occurred before the divergence of the two progenitor species, i.e., before polyploidization. After polyploidization and subsequent gene loss, only one of the two orthologous copies inherited from the progenitors was retained in the polyploid, turning it to diploid inheritance. We examined evolutionary changes in these R2R3-MYBs and in their expression, which reveals that the changes affecting patterning (including expression domain contraction, loss-of-function mutation, cis-regulatory mutation) occurred after polyploidization within the C. gracilis lineages. Our results thus suggest that polyploidization itself is not necessary in producing novel petal color patterns. By contrast, duplications of R2R3-MYB genes in the common ancestor of the two progenitors have apparently facilitated diversification of petal pigmentation patterns.
]]></description>
<dc:creator>Lin, R.-C.</dc:creator>
<dc:creator>Rausher, M. D.</dc:creator>
<dc:date>2021-04-27</dc:date>
<dc:identifier>doi:10.1101/2021.04.26.441548</dc:identifier>
<dc:title><![CDATA[Ancient gene duplications, rather than polyploidization, facilitate diversification of petal pigmentation patterns in Clarkia gracilis (Onagraceae)]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-04-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.05.03.442461v1?rss=1">
<title>
<![CDATA[
Misregulation of MYB16 causes stomatal cluster formation by disrupting polarity in asymmetric cell division 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.05.03.442461v1?rss=1</link>
<description><![CDATA[
Stomata and leaf cuticle regulate water evaporation from the plant body and balance the trade-off between photosynthesis and water loss. We identified MYB16, a key transcription factor controlling cutin biosynthesis, from previous stomatal lineage ground cell (SLGC)-enriched transcriptome study. The preferential localization of MYB16 in SLGCs but not meristemoids suggests a link between cutin synthesis and stomatal development. Here, we showed that downregulation of MYB16 in meristemoids was directly mediated by the stomatal master transcription factor, SPEECHLESS (SPCH). The suppression of MYB16 before asymmetric division was crucial for stomatal patterning because overexpression or ectopic expression of MYB16 in meristemoids increased impermeability and elevated stomatal density and clusters. The aberrant pattern of stomata was due to reduced and disrupted establishment of polarity during asymmetric cell division. Manipulating polarity by growing seedlings on hard agar rescued stomatal clusters and polarity defects in MYB16 ectopic lines. By expressing a cutinase in MYB16 ectopic lines, stomatal clustering was reduced, which suggests that the ectopic accumulation of cuticle affects the polarity in asymmetrically dividing cells and causes clustered stomata. Taken together, inhibiting MYB16 expression by SPCH in early stomatal lineage is required to correctly place the polarity complex for proper stomatal patterning during leaf morphogenesis.
]]></description>
<dc:creator>Yang, S.-L.</dc:creator>
<dc:creator>Tran, N.</dc:creator>
<dc:creator>Tsai, M.-Y.</dc:creator>
<dc:creator>Ho, C.-M. K.</dc:creator>
<dc:date>2021-05-03</dc:date>
<dc:identifier>doi:10.1101/2021.05.03.442461</dc:identifier>
<dc:title><![CDATA[Misregulation of MYB16 causes stomatal cluster formation by disrupting polarity in asymmetric cell division]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-05-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.05.03.442473v1?rss=1">
<title>
<![CDATA[
Binocular Mirror-Symmetric Microsaccadic Sampling of Hyperacute 3D-Vision 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.05.03.442473v1?rss=1</link>
<description><![CDATA[
Neural mechanisms behind stereopsis, which requires simultaneous disparity inputs from two eyes, have remained mysterious. Here we show how ultrafast mirror-symmetric photomechanical contractions in the frontal forward-facing left and right eye photoreceptors give Drosophila super-resolution 3D-vision. By interlinking multiscale in vivo assays with multiscale simulations, we reveal how these photoreceptor microsaccades - by verging, diverging and narrowing the eyes overlapping receptive fields - channel depth information, as phasic binocular image motion disparity signals in time. We further show how peripherally, outside stereopsis, microsaccadic sampling tracks a flying flys optic flow field to better resolve the world in motion. These results change our understanding of how insect compound eyes work and suggest a general dynamic stereo-information sampling strategy for animals, robots and sensors.

Significance statementTo move efficiently, animals must continuously work out their x,y,z-positions in respect to real-world objects, and many animals have a pair of eyes to achieve this. How photoreceptors actively sample the eyes optical image disparity is not understood because this fundamental information-limiting step has not been investigated in vivo over the eyes whole sampling matrix. This integrative multiscale study will advance our current understanding of stereopsis from static image disparity comparison to a new morphodynamic active sampling theory. It shows how photomechanical photoreceptor microsaccades enable Drosophila super-resolution 3D-vision and proposes neural computations for accurately predicting these flies depth-perception dynamics, limits, and visual behaviors.
]]></description>
<dc:creator>Kemppainen, J.</dc:creator>
<dc:creator>Scales, B.</dc:creator>
<dc:creator>Razban Haghighi, K.</dc:creator>
<dc:creator>Takalo, J.</dc:creator>
<dc:creator>Mansour, N.</dc:creator>
<dc:creator>McManus, J.</dc:creator>
<dc:creator>Lego, G.</dc:creator>
<dc:creator>Saari, P.</dc:creator>
<dc:creator>Hurcomb, J.</dc:creator>
<dc:creator>Antohi, A.</dc:creator>
<dc:creator>Suuronen, J.-P.</dc:creator>
<dc:creator>Blanchard, F.</dc:creator>
<dc:creator>Hardie, R. C.</dc:creator>
<dc:creator>song, z.</dc:creator>
<dc:creator>Hampton, M.</dc:creator>
<dc:creator>Eckermann, M.</dc:creator>
<dc:creator>Westermeier, F.</dc:creator>
<dc:creator>Frohn, J.</dc:creator>
<dc:creator>Hoekstra, H.</dc:creator>
<dc:creator>Lee, C.-H.</dc:creator>
<dc:creator>Huttula, M.</dc:creator>
<dc:creator>Mokso, R.</dc:creator>
<dc:creator>Juusola, M.</dc:creator>
<dc:date>2021-05-04</dc:date>
<dc:identifier>doi:10.1101/2021.05.03.442473</dc:identifier>
<dc:title><![CDATA[Binocular Mirror-Symmetric Microsaccadic Sampling of Hyperacute 3D-Vision]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-05-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.05.04.441029v1?rss=1">
<title>
<![CDATA[
Sex-biased response to and brain cell infection by SARS-CoV-2 in a highly susceptible human ACE2 transgenic model 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.05.04.441029v1?rss=1</link>
<description><![CDATA[
The COVID-19 pandemic is caused by SARS-CoV-2 infection. Human angiotensin-converting enzyme II (hACE2) has been identified as the receptor enabling SARS-CoV-2 host entry. To establish a mouse model for COVID-19, we generated transgenic mouse lines using the (HS4)2-pCAG-hACE2-HA-(HS4)2 transgene cassette, which expresses HA-tagged hACE2 under control of the CAG promoter and is flanked by HS4 insulators. Expression levels of the hACE2 transgene are respectively higher in lung, brain and kidney of our CAG-hACE2 transgenic mice and relatively lower in duodenum, heart and liver. The CAG-hACE2 mice are highly susceptibility to SARS-CoV-2 infection, with 100 PFU of SARS-CoV-2 being sufficient to induce 87.5% mortality at 9 days post-infection and resulting in a sole (female) survivor. Mortality was 100% at the higher titer of 1000 PFU. At lower viral titers, we also found that female mice exposed to SARS-CoV-2 infection suffered much less weight loss than male mice, implying sex-biased responses to SARS-CoV-2 infection. We subjected neuronal cultures to SARS-CoV-2 pseudovirus infection to ascertain the susceptibilities of neurons and astrocytes. Moreover, we observed that expression of SARS-CoV-2 Spike protein alters the synaptic responses of cultured neurons. Our transgenic mice may serve as a model for severe COVID-19 and sex-biased responses to SARS-CoV-2 infection, aiding in the development of vaccines and therapeutic treatments for this disease.
]]></description>
<dc:creator>Tsai, C.-Y.</dc:creator>
<dc:creator>Chou, Y.-C.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Jan, J.-T.</dc:creator>
<dc:creator>Chang, M.-L.</dc:creator>
<dc:creator>Lu, L.-A.</dc:creator>
<dc:creator>Huang, P.-Y.</dc:creator>
<dc:creator>Hsu, T.-T.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:date>2021-05-04</dc:date>
<dc:identifier>doi:10.1101/2021.05.04.441029</dc:identifier>
<dc:title><![CDATA[Sex-biased response to and brain cell infection by SARS-CoV-2 in a highly susceptible human ACE2 transgenic model]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-05-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.05.07.443067v1?rss=1">
<title>
<![CDATA[
Complete and high-quality genomes of novel microbial species from a meromictic lake using a workflow combining long- and short-read sequencing platforms 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.05.07.443067v1?rss=1</link>
<description><![CDATA[
BackgroundMost of Earths bacteria have yet to be cultivated. The metabolic and functional potentials of these uncultivated microorganisms thus remain mysterious, and the metagenome-assembled genome (MAG) approach is the most robust method for uncovering these potentials. However, MAGs discovered by conventional metagenomic assembly and binning methods are usually highly fragmented genomes with heterogeneous sequence contamination, and this affects the accuracy and sensitivity of genomic analyses. Though the maturation of long-read sequencing technologies provides a good opportunity to fix the problem of highly fragmented MAGs as mentioned above, the methods error-prone nature causes severe problems of long-read-alone metagenomics. Hence, methods are urgently needed to retrieve MAGs by a combination of both long- and short-read technologies to advance genome-centric metagenomics.

ResultsIn this study, we combined Illumina and Nanopore data to develop a new workflow to reconstruct 233 MAGs--six novel bacterial orders, 20 families, 66 genera, and 154 species--from Lake Shunet, a secluded meromictic lake in Siberia. Those new MAGs were underrepresented or undetectable in other MAGs studies using metagenomes from human or other common organisms or habitats. Using this newly developed workflow and strategy, the average N50 of reconstructed MAGs greatly increased 10-40-fold compared to when the conventional Illumina assembly and binning method were used. More importantly, six complete MAGs were recovered from our datasets, five of which belong to novel species. We used these as examples to demonstrate many novel and intriguing genomic characteristics discovered in these newly complete genomes and proved the importance of high-quality complete MAGs in microbial genomics and metagenomics studies.

ConclusionsThe results show that it is feasible to apply our workflow with a few additional long reads to recover numerous complete and high-quality MAGs from short-read metagenomes of high microbial diversity environment samples. The unique features we identified from five complete genomes highlight the robustness of this method in genome-centric metagenomic research. The recovery of 154 novel species MAGs from a rarely explored lake greatly expands the current bacterial genome encyclopedia and broadens our knowledge by adding new genomic characteristics of bacteria. It demonstrates a strong need to recover MAGs from diverse unexplored habitats in the search for microbial dark matter.
]]></description>
<dc:creator>Chen, Y.-H.</dc:creator>
<dc:creator>Chiang, P.-W.</dc:creator>
<dc:creator>Rogozin, D. Y.</dc:creator>
<dc:creator>Degermendzhy, A. G.</dc:creator>
<dc:creator>Chiu, H.-H.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:date>2021-05-07</dc:date>
<dc:identifier>doi:10.1101/2021.05.07.443067</dc:identifier>
<dc:title><![CDATA[Complete and high-quality genomes of novel microbial species from a meromictic lake using a workflow combining long- and short-read sequencing platforms]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-05-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.05.11.443686v1?rss=1">
<title>
<![CDATA[
Impacts on the structure-function relationship of SARS-CoV-2 spike by B.1.1.7 mutations 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.05.11.443686v1?rss=1</link>
<description><![CDATA[
The UK variant of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), known as B.1.1.7, harbors several point mutations and deletions on the spike (s) protein, which potentially alter its structural epitopes to evade host immunity while enhancing host receptor binding. Here we report the cryo-EM structures of the S protein of B.1.1.7 in its apo form and in the receptor ACE2-bound form. One or two of the three receptor binding domains (RBDs) were in the open conformation but no fully closed form was observed. In the ACE-bound form, all three RBDs were engaged in receptor binding. The B.1.1.7-specific A570D mutation introduced a salt bridge switch that could modulate the opening and closing of the RBD. Furthermore, the N501Y mutation in the RBD introduced a favorable {pi}-{pi} interaction manifested in enhanced ACE2 binding affinity. The N501Y mutation abolished the neutralization activity of one of the three potent neutralizing antibodies (nAbs). Cryo-EM showed that the cocktail of other two nAbs simultaneously bound to all three RBDs. Furthermore, the nAb cocktail synergistically neutralized different SARS-CoV-2 pseudovirus strains, including the B.1.1.7.
]]></description>
<dc:creator>Yang, T.-J.</dc:creator>
<dc:creator>Yu, P.-Y.</dc:creator>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Liang, K.-H.</dc:creator>
<dc:creator>Tso, H.-C.</dc:creator>
<dc:creator>Ho, M.-R.</dc:creator>
<dc:creator>Chen, W.-Y.</dc:creator>
<dc:creator>Lin, H.-T.</dc:creator>
<dc:creator>Wu, H.-C.</dc:creator>
<dc:creator>Hsu, S.-T. D.</dc:creator>
<dc:date>2021-05-12</dc:date>
<dc:identifier>doi:10.1101/2021.05.11.443686</dc:identifier>
<dc:title><![CDATA[Impacts on the structure-function relationship of SARS-CoV-2 spike by B.1.1.7 mutations]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-05-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.05.20.444927v1?rss=1">
<title>
<![CDATA[
Species boundaries in the Agrobacterium tumefaciens complex and multi-level modular evolution of their antibacterial type VI secretion system and tumor-inducing plasmids 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.05.20.444927v1?rss=1</link>
<description><![CDATA[
BackgroundMany bacterial taxa are species complexes and uncertainties regarding the organization of their genetic diversity challenge research efforts. We utilized Agrobacterium tumefaciens, a taxon known for its phytopathogenicity and applications in transformation, as a study system and devised strategies for investigating genome diversity and evolution of species complexes.

ResultsWe utilized 35 genome assemblies to achieve a comprehensive and balanced sampling of A. tumefaciens. Our confident inference of gene content and core-genome phylogeny supported a quantitative guideline for delineating 12 species and allowed for robust investigations of genes critical in fitness and ecology. For the type VI secretion system (T6SS) involved in interbacterial competition and thought to be conserved, we detected multiple losses and one horizontal gene transfer. For the tumor-inducing plasmids (pTi) and pTi-encoded type IV secretion system (T4SS) that are essential for agrobacterial phytopathogenicity, we uncovered novel diversity and hypothesized their involvement in shaping this species complex. Intriguingly, for both T6SS and T4SS, genes encoding structural components are highly conserved, whereas extensive diversity exists for genes encoding effectors and other proteins.

ConclusionsWe demonstrated that the combination of a phylogeny-guided sampling scheme and an emphasis on high-quality assemblies provides a cost-effective approach for robust analysis in evolutionary genomics. Our strategies for multi-level investigations at scales that range from whole-genomes to intragenic domains and phylogenetic depths of between- and within-species are applicable to other bacteria. Finally, modularity observed in the molecular evolution of genes and domains is useful for inferring functional constraints and informing experimental works.
]]></description>
<dc:creator>Chou, L.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Haryono, M.</dc:creator>
<dc:creator>Santos, M. N. M.</dc:creator>
<dc:creator>Cho, S.-T.</dc:creator>
<dc:creator>Weisberg, A. J.</dc:creator>
<dc:creator>Wu, C.-F.</dc:creator>
<dc:creator>Chang, J. H.</dc:creator>
<dc:creator>Lai, E.-M.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:date>2021-05-21</dc:date>
<dc:identifier>doi:10.1101/2021.05.20.444927</dc:identifier>
<dc:title><![CDATA[Species boundaries in the Agrobacterium tumefaciens complex and multi-level modular evolution of their antibacterial type VI secretion system and tumor-inducing plasmids]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-05-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.05.23.445330v1?rss=1">
<title>
<![CDATA[
Biomechanics and Myofibrillar Alignment Enhance Contractile Development and Reproducibility in Stem Cell Derived Cardiac Muscle 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.05.23.445330v1?rss=1</link>
<description><![CDATA[
Human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) allow novel investigations of human cardiac disease, but disorganized mechanics and immaturity of hPSC-CMs on two-dimensional (2D) surfaces have been hurdles for efficient and reproducible study of these cells. Here, we developed a platform of micron-scale 2D cardiac tissues (M2DCTs) to precisely control biomechanics in arrays of thousands of purified, independently contracting cardiac muscle strips in 2D. By defining geometry and workload in M2DCTs in this reductionist platform that does not incorporate other cell types, we show that myofibrillar alignment and auxotonic contractions at physiologic workload critically drive maturation of cardiac contractile function, calcium handling, and electrophysiology. Additionally, the organized biomechanics in this system facilitates rapid and automated extraction of contractile kinetic parameters from brightfield microscopy images, increasing the reproducibility and throughput of pharmacologic testing. Finally, we show that M2DCTs enable precise and efficient dissection of contractile kinetics in cardiomyopathy disease models.
]]></description>
<dc:creator>Tsan, Y.-C.</dc:creator>
<dc:creator>Zhao, Y.-T.</dc:creator>
<dc:creator>DePalma, S. J.</dc:creator>
<dc:creator>Capilnasiu, A.</dc:creator>
<dc:creator>Wu, Y.-W.</dc:creator>
<dc:creator>Elder, B.</dc:creator>
<dc:creator>Panse, I.</dc:creator>
<dc:creator>Friedline, S.</dc:creator>
<dc:creator>O'Leary, T. S.</dc:creator>
<dc:creator>Wubshet, N.</dc:creator>
<dc:creator>Ho, K. K. Y.</dc:creator>
<dc:creator>Previs, M. J.</dc:creator>
<dc:creator>Nordsletten, D.</dc:creator>
<dc:creator>Baker, B. M.</dc:creator>
<dc:creator>Isom, L. L.</dc:creator>
<dc:creator>Liu, A. P.</dc:creator>
<dc:creator>Helms, A. S.</dc:creator>
<dc:date>2021-05-23</dc:date>
<dc:identifier>doi:10.1101/2021.05.23.445330</dc:identifier>
<dc:title><![CDATA[Biomechanics and Myofibrillar Alignment Enhance Contractile Development and Reproducibility in Stem Cell Derived Cardiac Muscle]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-05-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.05.25.445523v1?rss=1">
<title>
<![CDATA[
Impact of Glycosylation on SARS-CoV-2 Infection and Broadly Protective Vaccine Design 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.05.25.445523v1?rss=1</link>
<description><![CDATA[
A major challenge to end the pandemic caused by SARS-CoV-2 is to develop a broadly protective vaccine. As the key immunogen, the spike protein is frequently mutated with conserved epitopes shielded by glycans. Here, we reveal that spike glycosylation has site-differential effects on viral infectivity and lung epithelial cells generate spike with more infective glycoforms. Compared to the fully glycosylated spike, immunization of spike protein with N-glycans trimmed to the monoglycosylated state (Smg) elicits stronger immune responses and better protection for hACE2 transgenic mice against variants of concern. In addition, a broadly neutralizing monoclonal antibody was identified from the Smg immunized mice, demonstrating that removal of glycan shields to better expose the conserved sequences is an effective and simple approach to broad-spectrum vaccine development.

One-Sentence SummaryRemoving glycan shields to expose conserved epitopes is an effective approach to develop a broad-spectrum SARS-CoV-2 vaccine.
]]></description>
<dc:creator>Liao, H.-Y.</dc:creator>
<dc:creator>Huang, H.-Y.</dc:creator>
<dc:creator>Chen, X.</dc:creator>
<dc:creator>Cheng, C.-W.</dc:creator>
<dc:creator>Wang, S.-W.</dc:creator>
<dc:creator>Shahed-Al-Mahmud, M.</dc:creator>
<dc:creator>Chen, T.-H.</dc:creator>
<dc:creator>Lo, J. M.</dc:creator>
<dc:creator>Liu, Y.-M.</dc:creator>
<dc:creator>Ma, H.-H.</dc:creator>
<dc:creator>Chang, Y.-H.</dc:creator>
<dc:creator>Tsai, C.-Y.</dc:creator>
<dc:creator>Huang, P.-Y.</dc:creator>
<dc:creator>Chang, S.-Y.</dc:creator>
<dc:creator>Chao, T.-L.</dc:creator>
<dc:creator>Kao, H.-C.</dc:creator>
<dc:creator>Tsai, Y.-M.</dc:creator>
<dc:creator>Chen, Y.-H.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Lee, K.-C.</dc:creator>
<dc:creator>Wu, C.-Y.</dc:creator>
<dc:creator>Jan, J.-T.</dc:creator>
<dc:creator>Lin, K.-I.</dc:creator>
<dc:creator>Cheng, T.-J. R.</dc:creator>
<dc:creator>Ma, C.</dc:creator>
<dc:creator>Wong, C.-H.</dc:creator>
<dc:date>2021-05-25</dc:date>
<dc:identifier>doi:10.1101/2021.05.25.445523</dc:identifier>
<dc:title><![CDATA[Impact of Glycosylation on SARS-CoV-2 Infection and Broadly Protective Vaccine Design]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-05-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.05.30.446323v1?rss=1">
<title>
<![CDATA[
Apical Actin-myosin Network Regulates the Tight Junction of Polarized Madin-Darby Canine Kidney Cells 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.05.30.446323v1?rss=1</link>
<description><![CDATA[
The tight junction outlines the apicolateral border of epithelial cells like a belt, sealing the paracellular space when cells form contacts with each other. The permeability and morphology of tight junction are regulated by actomyosin contractility, which has been conventionally thought from the purse-string-like circumferential actomyosin belt along tight junction. Spatially, the tight junction is close to the apical actin network, which exerts inward contractions orthogonal to the tight junction. To test the contributions from apical actin network, we laser-ablated spots on the apical surface of polarized Madin-Darby Canine Kidney (MDCK) epithelial cells. Laser ablation severed the apical cytoskeleton network, decreased in-plane tension, increased the apical surface area, and rendered the tight junction less tortuous in shape. Consistent with these observations, changes in MDCK cell sheet morphology due to cell proliferation, or perturbation with the ROCK inhibitor Y27632 increased the density of the apical actin network and decreased tight junction tortuosity. The morphological analysis revealed scutoids in flat MDCK cell sheets, contrary to predictions from a previous model that only considered cell-cell interactions as line tension. Additional cell-cell interactions from apical in-plane tension provides probable cause for the occurrence of scutoids on flat geometry. Taken together, our findings identify the importance of the apical actin network exerting in-plane apical tension to regulate tight-junction mechanobiology and epithelial cell shape.

Significance StatementThe tight junction is located at the apicolateral cell border and regulates paracellular diffusion. Adjacent to the tight junction, the actin cytoskeleton forms a dense network beneath the apical surface and an actomyosin belt that circumscribes the lateral surface of the cell. Tight junctions are connected to the actin cytoskeleton which regulates paracellular transport, but the role of tension-mediated regulation of the tight junction by various actin structures is poorly understood. Here, we provide evidence that tension on the tight junction is mediated by the apical actin network. Our results provide a reinterpretion of past reports and broaden our understanding the mechanobiology of tight junctions.
]]></description>
<dc:creator>Lu, C.-h.</dc:creator>
<dc:creator>Wen, F.-l.</dc:creator>
<dc:creator>Hsueh, S. C.-C.</dc:creator>
<dc:creator>Wu, W.-h.</dc:creator>
<dc:creator>Lin, Y.-F.</dc:creator>
<dc:creator>Prouveur, M.</dc:creator>
<dc:creator>Boudier, T.</dc:creator>
<dc:creator>Lin, K.-h.</dc:creator>
<dc:date>2021-05-30</dc:date>
<dc:identifier>doi:10.1101/2021.05.30.446323</dc:identifier>
<dc:title><![CDATA[Apical Actin-myosin Network Regulates the Tight Junction of Polarized Madin-Darby Canine Kidney Cells]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-05-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.06.02.446857v1?rss=1">
<title>
<![CDATA[
Chromatin enrichment for Proteomics in Plants (ChEP-P) implicates the histone reader ALFIN-LIKE 6 in jasmonate signalling 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.06.02.446857v1?rss=1</link>
<description><![CDATA[
Covalent modifications of core histones govern downstream DNA-templated processes such as transcription by altering chromatin structure and function. Previously, we reported that the plant homeodomain protein ALFIN-LIKE 6 (AL6), a bona fide histone reader that preferentially binds trimethylated lysin 4 on histone 3 (H3K4me3), is critical for recalibration of cellular phosphate (Pi) homeostasis and root hair elongation under Pi-deficient conditions. Here, we demonstrate that AL6 is also involved in the response of Arabidopsis seedlings to jasmonic acid (JA) during skotomorphogenesis, possibly by modulating chromatin dynamics that affect the transcriptional regulation of JA-responsive genes. Dark-grown al6 seedlings showed a compromised reduction in hypocotyl elongation upon exogenously supplied JA, a response that was calibrated by the availability of Pi in the growth medium. A comparison of protein profiles between wild-type and al6 mutant seedlings using a quantitative Chromatin Enrichment for Proteomics (ChEP) approach, that we modified for plant tissue and designated ChEP-P (ChEP in Plants), yielded a comprehensive suite of chromatin-associated proteins and candidates that may be causative for the mutant phenotype. Altered abundance of proteins involved in chromatin organization in al6 seedlings suggests a role of AL6 in coordinating the deposition of histone variants upon perception of internal or environmental stimuli.

HighlightCataloguing chromatin-associated proteins revealed that the plant homeodomain protein ALFIN-LIKE 6 orchestrates phosphate and jasmonate signaling in etiolated Arabidopsis seedlings through modulation of the chromatin structure.
]]></description>
<dc:creator>Velez-Bermudez, I. C.</dc:creator>
<dc:creator>Schmidt, W.</dc:creator>
<dc:date>2021-06-03</dc:date>
<dc:identifier>doi:10.1101/2021.06.02.446857</dc:identifier>
<dc:title><![CDATA[Chromatin enrichment for Proteomics in Plants (ChEP-P) implicates the histone reader ALFIN-LIKE 6 in jasmonate signalling]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-06-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.06.11.448000v1?rss=1">
<title>
<![CDATA[
A new method to identify global targets of RNA-binding proteins in plants 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.06.11.448000v1?rss=1</link>
<description><![CDATA[
BackgroundRNA-binding proteins (RBPs) play crucial roles in various aspects of post-transcriptional gene expression; their functions can vary between tissues, cell types, developmental stages, and environmental conditions. Identifying RBP target RNAs and investigating whether they are differentially bound by RBPs in different cell types, stages, or conditions could shed light on RBP functions. Although several strategies have been designed to identify RBP targets, they involve complicated biochemical steps and require large quantities of material, and only a few studies using these techniques have been performed in plants. The TRIBE (targets of RNA binding proteins identified by editing) method was recently developed to identify RBP targets using a RBP coupled to the catalytic domain of a Drosophila RNA editing enzyme and expressing this fusion protein in vivo. The resulting novel editing events can be identified by sequencing. This technique uses little material and does not require complex biochemical steps, however it is not yet adapted for use in plants.

ResultsWe successfully applied an optimized genome-wide TRIBE method in plants. We selected the splicing regulator polypyrimidine tract-binding protein (PTB) as a model protein for testing the TRIBE system in the moss Physcomitrium patens. We demonstrated that 13.81% of protein-coding gene transcripts in P. patens are targets of PTB. Most potential PTB binding sites are located in coding sequences and 3 untranslated regions, suggesting that PTB performs multiple functions besides pre-mRNA splicing in this moss. In addition, TRIBE showed reproducible results compared to other methods.

ConclusionsWe have developed an alternative method based on the TRIBE system to identify RBP targets in plants globally, and we provide guidance here for its application in plants.
]]></description>
<dc:creator>Cheng, Y.-L.</dc:creator>
<dc:creator>Hsieh, H.-Y.</dc:creator>
<dc:creator>Tu, S.-L.</dc:creator>
<dc:date>2021-06-11</dc:date>
<dc:identifier>doi:10.1101/2021.06.11.448000</dc:identifier>
<dc:title><![CDATA[A new method to identify global targets of RNA-binding proteins in plants]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-06-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.06.14.448173v1?rss=1">
<title>
<![CDATA[
The U1 snRNP component RBP45d regulates temperature-responsive flowering in Arabidopsis thaliana 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.06.14.448173v1?rss=1</link>
<description><![CDATA[
Pre-mRNA splicing is a crucial step of gene expression whereby the spliceosome produces constitutively and alternatively spliced transcripts that not only diversify the transcriptome but also play essential functions during plant development and responses to environmental changes. Numerous evidences indicate that regulation at the pre-mRNA splicing step is important for flowering time control, however the components and detailed mechanism underlying this process remain largely unknown. Here, we identified a previously unknown splicing factor in Arabidopsis thaliana, RNA BINDING PROTEIN 45d (RBP45d), a member of the RBP45/47 family. Using sequence comparison and biochemical analysis, we determined that RBP45d is a component of the U1 small nuclear ribonucleoprotein (U1 snRNP) with functions distinct from other family members. RBP45d associates with the U1 snRNP by interacting with pre-mRNA-processing factor 39a (PRP39a) and directly regulates alternative splicing (AS) for a specific set of genes. Plants with loss of RBP45d function exhibit defects in temperature-induced flowering potentially due to the mis-regulation of temperature-sensitive AS by RBP45d and PRP39a of the key flowering gene FLOWERING LOCUS M. Taken together, we report that RBP45d is a novel U1 snRNP component in plants that functions together with PRP39a in temperature-mediated flowering.
]]></description>
<dc:creator>Chang, P.</dc:creator>
<dc:creator>Hsieh, H.-Y.</dc:creator>
<dc:creator>Tu, S.-L.</dc:creator>
<dc:date>2021-06-14</dc:date>
<dc:identifier>doi:10.1101/2021.06.14.448173</dc:identifier>
<dc:title><![CDATA[The U1 snRNP component RBP45d regulates temperature-responsive flowering in Arabidopsis thaliana]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-06-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.06.27.450109v1?rss=1">
<title>
<![CDATA[
Carbohydrate sulfation as a mechanism for fine-tuning Siglec ligands 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.06.27.450109v1?rss=1</link>
<description><![CDATA[
The immunomodulatory family of Siglecs recognize sialic acid-containing glycans as  self, which is exploited in cancer for immune-evasion. The biochemical nature of Siglec ligands remains incompletely understood with emerging evidence suggesting the importance of carbohydrate sulfation. Here, we investigate how specific sulfate modifications affect Siglec ligands by overexpressing eight carbohydrate sulfotransferases (CHSTs) in five cell lines. Overexpression of three CHSTs (CHST1, CHST2, or CHST4) significantly enhances the binding of numerous Siglecs. Unexpectedly, two other CHSTs (Gal3ST2 and Gal3ST3) diminish Siglec binding, suggesting a new mode to modulate Siglec ligands via sulfation. Results are cell type dependent, indicating that the context in which sulfated glycans are presented is important. Moreover, pharmacological blockade of N- and O-glycan maturation reveals a cell type-specific pattern of importance for either class of glycan. Production of a highly homogenous CD33 (Siglec-3) fragment enabled a mass spectrometry-based binding assay to determine 10-fold and 3-fold enhanced affinity for Neu5Ac2-3(6-O-sulfo)Gal{beta}1-4GlcNAc and Neu5Ac2-3Gal{beta}1-4(6-O- sulfo)GlcNAc, respectively, over Neu5Ac2-3Gal{beta}1-4GlcNAc. CD33 showed significant additivity in affinity (36-fold) for the disulfated ligand, Neu5Ac2-3(6-O-sulfo)Gal{beta}1-4(6-O-sulfo)GlcNAc. Moreover, overexpression of both CHST1 and CHST2 in cells greatly enhanced the binding of several Siglecs, including CD33. Finally, we reveal that CHST1 is upregulated in numerous cancers, correlating with poorer survival rates and sodium chlorate sensitivity for the binding of Siglecs to cancer cell lines. These results provide new insights into carbohydrate sulfation as a modification that is a general mechanism for tuning Siglec ligands on cells, including in cancer.
]]></description>
<dc:creator>Jung, J.</dc:creator>
<dc:creator>Enterina, J. R.</dc:creator>
<dc:creator>Bui, D. T.</dc:creator>
<dc:creator>Mozaneh, F.</dc:creator>
<dc:creator>Lin, P.-H.</dc:creator>
<dc:creator>Nitin, H.</dc:creator>
<dc:creator>Kuo, C.-W.</dc:creator>
<dc:creator>Rodrigues, E.</dc:creator>
<dc:creator>Bhattacherjee, A.</dc:creator>
<dc:creator>Raeisimakiani, P.</dc:creator>
<dc:creator>Daskhan, G. C.</dc:creator>
<dc:creator>St. Laurent, C. D.</dc:creator>
<dc:creator>Khoo, K.-H.</dc:creator>
<dc:creator>Mahal, L. K.</dc:creator>
<dc:creator>Zandberg, W. F.</dc:creator>
<dc:creator>Huang, X.</dc:creator>
<dc:creator>Klassen, J. S.</dc:creator>
<dc:creator>Macauley, M. S.</dc:creator>
<dc:date>2021-06-28</dc:date>
<dc:identifier>doi:10.1101/2021.06.27.450109</dc:identifier>
<dc:title><![CDATA[Carbohydrate sulfation as a mechanism for fine-tuning Siglec ligands]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-06-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.06.30.450574v1?rss=1">
<title>
<![CDATA[
Rapid synaptic plasticity contributes to a learned conjunctive code of position and choice-related information in the hippocampus 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.06.30.450574v1?rss=1</link>
<description><![CDATA[
To successfully perform goal-directed navigation, animals must know where they are and what they are doing--e.g., looking for water, bringing food back to the nest, or escaping from a predator. Hippocampal neurons code for these critical variables conjunctively, but little is known about how this where/what code is formed or flexibly routed to other brain regions. To address these questions, we performed intracellular whole-cell recordings in mouse CA1 during a cued, two-choice virtual navigation task. We demonstrate that plateau potentials in CA1 pyramidal neurons rapidly strengthen synaptic inputs carrying conjunctive information about position and choice. Plasticity-induced response fields were modulated by cues only in animals previously trained to collect rewards based on these cues. Thus, we reveal that gradual learning is required for the formation of a conjunctive population code, upstream of CA1, while plateau-potential-induced synaptic plasticity in CA1 enables flexible routing of the code to downstream brain regions.
]]></description>
<dc:creator>Spruston, N.</dc:creator>
<dc:creator>Zhao, X.</dc:creator>
<dc:creator>Hsu, C.-L.</dc:creator>
<dc:date>2021-06-30</dc:date>
<dc:identifier>doi:10.1101/2021.06.30.450574</dc:identifier>
<dc:title><![CDATA[Rapid synaptic plasticity contributes to a learned conjunctive code of position and choice-related information in the hippocampus]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-06-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.07.06.451220v1?rss=1">
<title>
<![CDATA[
A cell-sorting-based nano-scale pipeline for cell-type-specific proteomics in plants 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.07.06.451220v1?rss=1</link>
<description><![CDATA[
Multicellular organisms such as plants contain different cell types with specialized functions. Analyzing the characteristics of each cell type reveals specific cell functions and enhances understanding of organization and function at the organismal level. Here we report a highly-sensitive and efficient cell type-specific multiomics pipeline, combining simplified flow cytometry-based cell sorting for fluorescent protoplasts and optimized nanoscale proteomics and metabolomics methods, which allow in-depth analysis of the proteomes and metabolomes of a particular cell type. Using this method, we quantitatively compared the proteomes and metabolomes of guard cells and mesophyll cells and revealed that the enrichment of signal transduction-related proteins enables guard cells to respond rapidly to various environmental stimuli. We uncovered a guard cell-specific kinase cascade whereby RAF15 and OST1 mediate ABA-induced stomatal closure. This pipeline can be applied to various cell types in plant or non-plant systems to learn how cells function in highly organized multicellular organisms.
]]></description>
<dc:creator>Wang, H.</dc:creator>
<dc:creator>Li, R.</dc:creator>
<dc:creator>Rong, J.</dc:creator>
<dc:creator>Sang, T.</dc:creator>
<dc:creator>Kim, C.</dc:creator>
<dc:creator>Song, C.-P.</dc:creator>
<dc:creator>Dai, S.</dc:creator>
<dc:creator>Hsu, C.-C.</dc:creator>
<dc:creator>Wang, P.</dc:creator>
<dc:date>2021-07-08</dc:date>
<dc:identifier>doi:10.1101/2021.07.06.451220</dc:identifier>
<dc:title><![CDATA[A cell-sorting-based nano-scale pipeline for cell-type-specific proteomics in plants]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-07-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.07.21.453140v1?rss=1">
<title>
<![CDATA[
Distinct shifts in site-specific glycosylation pattern of SARS-CoV-2 spike proteins associated with arising mutations in the D614G and Alpha variants 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.07.21.453140v1?rss=1</link>
<description><![CDATA[
Extensive glycosylation of the spike protein of SARS-CoV-2 virus not only shields the major part of it from host immune responses, but glycans at specific sites also act on its conformation dynamics and contribute to efficient host receptor binding, and hence infectivity. As variants of concern arise during the course of the COVID-19 pandemic, it is unclear if mutations accumulated within the spike protein would affect its site-specific glycosylation pattern. The Alpha variant derived from the D614G lineage is distinguished from others by having deletion mutations located right within an immunogenic supersite of the spike N-terminal domain that make it refractory to most neutralizing antibodies directed against this domain. Despite maintaining an overall similar structural conformation, our mass spectrometry-based site-specific glycosylation analyses of similarly produced spike proteins with and without the D614G and Alpha variant mutations reveal a significant shift in the processing state of N-glycans on one specific N-terminal domain site. Its conversion to a higher proportion of complex type structures is indicative of altered spatial accessibility attributable to mutations specific to the Alpha variant that may impact its transmissibility. This and other more subtle changes in glycosylation features detected at other sites provide crucial missing information otherwise not apparent in the available cryogenic electron microscopy-derived structures of the spike protein variants.
]]></description>
<dc:creator>Kuo, C.-W.</dc:creator>
<dc:creator>Yang, T.-J.</dc:creator>
<dc:creator>Chien, Y.-C.</dc:creator>
<dc:creator>Yu, P.-Y.</dc:creator>
<dc:creator>Hsu, S.-T. D.</dc:creator>
<dc:creator>Khoo, K.-H.</dc:creator>
<dc:date>2021-07-21</dc:date>
<dc:identifier>doi:10.1101/2021.07.21.453140</dc:identifier>
<dc:title><![CDATA[Distinct shifts in site-specific glycosylation pattern of SARS-CoV-2 spike proteins associated with arising mutations in the D614G and Alpha variants]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-07-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.07.26.453775v1?rss=1">
<title>
<![CDATA[
Cell-specific expression buffering promotes cell survival and cancer robustness 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.07.26.453775v1?rss=1</link>
<description><![CDATA[
Functional buffering that ensures biological robustness is critical for maintaining tissue homeostasis, organismal survival, and evolution of novelty. However, the mechanism underlying functional buffering, particularly in multicellular organisms, remains largely elusive. Here, we developed an inference index (C-score) for Cell-specific Expression- BUffering (CEBU), whereby functional buffering is mediated via expression of buffering genes in specific cells and tissues in humans. By computing C-scores across 684 human cell lines using genome-wide CRISPR screens and transcriptomic RNA-seq, we report that C- score-identified putative buffering gene pairs are enriched for members of the same duplicated gene family, pathway, and protein complex. Furthermore, CEBU is especially prevalent in tissues of low regenerative capacity (e.g., bone and neuronal tissues) and is weakest in highly regenerative blood cells, linking functional buffering to tissue regeneration. Clinically, the buffering capacity enabled by CEBU can help predict patient survival for multiple cancers. Our results reveal CEBU as a buffering mechanism contributing to tissue homeostasis and cancer robustness in humans.

Summary blurbWe unveil a genome-wide functional buffering mechanism, termed Cell-specific Expression Buffering (CEBU), whereby gene expression contributes to functional buffering in specific cell types and tissues. We link CEBU to genetic interactions, tissue homeostasis and cancer robustness.
]]></description>
<dc:creator>Lin, H.-K.</dc:creator>
<dc:creator>Cheng, J.-H.</dc:creator>
<dc:creator>Wu, C.-C.</dc:creator>
<dc:creator>Hsieh, F.-S.</dc:creator>
<dc:creator>Dunlap, C. A.</dc:creator>
<dc:creator>Chen, S.-h.</dc:creator>
<dc:date>2021-07-27</dc:date>
<dc:identifier>doi:10.1101/2021.07.26.453775</dc:identifier>
<dc:title><![CDATA[Cell-specific expression buffering promotes cell survival and cancer robustness]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-07-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.07.28.454192v1?rss=1">
<title>
<![CDATA[
Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.07.28.454192v1?rss=1</link>
<description><![CDATA[
Extracellular vesicles (EVs) have great potential as novel drug carriers for the treatment of various diseases. These lipid bilayer vesicles are naturally abundant in mammalian tissues and circulation, can be loaded with therapeutic small molecule drugs, (si)RNA, proteins and CRISPR/Cas9, and may be engineered for retention by specific tissues. However, many questions remain on the optimal dosing, administration route, and pharmacokinetics of EVs. Previous studies have addressed biodistribution and pharmacokinetics in rodents, but little evidence is available from larger animals. Here, we investigated the pharmacokinetics and biodistribution of Expi293F-derived EVs labelled with a highly sensitive nanoluciferase reporter (palmGRET) in a non-human primate model (Macaca nemestrina), comparing intravenous (IV) and intranasal (IN) administration over a 125-fold dose range. We report that EVs administered IV had markedly longer circulation times in plasma than previously reported in mice, and were detectable in cerebrospinal fluid (CSF) after 30-60 minutes. Already after one minute following IV administration, we observed EV uptake by PBMCs, most notably B-cells. EVs were detected in liver and spleen within one hour of IV administration. None of the IN doses resulted in readily detectable EV levels in plasma, CSF, or organs, suggesting that IN delivery of EVs in large animals including humans may require reconsideration or pretreatment approaches. Furthermore, EV circulation times strongly decreased after repeated IV administration, possibly due to immune responses and with clear implications for xenogeneic EV-based therapeutics. We hope that our findings from this baseline study in macaques will help to inform future research and therapeutic development of EVs.
]]></description>
<dc:creator>Driedonks, T.</dc:creator>
<dc:creator>Jiang, L.</dc:creator>
<dc:creator>Carlson, B.</dc:creator>
<dc:creator>Han, Z.</dc:creator>
<dc:creator>Liu, G.</dc:creator>
<dc:creator>Queen, S. E.</dc:creator>
<dc:creator>Shirk, E. N.</dc:creator>
<dc:creator>Gololobova, O.</dc:creator>
<dc:creator>Nyberg, L.</dc:creator>
<dc:creator>Lima, G.</dc:creator>
<dc:creator>Schonvisky, K.</dc:creator>
<dc:creator>Stover, M.</dc:creator>
<dc:creator>Guerrero-Martin, S.</dc:creator>
<dc:creator>Richardson, M. R.</dc:creator>
<dc:creator>Smith, B.</dc:creator>
<dc:creator>Lai, C. P.</dc:creator>
<dc:creator>Izzi, J. M.</dc:creator>
<dc:creator>Hutchinson, E. K.</dc:creator>
<dc:creator>Pate, K. A.</dc:creator>
<dc:creator>Witwer, K. W.</dc:creator>
<dc:date>2021-07-29</dc:date>
<dc:identifier>doi:10.1101/2021.07.28.454192</dc:identifier>
<dc:title><![CDATA[Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-07-29</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.08.03.454910v1?rss=1">
<title>
<![CDATA[
Vaccinia virus-based vaccines confer protective immunity against SARS-CoV-2 virus in Syrian hamsters 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.08.03.454910v1?rss=1</link>
<description><![CDATA[
COVID-19 in humans is caused by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that belongs to the beta family of coronaviruses. SARS-CoV-2 causes severe respiratory illness in 10-15% of infected individuals and mortality in 2-3%. Vaccines are urgently needed to prevent infection and to contain viral spread. Although several mRNA- and adenovirus-based vaccines are highly effective, their dependence on the "cold chain" transportation makes global vaccination a difficult task. In this context, a stable lyophilized vaccine may present certain advantages. Accordingly, establishing additional vaccine platforms remains vital to tackle SARS- CoV-2 and any future variants that may arise. Vaccinia virus (VACV) has been used to eradicate smallpox disease, and several attenuated viral strains with enhanced safety for human applications have been developed. We have generated two candidate SARS-CoV-2 vaccines based on two vaccinia viral strains, MVA and v-NY, that express full-length SARS-CoV-2 spike protein. Whereas MVA is growth-restricted in mammalian cells, the v-NY strain is replication-competent. We demonstrate that both candidate recombinant vaccines induce high titers of neutralizing antibodies in C57BL/6 mice vaccinated according to prime-boost regimens. Furthermore, our vaccination regimens generated TH1-biased immune responses in mice. Most importantly, prime-boost vaccination of a Syrian hamster infection model with MVA-S and v-NY-S protected the hamsters against SARS-CoV-2 infection, supporting that these two vaccines are promising candidates for future development. Finally, our vaccination regimens generated neutralizing antibodies that partially cross-neutralized SARS-CoV-2 variants of concern.
]]></description>
<dc:creator>Kulkarni, R.</dc:creator>
<dc:creator>Chen, W.-C.</dc:creator>
<dc:creator>Lee, Y.</dc:creator>
<dc:creator>Kao, C.-F.</dc:creator>
<dc:creator>Hu, S.-L.</dc:creator>
<dc:creator>Ma, H.-H.</dc:creator>
<dc:creator>Jan, J.-T.</dc:creator>
<dc:creator>Liao, C.-C.</dc:creator>
<dc:creator>Liang, J.-J.</dc:creator>
<dc:creator>Ko, H.-Y.</dc:creator>
<dc:creator>Sun, C.-P.</dc:creator>
<dc:creator>Lin, Y.-S.</dc:creator>
<dc:creator>Wang, Y.-C.</dc:creator>
<dc:creator>Wei, S.-C.</dc:creator>
<dc:creator>Lin, Y.-L.</dc:creator>
<dc:creator>Ma, C.</dc:creator>
<dc:creator>Chao, Y.-C.</dc:creator>
<dc:creator>Chou, Y.-C.</dc:creator>
<dc:creator>Chang, W.</dc:creator>
<dc:date>2021-08-03</dc:date>
<dc:identifier>doi:10.1101/2021.08.03.454910</dc:identifier>
<dc:title><![CDATA[Vaccinia virus-based vaccines confer protective immunity against SARS-CoV-2 virus in Syrian hamsters]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-08-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.08.06.455364v1?rss=1">
<title>
<![CDATA[
Identification of a developmental switch in information transfer between whisker S1 and S2 cortex in mice 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.08.06.455364v1?rss=1</link>
<description><![CDATA[
The whiskers of rodents are a key sensory organ that provides critical tactile information for animal navigation and object exploration throughout life. Previous work has explored the developmental sensory-driven activation of the primary sensory cortex processing whisker information (wS1), also called barrel cortex. This body of work has shown that the barrel cortex is already activated by sensory stimuli during the first post-natal week. However, it is currently unknown when over the course of development these stimuli begin being processed by higher order cortical areas, such as secondary whisker somatosensory area (wS2). Here we investigate for the first time the developmental engagement of wS2 by sensory stimuli and the emergence of cortico-cortical communication from wS1 to wS2. Using in vivo wide-field imaging and electrophysiological recordings in control and conditional knock-out mice we find that wS1 and wS2 are able to process bottom-up information coming from the thalamus already right after birth. We identify that it is only at the end of the first post-natal week that wS1 begins to provide excitation into wS2, a connection which begins to acquire feed-forward inhibition characteristics after the second post-natal week. Therefore, we have uncovered a developmental window during which excitatory versus inhibitory functional connectivity between wS1 and wS2 takes place.
]]></description>
<dc:creator>Karayannis, T.</dc:creator>
<dc:creator>Cai, L.</dc:creator>
<dc:creator>Yang, J.-W.</dc:creator>
<dc:creator>Chou, S.-J.</dc:creator>
<dc:creator>Wang, C.-F.</dc:creator>
<dc:creator>Luhmann, H. J.</dc:creator>
<dc:date>2021-08-08</dc:date>
<dc:identifier>doi:10.1101/2021.08.06.455364</dc:identifier>
<dc:title><![CDATA[Identification of a developmental switch in information transfer between whisker S1 and S2 cortex in mice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-08-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.08.17.456661v1?rss=1">
<title>
<![CDATA[
BioSANS: A Software Package for Symbolic and Numeric Biological Simulation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.08.17.456661v1?rss=1</link>
<description><![CDATA[
Modeling biochemical systems can provide insights into behaviors that are difficult to observe or understand. It requires software, programming, and understanding of the system to build a model and study it. Softwares exist for systems biology modeling, but most support only certain types of modeling tasks. Desirable features including ease in preparing input, symbolic or analytical computation, parameter estimation, graphical user interface, and systems biology markup language (SBML) support are not seen concurrently in one software package. In this study, we developed a python-based software that supports these features, with both deterministic and stochastic propagations. The software can be used by graphical user interface, command line, or as a python import. We also developed a semi-programmable and intuitively easy topology input method for the biochemical reactions. We tested the software with semantic and stochastic SBML test cases. Tests on symbolic solution and parameter estimation were also included. The software we developed is reliable, well performing, convenient to use, and compliant with most of the SBML tests. So far it is the only systems biology software that supports symbolic, deterministic, and stochastic modeling in one package that also features parameter estimation and SBML support. This work offers a comprehensive set of tools and allows for better availability and accessibility for studying kinetics and dynamics in biochemical systems.
]]></description>
<dc:creator>Fajiculay, E.</dc:creator>
<dc:creator>Hsu, C.-P.</dc:creator>
<dc:date>2021-08-17</dc:date>
<dc:identifier>doi:10.1101/2021.08.17.456661</dc:identifier>
<dc:title><![CDATA[BioSANS: A Software Package for Symbolic and Numeric Biological Simulation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-08-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.08.18.456372v1?rss=1">
<title>
<![CDATA[
Identification and comparative analysis of long non-coding RNAs in the brain of fire ant queens in two different reproductive states 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.08.18.456372v1?rss=1</link>
<description><![CDATA[
BackgroundMany long non-coding RNAs (lncRNAs) have been extensively identified in many higher eukaryotic species. The function of lncRNAs has been reported to play important roles in diverse biological processes, including developmental regulation and behavioral plasticity. However, there are no reports of systematic characterization of long non-coding RNAs in the fire ant Solenopsis invicta.

ResultsIn this study, we performed a genome-wide analysis of lncRNAs in the brains of S. invicta from RNA-seq. In total, 1,393 novel lncRNA transcripts were identified in the fire ant. In contrast to the annotated lncRNA transcripts having at least two exons, novel lncRNAs are monoexonic transcripts with a shorter length. Besides, the transcriptome from virgin alate and dealate mated queens were analyzed and compared. The results showed 295 differentially expressed mRNA genes (DEGs) and 65 differentially expressed lncRNA genes (DELs) between virgin and mated queens, of which 17 lncRNAs were highly expressed in the virgin alates and 47 lncRNAs were highly expressed in the mated dealates. By identifying the DEL:DEG pairs with high association in their expression (Spearmans |rho| > 0.8 and p-value < 0.01), many DELs were co-regulated with DEGs after mating. Furthermore, several remarkable lncRNAs (MSTRG.6523, MSTRG.588, and nc909) that were found to associate with particular coding genes may play important roles in the regulation of brain gene expression in reproductive transition in fire ants.

ConclusionThis study provides the first genome-wide identification of S. invicta lncRNAs in the brains in different reproductive states and will contribute to a fuller understanding of the transcriptional regulation underpinning reproductive changes.
]]></description>
<dc:creator>Tsai, C.-H.</dc:creator>
<dc:creator>Lin, T.-C.</dc:creator>
<dc:creator>Tsai, H.-K.</dc:creator>
<dc:creator>Chang, Y.-H.</dc:creator>
<dc:creator>Huang, J.-H.</dc:creator>
<dc:date>2021-08-18</dc:date>
<dc:identifier>doi:10.1101/2021.08.18.456372</dc:identifier>
<dc:title><![CDATA[Identification and comparative analysis of long non-coding RNAs in the brain of fire ant queens in two different reproductive states]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-08-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.08.23.457303v1?rss=1">
<title>
<![CDATA[
Insulin Signaling Attenuates GLUT4 Endocytosis in Muscle Cells via GSK3a-Dyn2-Bin1 Interplay 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.08.23.457303v1?rss=1</link>
<description><![CDATA[
Insulin-induced translocation of glucose transporter 4 (GLUT4) to the plasma membrane of skeletal muscle is critical for postprandial glucose uptake; however, whether the internalization of GLUT4 into cells is also regulated by insulin signaling remains unclear. Here, we discover that the activity of dynamin-2 (Dyn2), pivotal GTPase catalyzing GLUT4 internalization, is regulated by insulin signaling in muscle cells. The membrane fission activity of Dyn2 is inhibited in muscle cells through binding with the SH3 domain-containing protein Bin1. Phosphorylation of Serine848 on Dyn2 by GSK3 or the mutations of Bin1-SH3 in patients with centronuclear myopathy, elevate the activity of Dyn2 due to reduced binding affinity toward Bin1. The augmented Dyn2 fission activity in muscle cells leads to GLUT4 internalization and Bin1-tubule vesiculation. Together, our findings reveal a new role of insulin signaling in glucose metabolism and muscle physiology via attenuating Dyn2 activity thus regulating GLUT4 endocytosis in muscle cell.
]]></description>
<dc:creator>Liu, Y.-W.</dc:creator>
<dc:creator>Laiman, J.</dc:creator>
<dc:creator>Loh, J.</dc:creator>
<dc:creator>Tang, W.-C.</dc:creator>
<dc:creator>Chuang, M.-C.</dc:creator>
<dc:creator>Chen, B.-C.</dc:creator>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Chuang, L.-M.</dc:creator>
<dc:date>2021-08-24</dc:date>
<dc:identifier>doi:10.1101/2021.08.23.457303</dc:identifier>
<dc:title><![CDATA[Insulin Signaling Attenuates GLUT4 Endocytosis in Muscle Cells via GSK3a-Dyn2-Bin1 Interplay]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-08-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.08.25.457612v1?rss=1">
<title>
<![CDATA[
Gastrodia elata Blume prevents dopaminergic neuron degeneration via glial Nrf2 signaling in Lrrk2-G2019S Parkinson's disease models 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.08.25.457612v1?rss=1</link>
<description><![CDATA[
The most frequent missense mutations in familial Parkinsons disease (PD) occur in the highly conserved LRRK2/PARK8 gene with G2019S mutation. We previously established a fly model of PD carrying the LRRK2-G2019S mutation that exhibited the parkinsonism-like phenotypes. An herbal medicine--Gastrodia elata Blume (GE), has been reported to have neuroprotective effects in toxin- induced PD models. However, the underpinning molecular mechanisms of GE beneficiary to G2019S- induced PD remain unclear. Here, we show that these G2019S flies treated with water extracts of GE (WGE) and its bioactive compounds, gastrodin and 4-HBA, displayed locomotion improvement and dopaminergic neuron protection. WGE suppressed the accumulation and hyperactivation of G2019S proteins in dopaminergic neurons, and activated the antioxidation and detoxification factor Nrf2 mostly in the astrocyte-like and ensheathing glia. Glial activation of Nrf2 antagonizes G2019S-induced Mad/Smad signaling. Moreover, we treated LRRK2-G2019S transgenic mice with WGE and found the locomotion declines, the loss of dopaminergic neurons, and the number of hyperactive microglia were restored. WGE also suppressed the hyperactivation of G2019S proteins and regulated the Smad2/3 pathways in the mice brains. We conclude that WGE prevents locomotion defects and the neuronal loss induced by G2019S mutation via glial Nrf2/Mad signaling, unveiling a potential therapeutic avenue for PD.
]]></description>
<dc:creator>Lin, Y.-E.</dc:creator>
<dc:creator>Lin, C.-H.</dc:creator>
<dc:creator>Ho, E.-P.</dc:creator>
<dc:creator>Ke, Y.-C.</dc:creator>
<dc:creator>Petridi, S.</dc:creator>
<dc:creator>Elliott, C. J. H.</dc:creator>
<dc:creator>Sheen, L.-Y.</dc:creator>
<dc:creator>Chien, C.-T.</dc:creator>
<dc:date>2021-08-27</dc:date>
<dc:identifier>doi:10.1101/2021.08.25.457612</dc:identifier>
<dc:title><![CDATA[Gastrodia elata Blume prevents dopaminergic neuron degeneration via glial Nrf2 signaling in Lrrk2-G2019S Parkinson's disease models]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-08-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.09.01.458651v1?rss=1">
<title>
<![CDATA[
Genomically hardwired regulation of gene activity orchestrates cellular iron homeostasis in Arabidopsis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.09.01.458651v1?rss=1</link>
<description><![CDATA[
Iron (Fe) is an essential micronutrient that plays pivotal roles as electron donor and catalyst across organisms. In plants, variable, often insufficient Fe supply necessitates mechanisms that constantly attune Fe uptake rates and recalibrate cellular Fe homeostasis. Here, we show that short-term (0.5, 6, and 12 h) exposure of Arabidopsis thaliana plants to Fe deficiency triggered massive changes in gene activity governed by transcription and alternative splicing (AS), regulatory layers that were to a large extent mutually exclusive. Such preclusion was not observed for genes that are directly involved in the acquisition of Fe, which appears to be concordantly regulated by both expression and AS. Generally, genes with lower splice site strengths and higher intron numbers were more likely to be regulated by AS, no dependence was on gene architecture was observed for transcriptionally controlled genes. Conspicuously, specific processes were associated with particular genomic features and biased towards either regulatory mode, suggesting that genomic hardwiring is functionally biased. Early changes in splicing patterns were, in many cases, congruent with later changes in transcript or protein abundance, thus contributing to the pronounced transcriptome-proteome discordance observed in plants.
]]></description>
<dc:creator>Hsieh, E.-J.</dc:creator>
<dc:creator>Lin, W.</dc:creator>
<dc:creator>Schmidt, W.</dc:creator>
<dc:date>2021-09-02</dc:date>
<dc:identifier>doi:10.1101/2021.09.01.458651</dc:identifier>
<dc:title><![CDATA[Genomically hardwired regulation of gene activity orchestrates cellular iron homeostasis in Arabidopsis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-09-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.09.02.458763v1?rss=1">
<title>
<![CDATA[
A high resolution single molecule sequencing-based Arabidopsis transcriptome using novel methods of Iso-seq analysis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.09.02.458763v1?rss=1</link>
<description><![CDATA[
BackgroundAccurate and comprehensive annotation of transcript sequences is essential for transcript quantification and differential gene and transcript expression analysis. Single molecule long read sequencing technologies provide improved integrity of transcript structures including alternative splicing, and transcription start and polyadenylation sites. However, accuracy is significantly affected by sequencing errors, mRNA degradation or incomplete cDNA synthesis.

ResultsWe present a new and comprehensive Arabidopsis thaliana Reference Transcript Dataset 3 (AtRTD3). AtRTD3 contains over 160k transcripts - twice that of the best current Arabidopsis transcriptome and including over 1,500 novel genes. 79% of transcripts are from Iso-seq with accurately defined splice junctions and transcription start and end sites. We developed novel methods to determine splice junctions and transcription start and end sites accurately. Mis- match profiles around splice junctions provided a powerful feature to distinguish correct splice junctions and remove false splice junctions. Stratified approaches identified high confidence transcription start/end sites and removed fragmentary transcripts due to degradation. AtRTD3 is a major improvement over existing transcriptomes as demonstrated by analysis of an Arabidopsis cold response RNA-seq time-series. AtRTD3 provided higher resolution of transcript expression profiling and identified cold- and light-induced differential transcription start and polyadenylation site usage.

ConclusionsAtRTD3 is the most comprehensive Arabidopsis transcriptome currently available. It improves the precision of differential gene and transcript expression, differential alternative splicing, and transcription start/end site usage from RNA-seq data. The novel methods for identifying accurate splice junctions and transcription start/end sites are widely applicable and will improve single molecule sequencing analysis from any species.
]]></description>
<dc:creator>Zhang, R.</dc:creator>
<dc:creator>Kuo, R.</dc:creator>
<dc:creator>Coulter, M.</dc:creator>
<dc:creator>Calixto, C. P. G.</dc:creator>
<dc:creator>Entizne, J. C.</dc:creator>
<dc:creator>Guo, W.</dc:creator>
<dc:creator>Marquez, Y.</dc:creator>
<dc:creator>Milne, L.</dc:creator>
<dc:creator>Riegler, S.</dc:creator>
<dc:creator>Matsui, A.</dc:creator>
<dc:creator>Tanaka, M.</dc:creator>
<dc:creator>Harvey, S.</dc:creator>
<dc:creator>Yubang, G.</dc:creator>
<dc:creator>Wiebner-Kroh, T.</dc:creator>
<dc:creator>Crespi, M.</dc:creator>
<dc:creator>Denby, K.</dc:creator>
<dc:creator>Hur, A. b.</dc:creator>
<dc:creator>Huq, E.</dc:creator>
<dc:creator>Jantsch, M. F.</dc:creator>
<dc:creator>Jarmolowski, A.</dc:creator>
<dc:creator>Koester, T.</dc:creator>
<dc:creator>Laubinger, S.</dc:creator>
<dc:creator>Li, Q. Q.</dc:creator>
<dc:creator>Gu, L.</dc:creator>
<dc:creator>Seki, M.</dc:creator>
<dc:creator>Staiger, D.</dc:creator>
<dc:creator>Sunkar, R.</dc:creator>
<dc:creator>Szweykowska-Kulinska, Z.</dc:creator>
<dc:creator>Tu, S.-L.</dc:creator>
<dc:creator>Wachter, A.</dc:creator>
<dc:creator>Waugh, R.</dc:creator>
<dc:creator>Xiong, L.</dc:creator>
<dc:creator>Zhang, X.-N.</dc:creator>
<dc:creator>Reddy, A. S. N.</dc:creator>
<dc:creator>Barta, A.</dc:creator>
<dc:creator>Kalyna, M.</dc:creator>
<dc:creator>Brown, J. W.</dc:creator>
<dc:date>2021-09-03</dc:date>
<dc:identifier>doi:10.1101/2021.09.02.458763</dc:identifier>
<dc:title><![CDATA[A high resolution single molecule sequencing-based Arabidopsis transcriptome using novel methods of Iso-seq analysis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-09-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.09.06.459084v1?rss=1">
<title>
<![CDATA[
Comparative genomics of three Colletotrichum scovillei strains and genetic analysis revealed genes involved in fungal growth and virulence on chili pepper 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.09.06.459084v1?rss=1</link>
<description><![CDATA[
Colletotrichum scovillei is a virulent pathogen and the dominant species causing anthracnose of chili pepper in many Asian countries. Three strains of this pathogen, Coll-524, Coll-153 and Coll-365, show varied virulence on chili pepper fruit. Among the three strains, Coll-365 showed significant defects in growth and virulence. To decipher the genetic variations among these strains and identify genes contributing to growth and virulence, in this study, comparative genomic analysis and gene transformation to verify gene function were applied. The genomes of the three strains were sequenced and Coll-524 had 1.3% and 1.5% more genes than Coll-153 and Coll-365, respectively. Compared to Coll-524 and Coll-153, Coll-365 had numerous gene losses including 33 effector genes that are distributed in different scaffolds and a cluster of 14 genes in a 34-kb genomic fragment. Through gene transformation, three genes in the 34-kb fragment were identified to have functions in growth and/or virulence of C. scovillei. Gene 15019 encoding a protein related to phospholipase A2-activating protein enhanced the growth of Coll-365. A combination of 15019 with one transcription factor gene 15022 and one C6 zinc finger domain-containing protein gene 15029 was found to enhance the pathogenicity of Coll-365. Introduction of gene 15215, which encodes a LysM domain-containing protein, into Coll-365 caused a reduction in the germination rate of Coll-365. In conclusion, the higher virulent strain Coll-524 had more genes and encoded more pathogenicity related proteins and transposable elements than the other two strains, which may contribute to the high virulence of Coll-524. In addition, the absence of the 34-kb fragment plays a critical role in the defects of growth and virulence of strain Coll-365.

Author SummaryColletotrichum scovillei is a highly virulent and dominant pathogen causing anthracnose of chili that leads to significant economic loss in chili production in many Asia countries. In this study we focus on finding the gene differences of three C. scovillei strains with different pathogenicity in chili pepper infection and verifying the function of some genes in the lowest virulence strain. We sequenced them and did gene annotation and genome comparison. We setup a simple mathematical method to identify gene variations between strong and weak virulence strains. Our results show that the lowest virulence strain has less pathogenicity-related genes. We also found that the absence of 14 genes in a compact genomic fragment was part of the reason of growth and virulence defect of the lowest virulence strain. We identified four genes that play roles on fungal growth and/or virulence on chili pepper. We also found a group of effector genes that specifically appear in species collected form infected chili in C. acutatum species complex. Our research provides detailed information for why the three strains have different virulence on chili pepper.
]]></description>
<dc:creator>Hsieh, D.-K.</dc:creator>
<dc:creator>Chuang, S.-C.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Chao, Y.-T.</dc:creator>
<dc:creator>Lu, M.-Y. J.</dc:creator>
<dc:creator>Shih, M.-C.</dc:creator>
<dc:creator>Lee, M.-H.</dc:creator>
<dc:date>2021-09-06</dc:date>
<dc:identifier>doi:10.1101/2021.09.06.459084</dc:identifier>
<dc:title><![CDATA[Comparative genomics of three Colletotrichum scovillei strains and genetic analysis revealed genes involved in fungal growth and virulence on chili pepper]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-09-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.09.07.459046v1?rss=1">
<title>
<![CDATA[
Deep sampling of ancestral genetic diversity reveals Saccharomyces cerevisiae pre-domestication life histories 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.09.07.459046v1?rss=1</link>
<description><![CDATA[
The ecology and genetic diversity of model yeast Saccharomyces cerevisiae prior to human domestication remain poorly understood. Taiwan is regarded as part of this yeasts geographic birthplace where the most divergent natural lineage was discovered. Here, we deep sampled the broad-leaf forests across this continental island to probe the ancestral species diversity. We found that S. cerevisiae is distributed ubiquitously at low abundance in the forests. Whole-genome sequencing of 121 isolates revealed nine distinct lineages, the highest known in any region. Three lineages are endemic to Taiwan and six are widespread in Asia. Molecular dating placed the divergence of the Taiwanese and Asian lineages during the Pleistocene, when a transient continental shelf land bridge connected Taiwan to other major landmasses. Extensive historical and recent admixture events were detected between natural lineages. In particular, the genetic component from a lineage associated with fruits that spanned the widest geographical range was present in most admixed isolates. Collectively, Taiwanese isolates harbor genetic diversity comparable to that of the whole Asia continent, and different lineages have coexisted at a fine spatial scale even on the same tree. Patterns of variations within each lineage revealed that S. cerevisiae is highly clonal and predominantly reproduces asexually in nature. We detected prevalent purifying selection genome-wide, with lineage-specific signals of positive or directional selection independent between lineages. This study establishes that S. cerevisiae has rich natural diversity sheltered from human influences, making it a powerful model system in microbial ecology.
]]></description>
<dc:creator>Lee, T. J.</dc:creator>
<dc:creator>Liu, Y.-C.</dc:creator>
<dc:creator>Liu, W.-A.</dc:creator>
<dc:creator>Lin, Y.-F.</dc:creator>
<dc:creator>Lee, H.-H.</dc:creator>
<dc:creator>Ke, H.-M.</dc:creator>
<dc:creator>Huang, J.-P.</dc:creator>
<dc:creator>Lu, M.-Y. J.</dc:creator>
<dc:creator>Hsieh, C.-L.</dc:creator>
<dc:creator>Chung, K.-F.</dc:creator>
<dc:creator>Liti, G.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2021-09-08</dc:date>
<dc:identifier>doi:10.1101/2021.09.07.459046</dc:identifier>
<dc:title><![CDATA[Deep sampling of ancestral genetic diversity reveals Saccharomyces cerevisiae pre-domestication life histories]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-09-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.09.07.459217v1?rss=1">
<title>
<![CDATA[
GABOLA: A Reliable Gap-Filling Strategy for de novo Chromosome-Level Assembly 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.09.07.459217v1?rss=1</link>
<description><![CDATA[
We propose a novel method, GABOLA, which utilizes long-range genomic information provided by accurate linked short reads jointly with long reads to improve the integrity and resolution of whole genome assemblies especially in complex genetic regions. We validated GABOLA on human and Japanese eel genomes. On the two human samples, we filled in more bases spanning 23.3Mbp and 46.2Mbp than Supernova assembler, covering over 3,200 functional genes which includes 8,500 exons and 15,000 transcripts. Among them, multiple genes related to various types of cancer were identified. Moreover, we discovered additional 11,031,487 base pairs of repeat sequences and 218 exclusive repeat patterns, some of which are known to be linked to several disorders such as neuron degenerative diseases. As for the eel genome, we successfully raised the genetic benchmarking score to 94.6% while adding 24.7 million base pairs. These results manifest the capability of GABOLA in the optimization of whole genome assembly and the potential in precise disease diagnosis and high-quality non-model organism breeding.

Availability: The docker image and source code of GABOLA assembler are available at https://hub.docker.com/r/lsbnb/gabola and https://github.com/lsbnb/gabola respectively.
]]></description>
<dc:creator>Chuang, W.-H.</dc:creator>
<dc:creator>Cheng, H.-C.</dc:creator>
<dc:creator>Chang, Y.-J.</dc:creator>
<dc:creator>Fu, P.-Y.</dc:creator>
<dc:creator>Huang, Y.-C.</dc:creator>
<dc:creator>Hsieh, P.-H.</dc:creator>
<dc:creator>Chen, S.-H.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Ho, J.-M.</dc:creator>
<dc:date>2021-09-08</dc:date>
<dc:identifier>doi:10.1101/2021.09.07.459217</dc:identifier>
<dc:title><![CDATA[GABOLA: A Reliable Gap-Filling Strategy for de novo Chromosome-Level Assembly]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-09-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.09.08.459525v1?rss=1">
<title>
<![CDATA[
Phosphatidylglycerol synthesis facilitates plastid gene expression and light induction of nuclear photosynthetic genes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.09.08.459525v1?rss=1</link>
<description><![CDATA[
Phosphatidylglycerol (PG) is the only major phospholipid in the thylakoid membrane of chloroplasts. PG is essential for photosynthesis and loss of PG in Arabidopsis thaliana results in severe defects of growth and chloroplast development with decreased chlorophyll accumulation, impaired thylakoid formation, and downregulation of photosynthesis-associated genes encoded in nuclear and plastid genomes. However, how the absence of PG affects the gene expression and plant growth remains unclear. To elucidate this mechanism, we investigated the growth and transcriptional profiles of a PG-deficient Arabidopsis mutant pgp1-2 under various light conditions. Microarray analysis demonstrated that reactive oxygen species-responsive genes were upregulated in pgp1-2. Decreased growth light did not alleviated the impaired leaf development and the downregulation of photosynthesis-associated genes in pgp1-2, indicating limited impacts of photooxidative stress on the defects of pgp1-2. Illumination to dark-adapted pgp1-2 triggered downregulation of photosynthesis-associated nuclear-encoded genes (PhANGs), while plastid-encoded genes were constantly suppressed. Overexpression of GOLDEN2-LIKE1 (GLK1), a transcription factor regulating chloroplast development, in pgp1-2 upregulated PhANGs but not plastid-encoded genes along with chlorophyll accumulation. Our data suggest a broad impact of PG biosynthesis on nuclear-encoded genes partially via GLK1 and a specific involvement of this lipid in the plastid gene expression and plant development.
]]></description>
<dc:creator>Fujii, S.</dc:creator>
<dc:creator>Kobayashi, K.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Liu, Y.-c.</dc:creator>
<dc:creator>Nakamura, Y.</dc:creator>
<dc:creator>Wada, H.</dc:creator>
<dc:date>2021-09-10</dc:date>
<dc:identifier>doi:10.1101/2021.09.08.459525</dc:identifier>
<dc:title><![CDATA[Phosphatidylglycerol synthesis facilitates plastid gene expression and light induction of nuclear photosynthetic genes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-09-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.09.09.459700v1?rss=1">
<title>
<![CDATA[
Comparative Genome Analysis of 'Candidatus Phytoplasma luffae' Reveals the Influential Roles of Potential Mobile Units in Phytoplasma Evolution 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.09.09.459700v1?rss=1</link>
<description><![CDATA[
Phytoplasmas are insect-transmitted plant pathogens that cause substantial losses in agriculture. In addition to economic impact, phytoplasmas induce distinct disease symptoms in infected plants, thus attracting attention for research on molecular plant-microbe interactions and plant developmental processes. Due to the difficulty of establishing an axenic culture of these bacteria, culture-independent genome characterization is a crucial tool for phytoplasma research. However, phytoplasma genomes have strong nucleotide composition biases and are repetitive, which make it challenging to produce complete assemblies. In this study, we utilized Illumina and Oxford Nanopore sequencing technologies to obtain the complete genome sequence of  Candidatus Phytoplasma luffae strain NCHU2019 that is associated with witches broom disease of loofah (Luffa aegyptiaca) in Taiwan. The fully assembled circular chromosome is 769 kb in size and is the first representative genome sequence of group 16SrVIII phytoplasmas. Comparative analysis with other phytoplasmas revealed that NCHU2019 has an exceptionally repetitive genome, possessing a pair of 75 kb repeats and at least 13 potential mobile units (PMUs) that account for ~25% of its chromosome. This level of genome repetitiveness is exceptional for bacteria, particularly among obligate pathogens with reduced genomes. Our genus-level analysis of PMUs demonstrated that these phytoplasma-specific mobile genetic elements can be classified into three major types that differ in gene organization and phylogenetic distribution. Notably, PMU abundance explains nearly 80% of the variance in phytoplasma genome sizes, a finding that provides a quantitative estimate for the importance of PMUs in phytoplasma genome variability. Finally, our investigation found that in addition to horizontal gene transfer, PMUs also contribute to intra-genomic duplications of effector genes, which may provide redundancy for neofunctionalization or subfunctionalization. Taken together, this work improves the taxon sampling for phytoplasma genome research and provides novel information regarding the roles of mobile genetic elements in phytoplasma evolution.
]]></description>
<dc:creator>Huang, C.-T.</dc:creator>
<dc:creator>Cho, S.-T.</dc:creator>
<dc:creator>Tan, C.-M.</dc:creator>
<dc:creator>Chiu, Y.-C.</dc:creator>
<dc:creator>Yang, J.-Y.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:date>2021-09-11</dc:date>
<dc:identifier>doi:10.1101/2021.09.09.459700</dc:identifier>
<dc:title><![CDATA[Comparative Genome Analysis of 'Candidatus Phytoplasma luffae' Reveals the Influential Roles of Potential Mobile Units in Phytoplasma Evolution]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-09-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.09.12.459978v1?rss=1">
<title>
<![CDATA[
Structure-activity relationships of B.1.617 and other SARS-CoV-2 spike variants 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.09.12.459978v1?rss=1</link>
<description><![CDATA[
The surge of COVID-19 infection cases is spurred by emerging SARS-CoV-2 variants such as B.1.617. Here we report 38 cryo-EM structures, corresponding to the spike protein of the Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Kappa (B.1.617.1) variants in different functional states with and without its receptor, ACE2. Mutations on the N-terminal domain not only alter the conformation of the highly antigenic supersite of the Delta variant, but also remodel the glycan shield by deleting or adding N-glycans of the Delta and Gamma variants, respectively. Substantially enhanced ACE2 binding was observed for all variants, whose mutations on the receptor binding domain modulate the electrostatics of the binding interfaces. Despite their abilities to escape host immunity, all variants can be potently neutralized by three unique antibodies.
]]></description>
<dc:creator>Yang, T.-J.</dc:creator>
<dc:creator>Yu, P.-Y.</dc:creator>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Chang, N.-E.</dc:creator>
<dc:creator>Tsai, Y.-X.</dc:creator>
<dc:creator>Liang, K.-H.</dc:creator>
<dc:creator>Draczkowski, P.</dc:creator>
<dc:creator>Lin, B.</dc:creator>
<dc:creator>Wang, Y.-S.</dc:creator>
<dc:creator>Chien, Y.-C.</dc:creator>
<dc:creator>Khoo, K.-H.</dc:creator>
<dc:creator>Wu, H.-C.</dc:creator>
<dc:creator>Hsu, S.-T. D.</dc:creator>
<dc:date>2021-09-13</dc:date>
<dc:identifier>doi:10.1101/2021.09.12.459978</dc:identifier>
<dc:title><![CDATA[Structure-activity relationships of B.1.617 and other SARS-CoV-2 spike variants]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-09-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.09.15.459215v1?rss=1">
<title>
<![CDATA[
Signatures of adaptive evolution during human to mink SARS CoV2 cross species transmission inform estimates of the COVID19 pandemic timing 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.09.15.459215v1?rss=1</link>
<description><![CDATA[
One of the unique features of SARS-CoV-2 is that it mainly evolved neutrally or under purifying selection during the early pandemic. This contrasts with the preceding epidemics of the closely related SARS-CoV and MERS-CoV, both of which evolved adaptively. It is possible that the SARS-CoV-2 exhibits a unique or adaptive feature which deviates from other coronaviruses. Alternatively, the virus may have been cryptically circulating in humans for a sufficient time to have acquired adaptive changes for efficient transmission before the onset of the current pandemic. In order to test the above scenarios, we analyzed the SARS-CoV-2 sequences from minks (Neovision vision) and parenteral human strains. In the early phase of the mink epidemic (April to May 2020), nonsynonymous to synonymous mutation ratios per site within the spike protein was 2.93, indicating a selection process favoring adaptive amino acid changes. In addition, mutations within this protein concentrated within its receptor binding domain and receptor binding motif. Positive selection also left a trace on linked neutral variation. An excess of high frequency derived variants produced by genetic hitchhiking was found during middle (June to July 2020) and early late (August to September 2020) phases of the mink epidemic, but quickly diminished in October and November 2020. Strong positive selection found in SARS-CoV-2 from minks implies that the virus may be not unique in super-adapting to a wide range of new hosts. The mink study suggests that SARS-CoV-2 already went through adaptive evolution in humans, and likely been circulating in humans at least six months before the first case found in Wuhan, China. We also discuss circumstances under which the virus can be well-adapted to its host but fail to induce an outbreak.
]]></description>
<dc:creator>Tai, J.-H.</dc:creator>
<dc:creator>Chaw, S.-M.</dc:creator>
<dc:creator>Sun, H.-Y.</dc:creator>
<dc:creator>Tseng, Y.-C.</dc:creator>
<dc:creator>Li, G.</dc:creator>
<dc:creator>Chang, S.-Y.</dc:creator>
<dc:creator>Yeh, S.-H.</dc:creator>
<dc:creator>Chen, P.-J.</dc:creator>
<dc:creator>Wang, H.-Y.</dc:creator>
<dc:date>2021-09-16</dc:date>
<dc:identifier>doi:10.1101/2021.09.15.459215</dc:identifier>
<dc:title><![CDATA[Signatures of adaptive evolution during human to mink SARS CoV2 cross species transmission inform estimates of the COVID19 pandemic timing]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-09-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.09.27.461970v1?rss=1">
<title>
<![CDATA[
Response of Endozoicomonas montiporae to heat stress and coral host lysates 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.09.27.461970v1?rss=1</link>
<description><![CDATA[
Endozoicomonas, a core bacterial group in corals, may also be a coral symbiont. Endozoicomonas communities often decrease rapidly in corals under heat stress. However, how the bacteria respond to changes in temperature and coral host during heat stress is unknown. Here, we employed the cultivable, dominant species E. montiporae as a working organism to explore how Endozoicomonas responds to heat stress. We designed two experiments to clarify the extent to which E. montiporae is influenced by temperature and coral host. We detected differentially expressed protein (DEP) profiles in this bacterium at 31{degrees}C and 33{degrees}C compared to 25{degrees}C by tandem mass tags-based quantitative proteome analysis. Fifty DEPs, including many heat shock proteins, were detected when the temperature changed. The expression of antioxidant defense proteins and key pyruvate synthase proteins decreased, suggesting that E. montiporae were in a physiology of stress at 33{degrees}C. Furthermore, some proteins were differentially expressed because of the heat-stress-treated coral lysate specifically, suggesting that not only heat but also heat-induced host factors can affect the protein expression of the bacterium. This study provides an in-depth analysis of how the molecular mechanisms of Endozoicomonas are affected by heat stress and coral host.
]]></description>
<dc:creator>Chan, Y.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Lu, C.-Y.</dc:creator>
<dc:creator>Tu, Y.-C.</dc:creator>
<dc:creator>Tandon, K.</dc:creator>
<dc:creator>Shikina, S.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:date>2021-09-27</dc:date>
<dc:identifier>doi:10.1101/2021.09.27.461970</dc:identifier>
<dc:title><![CDATA[Response of Endozoicomonas montiporae to heat stress and coral host lysates]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-09-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.09.28.461843v1?rss=1">
<title>
<![CDATA[
The helper NLR immune protein NRC3 mediates the hypersensitive cell death caused by the cell-surface receptor Cf-4 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.09.28.461843v1?rss=1</link>
<description><![CDATA[
Cell surface pattern recognition receptors (PRRs) activate immune responses that can include the hypersensitive cell death. However, the pathways that link PRRs to the cell death response are poorly understood. Here, we show that the cell surface receptor-like protein Cf-4 requires the intracellular nucleotide-binding domain leucine-rich repeat containing receptor (NLR) NRC3 to trigger a confluent cell death response upon detection of the fungal effector Avr4 in leaves of Nicotiana benthamiana. This NRC3 activity requires an intact N-terminal MADA motif, a conserved signature of coiled-coil (CC)-type plant NLRs that is required for resistosome-mediated immune responses. A chimeric protein with the N-terminal 1 helix of Arabidopsis ZAR1 swapped into NRC3 retains the capacity to mediate Cf-4 hypersensitive cell death. Pathogen effectors acting as suppressors of NRC3 can suppress Cf-4-triggered hypersensitive cell-death. Our findings link the NLR resistosome model to the hypersensitive cell death caused by a cell surface PRR.
]]></description>
<dc:creator>Kourelis, J.</dc:creator>
<dc:creator>Contreras, M. P.</dc:creator>
<dc:creator>Harant, A.</dc:creator>
<dc:creator>Adachi, H.</dc:creator>
<dc:creator>Derevnina, L.</dc:creator>
<dc:creator>Wu, C.-H.</dc:creator>
<dc:creator>Kamoun, S.</dc:creator>
<dc:date>2021-09-28</dc:date>
<dc:identifier>doi:10.1101/2021.09.28.461843</dc:identifier>
<dc:title><![CDATA[The helper NLR immune protein NRC3 mediates the hypersensitive cell death caused by the cell-surface receptor Cf-4]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-09-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.09.29.462340v1?rss=1">
<title>
<![CDATA[
Single-cell transcriptomic analysis unveils spinal motor neuron subtype diversity underpinning the water-to-land transition in vertebrates 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.09.29.462340v1?rss=1</link>
<description><![CDATA[
Spinal motor neurons (MNs) integrate sensory stimuli and brain commands to generate motor movements in vertebrates. Distinct MN populations and their diversity has long been hypothesized to co-evolve with motor circuit to provide the neural basis from undulatory to ambulatory locomotion during aquatic-to-terrestrial transition of vertebrates. However, how these subtypes are evolved remains largely enigmatic. Using single-cell transcriptomics, we investigate heterogeneity in mouse MNs and discover novel segment-specific subtypes. Among limb-innervating MNs, we reveal a diverse neuropeptide code for delineating putative motor pool identities. We further uncovered that axial MNs are subdivided by three conserved and molecularly distinct subpopulations, defined by Satb2, Nr2f2 or Bcl11b expression. Although axial MNs are conserved from cephalochordates to humans, subtype diversity becomes prominent in land animals and appears to continue evolving in humans. Overall, our study provides a unified classification system for spinal MNs and paves the way towards deciphering how neuronal subtypes are evolved.
]]></description>
<dc:creator>Liau, E. S.</dc:creator>
<dc:creator>Jin, S.</dc:creator>
<dc:creator>Chen, Y.-C.</dc:creator>
<dc:creator>Liu, W.-S.</dc:creator>
<dc:creator>Yong, L. W.</dc:creator>
<dc:creator>Tsai, C.-T.</dc:creator>
<dc:creator>Calon, M.</dc:creator>
<dc:creator>Yu, J.-K.</dc:creator>
<dc:creator>Su, Y.-H.</dc:creator>
<dc:creator>Nedelec, S.</dc:creator>
<dc:creator>Nie, Q.</dc:creator>
<dc:creator>Chen, J.-A.</dc:creator>
<dc:date>2021-09-30</dc:date>
<dc:identifier>doi:10.1101/2021.09.29.462340</dc:identifier>
<dc:title><![CDATA[Single-cell transcriptomic analysis unveils spinal motor neuron subtype diversity underpinning the water-to-land transition in vertebrates]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-09-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.10.01.462710v1?rss=1">
<title>
<![CDATA[
Exploration of deep-learning based classification with human SNP image graphs 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.10.01.462710v1?rss=1</link>
<description><![CDATA[
BackgroundWith the advancement of NGS platform, large numbers of human variations and SNPs are discovered in human genomes. It is essential to utilize these massive nucleotide variations for the discovery of disease genes and human phenotypic traits. There are new challenges in utilizing such large numbers of nucleotide variants for polygenic disease studies. In recent years, deep-learning based machine learning approaches have achieved great successes in many areas, especially image classifications. In this preliminary study, we are exploring the deep convolutional neural network algorithm in genome-wide SNP images for the classification of human populations.

ResultsWe have processed the SNP information from more than 2,500 samples of 1000 genome project. Five major human races were used for classification categories. We first generated SNP image graphs of chromosome 22, which contained about one million SNPs. By using the residual network (ResNet 50) pipeline in CNN algorithm, we have successfully obtained classification models to classify the validation dataset. F1 scores of the trained CNN models are 95 to 99%, and validation with additional separate 150 samples indicates a 95.8% accuracy of the CNN model. Misclassification was often observed between the American and European categories, which could attribute to the ancestral origins. We further attempted to use SNP image graphs in reduced color representations or images generated by spiral shapes, which also provided good prediction accuracy. We then tried to use the SNP image graphs from chromosome 20, almost all CNN models failed to classify the human race category successfully, except the African samples.

ConclusionsWe have developed a human race prediction model with deep convolutional neural network. It is feasible to use the SNP image graph for the classification of individual genomes.
]]></description>
<dc:creator>Chen, C.-H.</dc:creator>
<dc:creator>Tung, K.-F.</dc:creator>
<dc:creator>Lin, W.-c.</dc:creator>
<dc:date>2021-10-01</dc:date>
<dc:identifier>doi:10.1101/2021.10.01.462710</dc:identifier>
<dc:title><![CDATA[Exploration of deep-learning based classification with human SNP image graphs]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-10-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.10.03.462954v1?rss=1">
<title>
<![CDATA[
Allometric scaling of RNA abundance from genes to communities 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.10.03.462954v1?rss=1</link>
<description><![CDATA[
The metabolic theory of ecology (MTE) and growth rate hypothesis (GRH) help explain the mechanistic basis of size (allometry) and temperature dependence on growth rate and whole-body-RNA content in organisms. However, testing RNA allometric scaling with next-generation sequencing is yet to be done. Here, we validated the assumptions of GRH and MTE on messenger RNA and ribosome abundance using mock community metatranscriptome analysis. Our findings highlight that fast-growing smaller species harbor greater RNA abundance per mass of tissue compared with species having larger body sizes and slower growth rates, where allometric slopes for genomic and gene-level RNA abundance range from -[1/3] to -1. We found that genome size and body size impose significant constraints in interspecific RNA abundance scaling, while the assumed temperature dependence appeared to be weak. Lastly, allometric scaling integration in community-level models may extend the use of metatranscriptomics as a reliable tool for estimating ecosystem processes.
]]></description>
<dc:creator>Lopez, M. L. D.</dc:creator>
<dc:creator>Lin, Y.-y.</dc:creator>
<dc:creator>Schneider, S. Q.</dc:creator>
<dc:creator>Machida, R. J.</dc:creator>
<dc:date>2021-10-04</dc:date>
<dc:identifier>doi:10.1101/2021.10.03.462954</dc:identifier>
<dc:title><![CDATA[Allometric scaling of RNA abundance from genes to communities]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-10-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.10.06.463370v1?rss=1">
<title>
<![CDATA[
Spatial differences in stoichiometry of EGR phosphatase and Microtubule-Associated Stress Protein 1 control root meristem activity during drought stress. 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.10.06.463370v1?rss=1</link>
<description><![CDATA[
During moderate severity drought and low water potential ({psi}w) stress, poorly understood signaling mechanisms restrict both meristem cell division and subsequent cell expansion. We found that the Clade E Growth-Regulating 2 (EGR2) protein phosphatase and Microtubule Associated Stress Protein 1 (MASP1) differed in their stoichiometry of expression across the root meristem and had opposing effects on root meristem activity at low {psi}w. Ectopic MASP1 or EGR expression increased or decreased, respectively, root meristem size and root elongation during low {psi}w stress. This, along with the ability of phosphomimic MASP1 to overcome EGR suppression of root meristem size and observation that ectopic EGR expression had no effect on unstressed plants, indicated that during low {psi}w EGR activation and attenuation of MASP1 phosphorylation in their overlapping zone of expression determines root meristem size and activity. Ectopic EGR expression also decreased root cell size at low {psi}w. Conversely, both the egr1-1egr2-1 and egr1-1egr2-1masp1-1 mutants had similarly increased root cell size; but, only egr1-1egr2-1 had increased cell division. These observations demonstrated that EGRs affect meristem activity via MASP1 but affect cell expansion via other mechanisms. Interestingly, EGR2 was highly expressed in the root cortex, a cell type important for growth regulation and environmental response.

One Sentence SummarySpatial differences in EGR-MASP1 expression and control of MASP1 phosphorylation adjust root meristem activity to regulate growth during drought stress.

The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantcell.org) is: Paul E. Verslues (paulv@gate.sinica.edu.tw).
]]></description>
<dc:creator>Longkumer, T.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Biancucci, M.</dc:creator>
<dc:creator>Badiger, B. G.</dc:creator>
<dc:creator>Verslues, P. E.</dc:creator>
<dc:date>2021-10-07</dc:date>
<dc:identifier>doi:10.1101/2021.10.06.463370</dc:identifier>
<dc:title><![CDATA[Spatial differences in stoichiometry of EGR phosphatase and Microtubule-Associated Stress Protein 1 control root meristem activity during drought stress.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-10-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.10.08.463626v1?rss=1">
<title>
<![CDATA[
Development of transcriptomics-based eukaryotes growth rate indices 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.10.08.463626v1?rss=1</link>
<description><![CDATA[
O_LIGrowth rate estimation is important to understand the flow of energy and nutrient elements in an ecosystem, but it has remained challenging, especially on microscopic organisms.
C_LIO_LIIn this study, we propose four growth rate indices that use mRNA abundance ratios between nuclear and mitochondrial genes: (1) total nuclear and mitochondrial mRNA ratio (Nuc:Mito-TmRNA), (2) nuclear and mitochondrial ribosomal protein mRNA ratio (Nuc:Mito-RPmRNA), (3) gene ontology (GO) terms and total mitochondrial mRNA ratios and (4) nuclear and mitochondrial specific gene mRNA ratio. We examine these proposed ratios using RNA-Seq datasets of Daphnia magna and Saccharomyces cerevisiae.
C_LIO_LIThe results showed that both Nuc:Mito-TmRNA and Nuc:Mito-RPmRNA ratio indices showed significant correlations with the growth rate for both species. A large number of GO terms mRNA ratios showed significant correlations with the growth rate of S. cerevisiae. Lastly, we identified mRNA ratios of several specific nuclear and mitochondrial gene pairs that showed significant correlations.
C_LIO_LIWe foresee future implications for the proposed mRNA ratios used in metatranscriptome analyses to estimate the growth rate of communities and species.
C_LI
]]></description>
<dc:creator>Kong, W.-L.</dc:creator>
<dc:creator>Machida, R. J.</dc:creator>
<dc:date>2021-10-09</dc:date>
<dc:identifier>doi:10.1101/2021.10.08.463626</dc:identifier>
<dc:title><![CDATA[Development of transcriptomics-based eukaryotes growth rate indices]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-10-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.10.09.463787v1?rss=1">
<title>
<![CDATA[
Trade-off between competition ability and invulnerability to predation in marine microbes; protist grazing versus viral lysis effects 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.10.09.463787v1?rss=1</link>
<description><![CDATA[
Trade-offs between competition ability and invulnerability to predation are important mechanisms explaining how predation promotes bacterial diversity. However, existence of these trade-offs has apparently not been investigated in natural marine bacterial communities. Here, we address this question with growth-based measurements for each marine bacterial taxon by conducting on-board dilution experiments to manipulate predation pressure and using high-throughput sequencing to assess the response of bacterial communities. We determined that bacterial taxa with a higher predation-free growth rate were accompanied with higher predation-caused mortality, supporting existence of competitiveness-invulnerability trade-off. This trade-off was stronger and more consistent under viral lysis than protist grazing. In addition, predation generally flattened out the rank-abundance distribution and increased the evenness and richness of the bacterial community. These findings supported the "Kill-the-Winner" hypothesis. All experiments supported a significant competitiveness-invulnerability trade-off, but there was substantial variation among bacterial communities in response to predation across experiments conducted in various sites and seasons. Therefore, we inferred that the Kill-the-Winner hypothesis is important but likely not the only deterministic mechanism explaining how predation shapes bacterial assemblages in natural marine systems.
]]></description>
<dc:creator>Yang, J. W.</dc:creator>
<dc:creator>Chang, F.-H.</dc:creator>
<dc:creator>Yeh, Y.-C.</dc:creator>
<dc:creator>Tsai, A.-Y.</dc:creator>
<dc:creator>Chiang, K.-P.</dc:creator>
<dc:creator>Shiah, F.-K.</dc:creator>
<dc:creator>Gong, G.-C.</dc:creator>
<dc:creator>Hsieh, C.-h.</dc:creator>
<dc:date>2021-10-09</dc:date>
<dc:identifier>doi:10.1101/2021.10.09.463787</dc:identifier>
<dc:title><![CDATA[Trade-off between competition ability and invulnerability to predation in marine microbes; protist grazing versus viral lysis effects]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-10-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.10.11.463889v1?rss=1">
<title>
<![CDATA[
Dynamin-2 Phosphorylation as A Critical Regulatory Target of Bin1 and GSK3α for Endocytosis in Muscle 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.10.11.463889v1?rss=1</link>
<description><![CDATA[
Tight regulation of endocytosis ensures accurate control of cellular signaling and membrane dynamics, which are crucial for tissue morphogenesis and functions. Mutations of Bin1 and dynamin-2 (Dyn2), proteins that generate membrane curvature and sever endocytic invaginations, respectively, cause progressive hereditary myopathy. Here, we show that Bin1 inhibits Dyn2 via direct interaction of its SRC Homology 3 (SH3) domain with the proline-rich domain (PRD) of Dyn2. Phosphorylation of S848 of Dyn2 by GSK3, a kinase downstream of insulin signaling, relieves Dyn2 from the inhibition of Bin1 and promotes endocytosis in muscle. Mutations of Bin1 associated with centronuclear myopathy disrupt its inhibition of Dyn2, thereby exaggerating Dyn2 fission activity and causing excessive fragmentation of T-tubules in the muscle cells. Our work reveals how Bin1-Dyn2 interaction fine-tunes membrane remodeling at the molecular level, and lay the foundation for future exploration of endocytic regulation and hereditary muscle diseases.
]]></description>
<dc:creator>Laiman, J.</dc:creator>
<dc:creator>Loh, J.</dc:creator>
<dc:creator>Tang, W.-C.</dc:creator>
<dc:creator>Chuang, M.-C.</dc:creator>
<dc:creator>Liu, H.-K.</dc:creator>
<dc:creator>Chen, B.-C.</dc:creator>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Chuang, L.-M.</dc:creator>
<dc:creator>Liu, Y.-W.</dc:creator>
<dc:date>2021-10-11</dc:date>
<dc:identifier>doi:10.1101/2021.10.11.463889</dc:identifier>
<dc:title><![CDATA[Dynamin-2 Phosphorylation as A Critical Regulatory Target of Bin1 and GSK3α for Endocytosis in Muscle]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-10-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.10.16.464627v1?rss=1">
<title>
<![CDATA[
Single-cell transcriptomics unveils xylem cell development and evolution 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.10.16.464627v1?rss=1</link>
<description><![CDATA[
As the most abundant tissue on Earth1, xylem is responsible for lateral growth in plants. Typical xylem has a radial system composed of ray parenchyma cells and an axial system of fusiform cells2. In most angiosperms, fusiform cells are a combination of vessel elements for water transportation and libriform fibers for mechanical support, while both functions are performed together by tracheids in other vascular plants2. However, little is known about the developmental programs and evolutionary relationships of these xylem cell types. Through both single-cell and laser-capture microdissection transcriptomic profiling, here we demonstrate the developmental lineages of ray and fusiform cells in stem-differentiating xylem across four divergent woody angiosperms. Cross-species analyses of single-cell trajectories reveal highly conserved ray, yet variable fusiform, lineages across angiosperms. Core eudicots Populus trichocarpa and Eucalyptus grandis share nearly identical fusiform lineages. The tracheids in the basal eudicot Trochodendron aralioides, an evolutionarily reversed character3, 4, exhibit strong transcriptomic similarity to vessel elements but not libriform fibers, suggesting that water transportation, instead of mechanical support, is the major feature. We also found that the more basal angiosperm Liriodendron chinense has a fusiform lineage distinct from that in core eudicots. This evo-developmental framework provides a comprehensive understanding of the formation of xylem cell lineages across multiple plant species spanning over a hundred million years of evolutionary history5.
]]></description>
<dc:creator>Tung, C.-C.</dc:creator>
<dc:creator>Kuo, S.-C.</dc:creator>
<dc:creator>Yang, C.-L.</dc:creator>
<dc:creator>Huang, C.-E.</dc:creator>
<dc:creator>Yu, J.-H.</dc:creator>
<dc:creator>Sun, Y.-H.</dc:creator>
<dc:creator>Shuai, P.</dc:creator>
<dc:creator>Su, J.-C.</dc:creator>
<dc:creator>Ku, C.</dc:creator>
<dc:creator>Lin, Y.-C. J.</dc:creator>
<dc:date>2021-10-16</dc:date>
<dc:identifier>doi:10.1101/2021.10.16.464627</dc:identifier>
<dc:title><![CDATA[Single-cell transcriptomics unveils xylem cell development and evolution]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-10-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.10.25.465649v1?rss=1">
<title>
<![CDATA[
Cancer malignancy is correlated with up-regulation of PCYT2-mediated glycerol phosphate modification of α-dystroglycan 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.10.25.465649v1?rss=1</link>
<description><![CDATA[
The dystrophin-glycoprotein complex connects the cytoskeleton with base membrane components such as laminin through unique O-glycans displayed on -dystroglycan (-DG). Genetic impairment of elongation of these glycans causes congenital muscular dystrophies. We previously identified that glycerol phosphate (GroP) can cap the core part of the -DG O-glycans and terminate their further elongation. This study examined the possible roles of the GroP modification in cancer malignancy, focusing on colorectal cancer. We found that the GroP modification critically depends on PCYT2, which serves as CDP-Gro synthase. Furthermore, we identified a significant positive correlation between cancer progression and GroP modification, which also correlated positively with PCYT2 expression. Moreover, we demonstrate that GroP modification promotes the migration of cancer cells. Based on these findings, we propose that the GroP modification by PCYT2 disrupts the glycan-mediated cell adhesion to the extracellular matrix and thereby enhances cancer metastasis. Thus, the present study suggests the possibility of novel approaches for cancer treatment by targeting the PCYT2-mediated GroP modification.
]]></description>
<dc:creator>Umezawa, F.</dc:creator>
<dc:creator>Natsume, M.</dc:creator>
<dc:creator>Fukusada, S.</dc:creator>
<dc:creator>Nakajima, K.</dc:creator>
<dc:creator>Yamasaki, F.</dc:creator>
<dc:creator>Kawashima, H.</dc:creator>
<dc:creator>Kuo, C.-W.</dc:creator>
<dc:creator>Khoo, K.-H.</dc:creator>
<dc:creator>Shimura, T.</dc:creator>
<dc:creator>Yagi, H.</dc:creator>
<dc:creator>Kato, K.</dc:creator>
<dc:date>2021-10-25</dc:date>
<dc:identifier>doi:10.1101/2021.10.25.465649</dc:identifier>
<dc:title><![CDATA[Cancer malignancy is correlated with up-regulation of PCYT2-mediated glycerol phosphate modification of α-dystroglycan]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-10-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.10.26.465869v1?rss=1">
<title>
<![CDATA[
Prevalent sex ratio bias in Caenorhabditis nematodes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.10.26.465869v1?rss=1</link>
<description><![CDATA[
Although equal sex ratio is ubiquitous and represents an equilibrium in evolutionary theory, biased sex ratios are predicted for certain local conditions. Cases of sex ratio bias have been mostly reported for single species, but little is known about its evolution above the species level. Here, we surveyed progeny sex ratios in 23 species of the nematode genus Caenorhabditis, including 19 for which we tested multiple strains. For the species with multiple strains, 5 species had female-biased and 2 had non-biased sex ratios in all strains, respectively. The other 12 species showed polymorphic sex ratios across strains. Female-biased sex ratios could be due to sperm competition whereby X-bearing sperm outcompete nullo-X sperm during fertilization. In this model, when sperm are limited allowing all sperm to be used, sex ratios are expected to be equal. However, in assays limiting mating to a few hours, most strains showed similarly biased sex ratios compared to unlimited mating experiments, except that one C. becei strain showed significantly reduced female bias compared to unlimited mating. Our study shows frequent polymorphism in sex ratios within Caenorhabditis species and that sperm competition alone cannot explain the sex ratio bias.
]]></description>
<dc:creator>Lo, Y.-H.</dc:creator>
<dc:creator>Huang, Y.</dc:creator>
<dc:creator>Le, T. S.</dc:creator>
<dc:creator>Hsu, J.-C.</dc:creator>
<dc:creator>Yang, F.-J.</dc:creator>
<dc:creator>Chang, T.</dc:creator>
<dc:creator>Braendle, C.</dc:creator>
<dc:creator>Wang, J.</dc:creator>
<dc:date>2021-10-26</dc:date>
<dc:identifier>doi:10.1101/2021.10.26.465869</dc:identifier>
<dc:title><![CDATA[Prevalent sex ratio bias in Caenorhabditis nematodes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-10-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.10.31.466697v1?rss=1">
<title>
<![CDATA[
Microbiome restructuring: dominant coral bacterium Endozoicomonas species display differential adaptive capabilities to environmental changes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.10.31.466697v1?rss=1</link>
<description><![CDATA[
Bacteria in the coral microbiome play a crucial role in determining coral health and fitness, and the coral host often restructures its microbiome composition in response to external factors. An important but often neglected factor determining this microbiome restructuring is the capacity of microbiome members to adapt to a new environment. To address this issue, we examined how the microbiome structure of Acropora muricata corals changed over 9 months following a reciprocal transplant experiment. Using a combination of metabarcoding, genomics, and comparative genomics approaches, we found that coral colonies separated by a small distance harbored different dominant Endozoicomonas related phylotypes belonging to two different species, including a novel species, Candidatus Endozoicomonas penghunesis 4G, whose chromosome level (complete) genome was also sequenced in this study. Furthermore, the two dominant Endozoicomonas species showed varied adaptation capabilities when coral colonies were transplanted in a new environment. The differential adaptation capabilities of dominant members of the microbiome can a) provide distinct advantages to coral hosts when subjected to changing environmental conditions and b) have positive implications for future reefs.
]]></description>
<dc:creator>Tandon, K.</dc:creator>
<dc:creator>Chiou, Y.-J.</dc:creator>
<dc:creator>Yu, S.-P.</dc:creator>
<dc:creator>Hsieh, H. J.</dc:creator>
<dc:creator>Lu, C.-Y.</dc:creator>
<dc:creator>Hsu, M.-T.</dc:creator>
<dc:creator>Chiang, P.-W.</dc:creator>
<dc:creator>Chen, H.-J.</dc:creator>
<dc:creator>Wada, N.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:date>2021-11-01</dc:date>
<dc:identifier>doi:10.1101/2021.10.31.466697</dc:identifier>
<dc:title><![CDATA[Microbiome restructuring: dominant coral bacterium Endozoicomonas species display differential adaptive capabilities to environmental changes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-11-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.11.02.466889v1?rss=1">
<title>
<![CDATA[
Maize AFP1 confers antifungal activity by inhibiting chitin deacetylases from a broad range of fungi 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.11.02.466889v1?rss=1</link>
<description><![CDATA[
Adapted plant pathogenic fungi deacetylate chitin to chitosan to avoid host perception and disarm the chitin-triggered plant immunity. Whether plants have evolved factors to counteract this fungal evasion mechanism in the plant-pathogen interface remains obscure. Here, we decipher the underlying mechanism of maize cysteine-rich receptor-like secreted proteins (CRRSPs)-AFP1, which exhibits mannose-binding dependent antifungal activity. AFP1 initials the action by binding to specific sites on the surface of yeast-like cells, filaments, and germinated spores of the biotrophic fungi Ustilago maydis. This could result in fungal cell growth and cell budding inhibition, delaying spore germination and subsequently reducing fungal viability in a mannose-binding dependence manner. The antifungal activity of AFP1 is conferred by its interaction with the PMT-dependent mannosylated chitin deacetylases (CDAs) and interfering with the conversion of chitin. Our finding that AFP1 targets CDAs from pathogenic fungi and nonpathogenic budding yeast suggests a potential application of the CRRSP in combating fungal diseases and reducing threats posed by the fungal kingdom.
]]></description>
<dc:creator>Ma, L.-S.</dc:creator>
<dc:creator>Tsai, W.-L.</dc:creator>
<dc:creator>Kalunke, R. M.</dc:creator>
<dc:creator>Xu, M.-Y.</dc:creator>
<dc:creator>Lin, Y.-H.</dc:creator>
<dc:creator>Damei, F. A.</dc:creator>
<dc:creator>Lee, H.-C.</dc:creator>
<dc:date>2021-11-02</dc:date>
<dc:identifier>doi:10.1101/2021.11.02.466889</dc:identifier>
<dc:title><![CDATA[Maize AFP1 confers antifungal activity by inhibiting chitin deacetylases from a broad range of fungi]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-11-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.11.02.466947v1?rss=1">
<title>
<![CDATA[
DNA-free CRISPR-Cas9 gene editing of tetraploid tomatoes using protoplast regeneration 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.11.02.466947v1?rss=1</link>
<description><![CDATA[
Wild tomatoes are important genomic resources for tomato research and breeding. Development of a foreign DNA-free CRISPR-Cas delivery system has potential to mitigate public concern about genetically modified organisms. Here, we established a DNA-free protoplast regeneration and CRISPR-Cas9 genome editing system for Solanum peruvianum, an important resource for tomato introgression breeding. We generated mutants for genes involved in small interfering RNAs (siRNA) biogenesis, RNA-DEPENDENT RNA POLYMERASE 6 (SpRDR6) and SUPPRESSOR OF GENE SILENCING 3 (SpSGS3); pathogen-related peptide precursors, PATHOGENESIS-RELATED PROTEIN-1 (SpPR-1) and PROSYSTEMIN (SpProsys); and fungal resistance (MILDEW RESISTANT LOCUS O, SpMlo1) using diploid or tetraploid protoplasts derived from in vitro-grown shoots. The ploidy level of these regenerants was not affected by PEG-calcium-mediated transfection, CRISPR reagents, or the target genes. By karyotyping and whole genome sequencing analysis, we confirmed that CRISPR-Cas9 editing did not introduce chromosomal changes or unintended genome editing sites. All mutated genes in both diploid and tetraploid regenerants were heritable in the next generation. spsgs3 null T0 regenerants and sprdr6 null T1 progeny had wiry, sterile phenotypes in both diploid and tetraploid lines. The sterility of the spsgs3 null mutant was partially rescued, and fruits were obtained by grafting to wild-type stock and pollination with wild-type pollen. The resulting seeds contained the mutated alleles. Tomato yellow leaf curl virus proliferated at higher levels in spsgs3 and sprdr6 mutants than in the wild type. Therefore, this protoplast regeneration technique should greatly facilitate tomato polyploidization and enable the use of CRISPR-Cas for S. peruvianum domestication and tomato breeding.

One-sentence summaryDNA-free CRISPR-Cas9 genome editing in wild tomatoes creates stable and inheritable diploid and tetraploid regenerants.
]]></description>
<dc:creator>Hsu, C.-T.</dc:creator>
<dc:creator>Yuan, Y.-H.</dc:creator>
<dc:creator>Zheng, P.-X.</dc:creator>
<dc:creator>Wu, F.-H.</dc:creator>
<dc:creator>Cheng, Q.-W.</dc:creator>
<dc:creator>Wu, Y.-L.</dc:creator>
<dc:creator>Lin, S.</dc:creator>
<dc:creator>Yue, J.-J.</dc:creator>
<dc:creator>Cheng, Y.-H.</dc:creator>
<dc:creator>Lin, S.-I. L.</dc:creator>
<dc:creator>Shih, M.-C.</dc:creator>
<dc:creator>Sheen, J.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Lin, C.-S.</dc:creator>
<dc:date>2021-11-02</dc:date>
<dc:identifier>doi:10.1101/2021.11.02.466947</dc:identifier>
<dc:title><![CDATA[DNA-free CRISPR-Cas9 gene editing of tetraploid tomatoes using protoplast regeneration]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-11-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.11.04.467238v1?rss=1">
<title>
<![CDATA[
Thymic macrophages consist of two populations with distinct localization and origin 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.11.04.467238v1?rss=1</link>
<description><![CDATA[
Tissue-resident macrophages are essential to protect from pathogen invasion and maintain organ homeostasis. The ability of thymic macrophages to engulf apoptotic thymocytes is well appreciated, but little is known about their ontogeny, maintenance, and diversity. Here, we characterized the surface phenotype and transcriptional profile of these cells and defined their expression signature. Thymic macrophages were most closely related to spleen red pulp macrophages and Kupffer cells and shared the expression of the transcription factor SpiC with these cells. Single-cell RNA sequencing showed that the macrophages in the adult thymus are composed of two populations distinguished by the expression of Timd4 and Cx3cr1. Remarkably, Timd4+ cells were located in the cortex, while Cx3cr1+ macrophages were restricted to the medulla and the cortico-medullary junction. Using shield chimeras, transplantation of embryonic thymuses, and genetic fate mapping, we found that the two populations have distinct origins. Timd4+ thymic macrophages are of embryonic origin, while Cx3cr1+ macrophages are derived from adult hematopoietic stem cells. Aging has a profound effect on the macrophages in the thymus. Timd4+ cells underwent gradual attrition, while Cx3cr1+ cells slowly accumulated with age and, in older mice, were the dominant macrophage population in the thymus. Altogether, our work defines the phenotype, origin, and diversity of thymic macrophages.
]]></description>
<dc:creator>Zhou, T.-A.</dc:creator>
<dc:creator>Hsu, H.-P.</dc:creator>
<dc:creator>Tu, Y.-H.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Chen, N.-J.</dc:creator>
<dc:creator>Tsai, J.-W.</dc:creator>
<dc:creator>Robey, E. A.</dc:creator>
<dc:creator>Huang, H.-C.</dc:creator>
<dc:creator>Hsu, C.-L.</dc:creator>
<dc:creator>Dzhagalov, I. L.</dc:creator>
<dc:date>2021-11-04</dc:date>
<dc:identifier>doi:10.1101/2021.11.04.467238</dc:identifier>
<dc:title><![CDATA[Thymic macrophages consist of two populations with distinct localization and origin]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-11-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.11.15.468391v1?rss=1">
<title>
<![CDATA[
An atypical NLR protein modulates the NRC immune receptor network 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.11.15.468391v1?rss=1</link>
<description><![CDATA[
The NRC immune receptor network has evolved in asterid plants from a pair of linked genes into a genetically dispersed and phylogenetically structured network of sensor and helper NLR (nucleotide-binding domain and leucine-rich repeat-containing) proteins. In some species, such as the model plant Nicotiana benthamiana and other Solanaceae, the NRC network forms up to half of the NLRome, and NRCs are scattered throughout the genome in gene clusters of varying complexities. Here, we describe NRCX, an atypical, but essential member of the NRC family that lacks canonical features of these NLR helper proteins, such as a functional N-terminal MADA motif and the capacity to trigger autoimmunity. In contrast to other NRCs, systemic gene silencing of NRCX markedly impairs plant growth resulting in a dwarf phenotype. Remarkably, dwarfism of NRCX silenced plants is partially dependent on NRCX paralogs NRC2 and NRC3, but not NRC4. Despite its negative impact on plant growth when silenced systemically, transient RNA interference of NRCX in mature N. benthamiana leaves doesnt result in visible cell death phenotypes. However, alteration of NRCX expression modulates the hypersensitive response mediated by NRC2 and NRC3 in a manner consistent with a negative role for NRCX in the NRC network. We conclude that NRCX is an atypical member of the NRC network that has evolved to contribute to the homeostasis of this genetically unlinked NLR network.
]]></description>
<dc:creator>Adachi, H.</dc:creator>
<dc:creator>Sakai, T.</dc:creator>
<dc:creator>Harant, A.</dc:creator>
<dc:creator>Duggan, C.</dc:creator>
<dc:creator>Bozkurt, T.</dc:creator>
<dc:creator>Wu, C.-H.</dc:creator>
<dc:creator>Kamoun, S.</dc:creator>
<dc:date>2021-11-15</dc:date>
<dc:identifier>doi:10.1101/2021.11.15.468391</dc:identifier>
<dc:title><![CDATA[An atypical NLR protein modulates the NRC immune receptor network]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-11-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.11.16.468793v1?rss=1">
<title>
<![CDATA[
Electrochemical biosensors based on peptide-kinase interactions at the kinase docking site 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.11.16.468793v1?rss=1</link>
<description><![CDATA[
Kinases are important cancer biomarkers and are conventionally detected based on their catalytic activity. Kinases regulate cellular activities by phosphorylation of motif-specific multiple substrate proteins, resulting in lack of selectivity of activity-based kinase biosensors. We present an alternative approach of sensing kinases based on the interactions of their allosteric docking sites with a specific partner protein. The new approach was demonstrated for the ERK2 kinase and its substrate ELK-1. A peptide derived from ELK-1 was bound to a gold electrode and ERK2 sensing was performed by electrochemical impedance spectroscopy. The sensors showed high level of target selectivity for ERK2 when compared with p38{gamma} kinase and BSA. ERK2 was detected in its cellular concentration range, 0.2-8.0 M. Using the flexibility of peptide design, our method is generic for developing sensitive and substrate-specific biosensors and other disease-related enzymes based on their interactions.



O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/468793v1_ufig1.gif" ALT="Figure 1">
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]]></description>
<dc:creator>Joshi, P. N.</dc:creator>
<dc:creator>Mervinetsky, E.</dc:creator>
<dc:creator>Solomon, O.</dc:creator>
<dc:creator>Chen, Y.-J.</dc:creator>
<dc:creator>Yitzchaik, S.</dc:creator>
<dc:creator>Friedler, A.</dc:creator>
<dc:date>2021-11-16</dc:date>
<dc:identifier>doi:10.1101/2021.11.16.468793</dc:identifier>
<dc:title><![CDATA[Electrochemical biosensors based on peptide-kinase interactions at the kinase docking site]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-11-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.11.21.469320v1?rss=1">
<title>
<![CDATA[
Laser Ablation and Fluid Flows Show a Single Force Mechanism Governs Spindle Positioning 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.11.21.469320v1?rss=1</link>
<description><![CDATA[
Few techniques are available for elucidating the nature of forces that drive subcellular behaviors. Here we develop two complementary ones: 1) femtosecond stereotactic laser ablation (FESLA), which rapidly creates complex cuts of subcellular structures, thereby allowing precise dissection of when, where, and in what direction forces are generated; and 2) assessment of subcellular fluid flows, by comparing direct flow measurements, using microinjected fluorescent nanodiamonds, to large-scale fluid-structure simulations of different models of force transduction. We apply these to study centrosomes in Caenorhabditis elegans early embryos, and use the data to construct a biophysically-based model of centrosome dynamics. Taken together, we demonstrate that cortical pulling forces provide a general explanation for many behaviors mediated by centrosomes, including pronuclear migration/centration and rotation, metaphase spindle positioning, asymmetric spindle elongation and spindle oscillations. In sum, this work establishes new methodologies for disentangling the forces responsible for cell biological phenomena.
]]></description>
<dc:creator>Wu, H.-Y.</dc:creator>
<dc:creator>Kabacaoglu, G.</dc:creator>
<dc:creator>Nazockdast, E.</dc:creator>
<dc:creator>Chang, H.-C.</dc:creator>
<dc:creator>Shelley, M. J.</dc:creator>
<dc:creator>Needleman, D. J.</dc:creator>
<dc:date>2021-11-22</dc:date>
<dc:identifier>doi:10.1101/2021.11.21.469320</dc:identifier>
<dc:title><![CDATA[Laser Ablation and Fluid Flows Show a Single Force Mechanism Governs Spindle Positioning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-11-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.11.22.469634v1?rss=1">
<title>
<![CDATA[
Discovering Novel Antimicrobial Peptides in Generative Adversarial Network 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.11.22.469634v1?rss=1</link>
<description><![CDATA[
Due to the growing number of clinical antibiotic resistance cases in recent years, novel antimicrobial peptides (AMPs) can become ideal for next-generation antibiotics. This study trained a deep convolutional generative adversarial network (GAN) with known AMPs to generate novel AMP candidates. The quality of the GAN-designed peptides was evaluated in silico, and eight of them named GAN-pep 1[~]8 were chosen to be synthesized for further experiments. Disk diffusion testing and minimum inhibitory concentration (MIC) determination were used to determine the antibacterial effects of the synthesized GAN-designed peptides. Seven out of the eight synthesized GAN-designed peptides showed antibacterial activities.

Additionally, GAN-pep 3 and GAN-pep 8 had a broad spectrum of antibacterial effects. Both of them were also effective against antibiotic-resistant bacteria strains such as methicillin-resistant Staphylococcus aureus (S. aureus) and carbapenem-resistant Pseudomonas aeruginosa (P. aeruginosa). GAN-pep 3, the most promising GAN-designed peptide candidate, had low MICs against all the tested bacteria.
]]></description>
<dc:creator>Lin, T.-T.</dc:creator>
<dc:creator>Yang, L.-Y.</dc:creator>
<dc:creator>Wang, C.-T.</dc:creator>
<dc:creator>Lai, G.-W.</dc:creator>
<dc:creator>Ko, C.-F.</dc:creator>
<dc:creator>Shih, Y.-H.</dc:creator>
<dc:creator>Chen, S.-H.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:date>2021-11-23</dc:date>
<dc:identifier>doi:10.1101/2021.11.22.469634</dc:identifier>
<dc:title><![CDATA[Discovering Novel Antimicrobial Peptides in Generative Adversarial Network]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-11-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.11.29.470292v1?rss=1">
<title>
<![CDATA[
Developing an Antiviral Peptides Predictor with Generative Adversarial Network Data Augmentation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.11.29.470292v1?rss=1</link>
<description><![CDATA[
MotivationNew antiviral drugs are urgently needed because of emerging viral pathogens increasing severity and drug resistance. Antiviral peptides (AVPs) have multiple antiviral properties and are appealing candidates for antiviral drug development. We developed a sequence-based binary classifier to identify whether an unknown short peptide has AVP activity. We collected AVP sequence data from six existing databases. We used a generative adversarial network to augment the number of AVPs in the positive training dataset and allow our deep convolutional neural network model to train on more data.

ResultsOur classifier achieved outstanding performance on the testing dataset compared with other state-of-the-art classifiers. We deployed our trained classifier on a user-friendly web server.

Availability and implementationAI4AVP is freely accessible at http://axp.iis.sinica.edu.tw/AI4AVP/

Contactcylin@iis.sinica.edu.tw

Supplementary informationSupplementary data is also available.
]]></description>
<dc:creator>Lin, T.-T.</dc:creator>
<dc:creator>Sun, Y.-Y.</dc:creator>
<dc:creator>Cheng, W.-C.</dc:creator>
<dc:creator>Lu, I.-H.</dc:creator>
<dc:creator>Chen, S.-H.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:date>2021-11-30</dc:date>
<dc:identifier>doi:10.1101/2021.11.29.470292</dc:identifier>
<dc:title><![CDATA[Developing an Antiviral Peptides Predictor with Generative Adversarial Network Data Augmentation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-11-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.12.07.470215v1?rss=1">
<title>
<![CDATA[
A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.12.07.470215v1?rss=1</link>
<description><![CDATA[
A major challenge of genome-wide association studies (GWAS) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations, and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels, and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. Two prioritized genes, CREBRF and RRBP1, show convergent evidence across functional datasets supporting their roles in lipid biology.
]]></description>
<dc:creator>Ramdas, S.</dc:creator>
<dc:creator>Judd, J.</dc:creator>
<dc:creator>Graham, S. E.</dc:creator>
<dc:creator>Kanoni, S.</dc:creator>
<dc:creator>Wang, Y.</dc:creator>
<dc:creator>Surakka, I.</dc:creator>
<dc:creator>Wenz, B.</dc:creator>
<dc:creator>Clarke, S. L.</dc:creator>
<dc:creator>Chesi, A.</dc:creator>
<dc:creator>Wells, A.</dc:creator>
<dc:creator>Bhatti, K. F.</dc:creator>
<dc:creator>Vedantam, S.</dc:creator>
<dc:creator>Winkler, T. W.</dc:creator>
<dc:creator>Locke, A. E.</dc:creator>
<dc:creator>Marouli, E.</dc:creator>
<dc:creator>Zajac, G. J.</dc:creator>
<dc:creator>Wu, K.-H. H.</dc:creator>
<dc:creator>Ntalla, I.</dc:creator>
<dc:creator>Hui, Q.</dc:creator>
<dc:creator>Klarin, D.</dc:creator>
<dc:creator>Hilliard, A. T.</dc:creator>
<dc:creator>Wang, Z.</dc:creator>
<dc:creator>Xue, C.</dc:creator>
<dc:creator>Thorleifsson, G.</dc:creator>
<dc:creator>Helgadottir, A.</dc:creator>
<dc:creator>Gudbjartsson, D. F.</dc:creator>
<dc:creator>Holm, H.</dc:creator>
<dc:creator>Olafsson, I.</dc:creator>
<dc:creator>Hwang, M. Y.</dc:creator>
<dc:creator>Han, S.</dc:creator>
<dc:creator>Akiyama, M.</dc:creator>
<dc:creator>Sakaue, S.</dc:creator>
<dc:creator>Terao, C.</dc:creator>
<dc:creator>Kanai, M.</dc:creator>
<dc:creator>Zhou, W.</dc:creator>
<dc:creator>Brumpton, B. M.</dc:creator>
<dc:creator>Rasheed, H.</dc:creator>
<dc:creator>Havulinna, A. S.</dc:creator>
<dc:creator>Veturi, Y.</dc:creator>
<dc:creator>Pacheco, J. A.</dc:creator>
<dc:creator>Rosenthal, E. A.</dc:creator>
<dc:creator>Lingren, T.</dc:creator>
<dc:creator>Feng, Q.</dc:creator>
<dc:creator>Kullo, I. J.</dc:creator>
<dc:creator>Narita, A.</dc:creator>
<dc:creator>Takayama,</dc:creator>
<dc:date>2021-12-08</dc:date>
<dc:identifier>doi:10.1101/2021.12.07.470215</dc:identifier>
<dc:title><![CDATA[A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-12-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.12.07.471020v1?rss=1">
<title>
<![CDATA[
BSImp: imputing partially observed methylation patterns for evaluating methylation heterogeneity 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.12.07.471020v1?rss=1</link>
<description><![CDATA[
DNA methylation is one of the most studied epigenetic modifications that has applications ranging from transcriptional regulation to aging, and can be assessed by bisulfite sequencing (BS-seq) at single base-pair resolution. The permutations of methylation statuses at bisulfite converted reads reflect the methylation patterns of individual cells. These patterns at specific genomic locations are sought to be indicative of cellular heterogeneity within a cellular population, which are predictive of developments and diseases; therefore, methylation heterogeneity has potentials in early detection of these changes. Computational methods have been developed to assess methylation heterogeneity using methylation patterns formed by four CpGs, but the nature of shotgun sequencing often give partially observed patterns, which makes very limited data available for downstream analysis. While many programs are developed to impute methylation levels genomewide, currently there is only one method developed for recovering partially observed methylation patterns; however, the program needs lots of data to train and cannot be used directly; therefore, we developed a probabilistic-based imputation method that uses information from neighbouring sites to recover partially observed methylation patterns speedily. It is demonstrated to allow for the evaluation of methylation heterogeneity at three times more regions genome-wide with high accuracy for data with moderate depth. To make it more user-friendly we also provide a computational pipeline for genome-screening, which can be used in both evaluating methylation levels and profiling methylation patterns genomewide for all cytosine contexts, which is the first of its kind. Our method allows for accurate estimation of methylation levels and makes evaluating methylation heterogeneity available for much more data with reasonable coverage, which has important implications in using methylation heterogeneity for monitoring changes within the cellular populations that were impossible to detect for the assessment of development and diseases.
]]></description>
<dc:creator>Chang, Y.-T.</dc:creator>
<dc:creator>Yen, M.-R.</dc:creator>
<dc:creator>Chen, P.-Y.</dc:creator>
<dc:date>2021-12-09</dc:date>
<dc:identifier>doi:10.1101/2021.12.07.471020</dc:identifier>
<dc:title><![CDATA[BSImp: imputing partially observed methylation patterns for evaluating methylation heterogeneity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-12-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.12.07.471703v1?rss=1">
<title>
<![CDATA[
Structural basis for the peptidoglycan editing activity of YfiH 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.12.07.471703v1?rss=1</link>
<description><![CDATA[
Bacterial cells are encased in peptidoglycan (PG), a polymer of disaccharide N-acetyl-glucosamine (GlcNAc) and N-acetyl-muramic acid (MurNAc) cross-linked by peptide stems. PG is synthesized in the cytoplasm as UDP-MurNAc-peptide precursors, of which the amino-acid composition of the peptide is unique, with L-Ala added at the first position in most bacteria but L-Ser or Gly in some bacteria. YfiH is a PG-editing factor whose absence causes misincorporation of L-Ser instead of L-Ala into peptide stems; but its mechanistic function is unknown. Here we report the crystal structures of substrate-bound and product-bound YfiH, showing that YfiH is a cytoplasmic amidase that controls the incorporation of the correct amino acid to the nucleotide precursors by preferentially cleaving the nucleotide precursor byproduct UDP-MurNAc-L-Ser. This work reveals an editing mechanism in the cytoplasmic steps of peptidoglycan biosynthesis.
]]></description>
<dc:creator>Lee, M.-S.</dc:creator>
<dc:creator>Hsieh, K.-Y.</dc:creator>
<dc:creator>Kuo, C.-I.</dc:creator>
<dc:creator>Lee, S.-H.</dc:creator>
<dc:creator>Chang, C.-I.</dc:creator>
<dc:date>2021-12-08</dc:date>
<dc:identifier>doi:10.1101/2021.12.07.471703</dc:identifier>
<dc:title><![CDATA[Structural basis for the peptidoglycan editing activity of YfiH]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-12-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.12.09.471910v1?rss=1">
<title>
<![CDATA[
NITROGEN LIMITATION ADAPTATION functions as a negative regulator of Arabidopsis immunity 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.12.09.471910v1?rss=1</link>
<description><![CDATA[
BackgroundPhosphorus is an important macronutrient required for plant growth and development. It is absorbed through the roots in the form of inorganic phosphate (Pi). To cope with Pi limitation, plants have evolved an array of adaptive mechanisms to facilitate Pi acquisition and protect them from stress caused by Pi starvation. The NITROGEN LIMITATION ADAPTION (NLA) gene plays a key role in the regulation of phosphate starvation responses (PSR), its expression being regulated by the microRNA miR827. Stress caused by Pi limiting conditions might also affect the plants response to pathogen infection. However, cross-talk between phosphate signaling pathways and immune responses remains unclear.

ResultsIn this study, we investigated whether NLA plays a role in Arabidopsis immunity. We show that loss-of-function of NLA and MIR827 overexpression causes an increase in phosphate (Pi) content which results in resistance to infection by the fungal pathogen Plectosphaerella cucumerina. The nla mutant plants accumulated callose in their leaves, a response that is also observed in wild-type plants that have been treated with high Pi. We also show that pathogen infection and treatment with fungal elicitors is accompanied by transcriptional activation of MIR827 and down-regulation of NLA. Upon pathogen challenge, nla plants exhibited higher levels of the phytoalexin camalexin compared to wild type plants. Camalexin level also increases in wild type plants treated with high Pi. Furthermore, the nla mutant plants accumulated salicylic acid (SA) and jasmonic acid (JA) in the absence of pathogen infection whose levels further increased upon pathogen.

ConclusionsThis study shows that NLA acts as a negative regulator of Arabidopsis immunity. Overaccumulation of Pi in nla plants positively affects resistance to infection by fungal pathogens. This piece of information reinforces the idea of signaling convergence between Pi and immune responses for the regulation of disease resistance in Arabidopsis.
]]></description>
<dc:creator>Val Torregrosa, B.</dc:creator>
<dc:creator>Bundo, M.</dc:creator>
<dc:creator>Chiou, T. J.</dc:creator>
<dc:creator>Flors, V.</dc:creator>
<dc:creator>San Segundo, B.</dc:creator>
<dc:date>2021-12-10</dc:date>
<dc:identifier>doi:10.1101/2021.12.09.471910</dc:identifier>
<dc:title><![CDATA[NITROGEN LIMITATION ADAPTATION functions as a negative regulator of Arabidopsis immunity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-12-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.12.09.471930v1?rss=1">
<title>
<![CDATA[
Phosphate-induced resistance to pathogen infection in Arabidopsis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.12.09.471930v1?rss=1</link>
<description><![CDATA[
In nature, plants are concurrently exposed to a number of abiotic and biotic stresses. Our understanding of convergence points between responses to combined biotic/abiotic stress pathways remains, however, rudimentary. Here we show that MIR399 overexpression, loss-of-function of PHO2 (PHOSPHATE2), or treatment with high Pi, is accompanied by an increase in phosphate (Pi) content and accumulation of reactive oxygen species (ROS) in Arabidopsis thaliana. High Pi plants (e.g. miR399 overexpressor, pho2 mutant, and plants grown under high Pi supply) exhibited resistance to infection by necrotrophic and hemibiotrophic fungal pathogens. In the absence of pathogen infection, the expression level of genes in the salicylic acid (SA)- and jasmonic acid (JA)-dependent signaling pathways was higher in high Pi plants compared to wild type plants, which is consistent with increased levels of SA and JA in non-infected high Pi plants. During infection, an opposite regulation in the two branches of the JA pathway (ERF1/PDF1.2 and MYC2/VSP2) occurs in high Pi plants. Thus, while the ERF1-PDF1 branch positively responds to fungal infection, the MYC2/VSP2 branch is negatively regulated during pathogen infection in high Pi plants. This study supports that Pi accumulation promotes resistance to infection by fungal pathogens in Arabidopsis, while providing a basis to better understand crosstalk between Pi signaling and hormonal signalling pathways for modulation of plant immune responses.

Significance statementThis study highlights the importance of phosphate (Pi) in regulating immune responses, hence, disease resistance in Arabidopsis thaliana. Increasing Pi content either by MIR399 overexpression (or loss-of-function of PHOSPHATE2), as well as by Pi treatment enhances resistance to infection by necrotrophic and hemibiotrophic fungal pathogens through modulation of SA- and JA-dependent signaling pathways. These results also support that miR399 functions as a regulator of Arabidopsis immunity.
]]></description>
<dc:creator>Val Torregrosa, B.</dc:creator>
<dc:creator>Bundo, M.</dc:creator>
<dc:creator>Cardoso, H. M.</dc:creator>
<dc:creator>Pages, M. B.</dc:creator>
<dc:creator>Chiou, T. J.</dc:creator>
<dc:creator>Flors, V.</dc:creator>
<dc:creator>San Segundo, B.</dc:creator>
<dc:date>2021-12-09</dc:date>
<dc:identifier>doi:10.1101/2021.12.09.471930</dc:identifier>
<dc:title><![CDATA[Phosphate-induced resistance to pathogen infection in Arabidopsis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-12-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.12.09.472030v1?rss=1">
<title>
<![CDATA[
Analysis of single-cell RNA-sequencing data to identify quiescent and proliferating neural cell populations in Glioblastoma 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.12.09.472030v1?rss=1</link>
<description><![CDATA[
BackgroundDiffuse Glioblastoma (GBM) has high mortality and remains one of the most challenging type of cancer to treat. Identifying and characterizing the cells populations driving tumor growth and therapy resistance has been particularly difficult owing to marked inter and intra tumoral heterogeneity observed in these tumors. These tumorigenic populations contain long lived cells associated with latency, immune evasion and metastasis.

MethodsHere, we analyzed the single-cell RNA-sequencing data of high grade glioblastomas from four different studies using integrated analysis of gene expression patterns, cell cycle stages and copy number variation to identify gene expression signatures associated with quiescent and cycling neuronal tumorigenic cells.

ResultsThe results show that while cycling and quiescent cells are present in GBM of all age groups, they exist in a much larger proportion in pediatric glioblastomas. These cells show similarities in their expression patterns of a number of pluripotency and proliferation related genes. Upon unbiased clustering, these cells explicitly clustered on their cell cycle stage. Quiescent cells in both the groups specifically overexpressed a number of genes for ribosomal protein, while the cycling cells were enriched in the expression of high-mobility group and heterogeneous nuclear ribonucleoprotein group genes. A number of well-known markers of quiescence and proliferation in neurogenesis showed preferential expression in the quiescent and cycling populations identified in our analysis. Through our analysis, we identify ribosomal proteins as key constituents of quiescence in glioblastoma stem cells.

ConclusionsThis study identifies gene signatures common to adult and pediatric glioblastoma quiescent and cycling stem cell niches. Further research elucidating their role in controlling quiescence and proliferation in tumorigenic cells in high grade glioblastoma will open avenues in more effective treatment strategies for glioblastoma patients.
]]></description>
<dc:creator>Vikram, R.</dc:creator>
<dc:creator>Chou, W.-C.</dc:creator>
<dc:creator>Wu, P.-E.</dc:creator>
<dc:creator>Chen, W.-T.</dc:creator>
<dc:creator>Shen, C.-Y.</dc:creator>
<dc:date>2021-12-10</dc:date>
<dc:identifier>doi:10.1101/2021.12.09.472030</dc:identifier>
<dc:title><![CDATA[Analysis of single-cell RNA-sequencing data to identify quiescent and proliferating neural cell populations in Glioblastoma]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-12-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.12.13.472487v1?rss=1">
<title>
<![CDATA[
Nanoscale details of mitochondrial fission revealed by cryo-electron tomography 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.12.13.472487v1?rss=1</link>
<description><![CDATA[
Mitochondrial fission is required for proper segregation during cell division, quality control, and cellular homeostasis (metabolism and energy production). Despite its importance, models of the process remain speculative. Here we apply cryogenic electron tomography to image the nanoscale architecture of mitochondrial fission in mammalian cells. We find that constriction of the inner and outer membranes is coordinated, suggesting that force on both membranes is applied externally. While we observe ER at constriction sites, it did not encircle constrictions. Instead, we find long bundles of both unbranched actin and septin filaments enriched at constrictions. Actin bundles align with the central region of division bridges and septin bundles with the necks on either side. Septin bundles appear to guide microtubules to constriction sites, suggesting, along with autolysosomes observed in the vicinity, a pathway for mitophagy. Together, our results rule out several existing models for mitochondrial fission and provide empirical parameters to inform the development of realistic coarse-grained models in the future.
]]></description>
<dc:creator>Mageswaran, S. K.</dc:creator>
<dc:creator>Grotjahn, D. A.</dc:creator>
<dc:creator>Zeng, X.</dc:creator>
<dc:creator>Barad, B. A.</dc:creator>
<dc:creator>Medina, M. A.</dc:creator>
<dc:creator>Hoang, M. H.</dc:creator>
<dc:creator>Dobro, M. J.</dc:creator>
<dc:creator>Chang, Y.-W.</dc:creator>
<dc:creator>Xu, M.</dc:creator>
<dc:creator>Yang, W. Y.</dc:creator>
<dc:creator>Jensen, G. J.</dc:creator>
<dc:date>2021-12-14</dc:date>
<dc:identifier>doi:10.1101/2021.12.13.472487</dc:identifier>
<dc:title><![CDATA[Nanoscale details of mitochondrial fission revealed by cryo-electron tomography]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-12-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.12.20.473467v1?rss=1">
<title>
<![CDATA[
Genomes of keystone Mortierella species lead to better in silico prediction of soil mycobiome functions from Taiwan's offshore islands 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.12.20.473467v1?rss=1</link>
<description><![CDATA[
The ability to correlate the functional relationship between microbial communities and their environment is critical to understanding microbial ecology. There is emerging knowledge on island biogeography of microbes but how island characteristics influence functions of microbial community remain elusive. Here, we explored soil mycobiomes from nine islands adjacent to Taiwan using ITS2 amplicon sequencing. Geographical distances and island size were positively correlated to dissimilarity in mycobiomes, and we identified 56 zero-radius operational taxonomic units (zOTUs) that were ubiquitously present across all islands, and as few as five Mortierella zOTUs dominate more than half of mycobiomes. Correlation network analyses revealed that seven of the 45 hub species were part of the ubiquitous zOTUs belonging to Mortierella, Trichoderma, Aspergillus, Clonostachys and Staphylotrichum. We sequenced and annotated the genomes of seven Mortierella isolates, and comparative predictions of KEGG orthologues using PICRUSt2 database updated with new genomes increased sequence reads coverage by 62.9% at the genus level. In addition, genes associated with carbohydrate and lipid metabolisms were differentially abundant between islands which remained undetected in the original database. Predicted functional pathways were similar across islands despite their geographical separation, difference in differentially abundant genes and composition. Our approach demonstrated the incorporation of the key taxa genomic data can improve functional gene prediction results and can be readily applied to investigate other niches of interests.
]]></description>
<dc:creator>Lin, Y.-f.</dc:creator>
<dc:creator>Liu, W.-A.</dc:creator>
<dc:creator>Liu, Y.-C.</dc:creator>
<dc:creator>Lee, H.-H.</dc:creator>
<dc:creator>Lin, Y.-J.</dc:creator>
<dc:creator>Chang, E.-H.</dc:creator>
<dc:creator>Lu, M.-Y. J.</dc:creator>
<dc:creator>Chiu, C.-Y.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2021-12-21</dc:date>
<dc:identifier>doi:10.1101/2021.12.20.473467</dc:identifier>
<dc:title><![CDATA[Genomes of keystone Mortierella species lead to better in silico prediction of soil mycobiome functions from Taiwan's offshore islands]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-12-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.12.21.473704v1?rss=1">
<title>
<![CDATA[
The role of the angular gyrus in semantic cognition - A synthesis of five functional neuroimaging studies 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.12.21.473704v1?rss=1</link>
<description><![CDATA[
Semantic knowledge is central to human cognition. The angular gyrus (AG) is widely considered a key brain region for semantic cognition. However, the role of the AG in semantic processing is controversial. Key controversies concern response polarity (activation vs. deactivation) and its relation to task difficulty, lateralization (left vs. right AG), and functional-anatomical subdivision (PGa vs. PGp subregions). Here, we combined the fMRI data of five studies on semantic processing (n = 172) and analyzed the response profiles from the same anatomical regions-of-interest for left and right PGa and PGp. We found that the AG was consistently deactivated during non-semantic conditions, whereas response polarity during semantic conditions was inconsistent. However, the AG consistently showed relative response differences between semantic and non-semantic conditions, and between different semantic conditions. A combined analysis across all studies revealed that AG responses could be best explained by separable effects of task difficulty and semantic processing demand. Task difficulty effects were stronger in PGa than PGp, regardless of hemisphere. Semantic effects were stronger in left than right AG, regardless of subregion. These results suggest that the AG is engaged in both domain-general task-difficulty-related processes and domain-specific semantic processes. In semantic processing, we propose that left AG acts as a "multimodal convergence zone" that binds different semantic features associated with the same concept, enabling efficient access to task-relevant features.
]]></description>
<dc:creator>Kuhnke, P.</dc:creator>
<dc:creator>Chapman, C. A.</dc:creator>
<dc:creator>Cheung, V. K. M.</dc:creator>
<dc:creator>Turker, S.</dc:creator>
<dc:creator>Graessner, A.</dc:creator>
<dc:creator>Martin, S.</dc:creator>
<dc:creator>Williams, K. A.</dc:creator>
<dc:creator>Hartwigsen, G.</dc:creator>
<dc:date>2021-12-23</dc:date>
<dc:identifier>doi:10.1101/2021.12.21.473704</dc:identifier>
<dc:title><![CDATA[The role of the angular gyrus in semantic cognition - A synthesis of five functional neuroimaging studies]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-12-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.12.22.473876v1?rss=1">
<title>
<![CDATA[
HSFA1 proteins mediate heat-induced accumulation of CPT7-derived polyprenols affecting thylakoid organization 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.12.22.473876v1?rss=1</link>
<description><![CDATA[
Polyprenols are ubiquitous isoprenoid compounds that accumulate in large quantities in plant photosynthetic tissues. While our knowledge of polyprenol biochemistry is constantly expanding, the regulation of their biosynthesis as well as the molecular basis of their cellular action are still poorly understood. In Arabidopsis, the polyprenols Pren-9, -10 and -11, synthesized by cis-prenyltransferase 7 (CPT7), are localized in plastidial membranes and affect the photosynthetic performance of chloroplasts.

In this report we present evidence that plastidial polyprenols are among the major constituents of thylakoid membranes. Disturbances in polyprenol level, caused by alterations in CPT7 expression, change chloroplast ultrastructure, affect aggregation of LHCII complexes and modulate non-photochemical quenching (NPQ). Moreover, we show that Arabidopsis responds to high temperature by upregulating expression of CPT7 and increasing the accumulation of CPT7-derived polyprenols. These heat-induced changes in polyprenol biosynthesis are mediated by Heat Shock Transcription Factors of the HSFA1 family, the master regulators of heat stress response. Collectively, results presented in this report bring us closer to understanding the mechanisms by which polyprenols affect plant physiology and provide an additional link between chloroplast biology and plant responses to changing environmental conditions.

One sentence summaryHeat Shock Transcription Factors induce biosynthesis of polyprenols - isoprenoid compounds that affect the organization and function of chloroplasts.
]]></description>
<dc:creator>Buszewicz, D.</dc:creator>
<dc:creator>Kowalewska, Łucja M.</dc:creator>
<dc:creator>Mazur, R.</dc:creator>
<dc:creator>Zajbt-Łuczniewska, M.</dc:creator>
<dc:creator>Surmacz, L.</dc:creator>
<dc:creator>Sosnowska, K.</dc:creator>
<dc:creator>Welc, R.</dc:creator>
<dc:creator>Jemioła-Rzeminska, M.</dc:creator>
<dc:creator>Link-Lenczowski, P.</dc:creator>
<dc:creator>Onysk, A.</dc:creator>
<dc:creator>Skorupinska-Tudek, K.</dc:creator>
<dc:creator>Liu, H.-C.</dc:creator>
<dc:creator>Charng, Y.-Y.</dc:creator>
<dc:creator>Archacki, R.</dc:creator>
<dc:creator>Gruszecki, W. I.</dc:creator>
<dc:creator>Swiezewska, E.</dc:creator>
<dc:date>2021-12-24</dc:date>
<dc:identifier>doi:10.1101/2021.12.22.473876</dc:identifier>
<dc:title><![CDATA[HSFA1 proteins mediate heat-induced accumulation of CPT7-derived polyprenols affecting thylakoid organization]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-12-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.12.23.474023v1?rss=1">
<title>
<![CDATA[
Identifying mutations in sd1, Pi54 and Pi-ta, and positively selected genes of TN1, the first semidwarf rice in Green Revolution 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.12.23.474023v1?rss=1</link>
<description><![CDATA[
BackgroundTaichung Native 1 (TN1) is the first semidwarf rice cultivar that initiated the Green Revolution. As TN1 is a direct descendant of the Dee-geo-woo-gen cultivar, the source of the sd1 semidwarf gene, the sd1 gene can be defined through TN1. Also, TN1 is susceptible to the blast disease and is described as being drought-tolerant. However, genes related to these characteristics of TN1 are unknown. Our aim was to identify and characterize TN1 genes related to these traits.

ResultsAligning the sd1 of TN1 to Nipponbare sd1, we found a 382-bp deletion including a frameshift mutation. Sanger sequencing validated this deleted region in sd1, and we proposed a model of the sd1 gene that corrects errors in the literature. We also predicted the blast disease resistant (R) genes of TN1. Orthologues of the R genes in Tetep, a well-known resistant cultivar that is commonly used as a donor for breeding new blast resistant cultivars, were then sought in TN1, and if they were present, we looked for mutations. The absence of Pi54, a well-known R gene, in TN1 partially explains why TN1 is more susceptible to blast than Tetep. We also scanned the TN1 genome using the PosiGene software and identified 11 genes deemed to have undergone positive selection. Some of them are associated with drought-resistance and stress response.

ConclusionsWe have redefined the deletion of the sd1 gene in TN1, a direct descendant of the Dee-geo-woo-gen cultivar, and have corrected some literature errors. Moreover, we have identified blast resistant genes and positively selected genes, including genes that characterize TN1s blast susceptibility and abiotic stress response. These new findings increase the potential of using TN1 to breed new rice cultivars.
]]></description>
<dc:creator>Panibe, J. P.</dc:creator>
<dc:creator>Wang, L.</dc:creator>
<dc:creator>Lee, Y.-C.</dc:creator>
<dc:creator>Wang, C.-S.</dc:creator>
<dc:creator>Li, W.-H.</dc:creator>
<dc:date>2021-12-24</dc:date>
<dc:identifier>doi:10.1101/2021.12.23.474023</dc:identifier>
<dc:title><![CDATA[Identifying mutations in sd1, Pi54 and Pi-ta, and positively selected genes of TN1, the first semidwarf rice in Green Revolution]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-12-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.12.28.474318v1?rss=1">
<title>
<![CDATA[
Chromatin state transition underlies the temporal changes in gene expression during cardiomyocyte maturation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.12.28.474318v1?rss=1</link>
<description><![CDATA[
Congenital heart disease (CHD) is often rooted in gene expression anomalies that occur during heart development. As cells commit to a specific lineage, chromatin dynamics and developmental plasticity generally become more limited. However, it remains unclear how differentiated cardiomyocytes (CMs) undergo morphological and functional adaptations to the postnatal environment during their maturation. In this work, we sought to identify the regulatory mechanisms controlling postnatal cardiac gene networks. A time-series transcriptomic analysis of postnatal hearts revealed an integrated, time-ordered transcriptional network that regulates CM maturation. Remarkably, depletion of histone H2B ubiquitin ligase RNF20 after formation of the four-chamber heart disrupted these highly coordinated gene networks. Its ablation also caused early-onset cardiomyopathy, a phenotype reminiscent of CHD. Furthermore, we found that dynamic RNF20-mediated modulation of chromatin accessibility during CM maturation was necessary for the operative binding of cardiac transcription factors known to drive transcriptional gene networks. Together, our results reveal how epigenetic-mediated chromatin state transitions modulate time-ordered gene expression during CM maturation.
]]></description>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Chang, Y.-M.</dc:creator>
<dc:creator>Tseng, H.-Y.</dc:creator>
<dc:creator>Shih, Y.-L.</dc:creator>
<dc:creator>Yeh, H.-H.</dc:creator>
<dc:creator>Chen, P.-L.</dc:creator>
<dc:creator>Chen, C.-C.</dc:creator>
<dc:creator>Yan, Y.-T.</dc:creator>
<dc:creator>Kao, C.-F.</dc:creator>
<dc:date>2021-12-28</dc:date>
<dc:identifier>doi:10.1101/2021.12.28.474318</dc:identifier>
<dc:title><![CDATA[Chromatin state transition underlies the temporal changes in gene expression during cardiomyocyte maturation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-12-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2021.12.29.474498v1?rss=1">
<title>
<![CDATA[
Macrophages break interneuromast cell quiescence by intervening the inhibition of Schwann cells in zebrafish lateral line 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2021.12.29.474498v1?rss=1</link>
<description><![CDATA[
In the zebrafish lateral line system, interneuromast cells (INCs) between neuromasts are normally kept quiescent by underlying Schwann cells (SWCs). Upon severe injuries that cause the complete loss of an entire neuromast, INCs can occasionally differentiate into neuromasts but how they escape from the inhibition by SWCs is still unclear. Using a genetic/chemical method to specifically ablate a neuromast, we found a small portion of larvae can regenerate a new neuromast, but the regeneration was hindered by inhibiting macrophages. By in toto imaging, we further discovered heterogeneities in macrophage behavior and distribution along lateral line. We witnessed the crawling of macrophages in between injured lateral line and SWCs during regeneration and also in between the second primordium and the first mature lateral line during development. It implies that macrophages may physically separate and alleviate the inhibition from pLLn and SWCs to break the quiescence of INCs during regeneration and development in the zebrafish lateral line.
]]></description>
<dc:creator>Lin, M.-J.</dc:creator>
<dc:creator>Lee, C.-M.</dc:creator>
<dc:creator>Hsu, W.-L.</dc:creator>
<dc:creator>Chen, B.-C.</dc:creator>
<dc:creator>Lee, S.-J.</dc:creator>
<dc:date>2021-12-30</dc:date>
<dc:identifier>doi:10.1101/2021.12.29.474498</dc:identifier>
<dc:title><![CDATA[Macrophages break interneuromast cell quiescence by intervening the inhibition of Schwann cells in zebrafish lateral line]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-12-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.01.02.474058v1?rss=1">
<title>
<![CDATA[
Optogenetic Manipulation of Cell Migration with High Spatiotemporal Resolution Using Lattice Lightsheet Microscopy 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.01.02.474058v1?rss=1</link>
<description><![CDATA[
Lattice lightsheet microscopy (LLSM) is modified with the aim of manipulating cellular behavior with subcellular resolution through three-dimensional (3D) optogenetic activation. In this study, we report a straightforward implementation of the activation source in LLSM in which the stimulating light can be generated by changing the spatial light modulator (SLM) patterns and the annual masks. As a result, a Bessel beam as a stimulation source is integrated into the LLSM without changing the optical configuration, achieving better spatiotemporal control of photoactivation. We show that the energy power required for optogenetic reactions is lower than 1 nW (or 24 mW/cm2), and membrane ruffling can be activated at different locations within a cell with subcellular resolution. We also demonstrate guided cell migration using optogenetic stimulation for up to 6 h, where 463 imaging volumes are collected, without noticeable damage to cells.
]]></description>
<dc:creator>Tang, W.-C.</dc:creator>
<dc:creator>Liu, Y.-T.</dc:creator>
<dc:creator>Yeh, C.-H.</dc:creator>
<dc:creator>Lin, Y.-L.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Hsu, T.-L.</dc:creator>
<dc:creator>Gao, L.</dc:creator>
<dc:creator>Chang, S.-W.</dc:creator>
<dc:creator>Chen, P.</dc:creator>
<dc:creator>Chen, B.-C.</dc:creator>
<dc:date>2022-01-02</dc:date>
<dc:identifier>doi:10.1101/2022.01.02.474058</dc:identifier>
<dc:title><![CDATA[Optogenetic Manipulation of Cell Migration with High Spatiotemporal Resolution Using Lattice Lightsheet Microscopy]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-01-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.01.04.475009v1?rss=1">
<title>
<![CDATA[
Three amphioxus reference genomes reveal gene and chromosome evolution of chordates 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.01.04.475009v1?rss=1</link>
<description><![CDATA[
The slow-evolving invertebrate amphioxus has an irreplaceable role in advancing our understanding into the vertebrate origin and innovations. Here we resolve the nearly complete chromosomal genomes of three amphioxus species, one of which best recapitulates the 17 chordate ancestor linkage groups. We reconstruct the fusions, retention or rearrangements between descendants of whole genome duplications (WGDs), which gave rise to the extant microchromosomes likely existed in the vertebrate ancestor. Similar to vertebrates, the amphioxus genome gradually establishes its 3D chromatin architecture at the onset of zygotic activation, and forms two topologically associated domains at the Hox gene cluster. We find that all three amphioxus species have ZW sex chromosomes with little sequence differentiation, and their putative sex-determining regions are nonhomologous to each other. Our results illuminate the unappreciated interspecific diversity and developmental dynamics of amphioxus genomes, and provide high-quality references for understanding the mechanisms of chordate functional genome evolution.
]]></description>
<dc:creator>Zhen, H.</dc:creator>
<dc:creator>Xu, L.</dc:creator>
<dc:creator>Cai, C.</dc:creator>
<dc:creator>Zhou, Y.</dc:creator>
<dc:creator>Liu, J.</dc:creator>
<dc:creator>Zhu, Z.</dc:creator>
<dc:creator>Kang, W.</dc:creator>
<dc:creator>Chen, D.</dc:creator>
<dc:creator>Pei, S.</dc:creator>
<dc:creator>Xue, T.</dc:creator>
<dc:creator>Cen, W.</dc:creator>
<dc:creator>Shi, C.</dc:creator>
<dc:creator>Wu, X.</dc:creator>
<dc:creator>Huang, Y.</dc:creator>
<dc:creator>Xu, C.</dc:creator>
<dc:creator>Yan, Y.</dc:creator>
<dc:creator>Yang, Y.</dc:creator>
<dc:creator>He, W.</dc:creator>
<dc:creator>Hu, X.</dc:creator>
<dc:creator>Zhang, Y.</dc:creator>
<dc:creator>Chen, Y.</dc:creator>
<dc:creator>Bi, C.</dc:creator>
<dc:creator>He, C.</dc:creator>
<dc:creator>Xue, L.</dc:creator>
<dc:creator>Xiao, S.</dc:creator>
<dc:creator>Yue, Z.</dc:creator>
<dc:creator>Jiang, Y.</dc:creator>
<dc:creator>Yu, J.-K.</dc:creator>
<dc:creator>Jarvis, E.</dc:creator>
<dc:creator>Li, G.</dc:creator>
<dc:creator>Lin, G.</dc:creator>
<dc:creator>Zhang, Q.</dc:creator>
<dc:creator>Zhou, Q.</dc:creator>
<dc:date>2022-01-05</dc:date>
<dc:identifier>doi:10.1101/2022.01.04.475009</dc:identifier>
<dc:title><![CDATA[Three amphioxus reference genomes reveal gene and chromosome evolution of chordates]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-01-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.01.05.475091v1?rss=1">
<title>
<![CDATA[
Phosphate transporter PHT1;1 as a key determinant of phosphorus acquisition in Arabidopsis natural accessions 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.01.05.475091v1?rss=1</link>
<description><![CDATA[
To understand the genetic basis in governing phosphorus (P) acquisition, we performed genome-wide association studies (GWAS) on a diversity panel of Arabidopsis thaliana by two primary determinants of P acquisition, phosphate (Pi)-uptake activity and PHOSPHATE TRANSPORTER 1 (PHT1) protein abundance. Association mapping revealed a shared significant peak on chromosome 5 (Chr5) where the PHT1;1/2/3 genes reside, suggesting a strong correlation between the regulation of Pi-uptake activity and PHT1 protein abundance. Genes encoding transcription factors, kinases, and a metalloprotease associated with both traits were also identified. Conditional GWAS followed by statistical analysis of genotype-dependent expression of PHT1;1 and transcription activity assays revealed an epistatic interaction between PHT1;1 and MYB DOMAIN PROTEIN 52 (MYB52) on Chr1. Analyses of F1 hybrids generated by crossing two subgroups of natural accessions carrying specific SNPs associated with PHT1;1 and MYB52 further revealed the strong effects of potential variants on PHT1;1 expression and Pi uptake activity. Notably, the soil P contents in A. thaliana habitats were found to coincide with PHT1;1 haplotype, underscoring how fine-tuning of the activity of P acquisition by natural variants allows plants to adapt to their environments. This study sheds light on the complex regulation of P acquisition and offers a framework to systematically assess the effectiveness of GWAS approaches in the study of quantitative traits.

One sentence summaryStepwise GWAS analyses reveal insights into the genetic basis in regulating phosphorus acquisition and associations between the phosphate transporter PHT1;1 haplotype and Arabidopsis habitats.
]]></description>
<dc:creator>Chien, P.-S.</dc:creator>
<dc:creator>Chao, Y.-T.</dc:creator>
<dc:creator>Chou, C.-H.</dc:creator>
<dc:creator>Hsu, Y.-Y.</dc:creator>
<dc:creator>Chiang, S.-F.</dc:creator>
<dc:creator>Tung, C.-W.</dc:creator>
<dc:creator>Chiou, T.-J.</dc:creator>
<dc:date>2022-01-06</dc:date>
<dc:identifier>doi:10.1101/2022.01.05.475091</dc:identifier>
<dc:title><![CDATA[Phosphate transporter PHT1;1 as a key determinant of phosphorus acquisition in Arabidopsis natural accessions]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-01-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.01.05.475094v1?rss=1">
<title>
<![CDATA[
New insights on the role of HCN in root hair elongation through single cell proteomics 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.01.05.475094v1?rss=1</link>
<description><![CDATA[
Root hairs are specialized structures involved in water and nutrient uptake by plants. They elongate from epidermal cells following a complex developmental program. {beta}-cyanoalanine synthase (CAS), which is mainly involved in hydrogen cyanide (HCN) detoxification in Arabidopsis thaliana, plays a role in root hair elongation, as evidenced by the fact that cas-c1 mutants show a severe defect in root hair shape. In addition to root hairs, CAS C1 is expressed in the quiescent center and meristem. However, the cas-c1 mutation has no visible effect on either tissue, in both control and nutrient-deprivation conditions. To identify its role in root hair formation, we conducted single cell proteomics analysis by isolating root hair cells using Fluorescence-Activated Cell Sorting (FACS) from wild type and cas-c1 mutants. We also analyzed the presence of S-cyanylation, a protein post-translational modification (PTM) mediated by HCN and affecting cysteine residues and protein activity, in proteins of wild type and cas-c1 mutants. We found that several proteins involved in root hair development, related to the receptor kinase FERONIA signaling and to DNA methylation, are modified by this new post-translational modification.

One sentence summaryArabidopsis root hair proteomics unveals that several proteins involved in root hair development are susceptible of modification by S-cyanylation.
]]></description>
<dc:creator>Garcia, I.</dc:creator>
<dc:creator>Arenas-Alfonseca, L.</dc:creator>
<dc:creator>Romero, L. C.</dc:creator>
<dc:creator>Yamada, M.</dc:creator>
<dc:date>2022-01-07</dc:date>
<dc:identifier>doi:10.1101/2022.01.05.475094</dc:identifier>
<dc:title><![CDATA[New insights on the role of HCN in root hair elongation through single cell proteomics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-01-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.01.31.478406v1?rss=1">
<title>
<![CDATA[
Omicron-specific mRNA vaccine induced potent neutralizing antibody against Omicron but not other SARS-CoV-2 variants 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.01.31.478406v1?rss=1</link>
<description><![CDATA[
The emerging SARS-CoV-2 variants of concern (VOC) harbor mutations associated with increasing transmission and immune escape, hence undermine the effectiveness of current COVID-19 vaccines. In late November of 2021, the Omicron (B.1.1.529) variant was identified in South Africa and rapidly spread across the globe. It was shown to exhibit significant resistance to neutralization by serum not only from convalescent patients, but also from individuals receiving currently used COVID-19 vaccines with multiple booster shots. Therefore, there is an urgent need to develop next generation vaccines against VOCs like Omicron. In this study, we develop a panel of mRNA-LNP-based vaccines using the receptor binding domain (RBD) of Omicron and Delta variants, which are dominant in the current wave of COVID-19. In addition to the Omicron- and Delta-specific vaccines, the panel also includes a "Hybrid" vaccine that uses the RBD containing all 16 point-mutations shown in Omicron and Delta RBD, as well as a bivalent vaccine composed of both Omicron and Delta RBD-LNP in half dose. Interestingly, both Omicron-specific and Hybrid RBD-LNP elicited extremely high titer of neutralizing antibody against Omicron itself, but few to none neutralizing antibody against other SARS-CoV-2 variants. The bivalent RBD-LNP, on the other hand, generated antibody with broadly neutralizing activity against the wild-type virus and all variants. Surprisingly, similar cross-protection was also shown by the Delta-specific RBD-LNP. Taken together, our data demonstrated that Omicron-specific mRNA vaccine can induce potent neutralizing antibody response against Omicron, but the inclusion of epitopes from other variants may be required for eliciting cross-protection. This study would lay a foundation for rational development of the next generation vaccines against SARS-CoV-2 VOCs.
]]></description>
<dc:creator>Lee, I.-J.</dc:creator>
<dc:creator>Sun, C.-P.</dc:creator>
<dc:creator>Wu, P.-Y.</dc:creator>
<dc:creator>Lan, Y.-H.</dc:creator>
<dc:creator>Wang, I.-H.</dc:creator>
<dc:creator>Liu, W.-C.</dc:creator>
<dc:creator>Tseng, S.-C.</dc:creator>
<dc:creator>Tsung, S.-I.</dc:creator>
<dc:creator>Chou, Y.-C.</dc:creator>
<dc:creator>Kumari, M.</dc:creator>
<dc:creator>Chang, Y.-W.</dc:creator>
<dc:creator>Chen, H.-F.</dc:creator>
<dc:creator>Lin, Y.-S.</dc:creator>
<dc:creator>Chen, T. -Y.</dc:creator>
<dc:creator>Chiu, C.-W.</dc:creator>
<dc:creator>Hsieh, C.-H.</dc:creator>
<dc:creator>Chuang, C.-Y.</dc:creator>
<dc:creator>Lin, C.-C.</dc:creator>
<dc:creator>Cheng, C.-M.</dc:creator>
<dc:creator>Lin, H.-T.</dc:creator>
<dc:creator>Chen, W.-Y.</dc:creator>
<dc:creator>Chiang, P.-C.</dc:creator>
<dc:creator>Lee, C.-C.</dc:creator>
<dc:creator>Liao, J. C.</dc:creator>
<dc:creator>Wu, H.-C.</dc:creator>
<dc:creator>Tao, M.-H.</dc:creator>
<dc:date>2022-01-31</dc:date>
<dc:identifier>doi:10.1101/2022.01.31.478406</dc:identifier>
<dc:title><![CDATA[Omicron-specific mRNA vaccine induced potent neutralizing antibody against Omicron but not other SARS-CoV-2 variants]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-01-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.02.01.478580v1?rss=1">
<title>
<![CDATA[
Peptide-based drug predictions for cancer therapy using deep learning 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.02.01.478580v1?rss=1</link>
<description><![CDATA[
BackgroundTherapeutic drugs used in cancer treatment have ineffectiveness and resistance to drug action problems. Anticancer peptides (ACPs) are selective and toxic to cancer cells and quickly produced. Thus, ACPs can be a satisfactory substitute for therapeutic drugs. We developed AI4ACP, a user-friendly web-server ACP predictor that can predict the anticancer property of query peptides, thus promoting the discovery of peptides with anticancer activity.

ResultOur results revealed that the performance of our ACP predictor trained using the new ACP collection was superior to that of the available high-performance ACP predictors.

ConclusionsAI4ACP is a user-friendly web-server ACP predictor that can be used to determine whether a query sequence is an ACP. This tool can be beneficial for drug development for cancer treatment. AI4ACP is freely accessible at https://axp.iis.sinica.edu.tw/AI4ACP/
]]></description>
<dc:creator>Sun, Y.-Y.</dc:creator>
<dc:creator>Lin, T.-T.</dc:creator>
<dc:creator>Cheng, W.-C.</dc:creator>
<dc:creator>Lu, I.-H.</dc:creator>
<dc:creator>Chen, S.-H.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:date>2022-02-04</dc:date>
<dc:identifier>doi:10.1101/2022.02.01.478580</dc:identifier>
<dc:title><![CDATA[Peptide-based drug predictions for cancer therapy using deep learning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-02-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.02.01.478701v1?rss=1">
<title>
<![CDATA[
CLEC5A and TLR2 are critical in SARS-CoV-2-induced NET formation and lung inflammation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.02.01.478701v1?rss=1</link>
<description><![CDATA[
Coronavirus-induced disease 19 (COVID-19) infects more than three hundred and sixty million patients worldwide, and people with severe symptoms frequently die of acute respiratory distress syndrome (ARDS). Autopsy demonstrates the presence of thrombosis and microangiopathy in the small vessels and capillaries. Recent studies indicated that excessive neutrophil extracellular traps (NETs) contributed to immunothrombosis, thereby leading to extensive intravascular coagulopathy and multiple organ dysfunction. Thus, understanding the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced NET formation would be helpful to reduce thrombosis and prevent ARDS. It has been shown that sera from individuals with COVID-19 triggered NET release in vitro, and spleen tyrosine kinase (Syk) inhibitor R406 inhibited NETosis caused by COVID-19 plasma. However, the serum components responsible for NET formation are still unknown. In this study, we found that virus-free extracellular vesicles (EVs) from COVID-19 patients (COVID-19 EVs) induced robust NET formation via Syk-coupled C-type lectin member 5A (CLEC5A). Blockade of CLEC5A inhibited COVID-19 EVs-induced NETosis, and simultaneous blockade of CLEC5A and TLR2 further suppressed SARS-CoV-2-induced NETosis in vitro. Moreover, thromboinflammation and lung fibrosis were attenuated dramatically in clec5a-/-/tlr2-/- mice. These results suggest that COVID-19 EVs play critical roles in SARS-CoV-2-induced immunothrombosis, and blockade of CLEC5A and TLR2 is a promising strategy to inhibit SARS-CoV-2-induced intravascular coagulopathy and reduce the risk of ARDS in COVID-19 patients.
]]></description>
<dc:creator>Sung, P.-S.</dc:creator>
<dc:creator>Yang, S.-P.</dc:creator>
<dc:creator>Peng, Y.-C.</dc:creator>
<dc:creator>Sun, C.-P.</dc:creator>
<dc:creator>Tao, M.-H.</dc:creator>
<dc:creator>Hsieh, S.-L.</dc:creator>
<dc:date>2022-02-02</dc:date>
<dc:identifier>doi:10.1101/2022.02.01.478701</dc:identifier>
<dc:title><![CDATA[CLEC5A and TLR2 are critical in SARS-CoV-2-induced NET formation and lung inflammation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-02-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.02.15.480616v1?rss=1">
<title>
<![CDATA[
Canonical Wnt signaling promotes formation of somatic permeability barrier for proper germ cell differentiation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.02.15.480616v1?rss=1</link>
<description><![CDATA[
Morphogen-mediated signaling is critical for proper organ development and stem cell function, and well-characterized mechanisms spatiotemporally limit the expression of ligands, receptors, and ligand-binding cell-surface glypicans. Here, we show that in the developing Drosophila ovary, canonical Wnt signaling promotes the formation of somatic escort cells (ECs) and their protrusions, which establish a physical permeability barrier to define morphogen territories for proper germ cell differentiation. The protrusions shield germ cells from Dpp and Wingless morphogens produced by the germline stem cell (GSC) niche and normally only received by GSCs. Genetic disruption of EC protrusions allows GSC progeny to also receive Dpp and Wingless, which subsequently disrupt germ cell differentiation. Our results reveal a role for canonical Wnt signaling in specifying the ovarian somatic cells necessary for germ cell differentiation. Additionally, we demonstrate the morphogen-limiting function of this physical permeability barrier, which may be a common mechanism in other organs across species.
]]></description>
<dc:creator>Chen, T.-A.</dc:creator>
<dc:creator>Lin, K.-Y.</dc:creator>
<dc:creator>Yang, S.-M.</dc:creator>
<dc:creator>Tseng, C.-Y.</dc:creator>
<dc:creator>Wang, Y.-T.</dc:creator>
<dc:creator>Lin, C.-H.</dc:creator>
<dc:creator>Luo, L.</dc:creator>
<dc:creator>Cai, Y.</dc:creator>
<dc:creator>Hsu, H.-J.</dc:creator>
<dc:date>2022-02-16</dc:date>
<dc:identifier>doi:10.1101/2022.02.15.480616</dc:identifier>
<dc:title><![CDATA[Canonical Wnt signaling promotes formation of somatic permeability barrier for proper germ cell differentiation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-02-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.02.16.480635v1?rss=1">
<title>
<![CDATA[
FAM21 is critical for TLR2-CLEC4E-mediated dendritic cell function against Candida albicans 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.02.16.480635v1?rss=1</link>
<description><![CDATA[
FAM21 (family with sequence similarity 21) is a component of the Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) protein complex that mediates actin polymerization at endosomal membranes to facilitate sorting of cargo-containing vesicles out of endosomes. To study the function of FAM21 in vivo, we generated conditional knockout (cKO) mice in the C57BL/6 background in which FAM21 was specifically knocked out of CD11c-positive dendritic cells. Bone marrow-derived dendritic cells (BMDC) from those mice displayed enlarged early endosomes, and altered cell migration and morphology relative to wildtype (WT) cells. FAM21-cKO cells were less competent in phagocytosis and antigen processing in vitro, though antigen presentation was not affected. More importantly, we identified the TLR2/CLEC4E signaling pathway as being downregulated in FAM21-cKO BMDCs when challenged with its specific ligand Candida albicans. Moreover, FAM21-cKO mice were more susceptible to C. albicans infection than WT mice. Reconstitution of WT BMDCs in FAM21-cKO mice rescued them from lethal C. albicans infection. Thus, our study highlights the importance of FAM21 in a host immune response against a significant pathogen.
]]></description>
<dc:creator>Kulkarni, R.</dc:creator>
<dc:creator>Kasani, S. K.</dc:creator>
<dc:creator>Tsai, C.-Y.</dc:creator>
<dc:creator>Tung, S.-Y.</dc:creator>
<dc:creator>Yeh, K.-H.</dc:creator>
<dc:creator>Yu, C.-H. A.</dc:creator>
<dc:creator>Chang, W.</dc:creator>
<dc:date>2022-02-17</dc:date>
<dc:identifier>doi:10.1101/2022.02.16.480635</dc:identifier>
<dc:title><![CDATA[FAM21 is critical for TLR2-CLEC4E-mediated dendritic cell function against Candida albicans]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-02-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.03.04.482938v1?rss=1">
<title>
<![CDATA[
The multi-level regulation of clownfish metamorphosis by thyroid hormones 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.03.04.482938v1?rss=1</link>
<description><![CDATA[
Most marine organisms have a biphasic life cycle during which a pelagic larva is transformed into a radically different juvenile. In vertebrates the role of thyroid hormones (TH) in triggering this transition is well known, but how the morphological and physiological changes are integrated in a coherent way with the ecological transition remains poorly explored. To gain insight into this question, we performed an integrative analysis of metamorphosis of a marine teleost, the clownfish Amphiprion ocellaris. We reveal how TH coordinate a change in color vision as well as a major metabolic shift in energy production, hence highlighting its central integrative role in regulating this transformation. By manipulating the activity of LXR, a major regulator of metabolism, we also reveal a tight link between metabolic changes and metamorphosis progression. Strikingly, we observed that these regulations are at play in the wild revealing how hormones coordinate energy needs with available resources during life cycle.
]]></description>
<dc:creator>Roux, N.</dc:creator>
<dc:creator>Miura, S.</dc:creator>
<dc:creator>Dussene, M.</dc:creator>
<dc:creator>Tara, Y.</dc:creator>
<dc:creator>Lee, S. h.</dc:creator>
<dc:creator>de Bernard, S.</dc:creator>
<dc:creator>Reynaud, M.</dc:creator>
<dc:creator>Salis, P.</dc:creator>
<dc:creator>Barua, A.</dc:creator>
<dc:creator>Boulahtouf, A.</dc:creator>
<dc:creator>Balaguer, P.</dc:creator>
<dc:creator>Gauthier, K.</dc:creator>
<dc:creator>Lecchini, D.</dc:creator>
<dc:creator>Gibert, Y.</dc:creator>
<dc:creator>Besseau, L.</dc:creator>
<dc:creator>Laudet, V. C.</dc:creator>
<dc:date>2022-03-04</dc:date>
<dc:identifier>doi:10.1101/2022.03.04.482938</dc:identifier>
<dc:title><![CDATA[The multi-level regulation of clownfish metamorphosis by thyroid hormones]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-03-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.03.08.483394v1?rss=1">
<title>
<![CDATA[
Insertion of YFP at the Arabidopsis AFL1 and P5CS1 loci shows the potential, and potential limitations, of gene targeting for functional analysis of stress-related genes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.03.08.483394v1?rss=1</link>
<description><![CDATA[
Crispr/CAS9-enabled homologous recombination to insert a tag in frame with an endogenous gene can circumvent difficulties such as context-dependent promoter activity that complicate analysis of gene expression and protein accumulation patterns. However, there have been few reports examining whether such Gene Targeting/Gene Tagging (GT) can alter expression of the target gene. The enzyme encoded by {Delta}1-pyrroline-5-carboxylate synthetase 1 (P5CS1) is key for stress-induced proline synthesis and drought resistance, yet its expression pattern and protein localization have been difficult to assay. We used GT to insert YFP in frame with the 5 or 3 ends of the endogenous P5CS1 and At14a-Like 1 (AFL1) coding regions. Insertion at the 3 end of either gene generated homozygous lines with expression of the gene-YFP fusion indistinguishable from the wild type allele. However, for P5CS1 this occurred only after selfing and advancement to the T5 generation allowed initial homozygous lethality of the insertion to be overcome. Once this was done, the GT-generated P5CS1-YFP plants revealed new information about P5CS1 localization and tissue-specific expression. In contrast, insertion of YFP at the 5 end of either gene blocked expression. The results demonstrate that GT can be useful for functional analyses of genes that are problematic to properly express by other means but also show that, in some cases, GT can disrupt expression of the target gene.

Summary statementGene tagging of Arabidopsis thaliana P5CS1 and AFL1 shows the potential of GT for functional analysis of stress-related genes, but also provides examples of how GT can dramatically disrupt expression of the target gene.
]]></description>
<dc:creator>Longkumer, T.</dc:creator>
<dc:creator>Grillet, L.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Putra, H.</dc:creator>
<dc:creator>Schmidt, W.</dc:creator>
<dc:creator>Verslues, P. E.</dc:creator>
<dc:date>2022-03-08</dc:date>
<dc:identifier>doi:10.1101/2022.03.08.483394</dc:identifier>
<dc:title><![CDATA[Insertion of YFP at the Arabidopsis AFL1 and P5CS1 loci shows the potential, and potential limitations, of gene targeting for functional analysis of stress-related genes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-03-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.03.08.483537v1?rss=1">
<title>
<![CDATA[
BMAL1 and MEX3A co-regulate intestinal stem cell succession 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.03.08.483537v1?rss=1</link>
<description><![CDATA[
Chemotherapeutic agents, such as 5-fluorouracil (5-FU), often induce intestinal mucositis due to toxicity to rapidly dividing intestinal stem cells (ISCs). Drug delivery at different times of day can alter 5-FU toxicity; however, the underlying biology is unclear. We found that homeostasis and succession between two ISC types, fast proliferating Lgr5+ crypt base columnar (CBC) cells and stress-resistant +4 cells (Bmi1+), are controlled by the circadian clock transcription factor BMAL1 and the BMAL1-regulated RNA-binding protein MEX3A via both direct transcriptional regulation and post-transcriptional control of Lgr5 mRNA stability. Bmal1 knockout in Lgr5+ CBCs reduced MEX3A expression and CBC numbers but increased Bmi1 expression in the crypts. Timing 5-FU delivery when crypt cells had low Lgr5 but peak level of Bmi1 protected ISCs from apoptosis. Together, these findings identify a novel role of BMAL1 in ISC homeostasis and provide a biological explanation for chronotherapeutic chemoprotection.
]]></description>
<dc:creator>Chang, F.-P.</dc:creator>
<dc:creator>Wang, C.-K.</dc:creator>
<dc:creator>Chou, Y.-C.</dc:creator>
<dc:creator>Chen, T.-J.</dc:creator>
<dc:creator>Wu, Y.-W.</dc:creator>
<dc:creator>Sridharan, S.</dc:creator>
<dc:creator>Hsu, P.-H.</dc:creator>
<dc:creator>Hwang-Verslues, W. W.</dc:creator>
<dc:date>2022-03-10</dc:date>
<dc:identifier>doi:10.1101/2022.03.08.483537</dc:identifier>
<dc:title><![CDATA[BMAL1 and MEX3A co-regulate intestinal stem cell succession]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-03-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.03.09.483723v1?rss=1">
<title>
<![CDATA[
Niche-based deterministic assembly processes strengthen the effects of β-diversity on metacommunity functioning of marine bacterioplankton 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.03.09.483723v1?rss=1</link>
<description><![CDATA[
Studies at a local community () level have shown that biodiversity positively affects ecosystem functioning due to niche-based deterministic processes like resource partitioning. Extending to a metacommunity ({beta}) level, we hypothesize that {beta} diversity also positively affects metacommunity functioning. We further hypothesize that the {beta} diversity effect is stronger (more positive) when {beta} diversity is increased by deterministic/non-random assembly processes. To test the hypotheses, we collected bacterioplankton along a transect of 6 stations in the southern East China Sea in 14 cruises. All 6 stations within a cruise were regarded as a metacommunity. For any pairs of the 6 stations, the Bray-Curtis index and summed bacterial biomass were calculated to represent {beta} diversity and metacommunity functioning, respectively. We also calculated deviation of observed mean pairwise phylogenetic similarities among species from random to represent the deterministic influences of assembly processes. We found that bacterial {beta} diversity generally positively affects metacommunity functioning; however, the {beta} diversity effect varied among cruises. Cross-cruise comparison indicates that the {beta} diversity effect increased with the deterministic assembly processes selecting for phylogenetically dissimilar species. This study extends the biodiversity-ecosystem functioning research to a metacommunity level, complementing the current framework by considering community assembly in natural environments.
]]></description>
<dc:creator>Chang, F.-H.</dc:creator>
<dc:creator>Yang, J. W.</dc:creator>
<dc:creator>Liu, A. C.-H.</dc:creator>
<dc:creator>Lu, H.-P.</dc:creator>
<dc:creator>Gong, G.-C.</dc:creator>
<dc:creator>Shiah, F.-K.</dc:creator>
<dc:creator>Hsieh, C.-h.</dc:creator>
<dc:date>2022-03-11</dc:date>
<dc:identifier>doi:10.1101/2022.03.09.483723</dc:identifier>
<dc:title><![CDATA[Niche-based deterministic assembly processes strengthen the effects of β-diversity on metacommunity functioning of marine bacterioplankton]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-03-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.03.21.485106v1?rss=1">
<title>
<![CDATA[
Niche hypervolume analysis revealed that water pollution reduces reproductive success of endangered landlocked salmon but does not directly impact their population density 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.03.21.485106v1?rss=1</link>
<description><![CDATA[
The critical information for conserving endangered species is to identify how different niche dimensions affect key life history stages of a population. However, it is often difficult to quantify how each ecological niche dimension affects different life history stages because environmental factors may affect each fitness component of organisms to various degrees. Here, we applied the recently developed hypervolume method that follows the idea of Hutchinsons n-dimensional hypervolume. We analyzed the niche space of different life history stages of the endangered landlocked salmon Oncorhynchus masou formosanus, the most southerly distributed of all salmonoids. We found no direct effect of water pollution on salmon population density but a significant negative effect on salmon reproductive success. Surprisingly, the niche hypervolume analysis showed that the size of hatching success niche hypervolume was only 17.9% and 18.4% of the natural redd site density or population density, respectively. This result demonstrates a much higher environmental requirement for salmon during the egg stage than that affecting population density or nesting environment. Our results suggest that understanding the behavioral and physiological mechanisms that influence crucial life history stages in the wild is critical to developing effective conservation programs, and the niche hypervolume is a valuable method to achieve this.
]]></description>
<dc:creator>Yi-An, C.</dc:creator>
<dc:creator>Liu, M.</dc:creator>
<dc:creator>Tzu-Man, H.</dc:creator>
<dc:creator>Lin-Yan, L.</dc:creator>
<dc:creator>Shen, S.-F.</dc:creator>
<dc:date>2022-03-22</dc:date>
<dc:identifier>doi:10.1101/2022.03.21.485106</dc:identifier>
<dc:title><![CDATA[Niche hypervolume analysis revealed that water pollution reduces reproductive success of endangered landlocked salmon but does not directly impact their population density]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-03-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.03.22.485260v1?rss=1">
<title>
<![CDATA[
Targeting Reductive Metabolic Shifts by T315I Mutation in BCR-ABL Myeloid Leukemia for Therapy 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.03.22.485260v1?rss=1</link>
<description><![CDATA[
T315I mutation of Bcr-Abl in chronic myeloid leukemia (CML) leads to therapeutic resistance. It is known that Bcr-Abl transformation causes ROS-induced DNA damages and replication stress, which can be exploited for anti-nucleotide therapy. We developed a small compound, JMF4073, which inhibited pyrimidylate kinases and selectively eliminated Bcr-Abl-transformed, but not untransformed myeloid cells, due to dTTP exhaustion and ROS-induced replication stress. However, T315I-Bcr-Abl-transformed cells were less vulnerable to JMF4073 because of higher dTTP pool and low replication stress. Unlike WT-Bcr-Abl-transformed cells, T315I-Bcr-Abl cells lacked Sirt1- regulated OXPHOS with increased glutamine flux to reductive carboxylation in TCA cycle and glutathione synthesis. Blocking mitochondrial pyruvate carrier (MPC) by UK-5099 reduced NADH and glutathione levels with replication stress induction, thereby converting T315I-Bcr-Abl cells sensitive to JMF4073 with dTTP and dCTP depletion. The combination of JMF4073 with UK-5099 showed in vivo eradication of T315I-Bcr-Abl-CML. These data reveal that T315I mutation causes reductive metabolic shifts in Bcr-Abl-CML, and demonstrate the therapeutic option by co-targeting MPC and pyrimidylate kinases.
]]></description>
<dc:creator>Huang, C. Y.</dc:creator>
<dc:creator>Chung, Y.-H.</dc:creator>
<dc:creator>Wu, S.-Y.</dc:creator>
<dc:creator>Wang, H.-Y.</dc:creator>
<dc:creator>Lin, Z.-Y.</dc:creator>
<dc:creator>Yang, T.-J.</dc:creator>
<dc:creator>Feng, J.-M.</dc:creator>
<dc:creator>Hu, C.-M.</dc:creator>
<dc:creator>Chang, Z.-F.</dc:creator>
<dc:date>2022-03-23</dc:date>
<dc:identifier>doi:10.1101/2022.03.22.485260</dc:identifier>
<dc:title><![CDATA[Targeting Reductive Metabolic Shifts by T315I Mutation in BCR-ABL Myeloid Leukemia for Therapy]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-03-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.03.22.485422v1?rss=1">
<title>
<![CDATA[
Fusarium solani species complex genomes reveal bases of compartmentalisation and animal pathogenesis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.03.22.485422v1?rss=1</link>
<description><![CDATA[
The Fusarium solani species complex (FSSC) comprises fungal pathogens responsible for mortality in a diverse range of animals and plants, but their genome diversity and transcriptome responses in animal pathogenicity remain to be elucidated. We sequenced and compared six chromosome-level FSSC clade 3 genomes of aquatic animal and plant host origins and revealed a spectrum of conservation patterns in chromosomes categorised into three compartments: core, fast-core (FC), and lineage-specific (LS). Each chromosome type varied in structural architectures, with FC and LS chromosomes containing significantly higher proportions of repetitive elements and methylation levels than core chromosomes, with genes exhibiting higher dN/dS and enriched in functions related to pathogenicity and niche expansion. Mesosynteny were detected between FC chromosomes of Fusarium genomes, indicating that these chromosomes were present in a common ancestor that predated FSSC species. These findings provide evidence that genome compartmentalisation was the outcome of multi-speed evolution amongst FSSC chromosomes. We further demonstrated that F. falciforme and F. keratoplasticum are opportunistic pathogens by inoculating Pelodiscus sinensis eggs and identified differentially expressed genes also associated with plant pathogenicity. These included the most upregulated genes encoding the CFEM (Common in Fungal Extracellular Membrane) domain. The study establishes genomic resources and an animal model for fungal pathogens of trans-kingdom hosts.
]]></description>
<dc:creator>Hoh, D. Z.</dc:creator>
<dc:creator>Lee, H.-H.</dc:creator>
<dc:creator>Wada, N.</dc:creator>
<dc:creator>Liu, W.-A.</dc:creator>
<dc:creator>Lu, M. R.</dc:creator>
<dc:creator>Lai, C.-K.</dc:creator>
<dc:creator>Ke, H.-M.</dc:creator>
<dc:creator>Sun, P. F.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:creator>Chung, W.-H.</dc:creator>
<dc:creator>Chen, Y.-L.</dc:creator>
<dc:creator>Chung, C.-L.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2022-03-23</dc:date>
<dc:identifier>doi:10.1101/2022.03.22.485422</dc:identifier>
<dc:title><![CDATA[Fusarium solani species complex genomes reveal bases of compartmentalisation and animal pathogenesis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-03-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.03.23.485571v1?rss=1">
<title>
<![CDATA[
Antimicrobial Susceptibility Test by Surface-enhanced Raman Scattering of Bacterial Metabolites directly from Positive Blood Cultures 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.03.23.485571v1?rss=1</link>
<description><![CDATA[
Effective management of sepsis requires timely administration of appropriate antibiotics; therefore, a reliable and rapid antimicrobial susceptibility test (AST) is crucial. To meet clinical needs, we developed a novel AST, referred to as SERS-AST, based on the surface-enhanced Raman Scattering (SERS) technology. In this study, we applied SERS-AST to eight most common pathogens causing bacteremia, including Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, E. faecium, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Acinetobacter baumannii. Seven different antibiotics were tested, including oxacillin, levofloxacin, vancomycin, ampicillin, cefotaxime, ceftazidime, levofloxacin, and imipenem. SERS-AST determines antibiotic susceptibility of bacteria directly from positive blood cultures based on variations in bacterial SERS signals derived from secreted purines and their derivatives. The whole process could be completed within 4 hours, and the agreement rates between SERS-AST and VITEK 2 results were 96% for Gram-positive bacteria and 97% for Gram-negative bacteria.
]]></description>
<dc:creator>HAN, Y.-Y.</dc:creator>
<dc:creator>Wang, J.-T.</dc:creator>
<dc:creator>Cheng, W.-C.</dc:creator>
<dc:creator>Chen, K.-L.</dc:creator>
<dc:creator>Chi, Y.</dc:creator>
<dc:creator>Teng, L.-J.</dc:creator>
<dc:creator>Wang, J.-K.</dc:creator>
<dc:creator>Wang, Y.-L.</dc:creator>
<dc:date>2022-03-24</dc:date>
<dc:identifier>doi:10.1101/2022.03.23.485571</dc:identifier>
<dc:title><![CDATA[Antimicrobial Susceptibility Test by Surface-enhanced Raman Scattering of Bacterial Metabolites directly from Positive Blood Cultures]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-03-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.03.24.485617v1?rss=1">
<title>
<![CDATA[
Nucleic Acid Adductomics - the Next Generation of Adductomics for Assessing Environmental Health Risk 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.03.24.485617v1?rss=1</link>
<description><![CDATA[
The exposome describes the totality of internal and external environmental exposures, across the life course. Components of the exposome have been linked to an increased risk of various, major diseases. To identify the precise nature, and size, of risk, in this complex mixture of exposures, powerful tools are needed to link exposure, cellular consequences, and health/disease. The most biologically informative biomarkers of the exposome should, to varying extents, reflect the dose of the exposure on the body or target organ(s), a subsequent effect on the biological system and, ideally, possess a role in disease. Modification of nucleic acids (NA) is a key consequence of environmental exposures, and while cellular DNA adductomics aims to evaluate the totality to DNA modifications in the genome, an approach which encompasses modifications of all nucleic acids, would be far more comprehensive, and therefore informative. To address this, we propose a cellular and urinary NA adductomics approach for the assessment of both DNA and RNA modifications, including modified (2-deoxy)ribonucleosides (2dN/rN), modified nucleobases (nB), plus: DNA-DNA, RNA-RNA, DNA-RNA, DNA-protein, and RNA-protein crosslinks (DDCL, RRCL, DRCL, DPCL, and RPCL, respectively). Supporting the feasibility of this approach, we presented preliminary, proof-of-principle results, which revealed the presence of over 1,000 modified NA moieties, and at least six types of NA modifications, in a representative, pooled urine from healthy subjects, including modified 2-dN, modified rN, modified nB, DRCL, RRCL and RPCL, many of which were novel/unexpected. We suggest that NA adductomics will provide a more comprehensive approach to the study of nucleic acid modifications, which will facilitate a range of advances, including the identification of novel, unexpected modifications e.g., RNA-RNA, and DNA-RNA crosslinks; key modifications associated with mutagenesis; agent-specific mechanisms; and adductome signatures of key environmental agents, leading to the dissection of the exposome, and its role in human health/disease, across the life course.
]]></description>
<dc:creator>Cooke, M. S.</dc:creator>
<dc:creator>Chang, Y.-J.</dc:creator>
<dc:creator>Chen, Y.-R.</dc:creator>
<dc:creator>Hu, C.-W.</dc:creator>
<dc:creator>Chao, M.-R.</dc:creator>
<dc:date>2022-03-28</dc:date>
<dc:identifier>doi:10.1101/2022.03.24.485617</dc:identifier>
<dc:title><![CDATA[Nucleic Acid Adductomics - the Next Generation of Adductomics for Assessing Environmental Health Risk]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-03-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.03.24.485721v1?rss=1">
<title>
<![CDATA[
Utilisation of Oxford Nanopore sequencing to generate six complete gastropod mitochondrial genomes as part of a biodiversity curriculum 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.03.24.485721v1?rss=1</link>
<description><![CDATA[
High-throughput sequencing has enabled genome skimming approaches to produce complete mitochondrial genomes (mitogenomes) for species identification and phylogenomics purposes. In particular, the portable sequencing device from Oxford Nanopore Technologies (ONT) has the potential to facilitate hands-on training from sampling to sequencing and interpretation of mitogenomes. In this study, we present the results from sampling and sequencing six gastropod mitogenomes (Aplysia argus, Cellana orientalis, Cellana toreuma, Conus ebraeus, Conus miles and Tylothais aculeata) from a graduate level biodiversity course. The students were able to produce mitochondrial genomes from sampling to annotation using existing protocols and programs. Approximately 4Gb of sequence was produced from 15 Flongle and two R9.4 Flowcells, averaging 235Mb and N50=4.4kb per Flowcell. Five of the six 14.1-18kb mitogenomes were circlised containing all 13 core protein coding genes. Additional Illumina sequencing reveal that the ONT assemblies were able to span over highly AT rich sequence in the control region that was otherwise missing in Illumina-assembled mitogenomes, but still contained a base error of one every 70.8-346.7bp with the majority occurring at homopolymer regions. Our findings suggest that ONT are portable and can be used to rapidly produce mitogenomes at low cost and tailored to genomics-based training in biodiversity research.
]]></description>
<dc:creator>De Vivo, M.</dc:creator>
<dc:creator>Lee, H.-H.</dc:creator>
<dc:creator>Huang, Y.-H.</dc:creator>
<dc:creator>Drever, N.</dc:creator>
<dc:creator>Fong, C.-l.</dc:creator>
<dc:creator>de Mattos, F. M. G.</dc:creator>
<dc:creator>Jain, D.</dc:creator>
<dc:creator>Wen, Y.-H. V.</dc:creator>
<dc:creator>Mwihaki, J. K.</dc:creator>
<dc:creator>Wang, T.-Y.</dc:creator>
<dc:creator>Machida, R. J.</dc:creator>
<dc:creator>Wang, J.</dc:creator>
<dc:creator>Chan, B. K. K.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2022-03-27</dc:date>
<dc:identifier>doi:10.1101/2022.03.24.485721</dc:identifier>
<dc:title><![CDATA[Utilisation of Oxford Nanopore sequencing to generate six complete gastropod mitochondrial genomes as part of a biodiversity curriculum]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-03-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.03.28.486113v1?rss=1">
<title>
<![CDATA[
Natural variation identifies new effectors of water use efficiency in Arabidopsis. 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.03.28.486113v1?rss=1</link>
<description><![CDATA[
Water use efficiency (WUE) is the ratio of biomass gained per unit of water consumed; thus, it can be altered by genetic factors that affect either side of the ratio. In the present study, we exploited natural variation for WUE as an unbiased approach to discover loci affecting either biomass accumulation or water use as factors affecting WUE. Genome-wide association (GWAS) analysis using integrated WUE measured through carbon isotope discrimination ({delta}13C) of Arabidopsis thaliana accessions identified genomic regions associated with WUE. Reverse genetic analysis of 70 candidate genes selected based on the GWAS results and transcriptome data identified 25 genes affecting WUE as measured by gravimetric and {delta}13C analyses. Mutants of four genes had higher WUE than wild type, while mutants of the other 21 genes had lower WUE. The differences in WUE were caused by either altered biomass or water consumption (or both). Stomatal density was not a primary cause of altered WUE in these mutants. Leaf surface temperatures indicated that transpiration differed for mutants of 16 genes, but generally biomass accumulation had greater effect on WUE. The genes we identified are involved in diverse cellular processes including hormone and calcium signaling, meristematic activity, photosynthesis, flowering time, leaf/vasculature development, and cell wall composition; however, none of them had been previously linked to WUE or traits related to plant water relations. Thus, our study successfully identified new effectors of WUE that can be used to understand the genetic basis of WUE and improve crop productivity.
]]></description>
<dc:creator>Badiger, B. G.</dc:creator>
<dc:creator>Lasky, J. R.</dc:creator>
<dc:creator>Razzaque, S.</dc:creator>
<dc:creator>Zhang, L.</dc:creator>
<dc:creator>Haque, T.</dc:creator>
<dc:creator>Bonnette, J. E.</dc:creator>
<dc:creator>Civelek, G. Z.</dc:creator>
<dc:creator>Verslues, P. E.</dc:creator>
<dc:creator>Juenger, T. E.</dc:creator>
<dc:date>2022-03-29</dc:date>
<dc:identifier>doi:10.1101/2022.03.28.486113</dc:identifier>
<dc:title><![CDATA[Natural variation identifies new effectors of water use efficiency in Arabidopsis.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-03-29</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.03.30.485724v1?rss=1">
<title>
<![CDATA[
Orphan nuclear receptors promote alternative lengthening of telomeres (ALT) through ALT-associated PML bodies 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.03.30.485724v1?rss=1</link>
<description><![CDATA[
Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere maintenance mechanism utilized by about 15% of cancers. Orphan nuclear receptors (NRs), such as COUP-TF1, COUP-TF2, EAR2, TR2, and TR4, associate with telomeres of ALT cells by binding to variant telomeric repeats. However, how these orphan NRs function in the ALT pathway remains to be characterized. Here, we have established an ALT-inducing cell model by tethering orphan NRs to telomeres in non-ALT BJ fibroblast cells. We demonstrate that recruitment of orphan NRs to telomeres is sufficient to initiate formation of ALT-associated promyelocytic leukemia nuclear bodies (APBs) and telomeric DNA synthesis at APBs. We found that the ability of orphan NRs to initiate APB formation and recombination is dependent on the orphan NR AF2 domain, the zinc-finger protein ZNF827, and PML protein. Depletion of orphan NRs in ALT cell lines reduced APB formation and telomeric DNA synthesis, confirming the role of orphan NRs in ALT cells. Furthermore, we found that ATRX/DAXX depletion, together with the telomeric localization of orphan NRs, induces APB formation, telomere clustering, and telomeric DNA synthesis more dramatically in non-ALT cells. Accordingly, we propose that these events in ALT, orphan NR recruitment to telomeres and ATRX/DAXX loss, operate in concert to activate the ALT pathway.
]]></description>
<dc:creator>Gaela, V. M. A.</dc:creator>
<dc:creator>Hsia, H.-Y.</dc:creator>
<dc:creator>Boudier, T.</dc:creator>
<dc:creator>Chen, L.-Y.</dc:creator>
<dc:date>2022-03-30</dc:date>
<dc:identifier>doi:10.1101/2022.03.30.485724</dc:identifier>
<dc:title><![CDATA[Orphan nuclear receptors promote alternative lengthening of telomeres (ALT) through ALT-associated PML bodies]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-03-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.04.10.486823v1?rss=1">
<title>
<![CDATA[
Subtyping of major SARS-CoV-2 variants reveals different transmission dynamics 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.04.10.486823v1?rss=1</link>
<description><![CDATA[
SARS-CoV-2 continues to evolve, causing waves of the pandemic. Up to March 2022, eight million genome sequences have accumulated, which are classified into five major variants of concern. With the growing number of sequenced genomes, analysis of the big dataset has become increasingly challenging. Here we developed systematic approaches for comprehensive subtyping and pattern recognition for transmission dynamics. By analyzing the first two million viral genomes as of July 2021, we found that different subtypes of the same variant exhibited distinct temporal trajectories. For example, some Delta subtypes did not spread rapidly, while others did. We identified sets of characteristic single nucleotide variations (SNVs) that appeared to enhance transmission or decrease efficacy of antibodies for some subtypes of the Delta and Alpha variants. We also identified a set of SNVs that appeared to suppress transmission or increase viral sensitivity to antibodies. These findings are later confirmed in an analysis of six million genomes as of December 2021. For the Omicron variant, the dominant type in the world, we identified the subtypes with enhanced and suppressed transmission in an analysis of seven million genomes as of January 2022 and further confirmed the findings in a later analysis of eight million genomes as of March 2022. While the "enhancer" SNVs exhibited an enriched presence on the spike protein, the "suppressor" SNVs are mainly elsewhere. Disruption of the SNV correlation largely destroyed the enhancer-suppressor phenomena. These results suggest the importance of fine subtyping of variants, and point to potential complex interactions among SNVs.
]]></description>
<dc:creator>Yang, H.-C.</dc:creator>
<dc:creator>Wang, J.-H.</dc:creator>
<dc:creator>Yang, C.-T.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Hsieh, H.-N.</dc:creator>
<dc:creator>Chen, P.-W.</dc:creator>
<dc:creator>Liao, H.-C.</dc:creator>
<dc:creator>Chen, C.-h.</dc:creator>
<dc:creator>Liao, J. C.</dc:creator>
<dc:date>2022-04-11</dc:date>
<dc:identifier>doi:10.1101/2022.04.10.486823</dc:identifier>
<dc:title><![CDATA[Subtyping of major SARS-CoV-2 variants reveals different transmission dynamics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-04-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.04.12.488038v1?rss=1">
<title>
<![CDATA[
A streamlined tandem tip-based workflow for sensitive nanoscale phosphoproteomics 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.04.12.488038v1?rss=1</link>
<description><![CDATA[
Effective phosphoproteome of nanoscale sample analysis remains a daunting task, primarily due to significant sample loss associated with non-specific surface adsorption during enrichment of low stoichiometric phosphopeptide. We developed a novel tandem tip phosphoproteomics sample preparation method that is capable of sample cleanup and enrichment without additional sample transfer, and its integration with our recently developed SOP (Surfactant-assisted One-Pot sample preparation) and iBASIL (improved Boosting to Amplify Signal with Isobaric Labeling) approaches provides a streamlined workflow enabling sensitive, high-throughput nanoscale phosphoproteome measurements. This approach significantly reduces both sample loss and processing time, allowing the identification of >3,000 (>9,500) phosphopeptides from 1 (10) {micro}g of cell lysate using the label-free method without a spectral library. It also enabled precise quantification of [~]600 phosphopeptides from 100 cells sorted by FACS (single-cell level input for the enriched phosphopeptides) and [~]700 phosphopeptides from human spleen tissue voxels with a spatial resolution of 200 {micro}m (equivalent to [~]100 cells) in a high-throughput manner. The new workflow opens avenues for phosphoproteome profiling of mass-limited samples at the low nanogram level.
]]></description>
<dc:creator>Tsai, C.-F.</dc:creator>
<dc:creator>Wang, Y.-T.</dc:creator>
<dc:creator>Hsu, C.-C.</dc:creator>
<dc:creator>Kitata, R. B.</dc:creator>
<dc:creator>Chu, R. K.</dc:creator>
<dc:creator>Velickovic, M.</dc:creator>
<dc:creator>Zhao, R.</dc:creator>
<dc:creator>Williams, S. M.</dc:creator>
<dc:creator>Chrisler, W. B.</dc:creator>
<dc:creator>Jorgensen, M. L.</dc:creator>
<dc:creator>Moore, R. J.</dc:creator>
<dc:creator>Zhu, Y.</dc:creator>
<dc:creator>Rodland, K. D.</dc:creator>
<dc:creator>Smith, R. D.</dc:creator>
<dc:creator>Wasserfall, C. H.</dc:creator>
<dc:creator>Shi, T.</dc:creator>
<dc:creator>Liu, T.</dc:creator>
<dc:date>2022-04-12</dc:date>
<dc:identifier>doi:10.1101/2022.04.12.488038</dc:identifier>
<dc:title><![CDATA[A streamlined tandem tip-based workflow for sensitive nanoscale phosphoproteomics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-04-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.04.13.463890v1?rss=1">
<title>
<![CDATA[
Systems Biology Approach of Understanding Insulin Resistance: Linkage between Type 2 Diabetes and Alzheimer's Disease 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.04.13.463890v1?rss=1</link>
<description><![CDATA[
Insulin resistance (IR) is a physiological condition in which cells in the body become resistant to insulin. It is a known risk factor associated to type 2 diabetes (T2D). Recently, the idea that IR plays an important role in the progression of Alzheimers disease (AD) has been gaining a lot of attention. Comparing the components of the insulin signalling pathway in relation to T2D and AD, there seems to be a lot of commonality. However, on what role IR plays in linking T2D and AD remains unknown. Through systems biology approach, we extended an existing mathematical model (i.e. ODE based) to study and understand the role IR plays in linking T2D and AD. The simulations, together with the experimental data collected from the literature, show that the common components in T2D and AD express the same dynamical behaviors. This result provides the bases for further modelling of the insulin signaling pathway in determining the link between T2D and AD.
]]></description>
<dc:creator>Lao, A. R.</dc:creator>
<dc:creator>Villasis, O. B. T.</dc:creator>
<dc:creator>Tan, D. S.</dc:creator>
<dc:creator>Mendoza, E.</dc:creator>
<dc:date>2022-04-15</dc:date>
<dc:identifier>doi:10.1101/2022.04.13.463890</dc:identifier>
<dc:title><![CDATA[Systems Biology Approach of Understanding Insulin Resistance: Linkage between Type 2 Diabetes and Alzheimer's Disease]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-04-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.04.19.488843v1?rss=1">
<title>
<![CDATA[
Broadly neutralizing antibodies against Omicron variants of SARS-CoV-2 derived from mRNA-lipid nanoparticle-immunized mice 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.04.19.488843v1?rss=1</link>
<description><![CDATA[
The COVID-19 pandemic continues to threaten human health worldwide, as new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged. Currently, the predominant circulating strains around the world are Omicron variants, which can evade many therapeutic antibodies. Thus, the development of new broadly neutralizing antibodies remains an urgent need. In this work, we address this need by using the mRNA-lipid nanoparticle immunization method to generate a set of Omicron-targeting monoclonal antibodies. Five of our novel K-RBD-mAbs show strong binding and neutralizing activities toward all SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, Delta and Omicron). Notably, the epitopes of these five K-RBD-mAbs are overlapping and localized around K417 and F486 of the spike protein receptor binding domain (RBD). Chimeric derivatives of the five antibodies (K-RBD-chAbs) neutralize Omicron sublineages BA.1 and BA.2 with low IC50 values that range from 5.7 to 12.9 ng/mL. Additionally, we performed antibody humanization on a broadly neutralizing chimeric antibody to create K-RBD-hAb-62, which still retains excellent neutralizing activity against Omicron. Our results collectively suggest that these five therapeutic antibodies may effectively combat current and emerging SARS-CoV-2 variants, including Omicron BA.1 and BA.2. Therefore, the antibodies can potentially be used as universal neutralizing antibodies against SARS-CoV-2.
]]></description>
<dc:creator>Lu, R.-M.</dc:creator>
<dc:creator>Liang, K.-H.</dc:creator>
<dc:creator>Chiang, H.-L.</dc:creator>
<dc:creator>Hsu, F.-F.</dc:creator>
<dc:creator>Lin, H.-T.</dc:creator>
<dc:creator>Chen, W.-Y.</dc:creator>
<dc:creator>Ke, F.-Y.</dc:creator>
<dc:creator>Kumari, M.</dc:creator>
<dc:creator>Chou, Y.-C.</dc:creator>
<dc:creator>Wu, H.-C.</dc:creator>
<dc:date>2022-04-20</dc:date>
<dc:identifier>doi:10.1101/2022.04.19.488843</dc:identifier>
<dc:title><![CDATA[Broadly neutralizing antibodies against Omicron variants of SARS-CoV-2 derived from mRNA-lipid nanoparticle-immunized mice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-04-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.04.20.488878v1?rss=1">
<title>
<![CDATA[
An Efficient Approach for SARS-CoV-2 Monoclonal Antibody Production via Modified mRNA-LNP Immunization 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.04.20.488878v1?rss=1</link>
<description><![CDATA[
Throughout the COVID-19 pandemic, many prophylactic and therapeutic drugs have been evaluated and introduced. Among these treatments, monoclonal antibodies (mAbs) that bind to and neutralize SARS-CoV-2 virus have been applied as complementary and alternative treatments to vaccines. Although different methodologies have been utilized to produce mAbs, traditional hybridoma fusion technology is still commonly used for this purpose due to its unmatched performance record. In this study, we coupled the hybridoma fusion strategy with mRNA-lipid nanoparticle (LNP) immunization. This time-saving approach can circumvent biological and technical hurdles, such as difficult to express membrane proteins, antigen instability, and the lack of posttranslational modifications on recombinant antigens. We used mRNA-LNP immunization and hybridoma fusion technology to generate mAbs against the receptor binding domain (RBD) of SARS-CoV-2 spike (S) protein. Compared with traditional protein-based immunization approaches, inoculation of mice with RBD mRNA-LNP induced higher titers of serum antibodies. In addition, the mAbs we obtained can bind to SARS-CoV-2 RBDs from several variants. Notably, RBD-mAb-3 displayed particularly high binding affinities and neutralizing potencies against both Alpha and Delta variants. In addition to introducing specific mAbs against SARS-CoV-2, our data generally demonstrate that mRNA-LNP immunization may be useful to quickly generate highly functional mAbs against emerging infectious diseases.
]]></description>
<dc:creator>Hsu, F.-F.</dc:creator>
<dc:creator>Liang, K.-H.</dc:creator>
<dc:creator>Kumari, M.</dc:creator>
<dc:creator>Chen, W. Y.</dc:creator>
<dc:creator>Lin, H. T.</dc:creator>
<dc:creator>Cheng, C. M.</dc:creator>
<dc:creator>Tao, M.-H.</dc:creator>
<dc:creator>Wu, H.-C.</dc:creator>
<dc:date>2022-04-22</dc:date>
<dc:identifier>doi:10.1101/2022.04.20.488878</dc:identifier>
<dc:title><![CDATA[An Efficient Approach for SARS-CoV-2 Monoclonal Antibody Production via Modified mRNA-LNP Immunization]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-04-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.04.20.488885v1?rss=1">
<title>
<![CDATA[
Adaptive plasticity in the healthy reading network investigated through combined neurostimulation and neuroimaging 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.04.20.488885v1?rss=1</link>
<description><![CDATA[
The reading network in the human brain comprises several regions, including the left inferior frontal cortex (IFC), ventral occipito-temporal cortex (vOTC) and dorsal temporo-parietal cortex (TPC). The left TPC is crucial for phonological decoding, i.e., for learning and retaining sound-letter mappings. Here, we tested the causal contribution of this area for reading with repetitive transcranial magnetic stimulation (rTMS) and explored the response of the reading network using functional magnetic resonance imaging (fMRI). 28 healthy adult readers overtly read simple and complex words and pseudowords during fMRI after effective or sham TMS over the left TPC. Behaviorally, effective stimulation slowed pseudoword reading. A multivariate pattern analysis showed a shift in activity patterns in the left IFC for pseudoword reading after effective relative to sham TMS. Furthermore, active TMS led to increased effective connectivity from the left vOTC to the left TPC, specifically for pseudoword processing. The observed changes in task-related activity and connectivity suggest compensatory reorganization in the reading network following TMS-induced disruption of the left TPC. Our findings provide first evidence for a causal role of the left TPC for overt pseudoword reading and emphasize the relevance of functional interactions in the healthy reading network for successful pseudoword processing.
]]></description>
<dc:creator>Turker, S.</dc:creator>
<dc:creator>Kuhnke, P.</dc:creator>
<dc:creator>Schmid, F. R.</dc:creator>
<dc:creator>Cheung, V. K. M.</dc:creator>
<dc:creator>Zeidler, B.</dc:creator>
<dc:creator>Seidel, K.</dc:creator>
<dc:creator>Eckert, L.</dc:creator>
<dc:creator>Hartwigsen, G.</dc:creator>
<dc:date>2022-04-21</dc:date>
<dc:identifier>doi:10.1101/2022.04.20.488885</dc:identifier>
<dc:title><![CDATA[Adaptive plasticity in the healthy reading network investigated through combined neurostimulation and neuroimaging]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-04-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.04.21.488980v1?rss=1">
<title>
<![CDATA[
Inducible lncRNA transgenic mice reveal continual role of HOTAIR in promoting breast cancer metastasis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.04.21.488980v1?rss=1</link>
<description><![CDATA[
HOTAIR is a 2.2 kb long noncoding RNA (lncRNA) whose dysregulation has been linked to oncogenesis, defects in pattern formation during early development, and irregularities during the process of epithelial-to-mesenchymal transition (EMT). However, the oncogenic transformation determined by HOTAIR in vivo and its impact on chromatin dynamics are incompletely understood. Here we generate a transgenic mouse model with doxycycline-inducible expression of human HOTAIR in the context of the MMTV-PyMT breast cancer-prone background to systematically interrogate the cellular mechanisms by which human HOTAIR lncRNA acts to promote breast cancer progression. We show that sustained high levels of HOTAIR over time increased breast metastatic capacity and invasiveness in breast cancer cells, promoting migration and subsequent metastasis to the lung. Subsequent withdrawal of HOTAIR overexpression reverted the metastatic phenotype, indicating oncogenic lncRNA addiction. Furthermore, HOTAIR overexpression altered both the cellular transcriptome and chromatin accessibility landscape of multiple metastasis-associated genes and promoted epithelial to mesenchymal transition. These alterations are abrogated within several cell cycles after HOTAIR expression is reverted to basal levels, indicating an erasable lncRNA-associated epigenetic memory. These results suggest that a continual role for HOTAIR in programming a metastatic gene regulatory program. Targeting HOTAIR lncRNA may potentially serve as a therapeutic strategy to ameliorate breast cancer progression.
]]></description>
<dc:creator>Ma, Q.</dc:creator>
<dc:creator>Yang, L.</dc:creator>
<dc:creator>Tolentino, K.</dc:creator>
<dc:creator>Zhao, Y.</dc:creator>
<dc:creator>Lizenburger, U. M.</dc:creator>
<dc:creator>Shi, Q.</dc:creator>
<dc:creator>Zhu, L.</dc:creator>
<dc:creator>Tsai, M.-C.</dc:creator>
<dc:creator>Chen, J.-A.</dc:creator>
<dc:creator>Lai, I.</dc:creator>
<dc:creator>Zeng, H.</dc:creator>
<dc:creator>Li, L.</dc:creator>
<dc:creator>Chang, H.</dc:creator>
<dc:date>2022-04-22</dc:date>
<dc:identifier>doi:10.1101/2022.04.21.488980</dc:identifier>
<dc:title><![CDATA[Inducible lncRNA transgenic mice reveal continual role of HOTAIR in promoting breast cancer metastasis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-04-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.04.21.489006v1?rss=1">
<title>
<![CDATA[
Detecting intragenic trans-splicing events with hybrid transcriptome sequencing in cancer cells 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.04.21.489006v1?rss=1</link>
<description><![CDATA[
Trans-splicing can generate non-co-linear (NCL) transcripts that consist of exons in an order topologically inconsistent with the corresponding DNA template. Detecting trans-spliced RNAs (ts-RNAs) may be interfered by false positives from experimental artifacts, circular RNAs (circRNAs), and genetic rearrangements. Particularly, intragenic ts-RNAs, which are derived from separate precursor mRNA molecules of the same genes, are often mistaken for circRNAs through analyses of high-throughput transcriptome sequencing (RNA-seq) data. In addition, the biogenesis and function of ts-RNAs remain elusive. Here we developed a bioinformatics pipeline, NCLscan-hybrid, with the integration of long and short RNA-seq reads to minimize false positives and identify intragenic ts-RNAs. We utilized two features of long reads, out-of-circle and rolling circle, to distinguish intragenic ts-RNAs from circRNAs. We also designed multiple experimental validation steps to examine each type of false positives and successfully confirmed an intragenic ts-RNA (ts-ARFGEF1) in breast cancer cells. On the basis of ectopic expression and CRISPR-based endogenous genome modification experiments, we confirmed that ts-ARFGEF1 formation was significantly dependent on the reverse complementary sequences in the flanking introns of the NCL junction. Subsequent in vitro and in vivo experiments demonstrated that ts-ARFGEF1 silencing can significantly inhibit tumor cell growth. We further showed the regulatory role of ts-ARFGEF1 in p53-mediated apoptosis through affecting the PERK/eIF2a/ATF4/CHOP signaling pathway in breast cancer cells. This study thus described both bioinformatics procedures and experimental validation steps for rigorous characterization of transcriptionally non-co-linear RNAs, expanding the discovery of this important but understudied class of RNAs.
]]></description>
<dc:creator>Chen, Y.-C.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Chiang, T.-W.</dc:creator>
<dc:creator>Chan, M.-H.</dc:creator>
<dc:creator>Hsiao, M.</dc:creator>
<dc:creator>Ke, H.-M.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:creator>Chuang, T.-J.</dc:creator>
<dc:date>2022-04-22</dc:date>
<dc:identifier>doi:10.1101/2022.04.21.489006</dc:identifier>
<dc:title><![CDATA[Detecting intragenic trans-splicing events with hybrid transcriptome sequencing in cancer cells]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-04-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.04.24.489284v1?rss=1">
<title>
<![CDATA[
The association between working memory precision and the nonlinear dynamics of frontal and parieto-occipital EEG activity. 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.04.24.489284v1?rss=1</link>
<description><![CDATA[
Electrophysiological working memory (WM) research has shown that distinct brain areas communicate through macroscopic oscillatory activities across multiple frequency bands. Such cross-frequency interactions generate nonlinear amplitude modulations (AM) in the observed signal. Traditionally, the AM of a signal is expressed as coupling strength between the signal and a pre-specified modulator at a lower frequency. Therefore, the idea of AM and coupling cannot be separately studied. This EEG study shows that the AM of parieto-occipital alpha/beta power and the coupling between frontal theta phase and parieto-occipital alpha/beta AM provide different information on WM processing. Thirty-three participants completed a color recall task with simultaneous EEG recording. The results showed that individual differences in WM precision are associated with frontal theta power enhancement and parieto-occipital alpha/beta power suppression. Furthermore, the AM of parieto-occipital alpha/beta power predicted WM precision after presenting a target-defining probe array. The phase-amplitude coupling (PAC) between frontal theta phase and parieto-occipital alpha/beta AM increased with WM load during the processing of incoming stimuli, but they did not predict the subsequent recall performance. These results indicate that the frontoparietal PAC reflects the executive control for selecting relevant WM representations, but whether the memorized information can be retrieved depends on the subsequent amplitude variation of parieto-occipital alpha/beta power. In conclusion, individuals with higher working memory precision are associated with enhanced frontal theta power and parieto-occipital alpha/beta power suppression.
]]></description>
<dc:creator>Chang, W.-S.</dc:creator>
<dc:creator>Liang, W.-K.</dc:creator>
<dc:creator>Li, D.-H.</dc:creator>
<dc:creator>Muggleton, N. G.</dc:creator>
<dc:creator>Balachandran, P.</dc:creator>
<dc:creator>Huang, N. E.</dc:creator>
<dc:creator>Juan, C.-H.</dc:creator>
<dc:date>2022-04-25</dc:date>
<dc:identifier>doi:10.1101/2022.04.24.489284</dc:identifier>
<dc:title><![CDATA[The association between working memory precision and the nonlinear dynamics of frontal and parieto-occipital EEG activity.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-04-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.04.25.489342v1?rss=1">
<title>
<![CDATA[
Sensor NLR immune proteins activate oligomerization of their NRC helper 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.04.25.489342v1?rss=1</link>
<description><![CDATA[
Nucleotide-binding domain and leucine-rich repeat (NLR) immune receptors are important components of plant and metazoan innate immunity that can function as individual units or as pairs or networks. Upon activation, NLRs form multiprotein complexes termed resistosomes or inflammasomes. Whereas metazoan paired NLRs, such as NAIP/NLRC4, activate into hetero-complexes, the molecular mechanisms underpinning activation of plant paired NLRs, especially whether they associate in resistosome hetero-complexes is unknown. In asterid plant species, the NLR required for cell death (NRC) immune receptor network is composed of multiple resistance protein sensors and downstream helpers that confer immunity against diverse plant pathogens. Here, we show that pathogen effector-activation of the NLR proteins Rx (confers virus resistance) and Bs2 (confers bacterial resistance) leads to oligomerization of the helper NLR NRC2. Activated Rx does not oligomerize or enter into a stable complex with the NRC2 oligomer and remains cytoplasmic. In contrast, activated NRC2 oligomers accumulate in membrane-associated puncta. We propose an activation-and-release model for NLRs in the NRC immune receptor network. This points to a distinct activation model compared to mammalian paired NLRs.
]]></description>
<dc:creator>Contreras, M. P.</dc:creator>
<dc:creator>Pai, H.</dc:creator>
<dc:creator>Tumtas, Y.</dc:creator>
<dc:creator>Duggan, C.</dc:creator>
<dc:creator>Yuen, E. L. H.</dc:creator>
<dc:creator>Vergara Cruces, A.</dc:creator>
<dc:creator>Kourelis, J.</dc:creator>
<dc:creator>Ahn, H.-K.</dc:creator>
<dc:creator>Wu, C.-H.</dc:creator>
<dc:creator>Bozkurt, T. O.</dc:creator>
<dc:creator>Derevnina, L.</dc:creator>
<dc:creator>Kamoun, S.</dc:creator>
<dc:date>2022-04-25</dc:date>
<dc:identifier>doi:10.1101/2022.04.25.489342</dc:identifier>
<dc:title><![CDATA[Sensor NLR immune proteins activate oligomerization of their NRC helper]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-04-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.04.28.489888v1?rss=1">
<title>
<![CDATA[
Divergence of trafficking and polarity mechanisms for PIN auxin transporters during land plant evolution 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.04.28.489888v1?rss=1</link>
<description><![CDATA[
The phytohormone auxin and its directional transport through tissues play a fundamental role in development of higher plants. This polar auxin transport predominantly relies on PIN-FORMED (PIN) auxin exporters. Hence, PIN polarization is crucial for development, but its evolution during the rise of morphological complexity in land plants remains unclear. Here, we performed a cross-species investigation by observing the trafficking and localization of endogenous and xenologous PINs in two bryophytes, Physcomitrium patens and Marchantia polymorpha, and in the flowering plant Arabidopsis thaliana. We confirmed that the GFP fusion did not compromise the auxin export function of all examined PINs by using radioactive auxin export assay and by observing the phenotypic changes in transgenic bryophytes. Endogenous PINs polarize to filamentous apices, while xenologous Arabidopsis PINs distribute symmetrically on the membrane in both bryophytes. In Arabidopsis root epidermis, bryophytic PINs show no defined polarity. Pharmacological interference revealed a strong cytoskeleton dependence of bryophytic but not Arabidopsis PIN polarization. The divergence of PIN polarization and trafficking is also observed within the bryophyte clade and between tissues in individual species. These results collectively reveal a divergence of PIN trafficking and polarity mechanisms throughout land plant evolution and a co-evolution of PIN sequence-based and cell-based polarity mechanisms.
]]></description>
<dc:creator>Tang, H.</dc:creator>
<dc:creator>Lu, K.-J.</dc:creator>
<dc:creator>Cheng, Y.-L.</dc:creator>
<dc:creator>Tu, S.-L.</dc:creator>
<dc:creator>Friml, J.</dc:creator>
<dc:date>2022-04-30</dc:date>
<dc:identifier>doi:10.1101/2022.04.28.489888</dc:identifier>
<dc:title><![CDATA[Divergence of trafficking and polarity mechanisms for PIN auxin transporters during land plant evolution]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-04-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.05.03.490475v1?rss=1">
<title>
<![CDATA[
Manufacturing highly potent CD20/CD19-targeted iCasp9 regulatable CAR-T cells using the Quantum pBac-based CAR-T (qCART) system for clinical application 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.05.03.490475v1?rss=1</link>
<description><![CDATA[
BackgroundCD19-targeted chimeric antigen receptor therapies (CAR19) have driven a paradigm shift in the treatment of relapsed/refractory B-cell malignancies. However, >50% of CAR19-treated patients experienced progressive disease mainly due to antigen escape and low persistence. Clinical prognosis is heavily influenced by CAR-T cell function and systemic cytokine toxicities. Furthermore, it remains a challenge to efficiently, cost-effectively, and consistently manufacture clinically relevant number of virally engineered CAR-T cells.

MethodsUsing a highly efficient piggyBac transposon-based vector, Quantum pBac, we developed a virus-free cell engineering system, Quantum CART (qCART), for development and production of multiplex CAR-T therapies.

ResultsHere, we demonstrated in vitro and in vivo that consistent, robust, and functional CD20/CD19 dual-targeted CAR-T stem cell memory (TSCM) cells can be efficiently manufactured using the qCART system for clinical application. qCART-manufactured CAR-T cells from cancer patients expanded efficiently, rapidly eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug.

ConclusionsThe qCART system is an elegant system for the manufacturing of CAR-T products having all the desired CAR-T therapy attributes. We believe that the simplicity of manufacturing multiplex CAR-T cells using the qCART system will not only significantly enhance the accessibility of CAR-T therapy but also unlock the full potential of armored CAR-T therapy for the treatment of solid tumors in the future.

What is already known on this topicDespite the considerable success which has been achieved with CD19-targeted chimeric antigen receptor therapies (CAR19), >50% of CAR19-treated patients still experienced progressive disease. Therefore, there is a need to further improve CAR19 therapies. Current CAR19 therapies commonly utilize virus-based cell engineering methods. CAR-T production using these methods face multiple hurdles, including difficulties to efficiently, cost-effectively, and consistently manufacture clinically relevant number of CAR-T cells. We have previously used a highly efficient piggyBac transposon-based vector, Quantum pBac, to establish Quantum CART (qCART) which is a virus-free cell engineering system for development and production of multiplex CAR-T therapies.

What this study addsIn this report, we further demonstrate in vitro and in vivo that consistent, robust, and functional iCasp9-regulatable, CD20/CD19 dual-targeted CAR-T stem cell memory (TSCM) cells can be efficiently manufactured using the qCART system for clinical application. These cells possess all the desired attributes for ensuring therapeutic efficacy in CAR-T therapy, including high CAR-TSCM, balanced CD8/CD4 ratio, low exhaustion and senescence marker expressions, and high ex vivo and in vivo expansion capacity. Importantly, we show that qCART-manufactured CAR-T cells from hematological cancer patients expanded efficiently, effectively eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug. We believe that the simplicity of manufacturing multiplex CAR-T cells using the qCART system will not only significantly enhance the accessibility of CAR-T therapy but also unlock the full potential of armored CAR-T therapy for the treatment of solid tumors in the future.

How this study might affect research, practice or policyOur findings demonstrate that qCART is a virus-free CAR-T engineering system for manufacturing CAR-TSCM cells from either healthy donors or hematological cancer patients, that possess all the desired attributes for a successful CAR-T therapy. These cells expanded efficiently, rapidly eradicated tumors, and can be safely controlled via activation of iCasp9. We expect that this simple yet robust system for manufacturing multiplex CAR-T cells will advance the CAR-T field.
]]></description>
<dc:creator>Chen, Y.-C.</dc:creator>
<dc:creator>Chang, P. S.</dc:creator>
<dc:creator>Hua, W.-K.</dc:creator>
<dc:creator>Hsu, J. C.</dc:creator>
<dc:creator>Tsai, J.-C.</dc:creator>
<dc:creator>Huang, Y.-W.</dc:creator>
<dc:creator>Kao, Y.-H.</dc:creator>
<dc:creator>Wu, P.-H.</dc:creator>
<dc:creator>Chang, Y.-F.</dc:creator>
<dc:creator>Chang, M. C.</dc:creator>
<dc:creator>Chang, Y. C.</dc:creator>
<dc:creator>Wen, K.-L. K.</dc:creator>
<dc:creator>Wu, S. C.-Y.</dc:creator>
<dc:date>2022-05-04</dc:date>
<dc:identifier>doi:10.1101/2022.05.03.490475</dc:identifier>
<dc:title><![CDATA[Manufacturing highly potent CD20/CD19-targeted iCasp9 regulatable CAR-T cells using the Quantum pBac-based CAR-T (qCART) system for clinical application]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-05-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.05.03.490558v1?rss=1">
<title>
<![CDATA[
The soil microbiome may offer solutions to ginger cultivation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.05.03.490558v1?rss=1</link>
<description><![CDATA[
The Taitung region is one of Taiwans main places for ginger agriculture. Due to issues with disease and nutrient, farmers cannot use continuous cropping techniques on ginger, meaning that the ginger industry is constantly searching for new lands. Continuous cropping increases the risk of infection by Pythium myriotylum and Ralstonia solanacearum, which cause soft rot disease and bacterial wilt, respectively. In addition, fertilizer additives cannot recover the soil when using continuous cropping on ginger, even when there is no decrease in trace elements observed in the soil. Although there may be other reasons for the reduction in production, such as soil microbes, we know little about the soil microbiome associated with ginger cultivation. Hence, in this study, we used the bacterial 16S V3-V4 hypervariable region of the 16S ribosomal RNA region to investigate microbe compositions in ginger soil to identify the difference between ginger soil with and without disease. Later, to investigate the influence of the well-known biocontrol agent-B. velezensis and fungicide Etridiazole on soil microbes and ginger productivity, we designed an experiment that collected the soil samples according to the different ginger cultivation periods to examine the microbial community dynamics in the rhizome and bulk soil. We demonstrated that B. velezensis is beneficial to ginger reproduction and suggest that it may influence the plant by adjusting its soil microbial composition. Etridiazole, on the other hand, may have some side effects on the ginger or beneficial bacteria in the soils, inhibiting ginger reproduction.
]]></description>
<dc:creator>Wang, C.-W.</dc:creator>
<dc:creator>Michelle Wong, J.-W.</dc:creator>
<dc:creator>Yeh, S.-S.</dc:creator>
<dc:creator>Eric Hsieh, Y.</dc:creator>
<dc:creator>Tseng, C.-H.</dc:creator>
<dc:creator>Yang, S.-H.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:date>2022-05-04</dc:date>
<dc:identifier>doi:10.1101/2022.05.03.490558</dc:identifier>
<dc:title><![CDATA[The soil microbiome may offer solutions to ginger cultivation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-05-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.05.31.493688v1?rss=1">
<title>
<![CDATA[
The histone variant H2A.W cooperates with chromatin modifications and linker histone H1 to maintain transcriptional silencing of transposons in Arabidopsis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.05.31.493688v1?rss=1</link>
<description><![CDATA[
Transposable elements (TEs) are marked by a complex array of chromatin modifications, but a central unifying mechanism for how they are silenced remains elusive. Histone H3 Lysine 9 methylation (H3K9me) is an important component of heterochromatin in most eukaryotes, including plants. In flowering plants, the specialized histone variant H2A.W occupies nucleosomes found at TE sequences. This variant is deposited by the chromatin remodeler DDM1 and confers specific biophysical properties to the nucleosomes.

Here we use genetic and genomic strategies to evaluate the role of H2A.W in transposon silencing in Arabidopsis. Compared with mutants lacking either H2A.W or H3K9me, the combined loss of both H2A.W and H3K9me causes a dramatic increase in both the number of expressed TEs and their expression levels. Synergistic effects are also observed when H2A.W is lost in combination with histone H1 or CH methylation. Collectively, these TEs are also upregulated in mutants lacking DDM1, which are impaired in H2A.W deposition and lose heterochromatic marks.

We conclude that H2A.W acts in combination with different elements of heterochromatin to maintain silencing across a large spectrum of TEs present primarily in pericentric heterochromatin in Arabidopsis. In mammals, the DDM1 ortholog LSH deposits macroH2A to heterochromatin and silences TEs. We thus propose that specialized H2A variants localized to heterochromatin interact with a complex array of histone modifications to silence TEs in eukaryotes.
]]></description>
<dc:creator>Bourguet, P.</dc:creator>
<dc:creator>Yelagandula, R.</dc:creator>
<dc:creator>To, T. K.</dc:creator>
<dc:creator>Osakabe, A.</dc:creator>
<dc:creator>Alishe, A.</dc:creator>
<dc:creator>Lu, R. J.-H.</dc:creator>
<dc:creator>Kakutani, T.</dc:creator>
<dc:creator>Chen, P.-Y.</dc:creator>
<dc:creator>Berger, F.</dc:creator>
<dc:date>2022-05-31</dc:date>
<dc:identifier>doi:10.1101/2022.05.31.493688</dc:identifier>
<dc:title><![CDATA[The histone variant H2A.W cooperates with chromatin modifications and linker histone H1 to maintain transcriptional silencing of transposons in Arabidopsis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-05-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.06.04.494804v1?rss=1">
<title>
<![CDATA[
ECM-derived biophysical cues mediate interstitial flow-induced sprouting angiogenesis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.06.04.494804v1?rss=1</link>
<description><![CDATA[
Sprouting angiogenesis is orchestrated by an intricate balance of biochemical and mechanical cues in the local microenvironment. Interstitial flow has been established as a potent regulator of angiogenesis. Similarly, extracellular matrix (ECM) physical properties, such as stiffness and microarchitecture, have also emerged as important mediators of angiogenesis. Yet, the interplay between interstitial flow and ECM physical properties in the initiation and control of angiogenesis is poorly understood. Using a 3-D microfluidic tissue analogue of angiogenic sprouting with defined interstitial flow, we found that the addition of hyaluronan (HA) to collagen-based matrices significantly enhances sprouting induced by interstitial flow compared to responses in collagen-only hydrogels. We confirmed that both the stiffness and matrix pore size of collagen-only hydrogels were increased by the addition of HA. Interestingly, interstitial flow-potentiated sprouting responses in collagen/HA matrices were not affected when functionally blocking the HA receptor CD44. In contrast, enzymatic depletion of HA in collagen/HA matrices with hyaluronidase (HAdase) resulted in decreased stiffness, pore size, and interstitial flow-mediated sprouting to the levels observed in collagen-only matrices. Taken together, these results suggest that HA enhances interstitial flow-mediated angiogenic sprouting through its alterations to collagen ECM stiffness and pore size.
]]></description>
<dc:creator>Chang, C.-W.</dc:creator>
<dc:creator>Shih, H.-C.</dc:creator>
<dc:creator>Cortes-Medina, M.</dc:creator>
<dc:creator>Beshay, P. E.</dc:creator>
<dc:creator>Avendano, A.</dc:creator>
<dc:creator>Seibel, A. J.</dc:creator>
<dc:creator>Liao, W.-H.</dc:creator>
<dc:creator>Tung, Y.-C.</dc:creator>
<dc:creator>Song, J. W.</dc:creator>
<dc:date>2022-06-05</dc:date>
<dc:identifier>doi:10.1101/2022.06.04.494804</dc:identifier>
<dc:title><![CDATA[ECM-derived biophysical cues mediate interstitial flow-induced sprouting angiogenesis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-06-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.06.09.495492v1?rss=1">
<title>
<![CDATA[
An atypical F-actin capping protein modulates cytoskeleton behaviors crucial to colonization of Trichomonas vaginalis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.06.09.495492v1?rss=1</link>
<description><![CDATA[
Cytoadherence and consequential migration are crucial for pathogens to establish colonization in the host. In contrast to the nonadherent isolate of Trichomonas vaginalis, the adherent one expresses more actin-related machinery proteins with more active flagellate-amoeboid morphogenesis, amoeba migration, and cytoadherence, activities that were abrogated by an actin assembly blocker. By immunoprecipitation coupled with label-free quantitative proteomics, an F-actin capping protein (TvFACP) was identified from the actin-centric interactome, with an atypically greater binding preference to G-actin than F-actin. TvFACP partially colocalized with F-actin at the parasite pseudopodia protrusion and formed the protein complexes with -actin through its c-terminal domain. Meanwhile, TvFACP overexpression suppresses F-actin polymerization, amoeboid morphogenesis, and cytoadherence in this parasite. Ser2 phosphorylation of TvFACP enriched in the amoeboid stage of adhered trophozoites was reduced by a CKII inhibitor. The site-directed mutagenesis and CKII inhibitor treatment revealed that Ser2 phosphorylation acts as a switching signal to alter TvFACP actin-binding activity and consequent actin cytoskeleton behaviors. Through CKII signaling, TvFACP also controls the conversion of adherent trophozoite from amoeboid migration to flagellate form with axonemal motility. Together, CKII-dependent Ser2 phosphorylation regulates TvFACP binding actin to fine-tune cytoskeleton dynamics and drive crucial behaviors underlying host colonization of T. vaginalis.
]]></description>
<dc:creator>Wang, K.-H.</dc:creator>
<dc:creator>Chang, J.-Y.</dc:creator>
<dc:creator>Li, F.-A.</dc:creator>
<dc:creator>Chen, Y.-J.</dc:creator>
<dc:creator>Wu, K.-Y.</dc:creator>
<dc:creator>Chu, T.-L.</dc:creator>
<dc:creator>Lin, J.</dc:creator>
<dc:creator>Hsu, H.-M.</dc:creator>
<dc:date>2022-06-09</dc:date>
<dc:identifier>doi:10.1101/2022.06.09.495492</dc:identifier>
<dc:title><![CDATA[An atypical F-actin capping protein modulates cytoskeleton behaviors crucial to colonization of Trichomonas vaginalis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-06-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.06.10.495707v1?rss=1">
<title>
<![CDATA[
Insights into deuterostome evolution from the biphasic transcriptional programmes of hemichordates 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.06.10.495707v1?rss=1</link>
<description><![CDATA[
Evolutionary history of deuterostomes remains unsolved and is intimately related to the origin of chordates. Among deuterostomes, hemichordates and echinoderms (collectively called Ambulacraria) are sister groups of chordates. Comparative studies involving these three groups provide valuable insights into deuterostome evolution. Indirect developing hemichordates produce planktonic larvae that bear resemblance to echinoderm larvae before undergoing metamorphosis into an adult body plan with anteroposterior polarity homologous to that of chordates. Therefore, understanding the developmental processes of indirect-developing hemichordates can help understand the evolution of deuterostomes and the origins of chordates. In this study, we analysed the transcriptomes and chromatin accessibility of multiple developmental stages of the indirect-developing hemichordate Ptychodera flava and discovered that it exhibits a biphasic developmental program controlled by distinct sets of transcription factors and their corresponding regulatory elements. Comparative analyses of transcriptomes and network analyses revealed that the gastrula transcriptome is relatively ancient, and the TFs orchestrating its gene expression are highly interconnected in networks of cis-regulatory interactions. Comparing the developmental transcriptomes of hemichordates, echinoderms, and amphioxus, revealed high conservation of gene expression during gastrulation that extends to the neurula stages of amphioxus, along with remarkable similarity in larval transcriptomes across the three species. Additionally, we show that P. flava possesses conserved interactions of transcription factors necessary for the development of echinoderm endomesoderm and chordate axial mesoderm, including conserved cis-regulatory elements of the FoxA transcription factor that is central to the two networks. These findings suggest the existence of a deuterostome phylotypic stage during gastrulation governed by gene regulatory networks with conserved cis-regulatory interactions. Conversely, integration of gene expression data with synteny data revealed that gene expression recapitulates the independent evolutionary history of the Ancestral Linkage Groups that underwent rearrangements in each deuterostome lineage, suggesting a potential role of genome rearrangement during the evolution of larval strategies in hemichordates and deuterostome body plans.
]]></description>
<dc:creator>Perez-Posada, A.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Chen, Y.-C.</dc:creator>
<dc:creator>Gomez-Skarmeta, J. L.</dc:creator>
<dc:creator>Yu, J.-K.</dc:creator>
<dc:creator>Su, Y.-H.</dc:creator>
<dc:creator>Tena, J. J.</dc:creator>
<dc:date>2022-06-12</dc:date>
<dc:identifier>doi:10.1101/2022.06.10.495707</dc:identifier>
<dc:title><![CDATA[Insights into deuterostome evolution from the biphasic transcriptional programmes of hemichordates]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-06-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.06.15.496250v1?rss=1">
<title>
<![CDATA[
Rapid compensatory evolution by secondary perturbation of a primary disrupted transcriptional network 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.06.15.496250v1?rss=1</link>
<description><![CDATA[
The discrete steps of transcriptional rewiring have been proposed to occur neutrally to ensure steady gene expression under stabilizing selection over long time-scales, especially when a regulon is being transferred from one transcription factor (TF) to another. Cooperative DNA binding between redundant regulatory components at the intermediate transition stage is believed to mediate this process, enabling a conflict-free switch between two TFs without a disruptive change in gene expression. Here, we have performed an evolutionary repair experiment on the Lachancea kluyveri yeast sef1{Delta} mutant by means of a suppressor development strategy. Complete loss of SEF1 forced cells to activate a rewiring process to compensate for the pleiotropic defects arising from misexpression of multiple TCA cycle genes. Using different selective conditions, we identified one generalist and one specialist suppressive loss-of-function mutation of IRA1 and AZF1, respectively. Our subsequent analyses show that Azf1 is a weak transcriptional activator regulated by the Ras1-PKA pathway. Azf1 loss-of-function triggers extensive gene expression changes responsible for both the compensatory and trade-off phenotypes. Our results indicate that the pleiotropic effects of dual perturbation of transcriptional networks are a potential mechanism for rapid adaptive compensation, facilitating the process of incipient transcriptional rewiring, and formation of complex traits.
]]></description>
<dc:creator>Hsu, P.-C.</dc:creator>
<dc:creator>Cheng, Y.-H.</dc:creator>
<dc:creator>Liao, C.-W.</dc:creator>
<dc:creator>Jhou, Y.-T.</dc:creator>
<dc:creator>Opoc, F. J. G.</dc:creator>
<dc:creator>Amine, A. A. A.</dc:creator>
<dc:creator>Leu, J.-Y.</dc:creator>
<dc:date>2022-06-16</dc:date>
<dc:identifier>doi:10.1101/2022.06.15.496250</dc:identifier>
<dc:title><![CDATA[Rapid compensatory evolution by secondary perturbation of a primary disrupted transcriptional network]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-06-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.07.04.498645v1?rss=1">
<title>
<![CDATA[
Spatial and temporal origin of the third SARS-CoV-2 Outbreak in Taiwan 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.07.04.498645v1?rss=1</link>
<description><![CDATA[
Since the first report of SARS-CoV-2 in December 2019, Taiwan has gone through three local outbreaks. Unlike the first two outbreaks, the spatial and temporal origin of the third outbreak (April 20 to November 5, 2021) is still unclear. We assembled and analyzed a data set of more than 6,000 SARS-CoV-2 genomes, including 300 from Taiwan and 5812 related sequences downloaded from GISAID as of 2021/12/08. We found that the third outbreak in Taiwan was caused by a single virus lineage belonging to Alpha (B.1.1.7) strain. This lineage, T-III (the third outbreak in Taiwan), carries a distinct genetic fingerprint, consisting of spike M1237I (S-M1237I) and three silent mutations, C5812T, C15895T, and T27869C. The T-III is closest to the sequences derived from Turkey on February 8, 2021. The estimated age of the most recent common ancestor (TMRCA) of T-III is March 23, 2021 (95% highest posterior density [HPD] February 24 - April 13, 2021), almost one month before the first three confirmed cases on April 20, 2021. The effective population size of the T-III showed approximately 20-fold increase after the onset of the outbreak and reached a plateau in early June 2021. Our results reconcile several unresolved observations, including the occurrence of two infection clusters at the same time without traceable connection and several airline pilots who were PCR negative but serum IgM-/IgG+ for SARS-CoV-2 in late April. Therefore, in contrast to the general notion that the third SARS-CoV-2 outbreak in Taiwan was sparked by two imported cases from USA on April 20, 2021, which, in turn, was caused by the partial relaxation of entry quarantine measures in early April 2021, our comprehensive analyses demonstrated that the outbreak was most likely originated from Europe in February 2021.
]]></description>
<dc:creator>Tai, J.-H.</dc:creator>
<dc:creator>Low, Y. K.</dc:creator>
<dc:creator>Lin, H.-F.</dc:creator>
<dc:creator>Wang, T.-Y.</dc:creator>
<dc:creator>Lin, Y.-Y.</dc:creator>
<dc:creator>Foster, C.</dc:creator>
<dc:creator>Lai, Y.-Y.</dc:creator>
<dc:creator>Yeh, S.-H.</dc:creator>
<dc:creator>Chen, P.-J.</dc:creator>
<dc:creator>Wang, H.-Y.</dc:creator>
<dc:date>2022-07-05</dc:date>
<dc:identifier>doi:10.1101/2022.07.04.498645</dc:identifier>
<dc:title><![CDATA[Spatial and temporal origin of the third SARS-CoV-2 Outbreak in Taiwan]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-07-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.07.12.499750v1?rss=1">
<title>
<![CDATA[
A glycine zipper motif governs translocation of type VI secretion toxic effectors across the cytoplasmic membrane of target cells 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.07.12.499750v1?rss=1</link>
<description><![CDATA[
Type VI secretion systems (T6SSs) can deliver diverse toxic effectors into eukaryotic and bacterial cells. Although much is known about the regulation and assembly of T6SS, the translocation mechanism of effectors into the periplasm and/or cytoplasm of target cells remains elusive. Here we use the Agrobacterium tumefaciens DNase effector Tde1 to unravel the mechanism of translocation from attacker to prey. We demonstrate that Tde1 binds to its adaptor Tap1 through the N-terminus, which harbours continuous copies of GxxxG motifs resembling the glycine zipper structure found in proteins involved in the membrane channel formation. Amino acid substitutions on G39xxxG43 motif does not affect Tde1-Tap1 interaction and secretion but abolish its membrane permeability and translocation of its fluorescent fusion protein into prey cells. The data suggest that G39xxxG43 governs the delivery of Tde1 into target cells by permeabilizing the cytoplasmic membrane. Considering the widespread presence of GxxxG motifs in bacterial effectors and pore-forming toxins, we propose that glycine zipper mediated permeabilization is a conserved mechanism used by bacterial effectors for translocation across target cell membranes.
]]></description>
<dc:creator>Ali, J.</dc:creator>
<dc:creator>Yu, M.</dc:creator>
<dc:creator>Sung, L.-K.</dc:creator>
<dc:creator>Cheung, Y. W.</dc:creator>
<dc:creator>Lai, E.-M.</dc:creator>
<dc:date>2022-07-13</dc:date>
<dc:identifier>doi:10.1101/2022.07.12.499750</dc:identifier>
<dc:title><![CDATA[A glycine zipper motif governs translocation of type VI secretion toxic effectors across the cytoplasmic membrane of target cells]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-07-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.07.20.500760v1?rss=1">
<title>
<![CDATA[
Structural basis of transcriptional activation by the OmpR/PhoB-family response regulator PmrA 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.07.20.500760v1?rss=1</link>
<description><![CDATA[
PmrA, an OmpR/PhoB-family response regulator, activates gene transcription responsible for polymyxin resistance in bacteria by recognizing promoters in which the canonical -35 element is replaced by the pmra-box, representing the PmrA recognition sequence. Here, we report a cryo-electron microscopy-derived structure of a bacterial PmrA-dependent transcription activation complex (TAC) containing a PmrA dimer, an RNA polymerase {sigma}70-holoenzyme (RNAPH), and the pbgP promoter DNA. Our structure reveals that the RNAPH mainly contacts the PmrA C-terminal DNA binding domain (DBD) via electrostatic interactions and reorients the DBD three base pairs upstream of the pmra-box, resulting in a dynamic TAC conformation. In vivo assays show that substitution of PmrA DNA-recognition residues eliminated its transcriptional activity, but variants with altered RNAPH-interacting residues exhibited elevated transcriptional activity. Our study indicates that both PmrA recognition-induced DNA distortion and PmrA promoter escape play important roles in its transcriptional activation.
]]></description>
<dc:creator>Lou, Y.-C.</dc:creator>
<dc:creator>Huang, H.-Y.</dc:creator>
<dc:creator>Yeh, H.-H.</dc:creator>
<dc:creator>Chiang, W.-H.</dc:creator>
<dc:creator>Chen, C.</dc:creator>
<dc:creator>Wu, K.-P.</dc:creator>
<dc:date>2022-07-21</dc:date>
<dc:identifier>doi:10.1101/2022.07.20.500760</dc:identifier>
<dc:title><![CDATA[Structural basis of transcriptional activation by the OmpR/PhoB-family response regulator PmrA]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-07-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.07.20.500890v1?rss=1">
<title>
<![CDATA[
Circulating androgen regulation by androgen-catabolizing gut bacteria in male mouse gut 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.07.20.500890v1?rss=1</link>
<description><![CDATA[
Abnormally high circulating androgen levels have been considered a causative factor for benign prostatic hypertrophy and prostate cancer. Recent studies suggested that gut bacteria can alter sex steroid profile of host; however, the underlying mechanisms and bacterial taxa remain elusive. Thauera sp. strain GDN1 is an unusual betaproteobacterium capable of aerobic and anaerobic androgen catabolism in environmental conditions (37{degrees}C) resembling the mammalian gut. The strain GDN1 administration to C57BL/6J mice through oral gavage profoundly affected gut bacterial community, along with an approximately 50% reduction in serum androgen level in male mice. Our RT-qPCR results revealed the differential expression of aerobic and anaerobic androgen catabolic genes in the mouse ileum (microaerobic) and caecum (anaerobic), respectively. Furthermore, androgenic ring-cleaved metabolites were detected in the mouse fecal extract. This study discovered that androgen serves as a carbon source of gut microbes and that androgen-catabolizing gut bacteria can modulate host circulating androgen levels.

HighlightsO_LIThauera sp. strain GDN1 administration through oral gavage regulated mouse serum androgen levels.
C_LIO_LIThe biochemical, genetic, and metabolite profile analyses revealed the occurrence of bacterial androgen catabolism in the mouse gut.
C_LIO_LIAndrogen catabolism proceeds through the O2-dependent and O2-independent catabolic pathways in mouse ileum and caecum, respectively.
C_LIO_LIA possibility to harness Thauera sp. strain GDN1 as a functional probiotic to treat hyperandrogenism.
C_LI

Graphical Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/500890v1_ufig1.gif" ALT="Figure 1">
View larger version (33K):
org.highwire.dtl.DTLVardef@515126org.highwire.dtl.DTLVardef@a696faorg.highwire.dtl.DTLVardef@1020beforg.highwire.dtl.DTLVardef@15da175_HPS_FORMAT_FIGEXP  M_FIG C_FIG In briefHsiao et al. found that oral administration of androgen-catabolizing Thauera species regulated mouse serum androgen level. They characterized the gut microbe-mediated androgen catabolism through genetic and biochemical analyses. Their discovery portends a possibility of harnessing androgen-catabolic gut bacteria as functional probiotics to treat hyperandrogenism.
]]></description>
<dc:creator>Hsiao, T.-H.</dc:creator>
<dc:creator>Chou, C.-H.</dc:creator>
<dc:creator>Chen, Y.-L.</dc:creator>
<dc:creator>Wang, P.-H.</dc:creator>
<dc:creator>Mong, G.-J. B.</dc:creator>
<dc:creator>Lee, T.-H.</dc:creator>
<dc:creator>Wu, T.-Y.</dc:creator>
<dc:creator>Li, P.-T.</dc:creator>
<dc:creator>Li, C.-W.</dc:creator>
<dc:creator>Lai, Y.-L.</dc:creator>
<dc:creator>Tseng, Y.-L.</dc:creator>
<dc:creator>Shih, C.-J.</dc:creator>
<dc:creator>Chen, M.-J.</dc:creator>
<dc:creator>Chiang, Y.-R.</dc:creator>
<dc:date>2022-07-20</dc:date>
<dc:identifier>doi:10.1101/2022.07.20.500890</dc:identifier>
<dc:title><![CDATA[Circulating androgen regulation by androgen-catabolizing gut bacteria in male mouse gut]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-07-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.07.28.501534v1?rss=1">
<title>
<![CDATA[
Amis Pacilo and Yami Cipoho are not the same as the Pacific breadfruit starch crop--Target enrichment phylogenomics of a long-misidentified Artocarpus species sheds light on the northward Austronesian migration from the Philippines to Taiwan 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.07.28.501534v1?rss=1</link>
<description><![CDATA[
Breadfruit is a common tree species in Taiwan. In the indigenous Austronesian Amis culture of eastern Taiwan,  breadfruit is known as Pacilo, and its fruits are consumed as food. On Lanyu (Botel Tobago) where the indigenous Yami people live,  breadfruit is called Cipoho and used for constructing houses and plank-boats. Elsewhere in Taiwan,  breadfruit is also a common ornamental tree. As an essential component of traditional Yami culture, Cipoho has long been assumed to have been transported from the Batanes Island of the Philippines to Lanyu. As such, it represents a commensal species that potentially can be used to test the hypothesis of the northward Austronesian migration  into Taiwan. However, recent phylogenomic studies using target enrichment show that Taiwanese  breadfruit might not be the same as the Pacific breadfruit (Artocarpus altilis) that was domesticated in Oceania and widely cultivated throughout the tropics. To resolve persistent misidentification of this culturally and economically important tree species of Taiwan, we sampled 36 trees of Taiwanese Artocarpus and used the Moraceae probe set to enrich 529 nuclear genes. Along with 28 archived Artocarpus sequence datasets (representing a dozen taxa from all subgenera), phylogenomic analyses showed that all Taiwanese  breadfruit samples, together with a cultivated ornamental tree from Hawaii, form a fully supported clade within the A. treculianus complex, which is composed only of endemic Philippine species. Morphologically, the Taiwanese  breadfruit matches the characters of A. treculianus. Within the Taiwanese samples of A. treculianus, Amis samples form a fully supported clade derived from within the paraphyletic grade composed of Yami samples, suggesting a Lanyu origin. Results of our target enrichment phylogenomics are consistent with the scenario that Cipoho was transported northward from the Philippines to Lanyu by Yami ancestors, though the possibility that A. treculianus is native to Lanyu cannot be ruled out completely.
]]></description>
<dc:creator>Chuang, C.-R.</dc:creator>
<dc:creator>Hsieh, C.-L.</dc:creator>
<dc:creator>Chang, C.-S.</dc:creator>
<dc:creator>Wang, C.-M.</dc:creator>
<dc:creator>Tandang, D. N.</dc:creator>
<dc:creator>Gardner, E. M.</dc:creator>
<dc:creator>Audi, L.</dc:creator>
<dc:creator>Zerega, N. J. C.</dc:creator>
<dc:creator>Chung, K.-F.</dc:creator>
<dc:date>2022-07-30</dc:date>
<dc:identifier>doi:10.1101/2022.07.28.501534</dc:identifier>
<dc:title><![CDATA[Amis Pacilo and Yami Cipoho are not the same as the Pacific breadfruit starch crop--Target enrichment phylogenomics of a long-misidentified Artocarpus species sheds light on the northward Austronesian migration from the Philippines to Taiwan]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-07-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.08.01.502255v1?rss=1">
<title>
<![CDATA[
Central visceral commands formatted as the slow rhythms encoded in the temporal structures of the sympathetic firing originated from the neonatal rat spinal cord in vitro 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.08.01.502255v1?rss=1</link>
<description><![CDATA[
Central sympathetic neural circuits continuously generate efferent commands to sustain rhythmic operations of their peripheral effectors. However, beyond the firing rates, in what configuration an effective visceral command is formatted by the spiking activities was largely unknown. This study used an in vitro splanchnic nerve-spinal cord preparation of the neonatal rats as an experimental model and recorded spontaneous efferent activities from single sympathetic fibers. The patterns of the fiber activities were quantitatively evaluated by a metric, the so-called local variation (Lv). Lv was derived from calculating the relative differences between adjacent interspike intervals (ISIs), and thus, described the spiking patterns from a regular spiking with Lv = 0 to that spiking in bursts with Lv >1. Along the time course, the dynamic components of Lv (dLv) displayed quasiperiodic oscillations. Continuous wavelet analysis showed that dLv oscillations registered a dominant power rhythm at [~]7 mHz. This slow rhythmicity was heterogeneously altered by application of various antagonists that interrupted endogenous neurotransmitter activities mediated by ionotropic glutamate receptors or GABAA receptors in the spinal cord. Thus, the oscillation of dLv manifested itself as a feature of neural network operation. On the assumption that the total power of the dLv oscillations reflects an activity status of neural network operation, the antagonist-induced change of the power fits well with a concomitant ISI change in a negative sigmoid relationship, which explains the heterogeneity of the antagonist-induced firing responses. In conclusion, dLv oscillations reflect a dynamic status of neural network operation. The slow rhythms embedded in the dLv oscillations are likely acting as an information coder and convey effective central visceral commands that can be followed by their downstream effectors.

Author summaryIn what format the information is encoded by the neural activity is relatively unknown. This is especially true for autonomic regulation of visceral functions. We seek to determine the format of the central sympathetic commands, by which it can generate an effective driving force to regulate the operation of their peripheral target organs. Because most visceral organs operate with certain rhythms, we anticipate that the central visceral commands are also formatted in rhythms. Two aspects of techniques were employed. One was the in vitro electrophysiological and pharmacological techniques to acquire and to manipulate the neural signals recorded from sympathetic single-fibers. The other was the computational techniques to extract the information embedded in the timing of the spiking behaviors and to examine how these features were altered by pharmacological manipulations. We found a spontaneous change of sympathetic spiking patterns displaying rhythms with a frequency that could match the rhythmic operation of many visceral organs. Thus, the meaningful information carried by the sympathetic neural circuits for the visceral controls is likely to be encoded in the dynamics of their spiking patterns. In summary, a dynamic change of neural spiking patterns could be used as a simple scheme for neural information coding.
]]></description>
<dc:creator>Su, C.-K.</dc:creator>
<dc:creator>Ho, C.-M.</dc:creator>
<dc:date>2022-08-03</dc:date>
<dc:identifier>doi:10.1101/2022.08.01.502255</dc:identifier>
<dc:title><![CDATA[Central visceral commands formatted as the slow rhythms encoded in the temporal structures of the sympathetic firing originated from the neonatal rat spinal cord in vitro]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-08-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.08.01.502406v1?rss=1">
<title>
<![CDATA[
Pregnenolone reorganizes cytoskeleton to promote neuron development via CLIP1 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.08.01.502406v1?rss=1</link>
<description><![CDATA[
Pregnenolone (P5) is a neurosteroid produced in the brain. It improves cognitive function and protects against cannabis intoxication as well as spinal cord injury. P5 activates CLIP1, which helps microtubule polymerization at its growing end; however, the significance of P5 activation of CLIP1 in the brain is still unknown. Here we examined the roles of P5 in cultured neurons and in zebrafish cerebellum. We show that P5 promotes neurite outgrowth and facilitates axon development of cultured cerebellar granule neurons. P5 also changes the morphology of axon growth cone and promotes dynamic microtubule invasion into the distal part of filopodia at the growth cone. We have used CRISPR to disrupt clip1a in zebrafish, disrupting the ability of P5 to change microtubule dynamics and growth cone morphology, as well as to reorganize cytoskeleton. In vivo, P5 accelerated cerebellum development in WT but not clip1a mutant zebrafish, and expression of exogenous CLIP1 in clip1a mutant promoted cerebellum development in response to P5. Thus, we have delineated the pathway by which P5 promotes cerebellum development by activating CLIP1 to promote microtubule dynamics leading to increased microtubule penetration into the growth cone and accelerated neurite outgrowth. This study reveals the mechanism by which P5 and CLIP1 function to promote neural development.

Significance Statement1. We have elucidated the mechanism of pregnenolone (P5) actionP5 enhances brain functions, but its mode of action was unclear. Here we show that P5 activates CLIP1 to promote microtubule dynamics at the growth cone and to accelerate neural development.

2. We have generated a zebrafish model of CLIP1 deficiencyCLIP1 deficiency causes intellectual disability and defective neural development. Our zebrafish model can be used to study mechanisms related to this disease and other microtubule defects.

3. We point to therapeutic intervention of neurological diseases using P5P5 is beneficial to the brain. We elucidate the mechanism of P5 action, thus accelerate the development of therapeutics using P5 and its derivatives.
]]></description>
<dc:creator>Kolas, V.</dc:creator>
<dc:creator>Wu, Y.-T.</dc:creator>
<dc:creator>Bandonil, J.</dc:creator>
<dc:creator>Chung, B.-c.</dc:creator>
<dc:date>2022-08-03</dc:date>
<dc:identifier>doi:10.1101/2022.08.01.502406</dc:identifier>
<dc:title><![CDATA[Pregnenolone reorganizes cytoskeleton to promote neuron development via CLIP1]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-08-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.08.05.503005v1?rss=1">
<title>
<![CDATA[
Chemoenzymatic Synthesis of Genetically-Encoded Multivalent Liquid N-glycan Arrays 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.08.05.503005v1?rss=1</link>
<description><![CDATA[
A hallmark of cellular glycosylation is its chemical complexity and heterogeneity, which can be challenging to capture synthetically. Using chemoenzymatic synthesis on M13 phage, we produce a genetically-encoded liquid glycan array (LiGA) of biantennary complex type N-glycans. Ligation of azido-functionalized sialylglycosyl-asparagine derived from egg yolk to phage functionalized with 50-1000 copies of dibenzocyclooctyne produced divergent intermediate that can be trimmed by glycosidases and extended by glycosyltransferases to yield a library of phages with different N-glycans. Post-reaction analysis by MALDI-TOF MS provided a rigorous approach to confirm N-glycan structure and density, both of which were encoded in the bacteriophage DNA. The binding of this N-glycan LiGA by ten lectins, including CD22 or DC-SIGN expressed on live cells, uncovered an optimal structure/density combination for recognition. Injection of the LiGA into mice identified glycoconjugates with structures and avidity necessary for enrichment in specific organs. This work provides an unprecedented quantitative evaluation of the interaction of complex N-glycans with GBPs in vitro and in vivo.
]]></description>
<dc:creator>Lin, C.-L.</dc:creator>
<dc:creator>Sojitra, M.</dc:creator>
<dc:creator>Carpenter, E. J.</dc:creator>
<dc:creator>Hayhoe, E. S.</dc:creator>
<dc:creator>Sarkar, S.</dc:creator>
<dc:creator>Volker, E. A.</dc:creator>
<dc:creator>Atrazhev, A.</dc:creator>
<dc:creator>Lowary, T. L.</dc:creator>
<dc:creator>Macauley, M. S.</dc:creator>
<dc:creator>Derda, R.</dc:creator>
<dc:date>2022-08-06</dc:date>
<dc:identifier>doi:10.1101/2022.08.05.503005</dc:identifier>
<dc:title><![CDATA[Chemoenzymatic Synthesis of Genetically-Encoded Multivalent Liquid N-glycan Arrays]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-08-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.08.13.503833v1?rss=1">
<title>
<![CDATA[
lncRNA HOTAIRM1 Coordinates with RNA Processing Factors in DNA Damage Repair 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.08.13.503833v1?rss=1</link>
<description><![CDATA[
The eukaryotic RNA processing factor Y14 participates in double-strand break (DSB) repair via its RNA-dependent interaction with the non-homologous end-joining (NHEJ) complex. We identified the long non-coding RNA HOTAIRM1 as a candidate that mediates this interaction. HOTAIRM1 localized to DNA damage sites induced by ionizing radiation. Depletion of HOTAIRM1 delayed the recruitment of DNA damage response and repair factors to DNA lesions and reduced DNA repair efficiency. Identification of the HOTAIRM1 interactome revealed a large set of RNA processing factors including mRNA surveillance factors. The surveillance factors Upf1 and SMG6 localized to DNA damage sites in a HOTAIRM1-dependent manner. Depletion of Upf1 or SMG6 increased the level of DSB-induced non-coding transcripts at damaged sites, indicating a pivotal role for Upf1/SMG6-mediated RNA degradation in DNA repair. We conclude that HOTAIRM1 serves as an assembly scaffold for both DNA repair and RNA processing factors that act in concert to repair DSBs.
]]></description>
<dc:creator>Chuang, T.-W.</dc:creator>
<dc:creator>Wu, P.-Y.</dc:creator>
<dc:creator>Chang, Y.-M.</dc:creator>
<dc:creator>Tarn, W.-Y.</dc:creator>
<dc:date>2022-08-13</dc:date>
<dc:identifier>doi:10.1101/2022.08.13.503833</dc:identifier>
<dc:title><![CDATA[lncRNA HOTAIRM1 Coordinates with RNA Processing Factors in DNA Damage Repair]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-08-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.08.19.504428v1?rss=1">
<title>
<![CDATA[
Cryo-EM reveals the structure and dynamics of a 723-residue malate synthase G 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.08.19.504428v1?rss=1</link>
<description><![CDATA[
Determination of sub-100 kilodalton (kDa) structures by cryo-electron microscopy (EM) is a longstanding but not straightforward goal. Here, we present a 2.9-[A] cryo-EM structure of a 723-amino acid apo-form malate synthase G (MSG) from Escherichia coli. The cryo-EM structure of the 82-kDa MSG exhibits the same global folding as structures resolved by crystallography and nuclear magnetic resonance (NMR) spectroscopy, and the crystal and cryo-EM structures are indistinguishable. Analyses of MSG dynamics reveal consistent conformational flexibilities among the three structural approaches, most notably that the /{beta} domain exhibits heterogeneity. We observed that sidechains of F453, L454, M629, and E630 residues involved in hosting the cofactor acetyl-CoA and substrate rotate differently between the cryo-EM apo-form and complex crystal structures. Our work demonstrates that the cryo-EM technique can be used to determine structures and conformational heterogeneity of sub-100 kDa biomolecules to a quality as high as that obtained from crystallography and NMR spectroscopy.
]]></description>
<dc:creator>Ho, M.-R.</dc:creator>
<dc:creator>Wu, Y.-M.</dc:creator>
<dc:creator>Lu, Y.-C.</dc:creator>
<dc:creator>Ko, T.-P.</dc:creator>
<dc:creator>Wu, K.-P.</dc:creator>
<dc:date>2022-08-19</dc:date>
<dc:identifier>doi:10.1101/2022.08.19.504428</dc:identifier>
<dc:title><![CDATA[Cryo-EM reveals the structure and dynamics of a 723-residue malate synthase G]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-08-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.08.19.504472v1?rss=1">
<title>
<![CDATA[
Structural analyses of the plant PRT6-UBR box in the Cys-Arg/N-degron pathway and insights into the plant submergence response 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.08.19.504472v1?rss=1</link>
<description><![CDATA[
The submergence response in higher plants is highly dependent on the protein stability of group VII ethylene response factors, which are primarily degraded through the oxygen-dependent Cys-Arg branch of the N-degron pathway of targeted proteolysis. Knockout of PRT6, an E3 ligase and a vital component of the N-degron pathway, improves submergence tolerance in Arabidopsis and barley but is associated with side effects such as germination deficiency. In this study, we determined structures of rice and Arabidopsis PRT6-UBR box in complex with various Arg/N-degron related peptides. We identified two highly conserved motifs in the plant PRT6-UBR box, which is responsible for Cys-Arg/N-degron recognition. Structural and mutagenesis studies revealed the importance of two conserved motifs for Cys-Arg/N-degron recognition. The phenotype of Arabidopsis seedlings with PRT6-UBR mutants in these newly identified conserved motifs showed superior submergence survival suggesting that rational manipulation of the PRT6-UBR box can improve flood tolerance. Our results provide an engineering platform for generating crops with improved submergence tolerance.
]]></description>
<dc:creator>Kim, L.</dc:creator>
<dc:creator>Lin, C.-C.</dc:creator>
<dc:creator>Lin, T.-J.</dc:creator>
<dc:creator>Cao, Y.-C.</dc:creator>
<dc:creator>Chen, M.-C.</dc:creator>
<dc:creator>Chou, M.-Y.</dc:creator>
<dc:creator>Lin, W.-H.</dc:creator>
<dc:creator>Kim, M.</dc:creator>
<dc:creator>Wu, J.-L.</dc:creator>
<dc:creator>Shih, M.-C.</dc:creator>
<dc:creator>Song, H. K.</dc:creator>
<dc:creator>Ho, M.-C.</dc:creator>
<dc:date>2022-08-19</dc:date>
<dc:identifier>doi:10.1101/2022.08.19.504472</dc:identifier>
<dc:title><![CDATA[Structural analyses of the plant PRT6-UBR box in the Cys-Arg/N-degron pathway and insights into the plant submergence response]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-08-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.08.29.505680v1?rss=1">
<title>
<![CDATA[
In vivo visualization of nitrate dynamics using a genetically encoded biosensor 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.08.29.505680v1?rss=1</link>
<description><![CDATA[
Nitrate (NO3-) uptake and distribution are critical to plant life. Although the upstream regulation of nitrate uptake and downstream responses to nitrate in a variety of cells have been well-studied, it is still not possible to directly visualize the spatial and temporal distribution of nitrate with high resolution at the cellular level. Here, we report a nuclear-localized, genetically encoded biosensor, nlsNitraMeter3.0, for the quantitative visualization of nitrate distribution in Arabidopsis thaliana. The biosensor tracked the spatiotemporal distribution of nitrate along the primary root axis and disruptions by genetic mutation of transport (low nitrate uptake) and assimilation (high nitrate accumulation). The developed biosensor effectively monitors nitrate concentrations at cellular level in real time and spatiotemporal changes during the plant life cycle.

One-Sentence SummaryA genetically encoded biosensor for in vivo visualization of spatiotemporal nitrate levels at a cellular resolution.
]]></description>
<dc:creator>Chen, Y.-N.</dc:creator>
<dc:creator>Cartwright, H. N.</dc:creator>
<dc:creator>Ho, C.-H.</dc:creator>
<dc:date>2022-08-29</dc:date>
<dc:identifier>doi:10.1101/2022.08.29.505680</dc:identifier>
<dc:title><![CDATA[In vivo visualization of nitrate dynamics using a genetically encoded biosensor]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-08-29</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.09.13.507733v1?rss=1">
<title>
<![CDATA[
The Aphelenchoides genomes reveal major events of horizontal gene transfers in clade IV nematodes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.09.13.507733v1?rss=1</link>
<description><![CDATA[
Aphelenchoides besseyi is a plant-parasitic nematode (PPN) in the Aphelenchoididae family capable of infecting more than 200 plant species. A. besseyi is also a species complex with strains exhibiting varying pathogenicity to plants. We present the genome and annotations of six Aphelenchoides species, four of which belonged to the A. besseyi species complex. Most Aphelenchoides genomes have a size of 44.7-47.4 Mb and are amongst the smallest in clade IV, with the exception of A. fujianensis, which has a size of 143.8 Mb and is the largest. Phylogenomic analysis successfully delimited the species complex into A. oryzae and A. pseudobesseyi and revealed a reduction of transposon elements in the last common ancestor of Aphelenchoides. Synteny analyses between reference genomes indicated that three chromosomes in A. besseyi were derived from fission and fusion events. A systematic identification of horizontal gene transfer (HGT) genes across 27 representative nematodes allowed us to identify two major episodes of acquisition corresponding to the last common ancestor of clade IV or major PPNs, respectively. These genes were mostly lost and differentially retained between clades or strains. Most HGT events were acquired from bacteria, followed by fungi, and also from plants; plant HGT was especially prevalent in Bursaphelenchus mucronatus. Our results comprehensively improve the understanding of horizontal gene transfer in nematodes.
]]></description>
<dc:creator>Lai, C.-K.</dc:creator>
<dc:creator>Lee, Y.</dc:creator>
<dc:creator>Ke, H.-M.</dc:creator>
<dc:creator>Lu, M. R.</dc:creator>
<dc:creator>Liu, W.-A.</dc:creator>
<dc:creator>Lee, H.-H.</dc:creator>
<dc:creator>Liu, Y.-C.</dc:creator>
<dc:creator>Yoshiga, T.</dc:creator>
<dc:creator>Kikuchi, T.</dc:creator>
<dc:creator>Chen, P. J.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2022-09-15</dc:date>
<dc:identifier>doi:10.1101/2022.09.13.507733</dc:identifier>
<dc:title><![CDATA[The Aphelenchoides genomes reveal major events of horizontal gene transfers in clade IV nematodes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-09-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.09.28.510006v1?rss=1">
<title>
<![CDATA[
Membrane Protein Modification Modulates Big and Small Extracellular Vesicle Biodistribution and Tumorigenic Potential in Breast Cancers In Vivo 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.09.28.510006v1?rss=1</link>
<description><![CDATA[
Extracellular vesicles (EVs) are released by cells to mediate intercellular communication under pathological and physiological conditions. While small EVs (sEVs; <100-200 nm, exosomes) are intensely investigated, the properties and functions of medium and large EVs (big EVs [bEVs]; >200 nm, microvesicles) are less well explored. Here, we identify bEVs and sEVs as distinct EV populations, and determine that bEVs are released in a greater bEV:sEV ratio in the aggressive human triple-negative breast cancer (TNBC) subtype. PalmGRET, bioluminescence resonance energy transfer (BRET)-based EV reporter, reveals dose- dependent EV biodistribution at non-lethal and physiological EV dosages, as compared to lipophilic fluorescent dyes. Remarkably, the bEVs and sEVs exhibit unique biodistribution profiles, et individually promote in vivo tumor growth in a syngeneic immunocompetent TNBC breast tumor murine model. The bEVs and sEVs share mass spectrometry (MS)- identified tumor progression-associated EV surface membrane proteins (tpEVSurfMEMs), which include SLC29A1, CD9 and CD44. tpEVSurfMEM depletion attenuates EV lung organotropism, alters biodistribution, and reduces protumorigenic potential. This study identifies distinct in vivo property and function of bEVs and sEVs in breast cancer, which suggest the significant role of bEVs in diseases, diagnostic and therapeutic applications.
]]></description>
<dc:creator>Magoling, B. J. A.</dc:creator>
<dc:creator>Chen, Y.-J.</dc:creator>
<dc:creator>Wu, A. Y.-T.</dc:creator>
<dc:creator>Wong, W. W.-T.</dc:creator>
<dc:creator>Chuo, S. T.-Y.</dc:creator>
<dc:creator>Huang, H.-C.</dc:creator>
<dc:creator>Sung, Y.-C.</dc:creator>
<dc:creator>Hsieh, H.-T.</dc:creator>
<dc:creator>Huang, P.</dc:creator>
<dc:creator>Lee, K.-Z.</dc:creator>
<dc:creator>Huang, K.-W.</dc:creator>
<dc:creator>Chen, R.-H.</dc:creator>
<dc:creator>Chen, Y.</dc:creator>
<dc:creator>Lai, C. P.</dc:creator>
<dc:date>2022-09-30</dc:date>
<dc:identifier>doi:10.1101/2022.09.28.510006</dc:identifier>
<dc:title><![CDATA[Membrane Protein Modification Modulates Big and Small Extracellular Vesicle Biodistribution and Tumorigenic Potential in Breast Cancers In Vivo]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-09-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.10.04.510905v1?rss=1">
<title>
<![CDATA[
Microbial mat compositions and localization patterns explain the virulence of black band disease in corals 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.10.04.510905v1?rss=1</link>
<description><![CDATA[
Black band disease (BBD) in corals is characterized by a distinctive, band-like microbial mat, which spreads across the tissues and often kills infected colonies. The microbial mat is dominated by cyanobacteria but also commonly contains sulfide-oxidizing bacteria (SOB), sulfate-reducing bacteria (SRB), and other microbes. The migration rate in BBD varies across different environmental conditions including temperature, light, and pH. However, whether variations in the migration rates reflect differences in the microbial consortium within the BBD mat remains unknown. Here, we show that the micro-scale surface structure, bacterial composition, and spatial distribution differed across BBD lesions with different migration rates. The migration rate was positively correlated with the relative abundance of potential SOBs belonging to Arcobacteraceae localized in the middle layer within the mat and negatively correlated with the relative abundance of other potential SOBs belonging to Rhodobacteraceae. Our study highlights the microbial composition in BBD as an important determinant of virulence.
]]></description>
<dc:creator>Wada, N.</dc:creator>
<dc:creator>Iguchi, A.</dc:creator>
<dc:creator>Urabe, Y.</dc:creator>
<dc:creator>Yoshioka, Y.</dc:creator>
<dc:creator>Abe, N.</dc:creator>
<dc:creator>Takase, K.</dc:creator>
<dc:creator>Hayashi, S.</dc:creator>
<dc:creator>Kawanabe, S.</dc:creator>
<dc:creator>Sato, Y.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:creator>Mano, N.</dc:creator>
<dc:date>2022-10-05</dc:date>
<dc:identifier>doi:10.1101/2022.10.04.510905</dc:identifier>
<dc:title><![CDATA[Microbial mat compositions and localization patterns explain the virulence of black band disease in corals]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-10-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.10.06.511139v1?rss=1">
<title>
<![CDATA[
The lectin receptor Clec4F participates in the capture of circulating parasite mucins by Kupffer cells in cystic echinococcosis. 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.10.06.511139v1?rss=1</link>
<description><![CDATA[
Cystic echinococcosis is caused by the larval stages (hydatids) of cestode parasites belonging to the species cluster Echinococcus granulosus sensu lato, with E. granulosus sensu stricto being the main infecting species. Hydatids are bladder-like structures that attain large sizes within various internal organs of livestock ungulates and humans. Hydatids are protected by the massive acellular laminated layer (LL), composed mainly by mucins. Parasite growth requires LL turnover, and abundant LL-derived particles are found at infection sites in infected humans, raising the question of how LL materials are dealt with by the hosts. In this article, we show that E. granulosus sensu stricto LL mucins injected into mice are taken up by Kupffer cells, the liver macrophages exposed to the vascular space. This uptake is largely dependent on the intact mucin glycans and on Clec4F, a C-type lectin receptor which in rodents is selectively expressed in Kupffer cells. This uptake mechanism operates on mucins injected both in soluble form i.v. and in particulate form i.p. In mice harbouring intraperitoneal infections by the same species, LL mucins were found essentially only at the infection site and in the liver, where they were taken up by Kupffer cells via Clec4F. Therefore, shed LL materials circulate in the host and Kupffer cells can act as a sink for these materials even when the parasite grows in sites other than the liver.
]]></description>
<dc:creator>Barrios, A. A.</dc:creator>
<dc:creator>Mouhape, C.</dc:creator>
<dc:creator>Schreiber, L.</dc:creator>
<dc:creator>Nell, J.</dc:creator>
<dc:creator>Suarez-Martins, M.</dc:creator>
<dc:creator>Schlapp, G.</dc:creator>
<dc:creator>Meikle, M. N.</dc:creator>
<dc:creator>Mulet, A. P.</dc:creator>
<dc:creator>Hsu, T.-L.</dc:creator>
<dc:creator>Hsieh, S.-L.</dc:creator>
<dc:creator>Mourglia-Ettlin, G.</dc:creator>
<dc:creator>Gonzalez, C.</dc:creator>
<dc:creator>Crispo, M.</dc:creator>
<dc:creator>Barth, T. F. E.</dc:creator>
<dc:creator>Casaravilla, C.</dc:creator>
<dc:creator>Jenkins, S. J.</dc:creator>
<dc:creator>Diaz, A.</dc:creator>
<dc:date>2022-10-07</dc:date>
<dc:identifier>doi:10.1101/2022.10.06.511139</dc:identifier>
<dc:title><![CDATA[The lectin receptor Clec4F participates in the capture of circulating parasite mucins by Kupffer cells in cystic echinococcosis.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-10-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.10.11.511768v1?rss=1">
<title>
<![CDATA[
Allee effects mediate the impact of land-use change on the thermal niche of social species 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.10.11.511768v1?rss=1</link>
<description><![CDATA[
Land-use change not only affects habitat availability, it can also reduce population density and limit opportunities for interactions with conspecifics, further influencing species resilience to environmental challenges. For social species whose conspecific interactions are typically cooperative in nature, little is known about how land-use change influences demography and social behavior, and how this interaction impacts a species climatic niche. Here, we develop a spatially explicit, individual-based model to explore how land-use changes influence population size and niche width in social organisms through the Allee effect, the positive impact of higher population density on individual fitness. We then empirically test key model predictions by studying the distribution and cooperative behavior of burying beetles (Nicrophorus nepalensis) along elevational gradients in Taiwan. In support of our model predictions, we find that beetle densities are lower in areas of greater land-use change, making it harder for individuals in these hotter environments to form cooperative groups to compete against blowflies, their primary interspecific competitor. Consequently, the beetles lower distributional boundary is higher in areas with greater land-use change, indicating that the beetles thermal niche is reduced via Allee effects in human-altered landscapes. Ultimately, land-use change not only reduces habitat availability, it also shrinks the thermal niche of social species, making them more vulnerable to climate change.
]]></description>
<dc:creator>Chan, S.-F.</dc:creator>
<dc:creator>Rubenstein, D. R.</dc:creator>
<dc:creator>Wang, T.-W.</dc:creator>
<dc:creator>Chen, Y.-Y.</dc:creator>
<dc:creator>Chen, I.-C.</dc:creator>
<dc:creator>Ni, D.-Z.</dc:creator>
<dc:creator>Shih, W.-K.</dc:creator>
<dc:creator>Shen, S.-F.</dc:creator>
<dc:date>2022-10-14</dc:date>
<dc:identifier>doi:10.1101/2022.10.11.511768</dc:identifier>
<dc:title><![CDATA[Allee effects mediate the impact of land-use change on the thermal niche of social species]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-10-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.10.15.512330v1?rss=1">
<title>
<![CDATA[
Predicting FDA approvability of small-molecule drugs 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.10.15.512330v1?rss=1</link>
<description><![CDATA[
A high rate of compound attrition makes drug discovery via conventional methods time-consuming and expensive. Here, we showed that machine learning models can be trained to classify compounds into distinctive groups according to their status in the drug development process, which can significantly reduce the compound attrition rate. Using molecular structure fingerprints and physicochemical properties as input, our models accurately predicted which drug compounds would proceed to trial, with an area under the receiver operating curve (AUC) of 0.94 {+/-} 0.01 (mean {+/-} standard deviation). Our models also identified which drugs in clinical trials would be approved by the US Food and Drug Administration (FDA) to go on the market, with an AUC of 0.73 {+/-} 0.02. The predictive power of our models could reduce the attrition rate of preclinical compounds to enter clinical trials from 65%, as with conventional methods, to 12% (with 92% sensitivity) and the clinical trial failure rate from 80-90% to 29% (with 83% sensitivity). The results largely held in additional tests on new clinical trial compounds and new FDA-approved drugs, as well as on drugs uniquely approved for use in Europe and Japan.

SIGNIFICANCE STATEMENTThe odds of developing a drug approved by the US Food and Drug Administration (FDA) are slim, meaning that the vast majority of drug candidates would fail tests for safety and efficacy in the drug discovery process, rendering it highly inefficient and costly. Here, we have developed machine learning models to predict drug compounds worthy of clinical trials with high accuracy, and clinical-trial compounds to receive FDA approval with a much higher success rate than that achieved by the traditional approach. Our computational prediction requires input of only the drug compounds chemical structure and physicochemical properties. It can help mitigate the long-standing problem of drug discovery.
]]></description>
<dc:creator>Huang, C.-H.</dc:creator>
<dc:creator>Hsu, J.</dc:creator>
<dc:creator>Yang, L.-y.</dc:creator>
<dc:creator>CHEN, T.-M.</dc:creator>
<dc:creator>Shih, E. S. C.</dc:creator>
<dc:creator>Hwang, M.-J.</dc:creator>
<dc:date>2022-10-18</dc:date>
<dc:identifier>doi:10.1101/2022.10.15.512330</dc:identifier>
<dc:title><![CDATA[Predicting FDA approvability of small-molecule drugs]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-10-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.10.15.512338v1?rss=1">
<title>
<![CDATA[
Daily turnover of active giant virus infection during algal blooms revealed by single-cell transcriptomics 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.10.15.512338v1?rss=1</link>
<description><![CDATA[
Viruses are the most abundant biological entity in the ocean and play a significant role in shaping the marine ecosystem. The past two decades have revealed an outstanding diversity of giant viruses infecting protists across the tree of life and, in particular, algae that form massive blooms in the ocean. Virus-induced bloom demise significantly impacts marine ecology and biogeochemistry, as well as the associated microbial community. Nevertheless, little is known about the infection dynamics of these giant viruses in the natural environment and their role in regulating algal blooms. Here, we provide evidence for a daily life cycle of giant viral infection in algal blooms by processing the transcriptome of over 12,000 single algal cells during different phases of interaction with their giant viruses. We revealed that viral infection occurs already at the exponential phase of the bloom and that the timing of infection can determine the magnitude of the bloom but not the fraction of infected cells. We further revealed that the same proportion of infected cells are in the early phase of the viral replication program (13.5%) throughout several consecutive days of the bloom, suggesting that a daily turnover of infection is at play during the bloom and demise phases of the algal population. This may imply that a continuous source of virocell-associated metabolites diffuses throughout the bloom succession and could fuel the microbial food webs. Finally, we link single cell infection state to host physiology and show that infected cells remained calcified even in the late stage of infection, contradicting common observation of bulk population in which viral infection is directly linked with decalcification. Together, these results highlight the importance of studying host-virus dynamics in natural populations at a single-cell resolution, which can provide a fresh view of the dynamics and propagation of viral infection. This approach will enable quantification of the impact of marine viruses on microbial food webs.
]]></description>
<dc:creator>Hevroni, G.</dc:creator>
<dc:creator>Vincent, F. J.</dc:creator>
<dc:creator>Ku, C.</dc:creator>
<dc:creator>Sheyn, U.</dc:creator>
<dc:creator>Vardi, A.</dc:creator>
<dc:date>2022-10-15</dc:date>
<dc:identifier>doi:10.1101/2022.10.15.512338</dc:identifier>
<dc:title><![CDATA[Daily turnover of active giant virus infection during algal blooms revealed by single-cell transcriptomics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-10-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.10.16.512416v1?rss=1">
<title>
<![CDATA[
Baculovirus Surface Display of Hemagglutinin and Neuraminidase for Monoclonal Antibody Production 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.10.16.512416v1?rss=1</link>
<description><![CDATA[
The H7N9 influenza virus that emerged in 2013 is a dangerous infectious disease with a high mortality rate of up to 40%. Developing effective monoclonal antibodies (mAbs) to detect and treat the infection of this virus is therefore critical. In this study, we expressed hemagglutinin (HA) and neuraminidase (NA) of H7N9 (A/Anhui/1/2013) on the surface of baculovirus (i.e., HA7-Bac and NA9-Bac). Our results showed that both HA or NA proteins displayed on HA7-Bac or NA9-Bac could well maintain their native biological function. Mice antisera derived from the injections of either HA7-Bac- or NA9-Bac exhibited high inhibitory activity in the hemagglutination and neuraminidase assay of H7N9 virus. mAbs generated by immunization with HA7-Bac exhibited high neutralizing activity against H7N9 virus infectivity in cell assays, whereas mAbs generated by immunization with NA9-Bac inhibited neuraminidase activity. These results proved that baculovirus display of HA and NA from H7N9 could be convenient agents to generate neutralizing mAbs against virus infection.
]]></description>
<dc:creator>Lo, H.-R.</dc:creator>
<dc:creator>Wu, C.-P.</dc:creator>
<dc:creator>Jan, J.-T.</dc:creator>
<dc:creator>Chao, Y.-C.</dc:creator>
<dc:creator>Tsai, C.-H.</dc:creator>
<dc:date>2022-10-18</dc:date>
<dc:identifier>doi:10.1101/2022.10.16.512416</dc:identifier>
<dc:title><![CDATA[Baculovirus Surface Display of Hemagglutinin and Neuraminidase for Monoclonal Antibody Production]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-10-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.10.28.514164v1?rss=1">
<title>
<![CDATA[
Assessing the impacts of various factors related to identification, conservation, biogenesis, and function on circular RNA reliability 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.10.28.514164v1?rss=1</link>
<description><![CDATA[
Circular RNAs (circRNAs) are non-polyadenylated RNAs with a continuous loop structure characterized by a non-co-linear back-splice junction (BSJ). While dozens of computational tools have been developed and identified millions of circRNA candidates in diverse species, it remains a major challenge for determining circRNA reliability due to various types of false positives. Here, we systematically assess the impacts of numerous factors related to identification, conservation, biogenesis, and function on circRNA reliability by comparisons of circRNA expression from mock (total RNAs) and the corresponding co-linear/polyadenylated RNA-depleted datasets based on three different RNA treatment approaches. Eight important indicators of circRNA reliability are determined. The relative contribution to variability explained analyses further reveal that the relative importance of these factors in affecting circRNA reliability is conservation level of circRNA > full-length circular sequences > supporting BSJ read count > both BSJ donor and acceptor splice sites at the same co-linear transcript isoforms > both BSJ donor and acceptor splice sites at the annotated exon boundaries > BSJs detected by multiple tools > supporting functional features > both BSJ donor and acceptor splice sites undergoing alternative splicing. By extracting RT-independent circRNAs, circRNAs passing multiple experimental validations, and database-specific circRNAs, we showed the additive effects of these important factors in determining circRNA reliability. This study thus provides a useful guideline and an important resource for selecting high-confidence circRNAs for further investigations.
]]></description>
<dc:creator>Chuang, T.-J.</dc:creator>
<dc:creator>Chiang, T.-W.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:date>2022-10-28</dc:date>
<dc:identifier>doi:10.1101/2022.10.28.514164</dc:identifier>
<dc:title><![CDATA[Assessing the impacts of various factors related to identification, conservation, biogenesis, and function on circular RNA reliability]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-10-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.10.28.514271v1?rss=1">
<title>
<![CDATA[
The antibacterial T6SS of Agrobacterium tumefacien promotes disease occurrence and influences crown gall microbiota composition 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.10.28.514271v1?rss=1</link>
<description><![CDATA[
The type VI secretion system (T6SS) is deployed by many proteobacteria to secrete effector proteins into bacterial competitors for competition or eukaryotic cells for pathogenesis. Agrobacteria, a group of soil-borne phytopathogens causing crown gall disease on various plant species, deploys the T6SS to attack closely- and distantly-related bacterial species in vitro and in planta. Current evidence suggests that the T6SS is not essential for pathogenesis under direct inoculation but it remains unknown whether the T6SS influences natural disease incidence or the microbial community within crown galls (i.e., gallobiome). To address these two key questions, we established a soil inoculation method on wounded tomato seedlings that mimics natural infections and developed a bacterial 16S rRNA gene amplicon enrichment sequencing platform. By comparing the Agrobacterium wild-type strain C58 with two T6SS mutants, we demonstrate that the T6SS influences both disease occurrence and gallobiome composition. Based on multiple inoculation trials across seasons, all three strains could induce tumors but the mutants had significantly lower disease incidences. The season of inoculation played a more important role than the T6SS in shaping the gallobiome. The influence of T6SS was evident in summer, in which two Sphingomonas species and the family Burkhoderiaceae were enriched in the gallobiome induced by the mutants. Further in vitro competition and colonization assay demonstrated the T6SS-mediated antagonism to a Sphingomonas sp. R1 strain isolated from tomato rhizosphere in this study. In conclusion, this work demonstrates that the Agrobacterium T6SS promotes tumorigenesis in infection process and provides competitive advantages in gall-associated microbiota.

IMPORTANCEThe T6SS is widespread among Proteobacteria and used for interbacterial competition by agrobacteria, which are soil inhabitants and opportunistic bacterial pathogens causing crown gall disease in a wide range of plants. Current evidence indicates that the T6SS is not required for gall formation when agrobacteria are inoculated directly on plant wounding sites. However, in natural settings, agrobacteria may need to compete with other bacteria in bulk soil to gain access to plant wounds and influence microbial community inside crown galls. The role of the T6SS in these critical aspects of disease ecology have remained largely unknown. In this study, we successfully developed a Soil Inoculation method coupled with Blocker-mediated enrichment of Bacterial 16S rRNA gene Amplicon Sequencing, named as SI-BBacSeq, to address these two important questions. We provided evidence that the T6SS promotes disease occurrence and influences crown gall microbiota composition by interbacterial competition.
]]></description>
<dc:creator>Wang, S.-C.</dc:creator>
<dc:creator>Chen, A.-P.</dc:creator>
<dc:creator>Chou, S.-J.</dc:creator>
<dc:creator>Kuo, C. H.</dc:creator>
<dc:creator>Lai, E.-M.</dc:creator>
<dc:date>2022-10-30</dc:date>
<dc:identifier>doi:10.1101/2022.10.28.514271</dc:identifier>
<dc:title><![CDATA[The antibacterial T6SS of Agrobacterium tumefacien promotes disease occurrence and influences crown gall microbiota composition]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-10-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.11.06.515354v1?rss=1">
<title>
<![CDATA[
Megacolonies: an alternative social organization in anemonefishes? 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.11.06.515354v1?rss=1</link>
<description><![CDATA[
Anemonefish are iconic examples of marine fishes living in mutualistic symbiosis with sea anemones. In a given sea anemone, the anemonefishes have a stereotyped social organization with a dominant female, a semi-dominant male, and several juveniles. A strict size-based hierarchy governs the social interactions within these colonies, with each individual differing from the previous or next fish in the order by +/- 20% size. This social organization is conserved across the Indo-Pacific in all 28 species of anemonefish found on any of ten giant sea anemone species. We report the existence of huge "megacolonies" of up to 100 fish living in large carpets of sea anemones. This alternative organization was observed for different fish and anemone species in different coral reef locations (French Polynesia, Japan, Taiwan, and Vietnam). In these colonies, the strict size-based hierarchy is no longer recognizable, and the level of aggressivity of the different members appears lower than in "normal" colonies. These megacolonies may correspond to a previously overlooked type of social organization that could be linked to host availability and offer a unique opportunity to understand anemonefishs behavioral, social, and hormonal plasticity.
]]></description>
<dc:creator>Mercader, M.</dc:creator>
<dc:creator>Zwahlen, J.</dc:creator>
<dc:creator>Hayashi, K.</dc:creator>
<dc:creator>Takamiyagi, H.</dc:creator>
<dc:creator>Tseng, Y.-C.</dc:creator>
<dc:creator>Nguyen, H.-T.</dc:creator>
<dc:creator>Asada, K.</dc:creator>
<dc:creator>Sowinski, J.</dc:creator>
<dc:creator>Rimer, J.</dc:creator>
<dc:creator>Lecchini, D.</dc:creator>
<dc:creator>Laudet, V.</dc:creator>
<dc:date>2022-11-07</dc:date>
<dc:identifier>doi:10.1101/2022.11.06.515354</dc:identifier>
<dc:title><![CDATA[Megacolonies: an alternative social organization in anemonefishes?]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-11-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.11.10.515791v1?rss=1">
<title>
<![CDATA[
Genomic innovation and horizontal gene transfer shaped plant colonization and biomass degradation strategies of a globally prevalent fungal pathogen 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.11.10.515791v1?rss=1</link>
<description><![CDATA[
Members of the fungal genus Armillaria are necrotrophic pathogens with efficient plant biomass-degrading strategies. The genus includes some of the largest terrestrial organisms on Earth, spreading underground and causing tremendous losses in diverse ecosystems. Despite their global importance, the mechanism by which Armillaria evolved pathogenicity in a clade of dominantly non-pathogenic wood-degraders (Agaricales) remains elusive. Here, using new genomic data, we show that Armillaria species, in addition to widespread gene duplications and de novo gene origins, appear to have at least 775 genes that were acquired via 101 horizontal gene transfer (HGT) events, primarily from Ascomycota. Functional and expression data suggest that HGT might have affected plant biomass-degrading and virulence abilities of Armillaria, two pivotal traits in their lifestyle. We further assayed gene expression during root and cambium colonization, and report putative virulence factors, extensive regulation of horizontally acquired and wood-decay related genes as well as novel pathogenicity-induced small secreted proteins (PiSSPs). Two PiSSPs induced necrosis in live plants, suggesting they are potential virulence effectors conserved across Armillaria. Overall, this study details how evolution knitted together horizontally and vertically inherited genes in complex adaptive traits, such as plant biomass degradation and pathogenicity, paving the way for development of infection models for one of the most influential pathogens of temperate forest ecosystems.
]]></description>
<dc:creator>Sahu, N.</dc:creator>
<dc:creator>Indjic, B.</dc:creator>
<dc:creator>Wong-Bajracharya, J.</dc:creator>
<dc:creator>Merenyi, Z.</dc:creator>
<dc:creator>Ke, H.-M.</dc:creator>
<dc:creator>Ahrendt, S.</dc:creator>
<dc:creator>Monk, T.-L.</dc:creator>
<dc:creator>Kocsube, S.</dc:creator>
<dc:creator>Drula, E.</dc:creator>
<dc:creator>Lipzen, A.</dc:creator>
<dc:creator>Balint, B.</dc:creator>
<dc:creator>Henrissat, B.</dc:creator>
<dc:creator>Andreopoulos, B.</dc:creator>
<dc:creator>Martin, F. M.</dc:creator>
<dc:creator>Harder, C. B.</dc:creator>
<dc:creator>Rigling, D.</dc:creator>
<dc:creator>Ford, K. L.</dc:creator>
<dc:creator>Foster, G. D.</dc:creator>
<dc:creator>Pangilinan, J.</dc:creator>
<dc:creator>Papanicolaou, A.</dc:creator>
<dc:creator>Barry, K.</dc:creator>
<dc:creator>LaButti, K.</dc:creator>
<dc:creator>Viragh, M.</dc:creator>
<dc:creator>Koriabine, M.</dc:creator>
<dc:creator>Yan, M.</dc:creator>
<dc:creator>Riley, R.</dc:creator>
<dc:creator>Champramary, S.</dc:creator>
<dc:creator>Plett, K. L.</dc:creator>
<dc:creator>Grigoriev, I. V.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:creator>Slot, J.</dc:creator>
<dc:creator>Sipos, G.</dc:creator>
<dc:creator>Plett, J.</dc:creator>
<dc:creator>Nagy, L. G.</dc:creator>
<dc:date>2022-11-13</dc:date>
<dc:identifier>doi:10.1101/2022.11.10.515791</dc:identifier>
<dc:title><![CDATA[Genomic innovation and horizontal gene transfer shaped plant colonization and biomass degradation strategies of a globally prevalent fungal pathogen]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-11-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.11.21.517443v1?rss=1">
<title>
<![CDATA[
RE2DC: a robust and efficient 2D classifier with visualization for processing massive and heterogeneous cryo-EM data 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.11.21.517443v1?rss=1</link>
<description><![CDATA[
Despite the fact that single particle cryo-EM has become a powerful method of structural biology, processing cryo-EM images are challenging due to the low SNR, high-dimension and un-label nature of the data. Selecting the best subset of particle images relies on 2D classification--a process that involves iterative image alignment and clustering. This process, however, represents a major time sink, particularly when the data is massive or overly heterogeneous. Popular approaches to this process often trade its robustness for efficiency. Here, we introduced a new unsupervised 2D classification method termed RE2DC. It is built upon a highly efficient variant of{gamma} -SUP, a robust statistical cryo-EM clustering algorithm resistant to the attractor effect. To develop this efficient variant, we employed a tree-based approximation to reduce the computation complexity from O(N2) to O(N), with N as the number of images. In addition, we exploited t-SNE visualization to unveil the process of 2D classification. Our tests of RE2DC using various datasets demonstrate it is both robust and efficient, with the potential to reveal subtle structural intermediates. Using RE2DC to curate a dataset of sub-millions of COVID-19 spike particles picked from 3,511 movies only takes 8 hours, suggesting its capability of accelerating cryo-EM structural determination. Currently, RE2DC is available with both CPU and GPU versions, where the implementation only requires modest hardware resources.
]]></description>
<dc:creator>Chung, S.-C.</dc:creator>
<dc:creator>Lin, H.-H.</dc:creator>
<dc:creator>Wu, K.-P.</dc:creator>
<dc:creator>Chen, T.-L.</dc:creator>
<dc:creator>Chang, W.-H.</dc:creator>
<dc:creator>Tu, I.-P.</dc:creator>
<dc:date>2022-11-24</dc:date>
<dc:identifier>doi:10.1101/2022.11.21.517443</dc:identifier>
<dc:title><![CDATA[RE2DC: a robust and efficient 2D classifier with visualization for processing massive and heterogeneous cryo-EM data]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-11-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.11.22.517520v1?rss=1">
<title>
<![CDATA[
Comparative single-cell profiling reveals distinct cardiac resident macrophages essential for zebrafish heart regeneration 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.11.22.517520v1?rss=1</link>
<description><![CDATA[
Zebrafish exhibit a robust ability to regenerate their hearts following injury, and the immune system plays a key role in this process. We previously showed that delaying macrophage recruitment by clodronate liposome (CL) treatment compromises neutrophil resolution and heart regeneration, even when the infiltrating macrophage number was restored within the first-week post injury (Lai et al., 2017). Here, we examined the molecular mechanisms underlying the cardiac repair of regenerative PBS-control hearts vs. non-regenerative CL-treated hearts. Bulk transcriptomic analyses revealed that CL-treated hearts exhibited disrupted inflammatory resolution and energy metabolism during cardiac repair. Temporal single-cell profiling of inflammatory cells in regenerative vs. non-regenerative conditions further identified heterogenous macrophages and neutrophils with distinct infiltration dynamics, gene expression, and cellular crosstalk. Among them, two residential macrophage subpopulations were enriched in regenerative hearts and barely recovered in non-regenerative hearts. Early CL treatment at 8 days or even 1 month before cryoinjury led to the depletion of resident macrophages without affecting the circulating macrophage recruitment to the injured area. Strikingly, these resident macrophage-deficient zebrafish still exhibited compromised neovascularization and scar resolution. Our results characterized the inflammatory cells of the zebrafish injured hearts and identified key resident macrophage subpopulations prerequisite for successful heart regeneration.
]]></description>
<dc:creator>Wei, K.-H.</dc:creator>
<dc:creator>Lin, I.-T.</dc:creator>
<dc:creator>Chowdhury, K.</dc:creator>
<dc:creator>Liu, K.-T.</dc:creator>
<dc:creator>Ko, T.-M.</dc:creator>
<dc:creator>Chang, Y.-M.</dc:creator>
<dc:creator>Yang, K.-C.</dc:creator>
<dc:creator>Lai, S.-L.</dc:creator>
<dc:date>2022-11-22</dc:date>
<dc:identifier>doi:10.1101/2022.11.22.517520</dc:identifier>
<dc:title><![CDATA[Comparative single-cell profiling reveals distinct cardiac resident macrophages essential for zebrafish heart regeneration]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-11-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.11.28.518189v1?rss=1">
<title>
<![CDATA[
A versatile method to archive and delipidate brain tissues for ensuing multiplexed immunolabeling and organ-level imaging 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.11.28.518189v1?rss=1</link>
<description><![CDATA[
Tissue clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain, and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.
]]></description>
<dc:creator>Lin, Y.-H.</dc:creator>
<dc:creator>Wang, L.-W.</dc:creator>
<dc:creator>Chen, Y.-H.</dc:creator>
<dc:creator>Chan, Y.-C.</dc:creator>
<dc:creator>Hu, S.-H.</dc:creator>
<dc:creator>Wu, S.-Y.</dc:creator>
<dc:creator>Chiang, C.-S.</dc:creator>
<dc:creator>Huang, G.-J.</dc:creator>
<dc:creator>Yang, S.-D.</dc:creator>
<dc:creator>Chu, S.-W.</dc:creator>
<dc:creator>Wang, K.-C.</dc:creator>
<dc:creator>Lin, C.-H.</dc:creator>
<dc:creator>Huang, P.-H.</dc:creator>
<dc:creator>Cheng, H.-J.</dc:creator>
<dc:creator>Chen, B.-C.</dc:creator>
<dc:creator>Chu, L.-A.</dc:creator>
<dc:date>2022-12-02</dc:date>
<dc:identifier>doi:10.1101/2022.11.28.518189</dc:identifier>
<dc:title><![CDATA[A versatile method to archive and delipidate brain tissues for ensuing multiplexed immunolabeling and organ-level imaging]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-12-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.12.06.519083v1?rss=1">
<title>
<![CDATA[
Large-scale benchmarking of circRNA detection tools reveals large differences in sensitivity but not in precision 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.12.06.519083v1?rss=1</link>
<description><![CDATA[
The detection of circular RNA molecules (circRNAs) is typically based on short-read RNA sequencing data processed by computational detection tools. During the last decade, a plethora of such tools have been developed, but a systematic comparison with orthogonal validation is missing. Here, we set up a circRNA detection tool benchmarking study, in which 16 tools were used and detected over 315,000 unique circRNAs in three deeply sequenced human cell types. Next, 1,516 predicted circRNAs were empirically validated using three orthogonal methods. Generally, tool-specific precision values are high and similar (median of 98.8%, 96.3%, and 95.5% for qPCR, RNase R, and amplicon sequencing, respectively) whereas the sensitivity and number of predicted circRNAs (ranging from 1,372 to 58,032) are the most significant tool differentiators. Furthermore, we demonstrate the complementarity of tools through the increase in detection sensitivity by considering the union of highly-precise tool combinations while keeping the number of false discoveries low. Finally, based on the benchmarking results, recommendations are put forward for circRNA detection and validation.
]]></description>
<dc:creator>Vromman, M.</dc:creator>
<dc:creator>Anckaert, J.</dc:creator>
<dc:creator>Bortoluzzi, S.</dc:creator>
<dc:creator>Buratin, A.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Chu, Q.</dc:creator>
<dc:creator>Chuang, T.-J.</dc:creator>
<dc:creator>Dehghannasiri, R.</dc:creator>
<dc:creator>Dieterich, C.</dc:creator>
<dc:creator>Dong, X.</dc:creator>
<dc:creator>Flicek, P.</dc:creator>
<dc:creator>Gaffo, E.</dc:creator>
<dc:creator>Gu, W.</dc:creator>
<dc:creator>He, C.</dc:creator>
<dc:creator>Hoffmann, S.</dc:creator>
<dc:creator>Izuogu, O.</dc:creator>
<dc:creator>Jackson, M. S.</dc:creator>
<dc:creator>Jakobi, T.</dc:creator>
<dc:creator>Lai, E. C.</dc:creator>
<dc:creator>Nuytens, J.</dc:creator>
<dc:creator>Salzman, J.</dc:creator>
<dc:creator>Santibanez-Koref, M.</dc:creator>
<dc:creator>Stadler, P.</dc:creator>
<dc:creator>Thas, O.</dc:creator>
<dc:creator>Vanden Eynde, E.</dc:creator>
<dc:creator>Verniers, K.</dc:creator>
<dc:creator>Wen, G.</dc:creator>
<dc:creator>Westholm, J.</dc:creator>
<dc:creator>Yang, L.</dc:creator>
<dc:creator>Ye, C.-Y.</dc:creator>
<dc:creator>Yigit, N.</dc:creator>
<dc:creator>Yuan, G.-H.</dc:creator>
<dc:creator>Zhang, J.</dc:creator>
<dc:creator>Zhao, F.</dc:creator>
<dc:creator>Vandesompele, J.</dc:creator>
<dc:creator>Volders, P.-J.</dc:creator>
<dc:date>2022-12-06</dc:date>
<dc:identifier>doi:10.1101/2022.12.06.519083</dc:identifier>
<dc:title><![CDATA[Large-scale benchmarking of circRNA detection tools reveals large differences in sensitivity but not in precision]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-12-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.12.07.519424v1?rss=1">
<title>
<![CDATA[
TWAS coupled with eQTL analysis reveals the genetic connection between gene expression and flowering time in Arabidopsis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.12.07.519424v1?rss=1</link>
<description><![CDATA[
Genome-wide association study (GWAS) has improved our understanding of complex traits, but challenges exist in distinguishing causation versus association caused by linkage disequilibrium. Instead, the transcriptome-wide association study (TWAS) detects direct associations between expression levels and phenotypic variations, providing an opportunity to better prioritize candidate genes. To assess the feasibility of TWAS, we investigated the association among transcriptomes, genomes, and various traits, including flowering time in Arabidopsis. First, the associated genes formerly known to regulate growth allometry or metabolite production were identified by TWAS. Then, for flowering time, six TWAS-newly identified genes were functionally validated. Analysis of expression quantitative trait locus (eQTL) further revealed a trans-regulatory hotspot affecting the expression of several TWAS-identified genes. The hotspot covers the FRIGIDA (FRI) gene body, which possesses multiple haplotypes differentially affecting the expression of downstream genes, such as FLOWERING LOCUS C (FLC) and SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1). We also revealed multiple independent paths towards the loss of FRI function in natural accessions. Altogether, this study demonstrates the potential of combining TWAS with eQTL analysis to identify important regulatory modules of the FRI-FLC-SOC1 for quantitative traits in natural populations.

HighlightCombining TWAS with eQTL analyses identifies haplotypes connecting flowering genes with their physiological trait, strengthening the importance of FRI-FLC-SOC1 regulatory module on flowering time among the Arabidopsis natural population.
]]></description>
<dc:creator>Chien, P.-S.</dc:creator>
<dc:creator>Chen, P.-H.</dc:creator>
<dc:creator>Lee, C.-R.</dc:creator>
<dc:creator>Chiou, T.-J.</dc:creator>
<dc:date>2022-12-10</dc:date>
<dc:identifier>doi:10.1101/2022.12.07.519424</dc:identifier>
<dc:title><![CDATA[TWAS coupled with eQTL analysis reveals the genetic connection between gene expression and flowering time in Arabidopsis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-12-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.12.08.519209v1?rss=1">
<title>
<![CDATA[
SARM1 detection in oligodendrocytes but not Schwann cells though sarm1/Sarm1 deletion does not perturb CNS nor PNS myelination in zebrafish and mice. 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.12.08.519209v1?rss=1</link>
<description><![CDATA[
SARM1 is a central regulator of programmed axon death and is required to initiate axon self-destruction after traumatic and toxic insults to the nervous system. Abnormal activation of this axon degeneration pathway is increasingly recognized as a contributor to human neurological disease and SARM1 knockdown or inhibition has become an attractive therapeutic strategy to preserve axon loss in a variety of disorders of the peripheral and central nervous system. Despite this, it remains unknown whether Sarm1/SARM1 is present in myelinating glia and whether it plays a role in myelination in the PNS or CNS. It is important to answer these questions to understand whether future therapies inhibiting SARM1 function may have unintended deleterious impacts on myelination. Here we show that Sarm1 mRNA is present in oligodendrocytes in zebrafish but only detectable at low levels in Schwann cells in both zebrafish and mice. We find SARM1 protein is readily detectable in murine oligodendrocytes in vitro and in vivo and activation of endogenous SARM1 in oligodendrocytes induces cell death. In contrast, SARM1 protein is not detectable in Schwann cells and satellite glia in the adult murine nervous system. Cultured Schwann cells contain negligible functional SARM1 and are insensitive to specific SARM1 activators. Using zebrafish and mouse Sarm1 mutants, we show that SARM1 is not required for initiation of myelination nor myelin sheath maintenance by oligodendrocytes and Schwann cells. Thus, strategies to inhibit SARM1 function in the nervous system to treat neurological disease are unlikely to perturb myelination in humans.

Main PointsO_LISARM1 protein is detectable in oligodendrocytes but not in Schwann cells
C_LIO_LIOligodendrocytes but not Schwann cells die in response to endogenous SARM1 activation
C_LIO_LICNS nor PNS myelination, in zebrafish and mice, is hindered by loss of sarm1/Sarm1
C_LI
]]></description>
<dc:creator>Fazal, S. V.</dc:creator>
<dc:creator>Mutschler, C.</dc:creator>
<dc:creator>Chen, C.</dc:creator>
<dc:creator>Turmaine, M.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:creator>Loreto, A.</dc:creator>
<dc:creator>Casillas-Bajo, A.</dc:creator>
<dc:creator>Cabedo, H.</dc:creator>
<dc:creator>Franklin, R. J.</dc:creator>
<dc:creator>Barker, R. A.</dc:creator>
<dc:creator>Monk, K.</dc:creator>
<dc:creator>Steventon, B.</dc:creator>
<dc:creator>Coleman, M.</dc:creator>
<dc:creator>Gomez-Sanchez, J. A.</dc:creator>
<dc:creator>Arthur-Farraj, P.</dc:creator>
<dc:date>2022-12-09</dc:date>
<dc:identifier>doi:10.1101/2022.12.08.519209</dc:identifier>
<dc:title><![CDATA[SARM1 detection in oligodendrocytes but not Schwann cells though sarm1/Sarm1 deletion does not perturb CNS nor PNS myelination in zebrafish and mice.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-12-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.12.11.519957v1?rss=1">
<title>
<![CDATA[
Resurrection of plant disease resistance proteins via helper NLR bioengineering 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.12.11.519957v1?rss=1</link>
<description><![CDATA[
Parasites counteract host immunity by suppressing helper NLR proteins that function as central nodes in immune receptor networks. Understanding the mechanisms of immunosuppression can lead to strategies for bioengineering disease resistance. Here, we show that a cyst nematode virulence effector binds and inhibits oligomerization of the helper NLR protein NRC2 by physically preventing intramolecular rearrangements required for activation. A single amino acid polymorphism at the binding interface between NRC2 and the inhibitor is sufficient for this helper NLR to evade immune suppression, thereby restoring the activity of multiple disease resistance genes. This points to a novel strategy for resurrecting disease resistance in crop genomes.

One sentence summaryA helper NLR is mutated to evade inhibition by a parasite effector.
]]></description>
<dc:creator>Contreras, M. P.</dc:creator>
<dc:creator>Pai, H.</dc:creator>
<dc:creator>Selvaraj, M.</dc:creator>
<dc:creator>Toghani, A.</dc:creator>
<dc:creator>Lawson, D. M.</dc:creator>
<dc:creator>Tumtas, Y.</dc:creator>
<dc:creator>Duggan, C.</dc:creator>
<dc:creator>Yuen, E. L. H.</dc:creator>
<dc:creator>Stevenson, C. E. M.</dc:creator>
<dc:creator>Harant, A.</dc:creator>
<dc:creator>Wu, C.-H.</dc:creator>
<dc:creator>Bozkurt, T. O.</dc:creator>
<dc:creator>Kamoun, S.</dc:creator>
<dc:creator>Derevnina, L.</dc:creator>
<dc:date>2022-12-11</dc:date>
<dc:identifier>doi:10.1101/2022.12.11.519957</dc:identifier>
<dc:title><![CDATA[Resurrection of plant disease resistance proteins via helper NLR bioengineering]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-12-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.12.12.520164v1?rss=1">
<title>
<![CDATA[
Alkalinity modulates a unique suite of genes to recalibrate growth and pH homeostasis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.12.12.520164v1?rss=1</link>
<description><![CDATA[
Alkaline soils pose a conglomerate of constraints to plants, restricting the growth and fitness of non-adapted species in habitats with low active proton concentrations. To thrive under such conditions, plants have to compensate for a potential increase in cytosolic pH and restricted softening of the cell wall to invigorate cell elongation in a proton-depleted environment. To discern mechanisms that aid in the adaptation to external pH, we grew plants on media with pH values ranging from 4.5 to 8.5. Growth was severely restricted at pH 4.5 and above pH 6.5, and associated with decreasing chlorophyll levels at alkaline pH. Bicarbonate treatment worsened plant performance, suggesting effects that differ from those exerted by pH as such. Transcriptional profiling of roots subjected to short-term transfer from optimal (pH 5.5) to alkaline (pH 7.5) media unveiled a large set of differentially expressed genes that were partially congruent with genes affected by low pH, bicarbonate and nitrate, but showed only a very small overlap with genes responsive to the availability of iron. Further analysis of selected genes disclosed pronounced responsiveness of their expression over a wide range of external pH values. Alkalinity altered the expression of various proton/anion co-transporters, possibly to recalibrate cellular proton homeostasis. Co-expression analysis of pH-responsive genes identified a module of genes encoding proteins with putative functions in the regulation of root growth, which appears to be conserved in plants subjected to low pH or bicarbonate. Our analysis provides an inventory of pH-sensitive genes and allows comprehensive insights into processes that are orchestrated by external pH.
]]></description>
<dc:creator>Bailey, M.</dc:creator>
<dc:creator>Hsieh, E.-J.</dc:creator>
<dc:creator>Tsai, H.-H.</dc:creator>
<dc:creator>Ravindran, A.</dc:creator>
<dc:creator>Schmidt, W.</dc:creator>
<dc:date>2022-12-14</dc:date>
<dc:identifier>doi:10.1101/2022.12.12.520164</dc:identifier>
<dc:title><![CDATA[Alkalinity modulates a unique suite of genes to recalibrate growth and pH homeostasis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-12-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.12.18.520953v1?rss=1">
<title>
<![CDATA[
A GFP splicing reporter in a coilin mutant background reveals links between alternative splicing, siRNAs and coilin function in Arabidopsis thaliana 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.12.18.520953v1?rss=1</link>
<description><![CDATA[
Coilin is a scaffold protein essential for the structure of Cajal bodies, which are nucleolar-associated, nonmembranous organelles that coordinate the assembly of nuclear ribonucleoproteins (RNPs) including spliceosomal snRNPs. To learn more about coilin functions and pathways in plants, we conducted a genetic suppressor screen using a coilin (coi1) mutant in Arabidopsis thaliana and performed an immunoprecipitation-mass spectrometry analysis on coilin protein. The coi1 mutations modify alternative splicing of a GFP reporter gene, resulting in a  hyper-GFP phenotype in young coi1 seedlings relative to the intermediate wild-type level. As shown here, this hyper-GFP phenotype is extinguished in older coi1 seedlings by posttranscriptional gene silencing triggered by siRNAs derived from aberrant splice variants of GFP pre-mRNA. In the coi1 suppressor screen, we identified suppressor mutations in WRAP53, a putative coilin-interacting protein; SMU2, a predicted splicing factor; and ZC3HC1, an incompletely characterized zinc finger protein. These suppressor mutations return the hyper-GFP fluorescence of young coi1 seedlings to the intermediate wild-type level. Additionally, zc3hc1 coi1 mutants display more extensive GFP silencing and elevated levels of GFP siRNAs, suggesting the involvement of wild-type ZC3HC1 in siRNA biogenesis or stability. The immunoprecipitation-mass spectrometry analysis reinforced coilins roles in pre-mRNA splicing, nucleolar chromatin structure, and rRNA processing. Coilins participation in these processes, at least some of which incorporate small RNAs, supports the hypothesis that coilin acts as a chaperone for small noncoding RNAs. Our study demonstrates the usefulness of the GFP splicing reporter for investigating alternative splicing, ribosome biogenesis, and siRNA-mediated silencing in the context of coilin function.
]]></description>
<dc:creator>Matzke, M.</dc:creator>
<dc:creator>Matzke, A.</dc:creator>
<dc:creator>Kanno, T. K.</dc:creator>
<dc:creator>Wu, M.-T. L.</dc:creator>
<dc:creator>Chiou, P.</dc:creator>
<dc:creator>Lin, W.</dc:creator>
<dc:date>2022-12-19</dc:date>
<dc:identifier>doi:10.1101/2022.12.18.520953</dc:identifier>
<dc:title><![CDATA[A GFP splicing reporter in a coilin mutant background reveals links between alternative splicing, siRNAs and coilin function in Arabidopsis thaliana]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-12-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.12.19.520999v1?rss=1">
<title>
<![CDATA[
Hybrid-DIA: Intelligent Data Acquisition for Simultaneous Targeted and Discovery Phosphoproteomics in Single Spheroids 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.12.19.520999v1?rss=1</link>
<description><![CDATA[
Achieving sufficient coverage of regulatory phosphorylation sites by mass spectrometry (MS)-based phosphoproteomics for signaling pathway reconstitution is challenging when analyzing tiny sample amounts. We present a novel hybrid data-independent acquisition (DIA) strategy (hybrid-DIA) that combines targeted and discovery proteomics through an Application Programming Interface (API) to dynamically intercalate DIA scans with accurate triggering of multiplexed tandem MS scans of predefined (phospho)peptide targets. By spiking-in heavy stable isotope labeled phosphopeptide standards covering seven major signaling pathways, we benchmarked hybrid-DIA against state-of-the-art targeted MS methods (i.e. SureQuant) using EGF-stimulated HeLa cells and found the quantitative accuracy and sensitivity to be comparable while hybrid-DIA also profiled the global phosphoproteome. To demonstrate the robustness, sensitivity and potential of hybrid-DIA, we profiled chemotherapeutic agents in single colon carcinoma multicellular spheroids and evaluated the difference of cancer cells in 2D vs 3D culture. Altogether, we showed that hybrid-DIA is the way-to-go method in highly sensitive phospho-proteomics experiments.
]]></description>
<dc:creator>Martinez del Val, A.</dc:creator>
<dc:creator>Fort, K.</dc:creator>
<dc:creator>Koenig, C.</dc:creator>
<dc:creator>van der Hoeven, L. R.</dc:creator>
<dc:creator>Franciosa, G.</dc:creator>
<dc:creator>Moehring, T.</dc:creator>
<dc:creator>Ishihama, Y.</dc:creator>
<dc:creator>Chen, Y.-J.</dc:creator>
<dc:creator>Makarov, A. A.</dc:creator>
<dc:creator>Xuan, Y.</dc:creator>
<dc:creator>Olsen, J. V.</dc:creator>
<dc:date>2022-12-20</dc:date>
<dc:identifier>doi:10.1101/2022.12.19.520999</dc:identifier>
<dc:title><![CDATA[Hybrid-DIA: Intelligent Data Acquisition for Simultaneous Targeted and Discovery Phosphoproteomics in Single Spheroids]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-12-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.12.19.521085v1?rss=1">
<title>
<![CDATA[
Is there an accurate and generalisable way to use soundscapes to monitor biodiversity? 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.12.19.521085v1?rss=1</link>
<description><![CDATA[
Acoustic monitoring has the potential to deliver biodiversity insight on vast scales. Whilst autonomous recording networks are being deployed across the world, existing analytical techniques struggle with generalisability. This limits the insight that can be derived from audio recordings in regions without ground-truth calibration data. By calculating 128 learned features and 60 soundscape indices of audio recorded during 8,023 avifaunal point counts from diverse ecosystems, we investigated the generalisability of soundscape approaches to biodiversity monitoring. Within each dataset, we found univariate correlations between several acoustic features and avian species richness, but features behaved unpredictably across datasets. Training a machine learning model on compound indices, we could predict species richness within datasets. However, models were uninformative when applied to datasets not used for training. We found that changes in soundscape features were correlated with changes in avian communities across all datasets. However, there were cases where avian communities changed without an associated shift in soundscapes. Our results suggest that there are no common hallmarks of biodiverse soundscapes across ecosystems. Therefore, soundscape monitoring should only be used when high quality ground-truth data exists for the region of interest, and in conjunction with more targeted and accurate in-person ecological surveys. By better understanding how to use interpret data reliably, we hope to unlock the scale at which acoustic monitoring can be used to deliver true impact for land managers and scientists monitoring biodiversity around the world.

SummaryWhilst eco-acoustic monitoring has the potential to deliver biodiversity insight on vast scales, existing analytical approaches behave unpredictably across studies. We collated 8,023 audio recordings with paired manual avifaunal point counts to investigate whether soundscapes could be used to monitor biodiversity across diverse ecosystems. We found that neither univariate indices nor machine learning models were predictive of species richness across datasets, but soundscape change was consistently indicative of community change. Our findings indicate that there are no common features of biodiverse soundscapes, and that soundscape monitoring should be used cautiously and in conjunction with more reliable in-person ecological surveys.
]]></description>
<dc:creator>Sethi, S. S.</dc:creator>
<dc:creator>Bick, A.</dc:creator>
<dc:creator>Ewers, R. M.</dc:creator>
<dc:creator>Klinck, H.</dc:creator>
<dc:creator>Ramesh, V.</dc:creator>
<dc:creator>Tuanmu, M.-N.</dc:creator>
<dc:creator>Coomes, D. A.</dc:creator>
<dc:date>2022-12-20</dc:date>
<dc:identifier>doi:10.1101/2022.12.19.521085</dc:identifier>
<dc:title><![CDATA[Is there an accurate and generalisable way to use soundscapes to monitor biodiversity?]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-12-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2022.12.30.522068v1?rss=1">
<title>
<![CDATA[
A thermally stable protein nanoparticle that stimulates long lasting humoral immune response 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2022.12.30.522068v1?rss=1</link>
<description><![CDATA[
Thermally stable vaccine platform is considered to be the missing piece of vaccine technology. In this article, we are reporting the development of a novel protein nanoparticle and evaluating its ability in withstanding extended high temperature incubation and stimulating long lasting humoral immune response. This protein nanoparticle is assembled from a fusion protein composed of an amphipathic helical peptide derived from M2 protein of H5N1 influenza virus (AH3) and a super folder green fluorescent protein(sfGFP). The proposed structure of this protein nanoparticle is modeled according to transmission electronic microscope (TEM) images of protein nanoparticle. From this proposed protein model, we have generated a mutant with two gain-of-function mutations that function synergistically on particle stability. Protein nanoparticle assembled from this gain-of-function mutant is able to remove a hydrophobic patch from the surface of protein nanoparticle. This gain-of-function mutant also contributes to higher thermostability of protein nanoparticle and stimulates long lasting humoral immune response after single immunization. This protein nanoparticle shows increasing particle stability in higher temperature and higher salt concentration. This novel protein nanoparticle may serve as a thermal-stable platform for vaccine development.
]]></description>
<dc:creator>Wong, T.-T.</dc:creator>
<dc:creator>Liou, G.-G.</dc:creator>
<dc:creator>Kan, M.-C.</dc:creator>
<dc:date>2022-12-30</dc:date>
<dc:identifier>doi:10.1101/2022.12.30.522068</dc:identifier>
<dc:title><![CDATA[A thermally stable protein nanoparticle that stimulates long lasting humoral immune response]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-12-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.01.19.524718v1?rss=1">
<title>
<![CDATA[
Widespread distribution and evolution of poxviral entry-fusion complex proteins in giant viruses 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.01.19.524718v1?rss=1</link>
<description><![CDATA[
Poxviruses are known to encode a set of proteins that form an entry-fusion complex (EFC) to mediate virus entry. However, the diversity, evolution, and origin of these EFC proteins remain poorly understood. Here we identify the EFC protein homologs in poxviruses and other giant viruses of phylum Nucleocytoviricota. The 11 EFC genes are present in almost all pox-viruses, with the two smallest, G3 and O3, absent in Entomopoxvirinae and basal lineages of Chordopoxvirinae. Five of the EFC genes are further grouped into two families, A16/G9/J5 and F9/L1, which are widely distributed across other major lineages of Nucleocytoviricota, including metagenome-assembled genomes, but are generally absent in viruses infecting algae or non-amoebozoan heterotrophic protists. The A16/G9/J5 and F9/L1 families co-occur, mostly as single copies, in 93% of the non-Poxviridae giant viruses that have at least one of them. Distribution and phylogenetic patterns suggest that both families originated in the ancestor of Nucleocytoviricota. In addition to the Poxviridae genes, homologs from each of the other Nucleo-cytoviricota families are largely clustered together, suggesting their ancient presence and vertical inheritance. Despite deep sequence divergences, we observed noticeable conservation of cysteine residues and predicted structures between EFC proteins of Poxviridae and other families. Overall, our study reveals widespread distribution of these EFC protein homologs beyond pox-viruses, implies the existence of a conserved membrane fusion mechanism, and sheds light on host range and ancient evolution of Nucleocytoviricota.

ImportanceFusion between virus and host membranes is critical for viruses to release genetic materials and to initiate infection. Whereas most viruses use a single protein for membrane fusion, poxviruses employ a multi-protein entry-fusion complex (EFC). We report that two major families of the EFC proteins are widely distributed within the virus phylum Nucleocytoviricota, which include poxviruses and other dsDNA "giant viruses" that infect animals, amoebozoans, algae, and various microbial eukaryotes. Each of these two protein families is structurally conserved, traces its origin to the root of Nucleocytoviricota, was passed down to the major subclades of Nucleocytoviricota, and is retained in most giant viruses known to infect animals and amoebozoans. The EFC proteins therefore represent a potential mechanism for virus entry in diverse giant viruses. We hypothesize that they may have facilitated the infection of an animal/amoebozoan-like host by the last Nucleocytoviricota common ancestor.
]]></description>
<dc:creator>Kao, S.</dc:creator>
<dc:creator>Kao, C.-F.</dc:creator>
<dc:creator>Chang, W.</dc:creator>
<dc:creator>Ku, C.</dc:creator>
<dc:date>2023-01-19</dc:date>
<dc:identifier>doi:10.1101/2023.01.19.524718</dc:identifier>
<dc:title><![CDATA[Widespread distribution and evolution of poxviral entry-fusion complex proteins in giant viruses]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-01-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.02.08.527720v1?rss=1">
<title>
<![CDATA[
Sensory diversity and precise adaptation enable independent bet-hedging strategies for multiple signals at the same time 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.02.08.527720v1?rss=1</link>
<description><![CDATA[
In uncertain environments, phenotypic diversity can be advantageous for survival. However, as the environmental uncertainty decreases, the relative advantage of having diverse phenotypes decreases. Here, we show how populations of E. coli integrate multiple chemical signals to adjust sensory diversity in response to changes in the prevalence of each ligand in the environment. Measuring kinase activity in single cells, we quantified the sensitivity distribution to various chemoattractants in different mixtures of background stimuli. We found that when ligands bind uncompetitively, the population tunes sensory diversity to each signal independently, decreasing diversity when the signal ambient concentration increases. However, amongst competitive ligands the population can only decrease sensory diversity one ligand at a time. Mathematical modeling suggests that sensory diversity tuning benefits E. coli populations by modulating how many cells are committed to tracking each signal proportionally as their prevalence changes.
]]></description>
<dc:creator>Moore, J. P.</dc:creator>
<dc:creator>Kamino, K.</dc:creator>
<dc:creator>Kottou, R.</dc:creator>
<dc:creator>Shimizu, T. S.</dc:creator>
<dc:creator>Emonet, T.</dc:creator>
<dc:date>2023-02-09</dc:date>
<dc:identifier>doi:10.1101/2023.02.08.527720</dc:identifier>
<dc:title><![CDATA[Sensory diversity and precise adaptation enable independent bet-hedging strategies for multiple signals at the same time]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-02-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.02.10.527437v1?rss=1">
<title>
<![CDATA[
Antagonistic pleiotropy plays an important role in governing the evolution and genetic diversity of SARS-CoV-2 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.02.10.527437v1?rss=1</link>
<description><![CDATA[
Analyses of the genomic diversity of SARS-CoV-2 found that some sites across the genome appear to have mutated independently multiple times with frequency significantly higher than four-fold sites, which can be either due to mutational bias, i.e., elevated mutation rate in some sites of the genome, or selection of the variants due to antagonistic pleiotropy, a condition where mutations increase some components of fitness at a cost to others. To examine how different forces shaped evolution of SARS-CoV-2 in 2020-2021, we analyzed a large set of genome sequences (~ 2 million). Here we show that while evolution of SARS-CoV-2 during the pandemic was largely mutation-driven, a group of nonsynonymous changes is probably maintained by antagonistic pleiotropy. To test this hypothesis, we studied the function of one such mutation, spike M1237I. Spike I1237 increases viral assembly and secretion, but decreases efficiency of transmission in vitro. Therefore, while the frequency of spike M1237I may increase within hosts, viruses carrying this mutation would be outcompeted at the population level. We also discuss how the antagonistic pleiotropy might facilitate positive epistasis to promote virus adaptation and reconcile discordant estimates of SARS-CoV-2 transmission bottleneck sizes in previous studies.
]]></description>
<dc:creator>Lee, D.-C.</dc:creator>
<dc:creator>Tai, J.-H.</dc:creator>
<dc:creator>Lin, H.-F.</dc:creator>
<dc:creator>Chao, T.-L.</dc:creator>
<dc:creator>Ruan, Y.</dc:creator>
<dc:creator>Cheng, Y.-W.</dc:creator>
<dc:creator>Chou, Y.-C.</dc:creator>
<dc:creator>Lin, Y.-Y.</dc:creator>
<dc:creator>Chang, S.-Y.</dc:creator>
<dc:creator>Chen, P.-J.</dc:creator>
<dc:creator>Yeh, S.-H.</dc:creator>
<dc:creator>Wang, H.-Y.</dc:creator>
<dc:date>2023-02-10</dc:date>
<dc:identifier>doi:10.1101/2023.02.10.527437</dc:identifier>
<dc:title><![CDATA[Antagonistic pleiotropy plays an important role in governing the evolution and genetic diversity of SARS-CoV-2]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-02-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.02.15.528623v1?rss=1">
<title>
<![CDATA[
The thermostability of a VADEX-Pro based protein nanoparticle 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.02.15.528623v1?rss=1</link>
<description><![CDATA[
We have adapted split GFP technology into the protein nanoparticle platform, Vaccine Delivery system X (VADEX), created in previous study. To evaluate the capability of this new platform, a model protein, maltose binding protein (MBP), was fused to the {beta}-strand 11 of sfGFP and co-expressed with VADEX-10 which was composed of LYRRLE peptide and N-terminal part up to {beta}-strand 10 of sfGFP. When these two fusion proteins were expressed in a cell, they were assembled into PNP spontaneously with a dynamic light scattering (DLS) particle size of 26 nm. This nanoparticle platform was renamed as VADEX-Pro for its capacity of expressing large protein on PNP. The thermostability of the assembled PNP was verified by both SDS-PAGE and DLS analysis following treatment. This PNP was stable at 25 {degrees}C and at temperatures as high as 40 {degrees}C for at least two months. Mutations that replaced cysteine residue of the LYRRLE peptide with serine or alanine destabilized and induced degradation of the VADEX-based PNP. The results in this study showed that the non-covalent complementation of split sfGFP became irreversible when reconstituted sfGFP was assembled in a VADEX-Pro PNP. This platform may be applied in developing thermostable vaccines.
]]></description>
<dc:creator>Kan, M.-C.</dc:creator>
<dc:date>2023-02-15</dc:date>
<dc:identifier>doi:10.1101/2023.02.15.528623</dc:identifier>
<dc:title><![CDATA[The thermostability of a VADEX-Pro based protein nanoparticle]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-02-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.02.21.529467v1?rss=1">
<title>
<![CDATA[
Testing the efficacy of different molecular tools for parasite conservation genetics: a case study using horsehair worms (Phylum Nematomorpha) 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.02.21.529467v1?rss=1</link>
<description><![CDATA[
In recent years, parasite conservation has become a globally significant issue. Because of this, there is a need for standardised methods for inferring population status and possible cryptic diversity. However, given the lack of molecular data for some groups, it is challenging to establish procedures for genetic diversity estimation. Therefore, universal tools, such as double digest restriction-site associated DNA sequencing (ddRADseq), could be useful when conducting conservation genetic studies on rarely studied parasites. Here, we generated a ddRADseq dataset that includes all three described Taiwanese horsehair worms (Phylum Nematomorpha), possibly one of the most understudied animal groups. Additionally, we produced data for a fragment of the cytochrome c oxidase subunit I (COXI) for said species. We used the COXI dataset in combination with previously published sequences of the same locus for inferring the effective population size (Ne) trends and possible population structure.

We found that a larger and geographically broader sample size combined with more sequenced loci resulted in a better estimation of changes in Ne. We were able to detect demographic changes associated with Pleistocene events in all the species. Furthermore, the ddRADseq dataset for Chordodes formosanus did not reveal a genetic structure based on geography, implying a great dispersal ability, possibly due to its hosts. We showed that different molecular tools can be used to reveal genetic structure and demographic history at different historical times and geographical scales, which can help with conservation genetic studies in rarely studied parasites.
]]></description>
<dc:creator>De Vivo, M.</dc:creator>
<dc:creator>Chen, W.-Y.</dc:creator>
<dc:creator>Huang, J.-P.</dc:creator>
<dc:date>2023-02-22</dc:date>
<dc:identifier>doi:10.1101/2023.02.21.529467</dc:identifier>
<dc:title><![CDATA[Testing the efficacy of different molecular tools for parasite conservation genetics: a case study using horsehair worms (Phylum Nematomorpha)]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-02-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.02.23.529696v1?rss=1">
<title>
<![CDATA[
A Suspension Trapping-Based Sample Preparation Workflow for Sensitive Plant Phosphoproteomics 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.02.23.529696v1?rss=1</link>
<description><![CDATA[
Plant phosphoproteomics provides a global view of phosphorylation-mediated signaling in plants; however, it demands high-throughput methods with sensitive detection and accurate quantification. Although protein precipitation is indispensable for removing contaminants and improving sample purity, it limits the sensitivity and throughput of plant phosphoproteomic analysis. The multiple handling steps involved in protein precipitation lead to sample loss and process variability. Herein, we developed an approach based on suspension trapping (S-Trap), termed tandem S-Trap-IMAC (immobilized metal ion affinity chromatography), by integrating an S-Trap micro column with an Fe-IMAC tip. Compared with a precipitation-based workflow, the tandem S-Trap-IMAC method deepened the coverage of the Arabidopsis (Arabidopsis thaliana) phosphoproteome by more than 30%, with improved quantification accuracy and short sample processing time. We applied the tandem S-Trap-IMAC method for studying abscisic acid (ABA) signaling in Arabidopsis seedlings. We thus identified 24,055 phosphopeptides and quantified several key phosphorylation sites on core ABA signaling components across four time points. Our results show that the optimized workflow aids high-throughput phosphoproteome profiling of low-input plant samples.
]]></description>
<dc:creator>Chen, C.-W.</dc:creator>
<dc:creator>Tsai, C.-F.</dc:creator>
<dc:creator>Lin, M.-H.</dc:creator>
<dc:creator>Lin, S.-Y.</dc:creator>
<dc:creator>Hsu, C.-C.</dc:creator>
<dc:date>2023-02-23</dc:date>
<dc:identifier>doi:10.1101/2023.02.23.529696</dc:identifier>
<dc:title><![CDATA[A Suspension Trapping-Based Sample Preparation Workflow for Sensitive Plant Phosphoproteomics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-02-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.03.13.532490v1?rss=1">
<title>
<![CDATA[
Adjuvant Effects of Amphipathic Helical Peptides 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.03.13.532490v1?rss=1</link>
<description><![CDATA[
Subunit vaccines are the focus of research in developing new vaccines against infectious diseases. Due to the low immunogenicity of recombinant proteins, adjuvants are required for the activation of humoral and cellular immunity against a protein antigen. In this study, we reported the identification of a novel pathway that can activate humoral immunity against a recombinant protein without inducing inflammatory responses. By fusing an amphipathic helical peptide to GFP, one can increases the immunogenicity of GFP by up to 1000 fold. This enhancement was correlated with the ability of amphipathic helical peptides to bind to cell membranes and cause lysosomal membrane permeabilization. We showed evidence that the amphipathic helical peptide may induce the delivery of antigen across the lysosomal membrane into cytosol. Amphipathic helical peptide fusion provided a new pathway for stimulating immune responses against recombinant proteins.
]]></description>
<dc:creator>Kan, M.-C.</dc:creator>
<dc:creator>Liou, G.-G.</dc:creator>
<dc:creator>Lyu, J.-H.</dc:creator>
<dc:creator>Wang, M.</dc:creator>
<dc:date>2023-03-15</dc:date>
<dc:identifier>doi:10.1101/2023.03.13.532490</dc:identifier>
<dc:title><![CDATA[Adjuvant Effects of Amphipathic Helical Peptides]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-03-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.03.15.532709v1?rss=1">
<title>
<![CDATA[
Engineering Nanomolar Potent Protein-based Inhibitors for Papain-like Protease Guided by Residue Correlation Network 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.03.15.532709v1?rss=1</link>
<description><![CDATA[
Identifying critical residues in protein-protein binding and efficiently designing stable and specific protein binders is challenging. In addition to direct contacts in a protein-protein binding interface, our study employs computation modeling to reveal the essential network of residue interaction and dihedral angle correlation critical in protein-protein recognition. We propose that mutating residues regions exhibited highly correlated motions within the interaction network can efficiently optimize protein-protein interactions to create tight and selective protein binders. We validated our strategy using ubiquitin (Ub) and MERS coronaviral papain-like protease (PLpro) complexes, where Ub is one central player in many cellular functions and PLpro is an antiviral drug target. Our designed UbV with 3 mutated residues resulted in a [~]3,500-fold increase in functional inhibition, compared with the wild-type Ub. Further optimization by incorporating 2 more residues within the network, the 5-point mutant achieved a KD of 1.5 nM and IC50 of 9.7 nM. The modification led to a 27,500-fold and 5,500-fold enhancements in affinity and potency, respectively, as well as improved selectivity, without destabilizing the UbV structure. Our study highlights residue correlation and interaction networks in protein-protein interaction, introduces an effective approach to design high affinity protein binders for cell biology and future therapeutics solutions.
]]></description>
<dc:creator>Huang, T. I.</dc:creator>
<dc:creator>Hsieh, Y.-J.</dc:creator>
<dc:creator>Lu, W.-L.</dc:creator>
<dc:creator>Wu, K.-P.</dc:creator>
<dc:creator>Chang, C.-e.</dc:creator>
<dc:date>2023-03-15</dc:date>
<dc:identifier>doi:10.1101/2023.03.15.532709</dc:identifier>
<dc:title><![CDATA[Engineering Nanomolar Potent Protein-based Inhibitors for Papain-like Protease Guided by Residue Correlation Network]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-03-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.03.19.533375v1?rss=1">
<title>
<![CDATA[
Protein Phosphorylation Orchestrates Acclimations of Arabidopsis Plants to Environmental pH 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.03.19.533375v1?rss=1</link>
<description><![CDATA[
Environment pH (pHe) is a key parameter that dictates a surfeit of conditions critical to plant survival and fitness. To elucidate the mechanisms that recalibrate cytoplasmic and apoplastic pH homeostasis, we conducted a comprehensive proteomic/phosphoproteomic inventory of plants subjected to transient exposure to acidic or alkaline pH, an approach that covered the majority of protein-coding genes of the model plant Arabidopsis thaliana. Our survey revealed a large set so far undocumented pHe-dependent and potentially pH-specific phospho-sites, indicative of extensive post-translational regulation of proteins involved in the acclimation to pHe. Changes in pHe altered both electrogenic H+ pumping via P-type ATPases and H+/anion co-transport processes, leading to massively altered net trans-plasma membrane translocation of H+ ions. In pH 7.5 plants, transport (but not the assimilation) of nitrogen via NRT2-type nitrate and AMT1- type ammonium transporters was induced, conceivably to increase the cytosolic H+ concentration. Exposure to acidic pH resulted in a marked repression of primary root elongation. No such cessation was observed in nrt2.1 mutants, suggesting a role of NRT2.1 in negatively regulating root growth in response to acidic pH. Sequestration of iron into the vacuole via phosphorylation and abundance of the vacuolar iron transporter VTL5 was inversely regulated in response to high and low pHe, presumptively in anticipation of changes in iron availability associated with alterations of pHe in the soil. A pH-dependent  phospho-switch was also observed for the ABC transporter PDR7, suggesting changes in activity and, possibly, substrate specificity. Unexpectedly, the effect of pHe was not restricted to roots and provoked pronounced changes in the leaf proteome. In both roots and shoots, the plant-specific TPLATE complex components AtEH1 and AtEH2 - essential for clathrin-mediated endocytosis - were differentially phosphorylated at multiple sites in response to pHe, indicating that the endocytic cargo protein trafficking is orchestrated by pHe.
]]></description>
<dc:creator>Jain, D.</dc:creator>
<dc:creator>Schmidt, W.</dc:creator>
<dc:date>2023-03-20</dc:date>
<dc:identifier>doi:10.1101/2023.03.19.533375</dc:identifier>
<dc:title><![CDATA[Protein Phosphorylation Orchestrates Acclimations of Arabidopsis Plants to Environmental pH]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-03-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.03.20.533392v1?rss=1">
<title>
<![CDATA[
Expansion microscopy with trypsin digestion and tyramide signal amplification (TT-ExM) for protein and lipid staining 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.03.20.533392v1?rss=1</link>
<description><![CDATA[
Expansion microscopy, whereby the relative positions of biomolecules are physically increased via hydrogel expansion, can be used to reveal ultrafine structures of cells under a conventional microscope. Despite its utility for achieving super-resolution imaging, expansion microscopy suffers two major drawbacks, namely proteolysis and swelling effects that, respectively, induce protein loss and dilute fluorescence signals. Here, we report two improvements to expansion microscopy that overcome these two challenges, i.e., deploying trypsin digestion to reduce protein loss and tyramide signal amplification to enhance fluorescence signal. We name our new methodology TT-ExM to indicate dual trypsin and tyramide treatments. TT-ExM may be applied for both antibody and lipid staining. Notably, we demonstrate better protein retention for endoplasmic reticulum and mitochondrial markers in COS-7 cell cultures following 2-h trypsin treatment. Subsequent lipid staining revealed the complex 3D membrane structures in entire cells. Through combined lipid and DNA staining, our TT-ExM methodology highlighted mitochondria by revealing their DNA and membrane structures in cytoplasm, as well as the lipid-rich structures formed via phase separation in nuclei at interphase. We also observed lipid-rich chromosome matrices in the mitotic cells. Thus, TT-ExM significantly enhances fluorescent signals and generates high-quality and ultrafine-resolution images under confocal microscopy.
]]></description>
<dc:creator>Wang, U.-T. T.</dc:creator>
<dc:creator>Tian, X.</dc:creator>
<dc:creator>Liou, Y.-H.</dc:creator>
<dc:creator>Lee, S.-P.</dc:creator>
<dc:creator>Lu, C.-H.</dc:creator>
<dc:creator>Chen, P.</dc:creator>
<dc:creator>Chen, B.-C.</dc:creator>
<dc:date>2023-03-21</dc:date>
<dc:identifier>doi:10.1101/2023.03.20.533392</dc:identifier>
<dc:title><![CDATA[Expansion microscopy with trypsin digestion and tyramide signal amplification (TT-ExM) for protein and lipid staining]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-03-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.03.20.533438v1?rss=1">
<title>
<![CDATA[
Two classes of His-Me finger superfamily nuclease effectors exerting synergy for Agrobacterium T6SS-mediated interbacterial competition 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.03.20.533438v1?rss=1</link>
<description><![CDATA[
Type VI secretion system (T6SS) assembles into a contractile nanomachine to inject effectors across bacterial membranes for secretion. Agrobacterium tumefaciens species complex is a group of soil inhabitants and phytopathogens that deploys T6SS as an antibacterial weapon against bacterial competitors at both inter-species and intra-species levels. A. tumefaciens strain 1D1609 genome encodes one main T6SS gene cluster and four vrgG genes (i.e. vgrGa-d), each encoding a spike protein as an effector carrier. Previous study reported that vgrGa-associated gene 2, named as v2a, encodes a His-Me finger nuclease toxin (also named as HNH/ENDO VII nuclease) contributing to DNase-mediated antibacterial activity. However, the functions and roles of other putative effectors remain unknown. In this study, we identified vgrGc- associated gene 2 (v2c) that encodes another His-Me finger nuclease but with distinct SHH motif differed from AHH motif of V2a. We demonstrated that the ectopic expression of V2c caused growth inhibition, plasmid DNA degradation, and cell elongation in Escherichia coli. The cognate immunity protein, V3c, neutralizes the DNase activity and rescues phenotypes of the growth inhibition and cell elongation. Ectopic expression of V2c DNase-inactive variants retains the cell elongation phenotype while V2a induced cell elongation in a DNase-mediated manner. We also showed that the amino acids of conserved SHH and HNH motifs are responsible for the V2c DNase activity in vivo and in vitro. Notably, V2c also mediated the DNA degradation and cell elongation of target cell in the context of interbacterial competition. Importantly, V2a and V2c exhibit different capacities against different bacterial species and function synergistically to exert stronger antibacterial activity against the soft rot phytopathogen, Dickeya dadantii.
]]></description>
<dc:creator>Santos, M. N. M.</dc:creator>
<dc:creator>Pintor, K. L.</dc:creator>
<dc:creator>Hsieh, P.-Y.</dc:creator>
<dc:creator>Cheung, Y.-W.</dc:creator>
<dc:creator>Sung, L.-K.</dc:creator>
<dc:creator>Shih, Y.-L.</dc:creator>
<dc:creator>Lai, E.-M.</dc:creator>
<dc:date>2023-03-20</dc:date>
<dc:identifier>doi:10.1101/2023.03.20.533438</dc:identifier>
<dc:title><![CDATA[Two classes of His-Me finger superfamily nuclease effectors exerting synergy for Agrobacterium T6SS-mediated interbacterial competition]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-03-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.04.01.535237v1?rss=1">
<title>
<![CDATA[
Self-Healable Spider Dragline Silk Materials 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.04.01.535237v1?rss=1</link>
<description><![CDATA[
Developing materials with structural flexibility that permits self-repair in response to external disturbances remains challenging. Spider silk, which combines an exceptional blend of strength and pliability in nature, serves as an ideal dynamic model for adaptive performance design. In this work, a novel self-healing material is generated using spider silk. Dragline silk from spider Nephila pilipes is demonstrated with extraordinary in situ self-repair property through a constructed thin film format, surpassing that of two other silks from spider Cyrtophora moluccensis and silkworm Bombyx mori. Subsequently, R2, a key spidroin associated with self-healing, is biosynthesized, with validated cohesiveness. R2 is further programmed with tunable healability (permanent and reversible) and conductivity (graphene doping; R2G) for electronics applications. In the first demonstration, film strips from R2 and R2G are woven manually into multidimensional (1D-3D) conductive fabrics for creating repairable logic gate circuits. In the second example, a reversibly-healable R2/R2G strip is fabricated as a re-configurable wearable ring probe to fit fingertips of varying widths while retaining its detecting capabilities. Such prototype displays a unique conformable wearable technology. Last, the remarkable finding of self-healing in spider silk could offer a new material paradigm for developing future adaptive biomaterials with tailored performance and environmental sustainability.
]]></description>
<dc:creator>Chen, W.-C.</dc:creator>
<dc:creator>Wang, R.-C.</dc:creator>
<dc:creator>Yu, S.-K.</dc:creator>
<dc:creator>Chen, J.-L.</dc:creator>
<dc:creator>Kao, Y.-H.</dc:creator>
<dc:creator>Wang, T.-Y.</dc:creator>
<dc:creator>Chang, P.-Y.</dc:creator>
<dc:creator>Sheu, H.-S.</dc:creator>
<dc:creator>Chen, S. C. C.</dc:creator>
<dc:creator>Liu, W.-R.</dc:creator>
<dc:creator>Yang, T.-I.</dc:creator>
<dc:creator>Wu, H.-C.</dc:creator>
<dc:date>2023-04-04</dc:date>
<dc:identifier>doi:10.1101/2023.04.01.535237</dc:identifier>
<dc:title><![CDATA[Self-Healable Spider Dragline Silk Materials]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-04-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.04.09.536141v1?rss=1">
<title>
<![CDATA[
Predicting splicing patterns from the transcription factor binding sites in the promoter with deep learning 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.04.09.536141v1?rss=1</link>
<description><![CDATA[
BackgroundAlternative splicing is a crucial mechanism of post-transcriptional modification responsible for the transcriptome plasticity and proteome diversity of a metazoan cell. Although many splicing regulations around the exon/intron regions have been discovered, the relationship between promoter-bound transcription factors and the downstream alternative splicing remains largely unexplored.

ResultsIn this study, we present computational approaches to decipher the regulation relationship connecting the promoter-bound transcription factor binding sites (TFBSs) and the splicing patterns. We curated a fine data set, including DNase I hypersensitive sites sequencing and transcriptome in fifteen human tissues from ENCODE. Specifically, we proposed different representations of TF binding context and splicing patterns to tackle the associations between the promoter and downstream splicing events. Our results demonstrated that the convolutional neural network (CNN) models learned from the TF binding changes in the promoter to predict the splicing pattern changes. Furthermore, through an in silico perturbation-based analysis of the CNN models, we identified several TFs that considerably reduced the model performance of splicing prediction.

ConclusionIn conclusion, our finding highlights the potential role of promoter-bound TFBSs in influencing the regulation of downstream splicing patterns and provides insights for discovering alternative splicing regulations.
]]></description>
<dc:creator>Lin, T.-C.</dc:creator>
<dc:creator>Tsai, C.-H.</dc:creator>
<dc:creator>Shiau, C.-K.</dc:creator>
<dc:creator>Huang, J.-H.</dc:creator>
<dc:creator>Tsai, H.-K.</dc:creator>
<dc:date>2023-04-09</dc:date>
<dc:identifier>doi:10.1101/2023.04.09.536141</dc:identifier>
<dc:title><![CDATA[Predicting splicing patterns from the transcription factor binding sites in the promoter with deep learning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-04-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.04.12.536584v1?rss=1">
<title>
<![CDATA[
PGSbuilder: An end-to-end platform for human genome association analysis and polygenic risk score predictions 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.04.12.536584v1?rss=1</link>
<description><![CDATA[
Understanding the genetic basis of human complex diseases is increasingly important in the development of precision medicine. Over the last decade, genome-wide association studies (GWAS) have become a key technique for detecting associations between common diseases and single nucleotide polymorphisms (SNPs) present in a cohort of individuals. Alternatively, the polygenic risk score (PRS), which often applies results from GWAS summary statistics, is calculated for the estimation of genetic propensity to a trait at the individual level. Despite many GWAS and PRS tools being available to analyze a large volume of genotype data, most clinicians and medical researchers are often not familiar with the bioinformatics tools and lack access to a high-performance computing cluster resource. To fill this gap, we provide a publicly available web server, PGSbuilder, for the GWAS and PRS analysis of human genomes with variant annotations. The user-friendly and intuitive PGSbuilder web server is developed to facilitate the discovery of the genetic variants associated with complex traits and diseases for medical professionals with limited computational skills. For GWAS analysis, PGSbuilder provides the most renowned analysis tool PLINK 2.0 package. For PRS, PGSbuilder provides six different PRS methods including Clumping and Thresholding, Lassosum, LDPred2, GenEpi, PRS-CS, and PRSice2. Furthermore, PGSbuilder provides an intuitive user interface to examine the annotated functional effects of variants from known biomedical databases and relevant literature using advanced natural language processing approaches. In conclusion, PGSbuilder offers a reliable platform to aid researchers in advancing the public perception of genomic risk and precision medicine for human disease genetics. PGSbuilder is freely accessible at http://pgsb.tw23.org.
]]></description>
<dc:creator>Lee, K.-H.</dc:creator>
<dc:creator>Lee, Y.-L.</dc:creator>
<dc:creator>Hsieh, T.-T.</dc:creator>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Wang, S.-S.</dc:creator>
<dc:creator>Fann, G.-Z.</dc:creator>
<dc:creator>Lin, W.-C.</dc:creator>
<dc:creator>Chen, T.-F.</dc:creator>
<dc:creator>Li, P.-H.</dc:creator>
<dc:creator>Kuo, Y.-L.</dc:creator>
<dc:creator>Chen, P.-L.</dc:creator>
<dc:creator>Juan, H.-F.</dc:creator>
<dc:creator>Tsai, H.-K.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Huang, J.-H.</dc:creator>
<dc:date>2023-04-13</dc:date>
<dc:identifier>doi:10.1101/2023.04.12.536584</dc:identifier>
<dc:title><![CDATA[PGSbuilder: An end-to-end platform for human genome association analysis and polygenic risk score predictions]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-04-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.04.17.537128v1?rss=1">
<title>
<![CDATA[
Single worm long read sequencing reveals genome diversity in free-living nematodes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.04.17.537128v1?rss=1</link>
<description><![CDATA[
Obtaining sufficient genetic material from a limited biological source is currently the primary operational bottleneck in studies investigating biodiversity and genome evolution. In this study, we employed multiple displacement amplification (MDA) and Smartseq2 to amplify nanograms of genomic DNA and mRNA, respectively from individual Caenorhabditis elegans. Although reduced genome coverage was observed in repetitive regions, we produced assemblies covering 98% of the reference genome using long-read sequences generated with Oxford Nanopore Technologies (ONT). Annotation with the sequenced transcriptome coupled with the available assembly revealed that gene predictions were more accurate, complete and contained far fewer false positives than de novo transcriptome assembly approaches. We sampled and sequenced the genomes and transcriptomes of 13 nematodes from Dorylaimia, Enoplia, and early-branching species in Chromadoria. These free-living species had larger genome sizes, ranging from 147-792 Mb, compared to those of the parasitic lifestyle. Nine mitogenomes were fully assembled and displaying a complete lack of synteny to other species. Phylogenomic analyses based on the new annotations revealed strong support for Enoplia as sister to the rest of Nematoda. Our result demonstrates the robustness of MDA in combination with ONT, paving the way for the study of genome diversity in the phylum Nematoda and beyond.
]]></description>
<dc:creator>Lee, Y.-C.</dc:creator>
<dc:creator>Lee, H.-H.</dc:creator>
<dc:creator>Ke, H.-M.</dc:creator>
<dc:creator>Liu, Y.-C.</dc:creator>
<dc:creator>Wang, M.-C.</dc:creator>
<dc:creator>Tseng, Y.-C.</dc:creator>
<dc:creator>Kikuchi, T.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2023-04-18</dc:date>
<dc:identifier>doi:10.1101/2023.04.17.537128</dc:identifier>
<dc:title><![CDATA[Single worm long read sequencing reveals genome diversity in free-living nematodes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-04-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.04.17.537135v1?rss=1">
<title>
<![CDATA[
AHL10 phosphorylation determines RRP6L1 chromatin association and growth suppression during water stress. 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.04.17.537135v1?rss=1</link>
<description><![CDATA[
Phosphorylation of AHL10, one of the AT-hook family of plant-specific DNA binding proteins, is critical for growth suppression during moderate severity drought (low water potential, {psi}w) stress. To understand how AHL10 phosphorylation determines drought response, we identified putative AHL10 interacting proteins and further characterized interaction with RRP6L1, a protein involved in epigenetic regulation. RRP6L1 and AHL10 mutants, as well as ahl10-1rrp6l1-2, had similar phenotype of increased growth maintenance during low {psi}w. Chromatin precipitation demonstrated that RRP6L1 chromatin association increased during low {psi}w stress and was dependent upon AHL10 phosphorylation. Transcriptome analyses showed that AHL10 and RRP6L1 have concordant effects on expression of stress- and development-related genes. Together these results indicate that stress signaling can act via AHL10 phosphorylation to control the chromatin association of the key regulatory protein RRP6L1. AHL10 and RRP6L1 interaction in meristem cells is part of a mechanism to down-regulate growth during low {psi}w stress. Interestingly, loss of AHL13, which is homologous to AHL10 and phosphorylated at similar C-terminal site, blocked the enhanced growth maintenance of ahl10-1. Thus, AHL10 and AHL13, despite their close homology, are not redundant but rather have distinct roles, likely related to the formation of AHL hetero-complexes.

Summary StatementPhosphorylation of Arabidopsis thaliana AHL10 is important to control growth during drought stress, a function which is distinct from the closely related AHL13. One way that phosphorylation determines AHL10 function is by altering its ability to mediate chromatin recruitment of RRP6L1.
]]></description>
<dc:creator>Wong, M. M.</dc:creator>
<dc:creator>Huang, X.-J.</dc:creator>
<dc:creator>Bau, Y.-C.</dc:creator>
<dc:creator>Verslues, P.</dc:creator>
<dc:date>2023-04-18</dc:date>
<dc:identifier>doi:10.1101/2023.04.17.537135</dc:identifier>
<dc:title><![CDATA[AHL10 phosphorylation determines RRP6L1 chromatin association and growth suppression during water stress.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-04-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.04.21.537849v1?rss=1">
<title>
<![CDATA[
Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.04.21.537849v1?rss=1</link>
<description><![CDATA[
A causal relationship exists among the aging process, organ decay and dis-function, and the occurrence of various diseases including cancer. A genetically engineered mouse model, termed Klf1K74R/K74R or Klf1(K74R), carrying mutation on the well-conserved sumoylation site of the hematopoietic transcription factor KLF1/ EKLF has been generated that possesses extended lifespan and healthy characteristics including cancer resistance. We show that the healthy longevity characteristics of the Klf1(K74R) mice, as exemplified by their higher anti- cancer capability, are likely gender-, age- and genetic background-independent. Significantly, the anti-cancer capability, in particular that against melanoma as well as hepatocellular carcinoma, and lifespan-extending property of Klf1(K74R) mice could be transferred to wild-type mice via transplantation of their bone marrow mononuclear cells at young age of the latter. Furthermore, NK(K74R) cells carry higher in vitro cancer cell-killing ability than wild type NK cells. Targeted/global gene expression profiling analysis has identified changes of the expression of specific proteins, including the immune checkpoint factors PDCD and CD274, and cellular pathways in the leukocytes of the Klf1(K74R) that are in the directions of anti-cancer and/or anti-aging. This study demonstrates the feasibility of developing a transferable hematopoietic/ blood system for long-term anti-cancer and, potentially, for anti-aging.
]]></description>
<dc:creator>Wang, J.-P.</dc:creator>
<dc:creator>Hung, C.-H.</dc:creator>
<dc:creator>Liou, Y.-H.</dc:creator>
<dc:creator>Liu, C.-C.</dc:creator>
<dc:creator>Yeh, K.-H.</dc:creator>
<dc:creator>Wang, K.-Y.</dc:creator>
<dc:creator>Lai, Z.-S.</dc:creator>
<dc:creator>Hsu, T.-C.</dc:creator>
<dc:creator>Lee, T.-L.</dc:creator>
<dc:creator>Shyu, Y.-C.</dc:creator>
<dc:creator>Hsiao, P.-W.</dc:creator>
<dc:creator>Chen, L.-Y.</dc:creator>
<dc:creator>Chuang, T.-J.</dc:creator>
<dc:creator>Yu, C.-H. A.</dc:creator>
<dc:creator>Liao, N.-S.</dc:creator>
<dc:creator>Shen, C.-K. J.</dc:creator>
<dc:date>2023-04-21</dc:date>
<dc:identifier>doi:10.1101/2023.04.21.537849</dc:identifier>
<dc:title><![CDATA[Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-04-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.05.10.540297v1?rss=1">
<title>
<![CDATA[
The NPH3-domain protein NRL5 is a plant specific type of GTPase essential for drought resistance 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.05.10.540297v1?rss=1</link>
<description><![CDATA[
The mechanisms of plant resistance to low water potential ({psi}w) during drought are unclear but may involve signaling and trafficking at the plasma membrane as well as metabolic reprogramming, including proline accumulation. Forward genetic screening using a Proline Dehydrogenase 1 (ProDH1) promoter:reporter line identified a mutant with extreme low {psi}w hypersensitivity due to a single amino acid substitution (P335L) in the Non-Phototrophic Hypocotyl3 (NPH3) domain of NPH3/RPT2-Like5 (NRL5)/Naked Pins in Yucca8 (NPY8). Further experiments found that NRL5, and other NPH3-domain proteins, are GTPases. NRL5 interacted with RAB small GTPases and the SNARE proteins VAMP721/722 and had polar localization. NRL5P335L had greatly reduced GTPase activity, impaired RAB and VAMP721/722 interaction and disrupted polar localization. These data demonstrate that NRL5-mediated restraint of proline catabolism is required for drought resistance and also more broadly define unexpected functions of the NPH3 domain such that the role of NPH3-domain proteins in signaling, trafficking, and cellular polarity can be critically re-evaluated.

One-Sentence SummaryA protein containing the plant-specific NPH3-domain has GTPase activity, trafficking interaction and drought resistance function.
]]></description>
<dc:creator>UPADHYAY-TIWARI, N.</dc:creator>
<dc:creator>Huang, X.-J.</dc:creator>
<dc:creator>Lee, Y.-C.</dc:creator>
<dc:creator>Singh, S. K.</dc:creator>
<dc:creator>Hsu, C.-C.</dc:creator>
<dc:creator>Huang, S.-S.</dc:creator>
<dc:creator>Verslues, P. E.</dc:creator>
<dc:date>2023-05-11</dc:date>
<dc:identifier>doi:10.1101/2023.05.10.540297</dc:identifier>
<dc:title><![CDATA[The NPH3-domain protein NRL5 is a plant specific type of GTPase essential for drought resistance]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-05-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.05.23.541893v1?rss=1">
<title>
<![CDATA[
Tight junctions regulate lumen morphology via hydrostatic pressure and junctional tension 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.05.23.541893v1?rss=1</link>
<description><![CDATA[
Formation of fluid filled lumen by epithelial tissues is a fundamental process for organ development. How epithelial cells regulate the hydraulic and cortical forces to control lumen morphology is not completely understood. Here, we quantified the mechanical role of tight junctions in lumen formation using genetically modified MDCKII cysts. We found that the paracellular ion barrier formed by claudin receptors is not required for hydraulic inflation of lumen. However, depletion of the zonula occludens scaffold resulted in lumen collapse and folding of apical membranes. Combining quantitative measurements and perturbations of hydrostatic lumen pressure and junctional tension with modelling, we were able to predict lumen morphologies from the pressure-tension force balance. We found that in MDCK tissue the tight junction promotes formation of spherical lumen by decreasing cortical tension via inhibition of myosin. In addition, we found that the apical surface area of cells is largely uncoupled from lumen volume changes, suggesting that excess apical area contributes to lumen opening in the low-pressure regime. Overall, our findings provide a mechanical understanding of how epithelial cells use tight junctions to modulate tissue and lumen shape.
]]></description>
<dc:creator>Mukenhirn, M.</dc:creator>
<dc:creator>Wang, C.-H.</dc:creator>
<dc:creator>Guyomar, T.</dc:creator>
<dc:creator>Bovyn, M. J.</dc:creator>
<dc:creator>Staddon, M. F.</dc:creator>
<dc:creator>Maraspini, R.</dc:creator>
<dc:creator>Lu, L.</dc:creator>
<dc:creator>Martin-Lemaitre, C.</dc:creator>
<dc:creator>Sano, M.</dc:creator>
<dc:creator>Hiraiwa, T.</dc:creator>
<dc:creator>Riveline, D.</dc:creator>
<dc:creator>Honigmann, A.</dc:creator>
<dc:date>2023-05-23</dc:date>
<dc:identifier>doi:10.1101/2023.05.23.541893</dc:identifier>
<dc:title><![CDATA[Tight junctions regulate lumen morphology via hydrostatic pressure and junctional tension]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-05-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.05.26.542455v1?rss=1">
<title>
<![CDATA[
Transcriptomic landscape of posterior regeneration in the annelid Platynereis dumerilii 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.05.26.542455v1?rss=1</link>
<description><![CDATA[
Background: Restorative regeneration, the capacity to reform a lost body part following amputation or injury, is an important and still poorly understood process in animals. Annelids, or segmented worms, show amazing regenerative capabilities, and as such are a crucial group to investigate. Elucidating the molecular mechanisms that underpin regeneration in this major group remains a key goal. Among annelids, the nereididae Platynereis dumerilii (re)emerged recently as a front-line regeneration model. Following amputation of its posterior part, Platynereis worms can regenerate both differentiated tissues of their terminal part as well as a growth zone that contains putative stem cells. While this regeneration process follows specific and reproducible stages that have been well characterized, the transcriptomic landscape of these stages remains to be uncovered.

Results: We generated a high quality de novo Reference transcriptome for the annelid Platynereis dumerilii. To do so, we produced and analyzed three RNA-sequencing datasets, encompassing five stages of posterior regeneration, along with blastema stages and non-amputated tissues as controls. We included these regeneration RNA-seq datasets, as well as embryonic and tissue-specific datasets from the literature to produce a Reference transcriptome. We used this Reference transcriptome to perform in depth analyzes of RNA-seq data during the course of regeneration to reveal the important dynamics of the gene expression, process with thousands of genes differentially expressed between stages, as well as unique and specific genes expression at each regeneration stage. The study of these genes highlighted the importance of the nervous system at both early and late stages of regeneration, as well as the enrichment of RNA-binding proteins (RBPs) during almost the entire regeneration process.

Conclusions: In this study, we provided a high-quality de novo Reference transcriptome for the annelid Platynereis that is useful for investigating various developmental processes, including regeneration. Our extensive stage-specific transcriptional analysis during the course of posterior regeneration shed light upon major molecular mechanisms and pathways, and will foster many specific studies in the future.
]]></description>
<dc:creator>Pare, L.</dc:creator>
<dc:creator>Bideau, L.</dc:creator>
<dc:creator>Baduel, L.</dc:creator>
<dc:creator>Dalle, C.</dc:creator>
<dc:creator>Benchouaia, M.</dc:creator>
<dc:creator>Schneider, S. Q.</dc:creator>
<dc:creator>Laplane, L.</dc:creator>
<dc:creator>Clement, Y.</dc:creator>
<dc:creator>Vervoort, M.</dc:creator>
<dc:creator>Gazave, E.</dc:creator>
<dc:date>2023-05-26</dc:date>
<dc:identifier>doi:10.1101/2023.05.26.542455</dc:identifier>
<dc:title><![CDATA[Transcriptomic landscape of posterior regeneration in the annelid Platynereis dumerilii]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-05-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.05.29.542778v1?rss=1">
<title>
<![CDATA[
OICNet: A Neural Network for Online EEG Source Separation using Independent Component Analysis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.05.29.542778v1?rss=1</link>
<description><![CDATA[
Online source separation of EEG signals plays a crucial role in understanding and interpreting brain dynamics in real-time applications such as brain-computer interfaces (BCIs). In this paper, we propose OICNet, a novel neural network designed specifically for online EEG source separation using independent component analysis, aiming to address the challenges of real-time computational efficiency and reliable extraction of independent components from EEG data streams. The OICNet is trained on a loss function that integrates non-Gaussianity measurement and an orthogonality constraint to achieve effective decomposition of multi-channel EEG signals. We conducted comprehensive evaluation of OICNet on both task-related and task-free EEG datasets with comparison against conventional and network-based ICA counterparts. The results demonstrate that OICNet outperforms existing methods in terms of accuracy and computational efficiency. Overall, OICNet provides high-efficiency real-time EEG source separation capabilities and paves the way for advancements in deep-learning EEG processing in real-world BCI applications.
]]></description>
<dc:creator>Yeh, P.-T.</dc:creator>
<dc:creator>Tsai, A. C.</dc:creator>
<dc:creator>Hsieh, C.-Y.</dc:creator>
<dc:creator>Yang, C.-C.</dc:creator>
<dc:creator>Wei, C.-S.</dc:creator>
<dc:date>2023-06-01</dc:date>
<dc:identifier>doi:10.1101/2023.05.29.542778</dc:identifier>
<dc:title><![CDATA[OICNet: A Neural Network for Online EEG Source Separation using Independent Component Analysis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-06-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.06.22.546044v1?rss=1">
<title>
<![CDATA[
Structural and functional analysis of vaccinia viral fusion complex component protein A28 through NMR and molecular dynamic simulations 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.06.22.546044v1?rss=1</link>
<description><![CDATA[
Host cell entry of vaccinia virus (a poxvirus) proceeds through multiple steps that involve many viral proteins to mediate cell infection. Upon binding to cells, vaccinia virus membrane fuses with host membranes via a viral entry fusion protein complex comprising 11 proteins: A16, A21, A28, F9, G3, G9, H2, J5, L1, L5 and O3. Despite vaccinia virus having two infectious forms, mature and enveloped, that have different membrane layers, both forms require an identical viral entry fusion complex for membrane fusion. Components of the poxvirus entry fusion complex that have been structurally assessed to date share no known homology with all other type I, II and III viral fusion proteins, and the large number of fusion protein components renders it a unique system to investigate poxvirus-mediated membrane fusion. Here, we determined the NMR structure of a truncated version of vaccinia A28 protein. We also expressed a soluble H2 protein and showed that A28 interacts with H2 protein at a 1:1 ratio in vitro. Furthermore, we performed extensive in vitro alanine mutagenesis to identify A28 protein residues that are critical for H2 binding, entry fusion complex formation, and virus-mediated membrane fusion. Finally, we used molecular dynamic simulations to model full-length A28-H2 subcomplex in membranes. In summary, we characterized vaccinia virus A28 protein and determines residues important in its interaction with H2 protein and membrane components. We also provide a structural model of the A28-H2 protein interaction to illustrate how it forms a 1:1 subcomplex on a modeled membrane.
]]></description>
<dc:creator>Kao, C.-F.</dc:creator>
<dc:creator>Tsai, M.-H.</dc:creator>
<dc:creator>Carillo, K. J.</dc:creator>
<dc:creator>Tzou, D.-L.</dc:creator>
<dc:creator>Chang, W.</dc:creator>
<dc:date>2023-06-22</dc:date>
<dc:identifier>doi:10.1101/2023.06.22.546044</dc:identifier>
<dc:title><![CDATA[Structural and functional analysis of vaccinia viral fusion complex component protein A28 through NMR and molecular dynamic simulations]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-06-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.06.22.546047v1?rss=1">
<title>
<![CDATA[
polo affects cell fate upon ionizing radiation in Drosophila hematopoietic progenitors by negatively regulating lok 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.06.22.546047v1?rss=1</link>
<description><![CDATA[
In response to ionizing radiation (IR), stem cells undergo cell cycle arrest, senescence, premature differentiation, or cell death. The decision between survival and death is critical during tumorigenesis and effective killing of cancer cells. We used the larval Drosophila lymph gland, a hematopoietic organ, as a model to understand the mechanism for cell fate decisions during stem cell development. The hematopoietic progenitors survived or died via apoptosis when larvae were irradiated in early or late third instar larval (L3) stages, respectively. In late L3 progenitors, the basal level of polo (Drosophila PLK1) was low, enabling IR-induced activation of lok (Drosophila CHK2), which was necessary and sufficient for inducing autophagy and reactive oxygen species (ROS) production resulting in cell death. The high level of polo in early L3 progenitors negatively regulated lok resulting in significantly low or undetectable levels of ROS or autophagy, respectively. The surviving early L3 progenitors underwent cell cycle arrest followed by premature differentiation affected by tefu (Drosophila ATM) and lok mutation. These results provide clues for designing effective therapeutic strategies for cancer.

Summary statementWe elucidated the mechanism underlying cell fate decisions during stem cell development in larval Drosophila, which will help develop effective cancer treatment modalities.
]]></description>
<dc:creator>Nguyen, T. T. N.</dc:creator>
<dc:creator>Shim, J.</dc:creator>
<dc:creator>Chen, G.-C.</dc:creator>
<dc:creator>Song, Y.-H.</dc:creator>
<dc:date>2023-06-22</dc:date>
<dc:identifier>doi:10.1101/2023.06.22.546047</dc:identifier>
<dc:title><![CDATA[polo affects cell fate upon ionizing radiation in Drosophila hematopoietic progenitors by negatively regulating lok]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-06-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.06.22.546131v1?rss=1">
<title>
<![CDATA[
Multifaceted roles of rice ABA/stress-induced intrinsically disordered proteins in augmenting drought resistance 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.06.22.546131v1?rss=1</link>
<description><![CDATA[
Water deficit stress causes devastating loss of crop yield worldwide. Improving crop drought resistance has become an urgent issue. Here we report that a group of abscisic acid (ABA)/drought stress-induced monocot-specific, intrinsically disordered, and highly proline-rich proteins, REPETITIVE PROLINE-RICH PROTEINS (RePRPs), play pivotal roles in drought resistance in rice seedlings. Rice ectopically expressing RePRPs outlived wild-type rice under extreme drought conditions primarily due to two underlying mechanisms. First, RePRP reduces water loss by decreasing stomata conductance in shoot. In addition, RePRP overexpression enhances the levels of extracellular water barriers such as lignin and suberin, primarily in the root vascular bundle. Several groups of genes involved in lignin biosynthesis, especially the wall-bound peroxidase responsible for the final assembly of the lignin network, were induced by RePRP. Second, overexpression of RePRP leads to lowered root osmotic potential. Root cell osmotic pressure was more negative in rice plants overexpressing RePRP2 than wild-type plants, and the concentration of a key osmolyte, proline, was enhanced. Furthermore, the protein levels of two aquaporins that are important for drought stress tolerance were elevated. Hence, ABA/stress-induced RePRP expression leads to several beneficial traits of drought resistance, including lower water loss rate upon dehydration and higher root water use efficiency under drought conditions. This group of unique stress proteins may be an important target for technology development in enhancing drought stress resistance in cereals.
]]></description>
<dc:creator>Lin, M.-C.</dc:creator>
<dc:creator>Tseng, I.-C.</dc:creator>
<dc:creator>Wang, C.-L.</dc:creator>
<dc:creator>Hsiao, W.-R.</dc:creator>
<dc:creator>Shih, Y.-J.</dc:creator>
<dc:creator>Lin, W.-D.</dc:creator>
<dc:creator>Yu, S.-M.</dc:creator>
<dc:creator>Ho, T.-h. D.</dc:creator>
<dc:date>2023-06-23</dc:date>
<dc:identifier>doi:10.1101/2023.06.22.546131</dc:identifier>
<dc:title><![CDATA[Multifaceted roles of rice ABA/stress-induced intrinsically disordered proteins in augmenting drought resistance]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-06-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.07.05.547781v1?rss=1">
<title>
<![CDATA[
The receptor binding domain of SARS-CoV-2 spike protein fused with the type IIb E. coli heat-labile enterotoxin A subunit as an intranasal booster after mRNA vaccination 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.07.05.547781v1?rss=1</link>
<description><![CDATA[
The outbreak of SARS-CoV-2 infections had led to the COVID-19 pandemic which has a significant impact on global public health and the economy. The spike (S) protein of SARS-CoV-2 contains the receptor binding domain (RBD) which binds to human angiotensin-converting enzyme 2 receptor. Numerous RBD-based vaccines have been developed and recently focused on the induction of neutralizing antibodies against the immune evasive Omicron BQ.1.1 and XBB.1.5 subvariants. In this preclinical study, we reported the use of a direct fusion of the type IIb Escherichia coli heat-labile enterotoxin A subunit with SARS CoV-2 RBD protein (RBD-LTA) as an intranasal vaccine candidate. The results showed that intranasal immunization with the RBD-LTA fusion protein in BALB/c mice elicited potent neutralizing antibodies against the Wuhan-Hu-1 and several SARS-CoV-2 variants as well as the production of IgA antibodies in bronchoalveolar lavage fluids (BALFs). Furthermore, the RBD-LTA fusion protein was used as a second-dose booster after bivalent mRNA vaccination. The results showed that the neutralizing antibody titers elicited by the intranasal RBD-LTA booster were similar to the bivalent mRNA booster, but the RBD-specific IgA titers in sera and BALFs significantly increased. Overall, this preclinical study suggests that the RBD-LTA fusion protein could be a promising candidate as a mucosal booster COVID-19 vaccine.
]]></description>
<dc:creator>Hsieh, H.-C.</dc:creator>
<dc:creator>Chen, C.-C.</dc:creator>
<dc:creator>Chou, P.-H.</dc:creator>
<dc:creator>Liu, W.-C.</dc:creator>
<dc:creator>Wu, S.-C.</dc:creator>
<dc:date>2023-07-05</dc:date>
<dc:identifier>doi:10.1101/2023.07.05.547781</dc:identifier>
<dc:title><![CDATA[The receptor binding domain of SARS-CoV-2 spike protein fused with the type IIb E. coli heat-labile enterotoxin A subunit as an intranasal booster after mRNA vaccination]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-07-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.07.13.548784v1?rss=1">
<title>
<![CDATA[
Four-dimensional omics data reveals ribosome heterogeneity, regulation of translation efficacy, and nonsense-mediated decay in the differentiation of spermatocyte to round spermatid. 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.07.13.548784v1?rss=1</link>
<description><![CDATA[
A protein expression is regulated by transcription, translation, and sequential processing. However, well correlated RNA and protein abundance just only proportionate 40%, and even poorer when cell was stressed, differentiated, or tumorigenic transformed. Here, we discovered spermatocyte (SP) differentiated to round spermatid (RS) had equal regulation extent which may related to ribosomal behavior alteration. The change of ribosome occupancy was related to SP and RS specific function in spermatogenesis. Interactome of functional ribosome in SP and RS revealed the activated ribosome in SP but stalled and nonsense-mediated decay (NMD) associated ribosome in RS. Functional ribosomes of RS occupied 5untranslated regions (5UTR) of SP specific transcripts and correlated its RNA and protein downregulation. These findings suggested a branched NMD pathway was activated in RS to eliminate SP specific transcripts and keep them from being translated. Our discovery suggested the heterogeneity of ribosomal interactome may play an important role in spermatogenesis.
]]></description>
<dc:creator>Lee, S. S.</dc:creator>
<dc:creator>Kung, Y.-C.</dc:creator>
<dc:creator>Jou, Y.-S.</dc:creator>
<dc:date>2023-07-13</dc:date>
<dc:identifier>doi:10.1101/2023.07.13.548784</dc:identifier>
<dc:title><![CDATA[Four-dimensional omics data reveals ribosome heterogeneity, regulation of translation efficacy, and nonsense-mediated decay in the differentiation of spermatocyte to round spermatid.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-07-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.07.14.548970v1?rss=1">
<title>
<![CDATA[
Tbr1 autism mouse model displays altered structural and functional amygdalar connectivity and abnormal whole-brain synchronization 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.07.14.548970v1?rss=1</link>
<description><![CDATA[
Autism spectrum disorders (ASD) are considered neural dysconnectivity syndromes. To better understand ASD and uncover potential treatments, it is imperative to know and dissect the connectivity deficits under conditions of autism. Here, we apply a whole-brain immunostaining and quantification platform to demonstrate impaired structural and functional connectivity and aberrant whole-brain synchronization in a Tbr1+/- autism mouse model. We express a channelrhodopsin variant oChIEF fused with Citrine at the basolateral amygdala (BLA) to outline the axonal projections of BLA neurons. By activating the BLA under blue light theta-burst stimulation (TBS), we then evaluate the effect of BLA activation on C-FOS expression at a whole brain level to represent neural activity. We show that Tbr1 haploinsufficiency almost completely disrupts contralateral BLA axonal projections and results in mistargeting in both ipsilateral and contralateral hemispheres, thereby globally altering BLA functional connectivity. Based on correlated C-FOS expression among brain regions, we further show that Tbr1 deficiency severely disrupts whole-brain synchronization in the absence of salient stimulation. Tbr1+/- and wild-type (WT) mice exhibit opposing responses to TBS-induced amygdalar activation, reducing synchronization in WT mice but enhancing it in Tbr1+/- mice. Whole-brain modular organization and inter-module connectivity are also affected by Tbr1 deficiency and amygdalar activation. Following BLA activation by TBS, the synchronizations of the whole brain and the default mode network, a specific subnetwork highly relevant to ASD, are enhanced in Tbr1+/- mice, implying a potential ameliorating effect of amygdalar stimulation on brain function. Indeed, TBS-mediated BLA activation increases nose-to-nose social interactions of Tbr1+/- mice, strengthening evidence for the role of amygdalar connectivity in social behaviors. Our high-resolution analytical platform reveals the inter- and intra-hemispheric connectopathies arising from ASD. Our study emphasizes the defective synchronization at a whole-brain scale caused by Tbr1 deficiency and implies a potential beneficial effect of deep brain stimulation at the amygdala for TBR1-linked autism.
]]></description>
<dc:creator>Hsu, T.-T.</dc:creator>
<dc:creator>Wang, C.-Y.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:date>2023-07-14</dc:date>
<dc:identifier>doi:10.1101/2023.07.14.548970</dc:identifier>
<dc:title><![CDATA[Tbr1 autism mouse model displays altered structural and functional amygdalar connectivity and abnormal whole-brain synchronization]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-07-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.07.20.549842v1?rss=1">
<title>
<![CDATA[
A Novel Genome Optimization Tool for Chromosome-Level Assembly across Diverse Sequencing Techniques 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.07.20.549842v1?rss=1</link>
<description><![CDATA[
This paper introduces a novel genome assembly optimization tool named LOCLA, which stands for "Local Optimization for Chromosome-Level Assembly". It identifies reads and contigs aligned locally with high quality on gap flanks or scaffold boundaries of draft assemblies for gap filling and scaffold connection. LOCLA applies to both de novo and reference-based assemblies. It can also utilize reads produced by diverse sequencing techniques, e.g., 10x Genomics (10xG) Linked-Reads, and PacBio HiFi reads.

We validated LOCLA on three human samples and one non-model organism. For the first two human samples, LLD0021C and CHM13, we generated de novo draft assemblies from 10xG Linked-Reads. On LLD0021C, LOCLA improves the draft assembly by adding 23.3 million bases using only 10xG Linked-Reads. These additional bases cover 28,746 protein-coding regions, particularly in pericentromeric and telomeric regions. On the CHM13 sample, we took 10xG Linked-Reads and PacBio HiFi reads as input. As a result, LOCLA added 46.2 million bases to the draft assembly. The increased content enables us to identify genes linked to complex diseases (e.g., ARHGAP11A) and critical biological pathways. We created two reference-guided draft assemblies on the third human sample, HG002, using contigs assembled from PacBio HiFi reads. LOCLA enhances the two draft assemblies by recovering 27.9 million bases (22.26%) and 35.7 million bases (30.93%) of the sequences discarded by the reference-guided assembly tool. The results indicate the robustness of LOCLAs contig detection algorithm on gap flanks. Furthermore, we show that 95% of the sequences filled in by LOCLA have over 80% accuracy compared with the HG002 reference genome published by the Human Pan-genome Reference Consortium. On the non-model organism, LOCLA enhanced the genome assembly of Bruguiera sexangula (JAHLGP000000000) by decreasing 41.4% of its gaps and raising the Benchmarking Universal Single-Copy Orthologs (BUSCO) analysis score to 98.10%.

LOCLA can optimize de novo and reference-guided assemblies using varied sequencing reads. The final assemblies produced by LOCLA have improved in both quantity and quality. The increased gene content may provide a valuable resource in advancing personalized medicine.
]]></description>
<dc:creator>Chuang, W. H.</dc:creator>
<dc:creator>Cheng, H.-C.</dc:creator>
<dc:creator>Chang, Y.-J.</dc:creator>
<dc:creator>Huang, Y.-C.</dc:creator>
<dc:creator>Fu, P.-Y.</dc:creator>
<dc:creator>Hsieh, P.-H.</dc:creator>
<dc:creator>Chen, S.-H.</dc:creator>
<dc:creator>Kwok, P.-Y.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Ho, J.-M.</dc:creator>
<dc:date>2023-07-24</dc:date>
<dc:identifier>doi:10.1101/2023.07.20.549842</dc:identifier>
<dc:title><![CDATA[A Novel Genome Optimization Tool for Chromosome-Level Assembly across Diverse Sequencing Techniques]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-07-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.07.22.550136v1?rss=1">
<title>
<![CDATA[
Transcriptome and translatome comparison of tissues from Arabidopsis thaliana 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.07.22.550136v1?rss=1</link>
<description><![CDATA[
Translation is one of the multiple complementary steps that orchestrates gene activity. In contrast to the straightforwardness of transcriptional surveys, genome-wide profiles of the translational landscape of plant cells remain technically challenging and are less well explored. Protein-coding genes are expressed at a variable degree of efficiency, resulting in pronounced discordance among the regulatory levels that govern gene activity. Ribo-Seq provides an extremely useful tool for estimating translation efficiency, but limited data sets are available for plants. Here, we provide comparative inventories of expressed and translated RNA populations, generated by mRNA sequencing (RNA-Seq) and ribosome footprinting (Ribo-Seq) of shoots and roots of Arabidopsis thaliana seedlings. Our data set provides information on the translational fitness of protein-coding mRNAs and lncRNAs that may aid in obtaining a comprehensive picture of the regulatory levels governing genes activity across the genome.
]]></description>
<dc:creator>Velez-Bermudez, I. C.</dc:creator>
<dc:creator>Lin, W.-D.</dc:creator>
<dc:creator>Chou, S.-J.</dc:creator>
<dc:creator>Chen, A.-P.</dc:creator>
<dc:creator>Schmidt, W.</dc:creator>
<dc:date>2023-07-25</dc:date>
<dc:identifier>doi:10.1101/2023.07.22.550136</dc:identifier>
<dc:title><![CDATA[Transcriptome and translatome comparison of tissues from Arabidopsis thaliana]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-07-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.07.25.550605v1?rss=1">
<title>
<![CDATA[
Overcoming the nutritional immunity by engineering iron scavenging bacteria for cancer therapy 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.07.25.550605v1?rss=1</link>
<description><![CDATA[
Certain bacteria demonstrate the ability to target and colonize the tumor microenvironment, a characteristic that positions them as innovative carriers for delivering various therapeutic agents in cancer therapy. Nevertheless, our understanding of how bacteria adapt their physiological condition to the tumor microenvironment remains elusive. In this work, we employed liquid chromatography-tandem mass spectrometry to examine the proteome of E. coli colonized in murine tumors. Comparing to E. coli cultivated in the rich medium, we found that E. coli colonized in tumors notably upregulated the processes related to ferric ions, including the enterobactin biosynthesis and iron homeostasis. This finding indicated that the tumor is an iron-deficient environment to E. coli. We also found that the colonization of E. coli in the tumor led to an increased expression of lipocalin 2 (LCN2), a hosts protein that can sequester the enterobactin. We therefore engineered E. coli in order to evade the nutritional immunity provided by LCN2. By introducing the IroA cluster, the E. coli synthesizes the glycosylated enterobactin, which creates steric hindrance to avoid the LCN2 sequestration. The IroA-E. coli showed enhanced resistance to LCN2 and significantly improved the anti-tumor activity in mice. Moreover, the mice cured by the IroA-E. coli treatment became resistant to the tumor re-challenge, indicating the establishment of immunological memory. Overall, our study underscores the crucial role of bacterias ability to acquire ferric ions within the tumor microenvironment for effective cancer therapy.
]]></description>
<dc:creator>Huang, S.-W.</dc:creator>
<dc:creator>Lim, S.-K.</dc:creator>
<dc:creator>Yu, Y.-A.</dc:creator>
<dc:creator>Lien, W.-J.</dc:creator>
<dc:creator>Mou, K. Y.</dc:creator>
<dc:date>2023-07-27</dc:date>
<dc:identifier>doi:10.1101/2023.07.25.550605</dc:identifier>
<dc:title><![CDATA[Overcoming the nutritional immunity by engineering iron scavenging bacteria for cancer therapy]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-07-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.08.01.551406v1?rss=1">
<title>
<![CDATA[
Growth-dependent concentration gradient of the oscillating Min system in Escherichia coli 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.08.01.551406v1?rss=1</link>
<description><![CDATA[
The Min system contributes to the spatiotemporal regulation of division sites in Escherichia coli. The MinD and MinE proteins of this system self-organize into oscillatory waves in the form of concentration gradients. How the intracellular Min protein concentration gradients are coordinated with cell growth to achieve spatiotemporal accuracy of cell division is unknown. Here, we report that the MinD concentration gradient becomes progressively steeper as cells elongate, suggesting that the division inhibitory activity at the midcell also decreases with cell growth. Interestingly, the oscillation period appears relatively stable across different cell lengths. Similar features were found in cells under carbon stress conditions, but the gradient was even steeper, likely favoring division at shorter cell lengths. The length-dependent variation of the concentration gradient was further examined in silico using a reaction-diffusion model, which not only supported the above features, but also revealed a decrease in the midcell concentration as the shape of the gradient becomes steeper in growing cells. This growth-dependent regulation of the midcell concentration of MinD may be coupled with the FtsZ ring formation through the MinD-interacting protein MinC. We found that the variable concentration gradients occur by coordinating the reaction rates of the recruitment of MinD and MinE to the membrane and the recharging of MinD with ATP in the cytoplasm. In conclusion, this work uncovers the plasticity of MinD concentration gradients during interpolar oscillations throughout cell growth, an intrinsic property integrated during cell division.
]]></description>
<dc:creator>Parada, C.</dc:creator>
<dc:creator>Yan, C.-C.</dc:creator>
<dc:creator>Hung, C.-Y.</dc:creator>
<dc:creator>Tu, I.-P.</dc:creator>
<dc:creator>Hsu, C.-P.</dc:creator>
<dc:creator>Shih, Y.-L.</dc:creator>
<dc:date>2023-08-02</dc:date>
<dc:identifier>doi:10.1101/2023.08.01.551406</dc:identifier>
<dc:title><![CDATA[Growth-dependent concentration gradient of the oscillating Min system in Escherichia coli]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-08-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.08.17.553655v1?rss=1">
<title>
<![CDATA[
The interplay between lumen pressure and cell proliferation determines organoid morphology in a multicellular phase field model 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.08.17.553655v1?rss=1</link>
<description><![CDATA[
Organoids are ideal systems to predict the phenotypes of organs. However, there is currently a lack of understanding regarding the generalized rules that enable use of simple cellular principles to make morphological predictions of entire organoids. Therefore, we employed a phase field model with the following basic components: the minimum conditions for the timing and volume of cell division, lumen nucleation rules, and lumenal pressure. Through our model, we could compute and generate a myriad of organoid phenotypes observed till date. We propose morphological indices necessary to characterize the shapes and construct phase diagrams and show their dependencies on proliferation time and lumen pressure. Additionally, we introduced the lumen-index parameter, which helped in examining the criteria to maintain organoids as spherical structures comprising a single layer of cells and enclosing an intact lumen. Finally, we predict a star-like organoid phenotype that did not undergo differentiation, suggesting that the volume constraint during cell division may determine the final phenotype. In summary, our approach provides researchers with guidelines to test the mechanisms of self-organization and predict the shape of organoid.

Author summaryIn nature, a wide variety of organ morphologies are observed. Owing to the complexity of the process underlying the acquisition of organs morphology, it is challenging to investigate the mechanisms that lead to such variations. A promising approach to study these variations is the use of "computational organoid" study, which is the computational-based study of self-organizing shapes in multicellular assemblies and fluid-filled cavities called lumens that develop from a few proliferating cells. This study explores general mechanisms that dictate how various mechanical factors affect the growing self-organized multicellular assembly. We relied on computer simulations of the mathematical model called multicellular phase-field model with lumens and explored the mechanical factor effects, such as the lumen pressure while considering the time and volume conditions required for cell division. These simulations generated and categorized a wide range of organoid phenotypes based on the varying lumen pressure and cell division conditions. These phenotypes were characterized into seven distinct classes, based on the morphological index sets, including a cellular monolayer/multilayer surrounding single or multiple lumens and branch formation. These phenotypes were obtained without the assumption of differentiation. Our study elucidates the mechanisms underlying the organoid and organ formation with different shapes, thereby highlighting the significance of mechanical forces in shaping these complex biological structures.
]]></description>
<dc:creator>Tanida, S.</dc:creator>
<dc:creator>Fuji, K.</dc:creator>
<dc:creator>Lu, L.</dc:creator>
<dc:creator>Guyomar, T.</dc:creator>
<dc:creator>Lee, B. H.</dc:creator>
<dc:creator>Honigmann, A.</dc:creator>
<dc:creator>Grapin-Botton, A.</dc:creator>
<dc:creator>Riveline, D.</dc:creator>
<dc:creator>Nonomura, M.</dc:creator>
<dc:creator>Sano, M.</dc:creator>
<dc:creator>Hiraiwa, T.</dc:creator>
<dc:date>2023-08-18</dc:date>
<dc:identifier>doi:10.1101/2023.08.17.553655</dc:identifier>
<dc:title><![CDATA[The interplay between lumen pressure and cell proliferation determines organoid morphology in a multicellular phase field model]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-08-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.08.20.553239v1?rss=1">
<title>
<![CDATA[
Insights into RAG evolution from the identification of "missing link" family A RAGL transposons 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.08.20.553239v1?rss=1</link>
<description><![CDATA[
A series of "molecular domestication" events are thought to have converted an invertebrate RAG-like (RAGL) transposase into the RAG1-RAG2 (RAG) recombinase, a critical enzyme for adaptive immunity in jawed vertebrates. The timing and order of these events is not well understood, in part because of a dearth of information regarding the invertebrate RAGL-A transposon family. In contrast to the abundant and divergent RAGL-B transposon family, RAGL-A most closely resembles RAG and is represented by a single orphan RAG1-like (RAG1L) gene in the genome of the hemichordate Ptychodera flava (PflRAG1L-A). Here, we provide evidence for the existence of complete RAGL-A transposons in the genomes of P. flava and several echinoderms. The predicted RAG1L-A and RAG2L-A proteins encoded by these transposons intermingle sequence features of jawed vertebrate RAG and RAGL-B transposases, leading to a prediction of DNA binding, catalytic, and transposition activities that are a hybrid of RAG and RAGL-B. Similarly, the terminal inverted repeats (TIRs) of the RAGL-A transposons combine features of both RAGL-B transposon TIRs and RAG recombination signal sequences. Unlike all previously described RAG2L proteins, PflRAG2L-A and echinoderm RAG2L-A contain an acidic hinge region, which we demonstrate is capable of efficiently inhibiting RAG-mediated transposition. Our findings provide evidence for a critical intermediate in RAG evolution and argue that certain adaptations thought to be specific to jawed vertebrates (e.g., the RAG2 acidic hinge) actually arose in invertebrates, thereby focusing attention on other adaptations as the pivotal steps in the completion of RAG domestication in jawed vertebrates.
]]></description>
<dc:creator>Martin, E. C.</dc:creator>
<dc:creator>Le Targa, L.</dc:creator>
<dc:creator>Tsakou-Ngouafo, L.</dc:creator>
<dc:creator>Fan, T.-P.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Xiao, J.</dc:creator>
<dc:creator>Su, Y.-H.</dc:creator>
<dc:creator>Petrescu, A.-J.</dc:creator>
<dc:creator>Pontarotti, P.</dc:creator>
<dc:creator>Schatz, D. G.</dc:creator>
<dc:date>2023-08-20</dc:date>
<dc:identifier>doi:10.1101/2023.08.20.553239</dc:identifier>
<dc:title><![CDATA[Insights into RAG evolution from the identification of "missing link" family A RAGL transposons]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-08-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.08.28.555102v1?rss=1">
<title>
<![CDATA[
Structural and functional analyses of viral H2 protein of the vaccinia virus entry fusion complex 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.08.28.555102v1?rss=1</link>
<description><![CDATA[
Virus-mediated membrane fusion involves conformational changes of the viral fusion protein to fuse the opposing viral and host lipid bilayers. Unlike all other known viruses that contain a single fusion protein, poxviruses harbor a multimeric protein complex of 11 subunits, termed the entry fusion complex (EFC), to mediate fusion with host membranes. Yet, how the poxviral EFC mediates membrane fusion remains enigmatic. To establish the mechanism of EFC-triggered membrane fusion, we are deciphering the structure and function of individual EFC components. Here, we determined the crystal structure of the H2 ectodomain by X-ray diffraction, revealing a folded conformation comprising a central five-stranded {beta}-sheet and three cladding -helices. We reconstructed the full-length H2 by in silico prediction, revealing that the N-terminal region (aa 51-90) of H2 protein may fold as a long helix connecting the ectodomain and transmembrane region. Using alanine-mutagenesis screening in a transient complementation system, coimmunoprecipitation, isothermal titration calorimetry and MV-triggered membrane fusion assays, we concluded that the surface of the ectodomain of H2 protein, including two loop regions, 170LGYSG174 and 125RRGTGDAW132, constitutes a broad A28-binding region. Moreover, although not involved in A28 binding, the N-terminal helical region approximal to the transmembrane part, encompassing 64RIK66, 72W, and 83ESDRGR88, is also crucial for viral EFC formation and MV infectivity.
]]></description>
<dc:creator>Kao, C.-F.</dc:creator>
<dc:creator>Liu, C.-Y.</dc:creator>
<dc:creator>Hsieh, C.-L.</dc:creator>
<dc:creator>Carillo, K. J. D.</dc:creator>
<dc:creator>Tzou, D.-L. M.</dc:creator>
<dc:creator>Wang, H.-C.</dc:creator>
<dc:creator>Chang, W.</dc:creator>
<dc:date>2023-08-28</dc:date>
<dc:identifier>doi:10.1101/2023.08.28.555102</dc:identifier>
<dc:title><![CDATA[Structural and functional analyses of viral H2 protein of the vaccinia virus entry fusion complex]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-08-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/210641v1?rss=1">
<title>
<![CDATA[
Rolling a mycobiome down a hill: endophytes in the Taiwanese Cloud Forest 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/210641v1?rss=1</link>
<description><![CDATA[
Fungal endophytes of plants are ubiquitous and important to host plant health. Despite their ecological importance, landscape-level patterns of microbial communities in plant hosts are not well-characterized. Fungal wood-inhabiting and foliar endophyte communities from multiple tree hosts were sampled at multiple spatial scales across a 25 ha subtropical research plot in northern Taiwan, using culture-free, community DNA amplicon sequencing methods. Fungal endophyte communities were distinct between leaves and wood, but the mycobiomes were highly variable across and within tree species. Of the variance that could be explained, host tree species was the most important driver of mycobiome community-composition. Within a single tree species, "core" mycobiomes were characterized using cooccurrence analysis. These core groups of endophytes in leaves and wood show divergent spatial patterns. For wood endophytes, a more consistent, "minimal" core mycobiome coexisted with the host across the extent of the study. For leaf endophytes, the core fungi resembled a more dynamic, "gradient" model of the core microbiome, changing across the topography and distance of the study.
]]></description>
<dc:creator>Thomas, D.</dc:creator>
<dc:creator>Vandegrift, R.</dc:creator>
<dc:creator>Ju, Y.-M.</dc:creator>
<dc:creator>Hsieh, H. M.</dc:creator>
<dc:creator>Roy, B. A.</dc:creator>
<dc:date>2017-10-28</dc:date>
<dc:identifier>doi:10.1101/210641</dc:identifier>
<dc:title><![CDATA[Rolling a mycobiome down a hill: endophytes in the Taiwanese Cloud Forest]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-10-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/227587v1?rss=1">
<title>
<![CDATA[
Intraflagellar transport proteins undergo nonaxonemal staged hindrance between the recruiting distal appendages and the cilium 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/227587v1?rss=1</link>
<description><![CDATA[
Primary cilia play a vital role in cellular sensing and signaling [1]. An essential component of ciliogenesis is intraflagellar transport (IFT), which first requires IFT-protein recruitment, IFT-protein-motor-protein assembly, axonemal engagement of IFT-protein complexes, and transition zone (TZ) gating [2-9]. The mechanistic understanding of these processes at the ciliary base was largely missing, because it is exceedingly challenging to observe the motion of IFT proteins in this crowded region using conventional microscopy. Here, we report short trajectory tracking of IFT proteins at the base of mammalian primary cilia by optimizing single-particle tracking photoactivated localization microscopy (sptPALM) [10, 11], balancing the imaging requirements of tracking speed, tracking duration, and localization precision for IFT88-mEOS4b in live human retinal pigment epithelial (hTERT-RPE-1) cells. Intriguingly, we found that mobile IFT proteins "switched gears" multiple times from the distal appendages (DAPs) to the ciliary compartment (CC), moving slowly in the DAPs, relatively fast in the proximal TZ, slowly again in the distal TZ, and then much faster in the CC. They could travel through the space between the DAPs and the axoneme without following DAP structures, and reached the space enveloped by the ciliary pocket in the proximal TZ. Together, our live-cell superresolution imaging revealed region-dependent slowdown of IFT proteins at the ciliary base, shedding light on staged control of ciliogenesis homeostasis.
]]></description>
<dc:creator>Yang, T.</dc:creator>
<dc:creator>Tran, M. N. T.</dc:creator>
<dc:creator>Chong, W. M.</dc:creator>
<dc:creator>Huang, C.-E.</dc:creator>
<dc:creator>Liao, J.-C.</dc:creator>
<dc:date>2017-12-01</dc:date>
<dc:identifier>doi:10.1101/227587</dc:identifier>
<dc:title><![CDATA[Intraflagellar transport proteins undergo nonaxonemal staged hindrance between the recruiting distal appendages and the cilium]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-12-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/243592v1?rss=1">
<title>
<![CDATA[
Naa10p promotes metastasis by stabilizing matrix metalloproteinase-2 protein in human osteosarcomas 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/243592v1?rss=1</link>
<description><![CDATA[
N--Acetyltransferase 10 protein (Naa10p) mediates N-terminal acetylation of nascent proteins. Oncogenic or tumor suppressive roles of Naa10p were reported in cancers. Here, we report an oncogenic role of Naa10p in promoting metastasis of osteosarcomas. Higher NAA10 transcripts were observed in metastatic osteosarcoma tissues compared to non-metastatic tissues and were also correlated with a worse prognosis of patients. Knockdown and overexpression of Naa10p in osteosarcoma cells respectively led to decreased and increased cell migratory/invasive abilities. Re-expression of Naa10p, but not an enzymatically inactive mutant, relieved suppression of the invasive ability in vitro and metastasis in vivo imposed by Naa10p-knockdown. According to protease array screening, we identified that matrix metalloproteinase (MMP)-2 was responsible for the Naa10p-induced invasive phenotype. Naa10p was directly associated with MMP-2 protein through its acetyltransferase domain and maintained MMP-2 protein stability via NatA complex activity. MMP-2 expression levels were also significantly correlated with Naa10p levels in osteosarcoma tissues. These results reveal a novel function of Naa10p in the regulation of cell invasiveness by preventing MMP-2 protein degradation that is crucial during osteosarcoma metastasis.
]]></description>
<dc:creator>Chien, M.-H.</dc:creator>
<dc:creator>Lee, W.-J.</dc:creator>
<dc:creator>Yang, Y.-C.</dc:creator>
<dc:creator>Tan, P.</dc:creator>
<dc:creator>Pan, K.-F.</dc:creator>
<dc:creator>Tsai, H.-C.</dc:creator>
<dc:creator>Hsu, C.-H.</dc:creator>
<dc:creator>Hsiao, M.</dc:creator>
<dc:creator>Hua, K.-T.</dc:creator>
<dc:date>2018-01-05</dc:date>
<dc:identifier>doi:10.1101/243592</dc:identifier>
<dc:title><![CDATA[Naa10p promotes metastasis by stabilizing matrix metalloproteinase-2 protein in human osteosarcomas]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-01-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/252916v1?rss=1">
<title>
<![CDATA[
UniLoc: A universal protein localization site predictor for eukaryotes and prokaryotes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/252916v1?rss=1</link>
<description><![CDATA[
There is a growing gap between protein subcellular localization (PSL) data and protein sequence data, raising the need for computation methods to rapidly determine subcellular localizations for uncharacterized proteins. Currently, the most efficient computation method involves finding sequence-similar proteins (hereafter referred to as similar proteins) in the annotated database and transferring their annotations to the target protein. When a sequence-similarity search fails to find similar proteins, many PSL predictors adopt machine learning methods for the prediction of localization sites. We proposed a universal protein localization site predictor - UniLoc - to take advantage of implicit similarity among proteins through sequence analysis alone. The notion of related protein words is introduced to explore the localization site assignment of uncharacterized proteins. UniLoc is found to identify useful template proteins and produce reliable predictions when similar proteins were not available.
]]></description>
<dc:creator>Lin, H.-N.</dc:creator>
<dc:creator>Chen, C.-T.</dc:creator>
<dc:creator>Sung, T.-Y.</dc:creator>
<dc:creator>Hsu, W.-L.</dc:creator>
<dc:date>2018-01-25</dc:date>
<dc:identifier>doi:10.1101/252916</dc:identifier>
<dc:title><![CDATA[UniLoc: A universal protein localization site predictor for eukaryotes and prokaryotes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-01-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/264184v1?rss=1">
<title>
<![CDATA[
Targeting redox regulatory site of protein kinase B impedes neutrophilic inflammation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/264184v1?rss=1</link>
<description><![CDATA[
Neutrophil activation has a pathogenic effect in inflammatory diseases. Protein kinase B (PKB)/AKT regulates diverse cellular responses. However, the significance of AKT in neutrophilic inflammation is still not well understood. Here, we identified CLLV-1 as a novel AKT inhibitor. CLLV-1 inhibited respiratory burst, degranulation, chemotaxis, and AKT phosphorylation in activated human neutrophils and dHL-60 cells. Significantly, CLLV-1 blocked AKT activity and covalently reacted with AKT Cys310 in vitro. The AKT309-313 peptide-CLLV-1 adducts were determined by NMR or mass spectrometry assay. The alkylation agent-conjugated AKT (reduced form) level was also inhibited by CLLV-1. Additionally, CLLV-1 ameliorated lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. CLLV-1 acts as a covalent allosteric AKT inhibitor by targeting AKT Cys310 to restrain inflammatory responses in human neutrophils and LPS-induced ALI in vivo. Our findings provide a mechanistic framework for redox modification of AKT that may serve as a novel pharmacological target to alleviate neutrophilic inflammation.
]]></description>
<dc:creator>Hwang, T.-L.</dc:creator>
<dc:creator>Chen, P.-J.</dc:creator>
<dc:creator>Ko, I.-L.</dc:creator>
<dc:creator>Lee, C.-L.</dc:creator>
<dc:creator>Hu, H.-C.</dc:creator>
<dc:creator>Chang, F.-R.</dc:creator>
<dc:creator>Wu, Y.-C.</dc:creator>
<dc:creator>Leu, Y.-L.</dc:creator>
<dc:creator>Wu, C.-C.</dc:creator>
<dc:creator>Tsai, Y.-F.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Pan, C.-Y.</dc:creator>
<dc:date>2018-02-13</dc:date>
<dc:identifier>doi:10.1101/264184</dc:identifier>
<dc:title><![CDATA[Targeting redox regulatory site of protein kinase B impedes neutrophilic inflammation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-02-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/270355v1?rss=1">
<title>
<![CDATA[
Arabidopsis inositol phosphate kinases, IPK1 and ITPK1, constitute a metabolic pathway in maintaining phosphate homeostasis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/270355v1?rss=1</link>
<description><![CDATA[
Emerging studies have implicated a close link between inositol phosphate (InsP) metabolism and cellular phosphate (Pi) homeostasis in eukaryotes; however, whether a common InsP species is deployed as an evolutionarily conserved metabolic messenger to mediate Pi signaling remains unknown. Here, using genetics and InsP profiling combined with Pi starvation response (PSR) analysis in Arabidopsis thaliana, we showed that the kinase activity of inositol pentakisphosphate 2-kinase (IPK1), an enzyme required for phytate (inositol hexakisphosphates; InsP6) synthesis, is indispensable for maintaining Pi homeostasis under Pi-replete conditions, and inositol 1,3,4-trisphosphate 5/6-kinase 1 (ITPK1) plays an equivalent role. Although both ipk1-1 and itpk1 mutants exhibited decreased levels of InsP6 and diphosphoinositol pentakisphosphate (PP-InsP5; InsP7), disruption of another ITPK family enzyme, ITPK4, which correspondingly caused depletion of InsP6 and InsP7, did not display similar Pi-related phenotypes, which precludes these InsP species as effectors. Notably, the level of D/L-Ins(3,4,5,6)P4 was concurrently elevated in both ipk1-1 and itpk1 mutants, which implies a potential role for InsP4 in regulating Pi homeostasis. However, the level of D/L-Ins(3,4,5,6)P4 is not responsive to Pi starvation that instead manifests a shoot-specific increase in InsP7 level. This study demonstrates a more nuanced picture of intersection of InsP metabolism and Pi homeostasis and PSR than has previously been elaborated, and additionally establishes intermediate steps to phytate biosynthesis in plant vegetative tissues.nnSignificance StatementRegulation of phosphate homeostasis and adaptive responses to phosphate limitation is critical for plant growth and crop yield. Accumulating studies implicate inositol phosphates as regulators of phosphate homeostasis in eukaryotes; however, the relationship between inositol phosphate metabolism and phosphate signaling in plants remain elusive. This study dissected the step where inositol phosphate metabolism intersects with phosphate homeostasis regulation and phosphate starvation responses.
]]></description>
<dc:creator>Kuo, H.-F.</dc:creator>
<dc:creator>Hsu, Y.-Y.</dc:creator>
<dc:creator>Lin, W.-C.</dc:creator>
<dc:creator>Chen, K.-Y.</dc:creator>
<dc:creator>Munnik, T.</dc:creator>
<dc:creator>Brearley, C.</dc:creator>
<dc:creator>Chiou, T.-J.</dc:creator>
<dc:date>2018-02-24</dc:date>
<dc:identifier>doi:10.1101/270355</dc:identifier>
<dc:title><![CDATA[Arabidopsis inositol phosphate kinases, IPK1 and ITPK1, constitute a metabolic pathway in maintaining phosphate homeostasis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-02-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/275685v1?rss=1">
<title>
<![CDATA[
A dengue monovalent vaccine with novel structure provides cross-protection against four serotypes of dengue virus 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/275685v1?rss=1</link>
<description><![CDATA[
Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. The vaccine candidates under development require a tetravalent immunogen to induce a balanced immunity against all four serotypes of dengue virus. Herein we show that mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher and broader neutralization antibodies (NtAbs) against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. The cryo-electron microscopy reconstruction showed that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes. Most importantly, maternally transferred antibodies derived from mD2VLP-vaccinated female mice protected suckling mice from lethal challenge by all four serotypes of DENV. Our results support the fact that a universal dengue vaccine that protects against all four serotypes of dengue viruses can be achieved by using an immunogen such as mD2VLP.
]]></description>
<dc:creator>Chao, D.-Y.</dc:creator>
<dc:creator>Shen, W.-F.</dc:creator>
<dc:creator>Galula, J. U.</dc:creator>
<dc:creator>Liu, J.-H.</dc:creator>
<dc:creator>Liao, M.- Y.</dc:creator>
<dc:creator>Huang, C.-H.</dc:creator>
<dc:creator>Wang, Y.-C.</dc:creator>
<dc:creator>Wu, H.-C.</dc:creator>
<dc:creator>Liang, J.-J.</dc:creator>
<dc:creator>Lin, Y.- L.</dc:creator>
<dc:creator>Whitney, M. T.</dc:creator>
<dc:creator>Chang, G.-J. J.</dc:creator>
<dc:creator>Chen, S.-R.</dc:creator>
<dc:creator>Wu, S.-R.</dc:creator>
<dc:date>2018-03-05</dc:date>
<dc:identifier>doi:10.1101/275685</dc:identifier>
<dc:title><![CDATA[A dengue monovalent vaccine with novel structure provides cross-protection against four serotypes of dengue virus]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-03-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/281857v1?rss=1">
<title>
<![CDATA[
Human Puf-A, a Novel Component of 90S Pre-ribosome, Links Ribosome Biogenesis to Cancer Progression 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/281857v1?rss=1</link>
<description><![CDATA[
We describe a novel biogenesis factor of the 90S pre-ribosome, Puf-A, which is a negative transcriptional target of p53. The expression of Puf-A is not only upregulated in advanced human lung cancer and tumors of patients especially with TP53 mutation, but also is highly prognostic for stage I lung cancer. Loss of Puf-A expression prevents KrasG12D/p53-/--induced tumor progression in the lungs and induces apoptosis in TP53- mutated cancers and c-Myc/p53-/--transformed cells as well. Overexpression of Puf-A enhances proliferation of normal cells after c-Myc induction and overcomes the cell-cycle checkpoints incurred by p53 expression. Mechanistically, Puf-A interacts with double-stranded structures of the 5.8S sequence within pre-rRNA and maintains the integrity of 90S pre-ribosomes, thereby impacting early ribosome assembly and export of ribosomes from nuclei. Silencing of Puf-A disrupts the assembly of 90S pre-ribosomes and induces the translocation of its associated nucleophosmin (NPM1) from nucleoli to the nucleoplasm, resulting in impairment of ribosome synthesis. Thus, Puf-A is crucial for over-activation of ribosome biogenesis and contributes to tumor progression and cancer growth.
]]></description>
<dc:creator>Yu, J.</dc:creator>
<dc:creator>Cho, H.-C.</dc:creator>
<dc:creator>Huang, Y.</dc:creator>
<dc:creator>Hung, J.-T.</dc:creator>
<dc:creator>Lai, L.-C.</dc:creator>
<dc:creator>Wang, S.-H.</dc:creator>
<dc:creator>Liu, Y.-H.</dc:creator>
<dc:creator>Cho, I.-M.</dc:creator>
<dc:creator>Kuo, M.-W.</dc:creator>
<dc:creator>Cheng, P.-Y.</dc:creator>
<dc:creator>Ho, M.-Y.</dc:creator>
<dc:creator>Lin, R.-J.</dc:creator>
<dc:creator>Yu, A. L.</dc:creator>
<dc:date>2018-03-13</dc:date>
<dc:identifier>doi:10.1101/281857</dc:identifier>
<dc:title><![CDATA[Human Puf-A, a Novel Component of 90S Pre-ribosome, Links Ribosome Biogenesis to Cancer Progression]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-03-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/292383v1?rss=1">
<title>
<![CDATA[
The Organization of Membranes Below 100 nm: Experimental Breakthroughs Occasion a Modeling Manifesto 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/292383v1?rss=1</link>
<description><![CDATA[
New experimental techniques reveal the plasma membrane to be heterogeneous and "scale-rich," from nanometers to microns, and from microseconds to seconds. This is critical information, as heterogeneous, scale-dependent transport governs the molecular encounters that underlie cellular signaling. The data are rich, and reaffirm the importance of the cortical cytoskeleton, protein aggregates, and lipidomic complexity to the statistics of molecular encounters. Moreover, the data demand simulation approaches with a particular set of features, hence the "manifesto". Together with the experimental data, simulations which satisfy these requirements hold the promise of a deeper understanding of membrane spatiotemporal organization. Several experimental breakthroughs are reviewed, the constraints that they place on simulations are discussed, and the status of simulation approaches which aim to meet them are detailed.
]]></description>
<dc:creator>Lyman, E.</dc:creator>
<dc:creator>Eggeling, C.</dc:creator>
<dc:creator>Hsieh, C.-L.</dc:creator>
<dc:date>2018-03-31</dc:date>
<dc:identifier>doi:10.1101/292383</dc:identifier>
<dc:title><![CDATA[The Organization of Membranes Below 100 nm: Experimental Breakthroughs Occasion a Modeling Manifesto]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-03-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/292912v1?rss=1">
<title>
<![CDATA[
A Con Artist: Phenylphenoxybenzamide is not a Glycosyltransferase Inhibitor 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/292912v1?rss=1</link>
<description><![CDATA[
To combat bacterial resistance against antibiotics, glycosyltransferase inhibiting molecules, which block the synthesis of the pre-cursor of the bacterial cell wall, need to be discovered and developed. In this study, we demonstrate that phenylphenoxybenzamide, a salicylanilide, is not a glycosyltransferase inhibiting molecule, despite claims in literature to the contrary, and through our work show that glycosyltransferase construct choice and detergent choice are crucial parameters to consider when designing glycosyltransferase assays that aim to discover and develop molecules that inhibit these types of enzymes.
]]></description>
<dc:creator>Wybenga, G. G.</dc:creator>
<dc:creator>Wu, W.-S.</dc:creator>
<dc:date>2018-04-11</dc:date>
<dc:identifier>doi:10.1101/292912</dc:identifier>
<dc:title><![CDATA[A Con Artist: Phenylphenoxybenzamide is not a Glycosyltransferase Inhibitor]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-04-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/319657v1?rss=1">
<title>
<![CDATA[
Programmed Variations of Cytokinesis Contribute to Morphogenesis in the C. elegans embryo 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/319657v1?rss=1</link>
<description><![CDATA[
While cytokinesis has been intensely studied, how it is executed during development is not well understood, despite a long-standing appreciation that various aspects of cytokinesis vary across cell and tissue types. To address this, we investigated cytokinesis during the invariant C. elegans embryo lineage and found several reproducibly altered parameters at different stages. During early divisions, furrow ingression asymmetry and midbody inheritance is consistent, suggesting specific regulation of these events. During morphogenesis, we find several unexpected alterations including migration of midbodies to the apical surface during epithelial polarization in different tissues. Aurora B kinase, which is essential for several aspects of cytokinesis, remains localized to the apical membrane after internalization of other midbody components. Inactivation of Aurora B causes cytokinesis failure, which disrupts polarization and tissue formation. Therefore, cytokinesis shows surprising diversity during development and is required during epithelial polarization to establish cellular architecture during morphogenesis.
]]></description>
<dc:creator>Bai, X.</dc:creator>
<dc:creator>Lee, P.-Y.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Simmons, J. R.</dc:creator>
<dc:creator>Nebenfuehr, B.</dc:creator>
<dc:creator>Mitchell, D.</dc:creator>
<dc:creator>Klebanow, L. R.</dc:creator>
<dc:creator>Mattson, N.</dc:creator>
<dc:creator>Turpin, C.</dc:creator>
<dc:creator>Chen, B.-C.</dc:creator>
<dc:creator>Betzig, E.</dc:creator>
<dc:creator>Bembenek, J. N.</dc:creator>
<dc:date>2018-05-10</dc:date>
<dc:identifier>doi:10.1101/319657</dc:identifier>
<dc:title><![CDATA[Programmed Variations of Cytokinesis Contribute to Morphogenesis in the C. elegans embryo]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-05-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/320135v1?rss=1">
<title>
<![CDATA[
Dlk1-Dio3 Locus-Derived LncRNAs Perpetuate Postmitotic Motor Neuron Cell Fate and Subtype Identity 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/320135v1?rss=1</link>
<description><![CDATA[
The mammalian imprinted Dlk1-Dio3 locus produces multiple long non-coding RNAs (lncRNAs) from the maternally inherited allele, including Meg3 (i.e. Gtl2) in the mammalian genome. Although this locus has well-characterized functions in stem cell and tumor contexts, its role during neural development is unknown. By transcriptome profiling cell types at each stage of spinal cord development, we uncovered that lncRNAs expressed from the Dlk1-Dio3 locus are predominantly and gradually enriched in rostral motor neurons (MNs). Mechanistically, Meg3 and other Dlk1-Dio3 locus-derived lncRNAs facilitate Jarid2-Ezh2 interactions. Loss of these lncRNAs compromises the H3K27me3 landscape, leading to aberrant expression of progenitor and caudal Hox genes in postmitotic MNs. Our data illustrate that these lncRNAs in the Dlk1-Dio3 locus play a critical role in maintaining postmitotic MN cell fate by repressing progenitor genes and they shape MN subtype identity by regulating Hox genes, providing strong evidence of how lncRNAs function during embryonic development.
]]></description>
<dc:creator>Yen, Y.-P.</dc:creator>
<dc:creator>Hsieh, W.-F.</dc:creator>
<dc:creator>Lu, Y.-L.</dc:creator>
<dc:creator>Liau, E. S.</dc:creator>
<dc:creator>Hsu, H.-C.</dc:creator>
<dc:creator>Chen, Y.-C.</dc:creator>
<dc:creator>Liu, T.-C.</dc:creator>
<dc:creator>Chang, M.</dc:creator>
<dc:creator>Li, J.</dc:creator>
<dc:creator>Lin, S.-P.</dc:creator>
<dc:creator>Hung, J.-H.</dc:creator>
<dc:creator>Chen, J.-A.</dc:creator>
<dc:date>2018-05-11</dc:date>
<dc:identifier>doi:10.1101/320135</dc:identifier>
<dc:title><![CDATA[Dlk1-Dio3 Locus-Derived LncRNAs Perpetuate Postmitotic Motor Neuron Cell Fate and Subtype Identity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-05-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/324996v1?rss=1">
<title>
<![CDATA[
Pristionchus nematodes occur frequently in diverse rotting vegetal substrates and are not exclusively necromenic, while Panagrellus redivivoides is found specifically in rotting fruits 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/324996v1?rss=1</link>
<description><![CDATA[
The lifestyle and feeding habits of nematodes are highly diverse. Several species of Pristionchus (Nematoda: Diplogastridae), including Pristionchus pacificus, have been reported to be necromenic, i.e. to associate with beetles in their dauer diapause stage and wait until the death of their host to resume development and feed on microbes in the decomposing beetle corpse. We review the literature and suggest that the association of Pristionchus to beetles may be phoretic and not necessarily necromenic. The view that Pristionchus nematodes have a necromenic lifestyle is based on studies that have sought Pristionchus only by sampling live beetles. By surveying for nematode genera in different types of rotting vegetal matter, we found Pristionchus spp. at a similar high frequency as Caenorhabditis, often in large numbers and in feeding stages. Thus, these Pristionchus species may feed in decomposing vegetal matter. In addition, we report that one species of Panagrellus (Nematoda: Panagrolaimidae), Panagrellus redivivoides, is found in rotting fruits but not in rotting stems, with a likely association with Drosophila fruitflies. Based on our sampling and the observed distribution of feeding and dauer stages, we propose a life cycle for Pristionchus nematodes and Panagrellus redivivoides that is similar to that of C. elegans, whereby they feed on the microbial blooms on decomposing vegetal matter and are transported between food patches by coleopterans for Pristionchus spp., fruitflies for Panagrellus redivivoides and isopods and terrestrial molluscs for C. elegans.
]]></description>
<dc:creator>Felix, M.-A.</dc:creator>
<dc:creator>Ailion, M.</dc:creator>
<dc:creator>Hsu, J.-C.</dc:creator>
<dc:creator>Richaud, A.</dc:creator>
<dc:creator>Wang, J.</dc:creator>
<dc:date>2018-05-18</dc:date>
<dc:identifier>doi:10.1101/324996</dc:identifier>
<dc:title><![CDATA[Pristionchus nematodes occur frequently in diverse rotting vegetal substrates and are not exclusively necromenic, while Panagrellus redivivoides is found specifically in rotting fruits]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-05-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/326116v1?rss=1">
<title>
<![CDATA[
RBPMetaDB: A comprehensive annotation of mouse RNA-Seq datasets with perturbations of RNA-binding proteins 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/326116v1?rss=1</link>
<description><![CDATA[
RNA-binding proteins may play a critical role in gene regulation in various diseases or biological processes by controlling post-transcriptional events such as polyadenylation, splicing, and mRNA stabilization via binding activities to RNA molecules. Due to the importance of RNA-binding proteins in gene regulation, a great number of studies have been conducted, resulting in a large amount of RNA-Seq datasets. However, these datasets usually do not have structured organization of metadata, which limits their potentially wide use. To bridge this gap, the metadata of a comprehensive set of publicly available mouse RNA-Seq datasets with perturbed RNA-binding proteins were collected and integrated into a database called RBPMetaDB. This database contains 278 mouse RNA-Seq datasets for a comprehensive list of 163 RNA-binding proteins. These RNA-binding proteins account for only [~]10% of all known RNA-binding proteins annotated in Gene Ontology, indicating that most are still unexplored using high-throughput sequencing. This negative information provides a great pool of candidate RNA-binding proteins for biologists to conduct future experimental studies. In addition, we found that DNA-binding activities are significantly enriched among RNA-binding proteins in RBPMetaDB, suggesting that prior studies of these DNA- and RNA-binding factors focus more on DNA-binding activities instead of RNA-binding activities. This result reveals the opportunity to efficiently reuse these data for investigation of the roles of their RNA-binding activities. A web application has also been implemented to enable easy access and wide use of RBPMetaDB. It is expected that RBPMetaDB will be a great resource for improving understanding of the biological roles of RNA-binding proteins.nnDatabase URL: http://rbpmetadb.yubiolab.org
]]></description>
<dc:creator>Li, J.</dc:creator>
<dc:creator>Deng, S.-P.</dc:creator>
<dc:creator>Vieira, J.</dc:creator>
<dc:creator>Thomas, J.</dc:creator>
<dc:creator>Costa, V.</dc:creator>
<dc:creator>Tseng, C.-S.</dc:creator>
<dc:creator>Ivankovic, F.</dc:creator>
<dc:creator>Ciccodicola, A.</dc:creator>
<dc:creator>Yu, P.</dc:creator>
<dc:date>2018-05-18</dc:date>
<dc:identifier>doi:10.1101/326116</dc:identifier>
<dc:title><![CDATA[RBPMetaDB: A comprehensive annotation of mouse RNA-Seq datasets with perturbations of RNA-binding proteins]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-05-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/332569v1?rss=1">
<title>
<![CDATA[
In situ quantification of individual mRNA transcripts in melanocytes discloses gene regulation of relevance to speciation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/332569v1?rss=1</link>
<description><![CDATA[
Functional validation of candidate genes for adaptation and speciation remains challenging. We here exemplify the utility of a method quantifying individual mRNA transcripts in revealing the molecular basis of divergence in feather pigment synthesis during early-stage speciation in crows. Using a padlock probe assay combined with rolling circle amplification we quantified cell-type specific gene expression in the native, histological context of growing feather follicles. Expression of Tyrosinase related protein 1 (TYRP1), Solute carrier family 45 member 2 (SLC45A2) and Hematopoietic prostaglandin D synthase (HPGDS) was melanocyte-limited and significantly reduced in follicles from hooded crow explaining the substantially lower melanin content in grey vs. black feathers. The central upstream transcription factor Microphthalmia-associated transcription factor (MITF) only showed differential expression specific to melanocytes - a feature not captured by bulk RNA-seq. Overall, this study provides insight into the molecular basis of an evolutionary young transition in pigment synthesis, and demonstrates the power of histologically explicit, statistically substantiated single-cell gene expression quantification for functional genetic inference in natural populations.
]]></description>
<dc:creator>Wu, C.-C.</dc:creator>
<dc:creator>Klaesson, A.</dc:creator>
<dc:creator>Buskas, J.</dc:creator>
<dc:creator>Ranefall, P.</dc:creator>
<dc:creator>Mirzazadeh, R.</dc:creator>
<dc:creator>Söderberg, O.</dc:creator>
<dc:creator>Wolf, J. B. W.</dc:creator>
<dc:date>2018-05-28</dc:date>
<dc:identifier>doi:10.1101/332569</dc:identifier>
<dc:title><![CDATA[In situ quantification of individual mRNA transcripts in melanocytes discloses gene regulation of relevance to speciation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-05-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/344275v1?rss=1">
<title>
<![CDATA[
Targeting BMI1 and MCL1 for Lung Adenocarcinoma Treatment 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/344275v1?rss=1</link>
<description><![CDATA[
Lung cancer is the leading cause of cancer-associated death worldwide. Early metastasis and the recurrence remain major challenges for lung cancer treatment in clinic. Targeting the cancer stemness could be a potential strategy to restrain tumor progression. In the current study, we found that in lung adenocarcinoma (LAC), BMI1 and MCL1 play crucial roles in invasion, chemo-resistance, and tumor initiation. JNK signaling is a link between oncogenic pathway or environment stress to cancer stemness. The activation of JNK, either by EGFR or chemotherapy agent, stabilized BMI1 and MCL1 proteins through suppressing the expression of E3-ubiquitin ligase HUWE1. In lung cancer patient samples, high level of BMI1 is correlated with poor survival, and the expression of BMI1 is positively correlated with MCL1. A novel small-molecule BI-44 was synthesized, which effectively suppressed BMI1/MCL1 expression and inhibited tumor formation and progression in preclinical models. Targeting BMI1/MCL1 provides the basis for a new therapeutic approach in the treatment of LAC.
]]></description>
<dc:creator>Lin, E.-H.</dc:creator>
<dc:creator>Hsu, C.-F.</dc:creator>
<dc:creator>Jan, Y.-H.</dc:creator>
<dc:creator>Lin, T.-H.</dc:creator>
<dc:creator>Chang, H.-Y.</dc:creator>
<dc:creator>Cheng, C.-M.</dc:creator>
<dc:creator>Hsu, H.-J.</dc:creator>
<dc:creator>Chen, W.-W.</dc:creator>
<dc:creator>Chen, B.-H.</dc:creator>
<dc:creator>Tsai, H.-F.</dc:creator>
<dc:creator>Li, J.-J.</dc:creator>
<dc:creator>Huang, C.-Y.</dc:creator>
<dc:creator>Chuang, S.-H.</dc:creator>
<dc:creator>Chang, J.-M.</dc:creator>
<dc:creator>Hsiao, M.</dc:creator>
<dc:creator>Wu, C.-W.</dc:creator>
<dc:date>2018-06-12</dc:date>
<dc:identifier>doi:10.1101/344275</dc:identifier>
<dc:title><![CDATA[Targeting BMI1 and MCL1 for Lung Adenocarcinoma Treatment]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-06-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/351635v1?rss=1">
<title>
<![CDATA[
IRON MAN, a ubiquitous family of peptides that control iron transport in plants 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/351635v1?rss=1</link>
<description><![CDATA[
Iron (Fe) is an essential mineral nutrient which severely affects the growth, yield and nutritional quality of plants if not supplied in sufficient quantities. We here report that a short C-terminal amino acid sequence consensus motif (IRON MAN; IMA) conserved across numerous, highly diverse peptides in angiosperms, is essential for Fe uptake in plants. Overexpression of the IMA sequence in Arabidopsis induced Fe uptake genes in roots, causing accumulation of Fe and manganese in all plant parts including seeds. Silencing of all eight IMA genes harbored by the Arabidopsis genome abolished Fe uptake and caused severe chlorosis; increasing the Fe supply or overexpressing IMA1 restored the wild-type phenotype. IMA1 is predominantly expressed in the phloem, preferentially in leaves, and reciprocal grafting showed that IMA1 peptides in shoots positively regulate Fe uptake in roots. IMA homologs are highly responsive to the Fe status and functional wh ...
]]></description>
<dc:creator>Grillet, L.</dc:creator>
<dc:creator>Lan, P.</dc:creator>
<dc:creator>Li, W.</dc:creator>
<dc:creator>Mokkapati, G.</dc:creator>
<dc:creator>Schmidt, W.</dc:creator>
<dc:date>2018-06-20</dc:date>
<dc:identifier>doi:10.1101/351635</dc:identifier>
<dc:title><![CDATA[IRON MAN, a ubiquitous family of peptides that control iron transport in plants]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-06-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/351700v1?rss=1">
<title>
<![CDATA[
An epitope-resurfaced virus-like particle can induce broad neutralizing antibody against four serotypes of dengue virus 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/351700v1?rss=1</link>
<description><![CDATA[
Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. Virus-like particles (VLPs) containing flavivirus prM/E proteins have been demonstrated to be a potential vaccine candidate; however, the structure of dengue VLP is poorly understood. Herein we show for the first time that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes through cryo-electron microscopy reconstruction. Mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher cross reactive (CR) neutralization antibodies (NtAbs) and were protected against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. Our results revealed that a "epitope-resurfaced" mature-form dengue VLP has the potential to induce quaternary structure-recognizing broad CR NtAbs.
]]></description>
<dc:creator>Shen, W.-F.</dc:creator>
<dc:creator>Galula, J. U.</dc:creator>
<dc:creator>Liu, J.-H.</dc:creator>
<dc:creator>Liao, M.-Y.</dc:creator>
<dc:creator>Huang, C.-H.</dc:creator>
<dc:creator>Wang, Y.-C.</dc:creator>
<dc:creator>Wu, H.-C.</dc:creator>
<dc:creator>Liang, J.-J.</dc:creator>
<dc:creator>Lin, Y.-L.</dc:creator>
<dc:creator>Whitney, M. T.</dc:creator>
<dc:creator>Chang, G.-J. J.</dc:creator>
<dc:creator>Chen, S.-R.</dc:creator>
<dc:creator>Wu, S.-R.</dc:creator>
<dc:creator>Chao, D.-Y.</dc:creator>
<dc:date>2018-06-20</dc:date>
<dc:identifier>doi:10.1101/351700</dc:identifier>
<dc:title><![CDATA[An epitope-resurfaced virus-like particle can induce broad neutralizing antibody against four serotypes of dengue virus]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-06-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/363796v1?rss=1">
<title>
<![CDATA[
Long-term blooming filamentous calcareous alga provides substrate for other coral-competitive macroalgae in the degraded lagoon of Dongsha Atoll (Pratas), Taiwan 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/363796v1?rss=1</link>
<description><![CDATA[
BackgroundThe chemically-rich seaweed Galaxaura is not only highly competitive with corals, but also provides substrate for other macroalgae. Its ecology and associated epiphytes remain largely unexplored. To fill this knowledge gap, we herein undertook an ecological assessment to explore the spatial variation, temporal dynamics, and epiphytic macroalgae of G. divaricata on patch reefs in the lagoon of Dongsha Atoll, a shallow coral reef ecosystem in the northern South China Sea, repeatedly impacted by mass coral bleaching events.nnMethodsTwelve spatially independent patch reefs in the Dongsha lagoon were first surveyed to assess the benthic composition in April 2016, and then revisited to determine G. divaricata percent cover in September 2017, with one additional Galaxaura-dominated reef (site 9). Four surveys over a period of 17 months were carried out on a degraded patch reef (site 7) to assess the temporal variation in G. divaricata cover. Epiphytic macroalgae associated with G. divaricata were quantified and identified through the aid of DNA barcoding.nnResultsPatch reefs in the Dongsha lagoon were degraded, exhibiting relatively low live coral cover (5-43%), but high proportions of macroalgae (13-58%) and other substrates (rubble and dead corals; 23-69%). The distribution of G. divaricata was heterogeneous across the lagoon, with highest abundance (16-41%) in the southeast area. Temporal surveys from site 7 and photo-evidence from site 9 suggested that an overgrowth by G. divaricata was still present to a similar extend after 17 months and 3.5 years. Yet, G. divaricata provides a suitable substrate some allelopathic macroalgae (e.g., Lobophora sp.).nnConclusionsOur study demonstrates that an allelopathic seaweed, such as G. divaricata, can overgrow degraded coral reefs for extended periods of time. By providing habitat for harmful macroalgae, a prolonged Galaxaura overgrowth could strengthen negative feedback loops on degraded coral reefs, further decreasing their recovery potential.
]]></description>
<dc:creator>Nieder, C.</dc:creator>
<dc:creator>Chen, C. A.</dc:creator>
<dc:creator>Liu, S.-L.</dc:creator>
<dc:date>2018-07-06</dc:date>
<dc:identifier>doi:10.1101/363796</dc:identifier>
<dc:title><![CDATA[Long-term blooming filamentous calcareous alga provides substrate for other coral-competitive macroalgae in the degraded lagoon of Dongsha Atoll (Pratas), Taiwan]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-07-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/369892v1?rss=1">
<title>
<![CDATA[
Long term impact of intensive post graduate laboratory training at the Cold Spring Harbor Neurobiology of Drosophila summer course 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/369892v1?rss=1</link>
<description><![CDATA[
Intensive postgraduate courses provide an opportunity for junior and senior level scientists to learn concepts and techniques that will advance their training and research programs. It is commonly assumed that short intensive courses have positive impacts within fields of research; however, these assumptions are rarely tested. Here we describe the framework of a long running postgraduate summer course at Cold Spring Harbor and attempt to quantify the impact made over its history. For over three decades, the Drosophila Neurobiology: Genes, Circuits & Behavior Summer Course at Cold Spring Harbor Laboratories (CSHL) has provided participants with intense instruction on a wide variety of topics and techniques in integrative neuroscience using Drosophila as a model organism. Students are introduced to the latest approaches for studying nervous system development, activity and connectivity, as well as complex behaviors and diseases. The course has a long history of successful alumni, many of whom describe participation in the course as foundational to their training. Student surveys of recent participants indicate a high level of satisfaction, improved career outcomes, and direct impact on publications. Analysis of student success reveals that over 64% of participants obtain independent faculty positions. Further, we describe ongoing efforts to enhance diversity and encourage access to scientific research at undergraduate-focused institutions. Together, our findings suggest that laboratory-intensive postgraduate courses provide a highly effective mechanism for scientific training that has lasting positive impacts on trainees.
]]></description>
<dc:creator>Ly, S.</dc:creator>
<dc:creator>Kaun, K.</dc:creator>
<dc:creator>Li, C.-h.</dc:creator>
<dc:creator>Stewart, D.</dc:creator>
<dc:creator>Pulver, S. R.</dc:creator>
<dc:creator>Keene, A. C.</dc:creator>
<dc:date>2018-07-16</dc:date>
<dc:identifier>doi:10.1101/369892</dc:identifier>
<dc:title><![CDATA[Long term impact of intensive post graduate laboratory training at the Cold Spring Harbor Neurobiology of Drosophila summer course]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-07-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/371112v1?rss=1">
<title>
<![CDATA[
Stout camphor tree genome fills gaps in understanding of flowering plant genome and gene family evolution 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/371112v1?rss=1</link>
<description><![CDATA[
We present reference-quality genome assembly and annotation for the stout camphor tree (SCT; Cinnamomum kanehirae [Laurales, Lauraceae]), the first sequenced member of the Magnoliidae comprising four orders (Laurales, Magnoliales, Canellales, and Piperales) and over 9,000 species. Phylogenomic analysis of 13 representative seed plant genomes indicates that magnoliid and eudicot lineages share more recent common ancestry relative to monocots. Two whole genome duplication events were inferred within the magnoliid lineage, one before divergence of Laurales and Magnoliales and the other within the Lauraceae. Small scale segmental duplications and tandem duplications also contributed to innovation in the evolutionary history of Cinnamomum. For example, expansion of terpenoid synthase subfamilies within the Laurales spawned the diversity of Cinnamomum monoterpenes and sesquiterpenes.
]]></description>
<dc:creator>Chaw, S.-M.</dc:creator>
<dc:creator>Liu, Y.-C.</dc:creator>
<dc:creator>Wang, H.-Y.</dc:creator>
<dc:creator>Wu, Y.-W.</dc:creator>
<dc:creator>Lin, C.-Y. I.</dc:creator>
<dc:creator>Wu, C.-S.</dc:creator>
<dc:creator>Ke, H.-M.</dc:creator>
<dc:creator>Chang, L.-Y.</dc:creator>
<dc:creator>Hsu, C.-Y.</dc:creator>
<dc:creator>Yang, H.-T.</dc:creator>
<dc:creator>Sudianto, E.</dc:creator>
<dc:creator>Hsu, M.-H.</dc:creator>
<dc:creator>Wu, K.-P.</dc:creator>
<dc:creator>Wang, N.-N.</dc:creator>
<dc:creator>Leebens-Mack, J.</dc:creator>
<dc:creator>Tsai, I. J. J.</dc:creator>
<dc:date>2018-07-18</dc:date>
<dc:identifier>doi:10.1101/371112</dc:identifier>
<dc:title><![CDATA[Stout camphor tree genome fills gaps in understanding of flowering plant genome and gene family evolution]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-07-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/376186v1?rss=1">
<title>
<![CDATA[
Glucose intake hampers PKA-regulated HSP90 chaperone activity 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/376186v1?rss=1</link>
<description><![CDATA[
Aging is an intricate phenomenon associated with the gradual loss of physiological functions, and both nutrient sensing and proteostasis control lifespan. Although multiple approaches have facilitated the identification of candidate genes that govern longevity, the molecular mechanisms that link aging pathways are still elusive. Here, we conducted a quantitative mass spectrometry screen and identified all phosphorylation/dephosphorylation sites on yeast proteins that significantly responded to calorie restriction, a well-established approach to extend lifespan. Functional screening of 135 potential regulators uncovered that Ids2 is activated by PP2C under CR and inactivated by PKA under glucose intake. ids2{Delta} or ids2 phosphomimetic cells displayed heat sensitivity and lifespan shortening. Ids2 serves as a co-chaperone to form a complex with Hsc82 or the redundant Hsp82, and phosphorylation of Ids2 impedes its association with chaperone HSP90. Thus, PP2C and PKA orchestrate glucose sensing and protein folding to enable cells to maintain protein quality for sustained longevity.
]]></description>
<dc:creator>Chen, Y.-C.</dc:creator>
<dc:creator>Jiang, P.-H.</dc:creator>
<dc:creator>Chen, H.-M.</dc:creator>
<dc:creator>Chen, C.-H.</dc:creator>
<dc:creator>Wang, Y.-T.</dc:creator>
<dc:creator>Chen, Y.-J.</dc:creator>
<dc:creator>Yu, C.-J.</dc:creator>
<dc:creator>Teng, S.-C.</dc:creator>
<dc:date>2018-07-24</dc:date>
<dc:identifier>doi:10.1101/376186</dc:identifier>
<dc:title><![CDATA[Glucose intake hampers PKA-regulated HSP90 chaperone activity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-07-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/381418v1?rss=1">
<title>
<![CDATA[
Modelling bistable tumour population dynamics to design effective treatment strategies 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/381418v1?rss=1</link>
<description><![CDATA[
Despite recent advances in targeted drugs and immunotherapy, cancer remains "the emperor of all maladies" due to inevitable emergence of resistance. Drug resistance is thought to be driven by mutations and/or dynamic plasticity that deregulate pathway activities and regulatory programs of a highly heterogeneous tumour. In this study, we propose a modelling framework to simulate population dynamics of heterogeneous tumour cells with reversible drug resistance. Drug sensitivity of a tumour cell is determined by its internal states, which are demarcated by coordinated activities of multiple interconnected oncogenic pathways. Transitions between cellular states depend on the effects of targeted drugs and regulatory relations between the pathways. Under this framework, we build a simple model to capture drug resistance characteristics of BRAF-mutant melanoma, where two cell states are described by two mutually inhibitory - main and alternative - pathways. We assume that cells with an activated main pathway are proliferative yet sensitive to the BRAF inhibitor, and cells with an activated alternative pathway are quiescent but resistant to the drug. We describe a dynamical process of tumour growth under various drug regimens using the explicit solution of mean-field equations. Based on these solutions, we compare efficacy of three treatment strategies: static treatments with continuous and constant dosages, periodic treatments with regular intermittent phases and drug holidays, and treatments derived from optimal control theory (OCT). Based on these analysis, periodic treatments outperform static treatments with a considerable margin, while treatments based on OCT outperform the best periodic treatment. Our results provide insights regarding optimal cancer treatment modalities for heterogeneous tumours, and may guide the development of optimal therapeutic strategies to circumvent drug resistance and due to tumour plasticity.
]]></description>
<dc:creator>Akhmetzhanov, A. R.</dc:creator>
<dc:creator>Kim, J. W.</dc:creator>
<dc:creator>Sullivan, R.</dc:creator>
<dc:creator>Beckman, R. A.</dc:creator>
<dc:creator>Tamayo, P.</dc:creator>
<dc:creator>Yeang, C.-H.</dc:creator>
<dc:date>2018-07-31</dc:date>
<dc:identifier>doi:10.1101/381418</dc:identifier>
<dc:title><![CDATA[Modelling bistable tumour population dynamics to design effective treatment strategies]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-07-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/383182v1?rss=1">
<title>
<![CDATA[
The borders of cis-regulatory DNA sequences harbor the divergent transcription factor binding motifs in the human genome 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/383182v1?rss=1</link>
<description><![CDATA[
Changes in the cis-regulatory DNA sequences and transcription factor (TF) repertoires provide major sources that shape the gene regulatory evolution in eukaryotes. However, it is currently unclear how dynamic change of DNA sequences introduce various divergence level of TF binding motifs in the genome over evolutionary time. Here, we estimated the evolutionary divergence level of the TF binding motifs, and quantified their occurrences in the DNase I hypersensitive sites. Results from our in silico motif scan and empirical TF-ChIP (chromatin immunoprecipitation) demonstrate that the divergent motifs tend to be introduced at the borders of the cis-regulatory regions, that are likely accompanied with the expansion through evolutionary time. Accordingly, we propose that an expansion by incorporating divergent motifs within the cis-regulatory regions provides a rationale for the evolutionary divergence of regulatory circuits.
]]></description>
<dc:creator>Huang, J.-H.</dc:creator>
<dc:creator>Kwan, R. S.-Y.</dc:creator>
<dc:creator>Tsai, Z. T.-Y.</dc:creator>
<dc:creator>Tsai, H.-K.</dc:creator>
<dc:date>2018-08-02</dc:date>
<dc:identifier>doi:10.1101/383182</dc:identifier>
<dc:title><![CDATA[The borders of cis-regulatory DNA sequences harbor the divergent transcription factor binding motifs in the human genome]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-08-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/389163v1?rss=1">
<title>
<![CDATA[
A Chemically-triggered Transition from Conflict to Cooperation in Burying Beetles 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/389163v1?rss=1</link>
<description><![CDATA[
Although interspecific competition has long been recognized as a major driver of trait divergence and adaptive evolution1-3, relatively little effort has focused on how it influences the evolution of intraspecific cooperation4-6. Here we identify the mechanism by which the perceived pressure of interspecific competition influences the transition from intraspecific conflict to cooperation in a facultative cooperatively breeding species, the Asian burying beetle Nicrophorus nepalensis. In their natural environment in central Taiwan, N. nepalensis are typically aggressive to conspecifics and only cooperate with others of their own species at critical carcass resources in the presence of blowflies, their primary competitors7. We demonstrate that beetles form larger groups and are more cooperative in carcass preparation in warmer environments where the pressure of interspecific competition with blowflies is highest8. To test the hypothesis that the presence of blowflies promotes beetle cooperation and to identify the mechanism by which this occurs, we manipulated blowfly larvae on carcasses in the lab. We not only found that beetles are more cooperative at carcasses when blowfly maggots have begun to digest the tissue, but that this social cooperation appears to be triggered by a single chemical cue-- dimethyl disulfide (DMDS)--emitted from carcasses consumed by blowflies but not from control carcasses lacking blowflies. Our results provide experimental evidence that interspecific competition promotes the transition from intraspecific conflict to cooperation in N. nepalensis via a surprisingly simple social chemical cue that is a reliable indicator of interspecific competition. This finding helps bridge the gap between the proximate and ultimate factors regulating the transition between cooperation and conflict and moves toward a more comprehensive understanding of the evolution of mechanisms governing intraspecific variation in social behaviour.
]]></description>
<dc:creator>Chen, B.-F.</dc:creator>
<dc:creator>Liu, M.</dc:creator>
<dc:creator>Rubenstein, D. R.</dc:creator>
<dc:creator>Sun, S.-J.</dc:creator>
<dc:creator>Liu, J.-N.</dc:creator>
<dc:creator>Lin, Y.-H.</dc:creator>
<dc:creator>Shen, S.-F.</dc:creator>
<dc:date>2018-08-09</dc:date>
<dc:identifier>doi:10.1101/389163</dc:identifier>
<dc:title><![CDATA[A Chemically-triggered Transition from Conflict to Cooperation in Burying Beetles]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-08-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/391474v1?rss=1">
<title>
<![CDATA[
A single-cell level and connectome-derived computational model of the Drosophila brain 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/391474v1?rss=1</link>
<description><![CDATA[
Computer simulations play an important role in testing hypotheses, integrating knowledge, and providing predictions of neural circuit functions. While considerable effort has been dedicated into simulating primate or rodent brains, the fruit fly (Drosophila melanogaster) is becoming a promising model animal in computational neuroscience for its small brain size, complex cognitive behavior, and abundancy of data available from genes to circuits. Moreover, several Drosophila connectome projects have generated a large number of neuronal images that account for a significant portion of the brain, making a systematic investigation of the whole brain circuit possible. Supported by FlyCircuit (http://www.flycircuit.tw), one of the largest Drosophila neuron image databases, we began a long-term project with the goal to construct a whole-brain spiking network model of the Drosophila brain. In this paper, we report the outcome of the first phase of the project. We developed the Flysim platform, which 1) identifies the polarity of each neuron arbor, 2) predicts connections between neurons, 3) translates morphology data from the database into physiology parameters for computational modeling, 4) reconstructs a brain-wide network model, which consists of 20,089 neurons and 1,044,020 synapses, and 5) performs computer simulations of the resting state. We compared the reconstructed brain network with a randomized brain network by shuffling the connections of each neuron. We found that the reconstructed brain can be easily stabilized by implementing synaptic short-term depression, while the randomized one exhibited seizure-like firing activity under the same treatment. Furthermore, the reconstructed Drosophila brain was structurally and dynamically more diverse than the randomized one and exhibited both Poisson-like and patterned firing activities. Despite being at its early stage of development, this single-cell level brain model allows us to study some of the fundamental properties of neural networks including network balance, critical behavior, long-term stability, and plasticity.
]]></description>
<dc:creator>Huang, Y.-C.</dc:creator>
<dc:creator>Wang, C.-T.</dc:creator>
<dc:creator>Su, T.-S.</dc:creator>
<dc:creator>Kao, K.-W.</dc:creator>
<dc:creator>Lin, Y.-J.</dc:creator>
<dc:creator>Chiang, A.-S.</dc:creator>
<dc:creator>Lo, C.-C.</dc:creator>
<dc:date>2018-08-14</dc:date>
<dc:identifier>doi:10.1101/391474</dc:identifier>
<dc:title><![CDATA[A single-cell level and connectome-derived computational model of the Drosophila brain]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-08-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/392357v1?rss=1">
<title>
<![CDATA[
Enlarged and highly repetitive plastome of Lagarostrobos and plastid phylogenomics of Podocarpaceae 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/392357v1?rss=1</link>
<description><![CDATA[
Podocarpaceae is the largest family in cupressophytes (conifers II), but their plastid genomes (plastomes) are poorly studied, with plastome data currently existing for only four of the 19 Podocarpaceous genera. In this study, we assembled the plastomes from representatives of eight additional genera, including Afrocarpus, Dacrydium, Lagarostrobos, Lepidothamnus, Microstrobos, Phyllocladus, Prumnopitys, and Saxegothaea. We found that Lagarostrobos, a monotypic genus native to Tasmania, has the largest plastome among any cupressophytes studied to date (151,496 bp). Plastome enlargement in Lagarostrobos coincides with increased intergenic spacers, repeats, and duplicated genes. Among Podocarpaceae, Lagarostrobos has the most rearranged plastome, but its substitution rates are modest. Plastid phylogenomic analyses clarify the positions of previously conflicting Podocarpaceous genera. Tree topologies firmly support the division of Podocarpaceae into two sister clades: (1) the Prumnopityoid clade and (2) the clade containing Podocarpoid, Dacrydioid, Microstrobos, and Saxegothaea. The Phyllocladus is nested within the Podocarpaceae, thus familial status of the monotypic Phyllocladaceae is not supported.
]]></description>
<dc:creator>Sudianto, E.</dc:creator>
<dc:creator>Wu, C.-S.</dc:creator>
<dc:creator>Leonhard, L.</dc:creator>
<dc:creator>Martin, W. F.</dc:creator>
<dc:creator>Chaw, S.-M.</dc:creator>
<dc:date>2018-08-16</dc:date>
<dc:identifier>doi:10.1101/392357</dc:identifier>
<dc:title><![CDATA[Enlarged and highly repetitive plastome of Lagarostrobos and plastid phylogenomics of Podocarpaceae]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-08-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/411223v1?rss=1">
<title>
<![CDATA[
Karyopherin Kap114p regulates TATA-binding protein-mediated transcription 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/411223v1?rss=1</link>
<description><![CDATA[
Gene expression is regulated by nuclear accessibility of transcription factors controlled by transport receptors and competitive inhibitors. Multiple karyopherin-{beta}s (Kap-{beta}s) facilitate nuclear import of yeast TATA-binding protein (yTBP). However, only Kap114p suppresses temperature-sensitive yTBP mutations, suggesting Kap114p executes undefined non-transport functions. We show that yTBP preferably binds Kap114p with an affinity three orders of magnitude higher than other Kap-{beta}s facilitating yTBP nuclear import. Our crystal structure of Kap114p reveals an extensively negatively-charged concave surface, accounting for high-affinity basic-protein binding. Furthermore, we biochemically demonstrate that two intra-HEAT-repeat inserts act as regulatory TBP-binding domains carried by TBP-associated factor 1 (TAF1-TAND), suppressing binding of yTBP with DNA and the transcription factor IIA. Remarkably, dual-knockout of Kap114 and TAF1-TAND in yeast synergistically suppresses cell growth. Our study reveals that Kap114p has a dual function that modulates the nuclear localization and activity of yTBP, illuminating how the nuclear transport machinery regulates yTBP-mediated transcription.
]]></description>
<dc:creator>Liao, C.-C.</dc:creator>
<dc:creator>Shankar, S.</dc:creator>
<dc:creator>Ahmed, G. R.</dc:creator>
<dc:creator>Hsia, K.-C.</dc:creator>
<dc:date>2018-09-07</dc:date>
<dc:identifier>doi:10.1101/411223</dc:identifier>
<dc:title><![CDATA[Karyopherin Kap114p regulates TATA-binding protein-mediated transcription]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-09-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/413013v1?rss=1">
<title>
<![CDATA[
Phosphoproteomics of Highly ABA-Induced1 identifies AT Hook Like10 phosphorylation required for growth regulation during stress 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/413013v1?rss=1</link>
<description><![CDATA[
The Clade A protein phosphatase 2C Highly ABA-Induced 1 (HAI1) plays an important role in stress signaling yet little information is available on HAI1-regulated phosphoproteins. Quantitative phosphoproteomics identified phosphopeptides of increased abundance in hai1-2 in unstressed plants and in plants exposed to low water potential (drought) stress. The identity and localization of the phosphoproteins as well as enrichment of specific phosphorylation motifs indicated that these phosphorylation sites may be regulated directly by HAI1 or by HAI1-regulated kinases including Mitogen-Activated Protein Kinases (MPKs), Sucrose-non fermenting Related Kinase 2 (SnRK2s) or Casein Kinases. One of the phosphosites putatively regulated by HAI1 was S313/S314 of AT Hook-Like10 (AHL10), a DNA binding protein of unclear function. HAI1 could directly dephosphorylate AHL10 in vitro and the level of HAI1 expression affected the abundance of phosphorylated AHL10 in vivo. AHL10 S314 phosphorylation was critical for restriction of plant growth under low water potential stress and for regulation of Jasmonic Acid and Auxin-related gene expression as well as expression of developmental regulators including Shootmeristemless (STM). These genes were also mis-regulated in hai1-2. AHL10 S314 phosphorylation was required for AHL10 complexes to form foci within the nucleoplasm, suggesting that S314 phosphorylation may control AHL10 association with the nuclear matrix or with other transcriptional regulators. These data identify a set of HAI1-affected phosphorylation sites, show that HAI1-regulated phosphorylation of AHL10 S314 controls AHL10 function and localization and also indicate that HAI1-AHL10 signaling coordinates growth with stress and defense responses.
]]></description>
<dc:creator>Wong, M. M.</dc:creator>
<dc:creator>Bhaskara, G. B.</dc:creator>
<dc:creator>Wen, T.-N.</dc:creator>
<dc:creator>Lin, W.-D.</dc:creator>
<dc:creator>Nguyen, T. T.</dc:creator>
<dc:creator>Chong, G. L.</dc:creator>
<dc:creator>Verslues, P.</dc:creator>
<dc:date>2018-09-10</dc:date>
<dc:identifier>doi:10.1101/413013</dc:identifier>
<dc:title><![CDATA[Phosphoproteomics of Highly ABA-Induced1 identifies AT Hook Like10 phosphorylation required for growth regulation during stress]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-09-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/418384v1?rss=1">
<title>
<![CDATA[
Active Transport of Membrane Components by Self-Organization of the Min Proteins 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/418384v1?rss=1</link>
<description><![CDATA[
Heterogeneous distribution of components in the biological membrane is critical in the process of cell polarization. However, little is known about the mechanisms that can generate and maintain the heterogeneous distribution of the membrane components. Here we report that the propagating wave patterns of the bacterial Min proteins can impose corresponding steric pressure on the membrane to establish a directional accumulation of the membrane components, resulting in segregation of the components in the membrane. The diffusivity, influenced by the membrane anchor of the component, and the repulsed ability, influenced by the steric property of the soluble region of the component and molecular crowding, determine the differential spatial distribution of the component in the membrane. Thus, transportation of the membrane components by the Min proteins follows a simple physical principle, which resembles a linear peristaltic pumping process, to selectively segregate and maintain heterogeneous distribution of materials in the membrane.
]]></description>
<dc:creator>Shih, Y.-L.</dc:creator>
<dc:creator>Huang, L.-T.</dc:creator>
<dc:creator>Tu, Y.-M.</dc:creator>
<dc:creator>Lee, B.-F.</dc:creator>
<dc:creator>Bau, Y.-C.</dc:creator>
<dc:creator>Hong, C. Y.</dc:creator>
<dc:creator>Lee, H.-l.</dc:creator>
<dc:creator>Shih, Y.-P.</dc:creator>
<dc:creator>Hsu, M.-F.</dc:creator>
<dc:creator>Chen, J.-S.</dc:creator>
<dc:creator>Lu, Z.-X.</dc:creator>
<dc:creator>Chao, L.</dc:creator>
<dc:date>2018-09-14</dc:date>
<dc:identifier>doi:10.1101/418384</dc:identifier>
<dc:title><![CDATA[Active Transport of Membrane Components by Self-Organization of the Min Proteins]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-09-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/421719v1?rss=1">
<title>
<![CDATA[
GenEpi: Gene-based Epistasis Discovery Using Machine Learning 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/421719v1?rss=1</link>
<description><![CDATA[
Genome-wide association studies (GWAS) provide a powerful means to identify associations between genetic variants and phenotypes. However, GWAS techniques for detecting epistasis, the interactions between genetic variants associated with phenotypes, are still limited. We believe that developing an efficient and effective GWAS method to detect epistasis will be a key for discovering sophisticated pathogenesis, which is especially important for complex diseases such as Alzheimers disease (AD). In this regard, this study presents GenEpi, a computational package to uncover epistasis associated with phenotypes by the proposed machine learning approach. GenEpi identifies both within-gene and cross-gene epistasis through a two-stage modeling workflow. In both stages, GenEpi adopts two-element combinatorial encoding when producing features and constructs the prediction models by L1-regularized regression with stability selection. The simulated data showed that GenEpi outperforms other widely-used methods on detecting ground-truth epistasis. As real data is concerned, this study uses AD as an example to reveal the capability of GenEpi in finding disease-related variants and variant interactions that show both biological meanings and predictive power. Availability: GenEpi is an open-source python package and available free of charge only for non-commercial users. The package can be downloaded from https://github.com/Chester75321/GenEpi, and has also been published on The Python Package Index.
]]></description>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Wu, J.-T.</dc:creator>
<dc:creator>Hong, M.-Y.</dc:creator>
<dc:creator>Tung, Y.-A.</dc:creator>
<dc:creator>Hsieh, P.-H.</dc:creator>
<dc:creator>Yee, S. W.</dc:creator>
<dc:creator>Giacomini, K. M.</dc:creator>
<dc:creator>Oyang, Y.-J.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Alzheimer's Disease Neuroimaging Initiative,</dc:creator>
<dc:date>2018-09-20</dc:date>
<dc:identifier>doi:10.1101/421719</dc:identifier>
<dc:title><![CDATA[GenEpi: Gene-based Epistasis Discovery Using Machine Learning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-09-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/431460v1?rss=1">
<title>
<![CDATA[
Altered Gene Regulatory Networks are Associated with the Transition from C3 to Crassulacean Acid Metabolism in Erycina (Oncidiinae: Orchidaceae) 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/431460v1?rss=1</link>
<description><![CDATA[
Crassulacean acid metabolism (CAM) photosynthesis is a modification of the core C3 photosynthetic pathway that improves the ability of plants to assimilate carbon in water-limited environments. CAM plants fix CO2 mostly at night, when transpiration rates are low. All of the CAM pathway genes exist in ancestral C3 species, but the timing and magnitude of expression are greatly altered between C3 and CAM species. Understanding these regulatory changes is key to elucidating the mechanism by which CAM evolved from C3. Here we use two closely related species in the Orchidaceae, Erycina pusilla (CAM) and Erycina crista-galli (C3), to conduct comparative transcriptomic analyses across multiple time points. Clustering of genes with expression variation across the diel cycle revealed some canonical CAM pathway genes similarly expressed in both species, regardless of photosynthetic pathway. However, gene network construction indicated that 149 gene families had significant differences in network connectivity and were further explored for these functional enrichments. Genes involved in light sensing and ABA signaling were some of the most differently connected genes between the C3 and CAM Erycina species, in agreement with the contrasting diel patterns of stomatal conductance in C3 and CAM plants. Our results suggest changes to transcriptional cascades are important for the transition from C3 to CAM photosynthesis in Erycina.
]]></description>
<dc:creator>Heyduk, K.</dc:creator>
<dc:creator>Hwang, M.</dc:creator>
<dc:creator>Albert, V.</dc:creator>
<dc:creator>Silvera, K.</dc:creator>
<dc:creator>Lan, T.</dc:creator>
<dc:creator>Winter, K.</dc:creator>
<dc:creator>Leebens-Mack, J.</dc:creator>
<dc:date>2018-10-02</dc:date>
<dc:identifier>doi:10.1101/431460</dc:identifier>
<dc:title><![CDATA[Altered Gene Regulatory Networks are Associated with the Transition from C3 to Crassulacean Acid Metabolism in Erycina (Oncidiinae: Orchidaceae)]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/449330v1?rss=1">
<title>
<![CDATA[
Transcriptional dynamics following freezing stress reveal selection for mechanisms of freeze tolerance at the poleward range margin in the cold water intertidal barnacle Semibalanus balanoides 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/449330v1?rss=1</link>
<description><![CDATA[
The ability to survive freezing has repeatedly evolved across multiple phyla. This suggests that the mechanisms of freeze tolerance must be readily evolvable from basal physiological traits. While several biochemical correlates to freeze tolerance have been described, the mechanism that confers freeze tolerance is still not well understood. To understand both the basic biochemical mechanisms of freeze tolerance as well as their role in local adaptation at the poleward range edge, we conducted a transcriptomic study on two populations (one from the poleward range margin in the White Sea, Russia, and one from the central coast of British Columbia, Canada) of the cold water acorn barnacle Semibalanus balanoides on a time series following a freezing event. We found that the British Columbia population (at the equatorward range margin) was significantly less freeze tolerant than the White Sea population (at the poleward range margin). After assembling and annotating a de novo transcriptome for S. balanoides, we found that the patterns of differential transcript expression following freezing were almost entirely non-overlapping between the two populations, with the White Sea population expressing a series of heat shock proteins in response to freezing stress as well as several aquaporins, while the British Columbia population expressed a series of proteases instead, indicating severe protein damage. We found strong evidence of purifying selection on the significantly upregulated transcripts in the White Sea population, suggesting local adaptation to freezing threat. Taken together, this shows the importance of freeze tolerance to population survival at the poleward range margin, and highlights the central roles of aquaporins and heat shock proteins to the trait of freeze tolerance across taxa.
]]></description>
<dc:creator>Marshall, K. E.</dc:creator>
<dc:creator>Dowle, E. J.</dc:creator>
<dc:creator>Petrunina, A.</dc:creator>
<dc:creator>Kolbasov, G.</dc:creator>
<dc:creator>Chan, B. K. K.</dc:creator>
<dc:date>2018-10-24</dc:date>
<dc:identifier>doi:10.1101/449330</dc:identifier>
<dc:title><![CDATA[Transcriptional dynamics following freezing stress reveal selection for mechanisms of freeze tolerance at the poleward range margin in the cold water intertidal barnacle Semibalanus balanoides]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-10-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/454942v1?rss=1">
<title>
<![CDATA[
Visualization of axonal protein allocation in Drosophila with whole brain localization microscopy 
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</title>
<link>https://biorxiv.org/content/10.1101/454942v1?rss=1</link>
<description><![CDATA[
Long-term memory (LTM) formation requires learning-induced protein synthesis in specific neurons and synapses within a neural circuit. Precisely how neural activity allocates new proteins to specific synaptic ensembles, however, remains unknown. We developed a deep-tissue super-resolution imaging tool suitable for single-molecule localization in intact adult Drosophila brain, and focused on the axonal protein allocation in mushroom body (MB), a central neuronal structure involved in olfactory memory formation. We found that insufficient training suppresses LTM formation by inducing the synthesis of vesicular monoamine transporter (VMAT) proteins within a dorsal paired medial (DPM) neuron, which innervates all axonal lobes of the MB. Surprisingly, using our localization microscopy, we found that these learning-induced proteins are distributed only in a subset of DPM axons in specific sectors along the MB lobes. This neural architecture suggests that sector-specific modulation of neural activity from MB neurons gates consolidation of early transient memory into LTM.
]]></description>
<dc:creator>Chu, L.-A.</dc:creator>
<dc:creator>Lu, C.-H.</dc:creator>
<dc:creator>Yang, S.-M.</dc:creator>
<dc:creator>Feng, K.-L.</dc:creator>
<dc:creator>Liu, Y.-T.</dc:creator>
<dc:creator>Chen, C.-C.</dc:creator>
<dc:creator>Tsai, Y.-C.</dc:creator>
<dc:creator>Chen, P.</dc:creator>
<dc:creator>Lee, T.-K.</dc:creator>
<dc:creator>Hwu, Y.-K.</dc:creator>
<dc:creator>Chen, B.-C.</dc:creator>
<dc:creator>Chiang, A.-S.</dc:creator>
<dc:date>2018-10-27</dc:date>
<dc:identifier>doi:10.1101/454942</dc:identifier>
<dc:title><![CDATA[Visualization of axonal protein allocation in Drosophila with whole brain localization microscopy]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-10-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/457762v1?rss=1">
<title>
<![CDATA[
Biological adaptation under fluctuating selection 
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</title>
<link>https://biorxiv.org/content/10.1101/457762v1?rss=1</link>
<description><![CDATA[
Bet-hedging--an evolutionary strategy that reduces fitness variance at the expense of lower mean fitness--is the primary explanation for most forms of biological adaptation to environmental unpredictability. However, most applications of bet-hedging theory to biological problems have largely made unrealistic demographic assumptions, such as non-overlapping generations and fixed population sizes. Consequently, the generality and applicability of bet-hedging theory to real world phenomena remains unclear. Here we use continuous-time, stochastic Lotka-Volterra models to relax overly restrictive demographic assumptions and explore a suite of biological adaptations to fluctuating environments. We discover a novel "rising-tide strategy" that--unlike the bet-hedging strategy--generates both a higher mean and variance in fitness. The positive fitness effects of the rising-tide strategys specialization to good years can overcome any negative effects of higher fitness variance in unpredictable environments. Moreover, we show not only that the rising-tide strategy will be selected for over a much broader range of environmental conditions than the bet-hedging strategy, but also under more realistic demographic circumstances. Ultimately, our model demonstrates that there are likely to be a wide range of ways that organisms respond to environmental unpredictability.
]]></description>
<dc:creator>Liu, M.</dc:creator>
<dc:creator>Rubenstein, D.</dc:creator>
<dc:creator>Liu, W.-C.</dc:creator>
<dc:creator>Shen, S.-F.</dc:creator>
<dc:date>2018-10-31</dc:date>
<dc:identifier>doi:10.1101/457762</dc:identifier>
<dc:title><![CDATA[Biological adaptation under fluctuating selection]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-10-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/462390v1?rss=1">
<title>
<![CDATA[
Nonsynonymous A-to-I RNA editing contributes to burden of deleterious missense variants in healthy individuals 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/462390v1?rss=1</link>
<description><![CDATA[
ABSTARCTAdenosine-to-inosine (A-to-I) RNA editing is a very common post-transcriptional modification that can lead to A-to-G changes at the RNA level and compensate for G-to-A genomic changes to a certain extent. It has been shown that each healthy individual can carry dozens of missense variants predicted to be severely deleterious. Why strongly detrimental variants are preserved in a population and not eliminated by negative natural selection remains mostly unclear. Here we ask if RNA editing correlates with the burden of deleterious A/G polymorphisms in a population. Integrating genome and transcriptome sequencing data from 447 human lymphoblastoid cell lines, we show that nonsynonymous editing activities (prevalence/level) are negatively correlated with the deleteriousness of A-to-G genomic changes and positively correlated with that of G-to-A genomic changes within the population. We find a significantly negative correlation between nonsynonymous editing activities and allele frequency of A within the population. This negative editing-allele frequency correlation is particularly strong when editing sites are located in highly important genes/loci. Examinations of deleterious missense variants from the 1000 genomes project further show a significantly higher mutational burden in G-to-A changes than in other types of changes. The level of the mutational burden in G-to-A changes increases with increasing deleterious effects of the changes. Moreover, the deleteriousness of G-to-A changes is significantly positively correlated with the percentage of binding motif of editing enzymes at the variants. Overall, we show that nonsynonymous editing contributes to the increased burden of G-to-A missense mutations in healthy individuals, expanding RNA editing in pathogenomics studies.
]]></description>
<dc:creator>Mai, T.-L.</dc:creator>
<dc:creator>Chuang, T.-J.</dc:creator>
<dc:date>2018-11-05</dc:date>
<dc:identifier>doi:10.1101/462390</dc:identifier>
<dc:title><![CDATA[Nonsynonymous A-to-I RNA editing contributes to burden of deleterious missense variants in healthy individuals]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-11-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/479725v1?rss=1">
<title>
<![CDATA[
A Statistical Procedure for Genome-wide Detection of QTL Hotspots Using Public Databases with Application to Rice 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/479725v1?rss=1</link>
<description><![CDATA[
Genome-wide detection of quantitative trait loci (QTL) hotspots underlying variation in many molecular and phenotypic traits has been a key step in various biological studies since the QTL hotspots are highly informative and can be linked to the genes for the quantitative traits. Several statistical methods have been proposed to detect QTL hotspots. These hotspot detection methods rely heavily on permutation tests performed on summarized QTL data or individual-level data (with genotypes and phenotypes) from the genetical genomics experiments. In this article, we propose a statistical procedure for QTL hotspot detection by using the summarized QTL (interval) data collected in public web-accessible databases. First, a simple statistical method based on the uniform distribution is derived to convert the QTL interval data into the expected QTL frequency (EQF) matrix. And then, to account for the correlation structure among traits, the QTLs for correlated traits are grouped together into the same categories to form a reduced EQF matrix. Furthermore, a permutation algorithm on the EQF elements or on the QTL intervals is developed to compute a sliding scale of EQF thresholds, ranging from strict to liberal, for assessing the significance of QTL hotspots. With grouping, much stricter thresholds can be obtained to avoid the detection of spurious hotspots. Real example analysis and simulation study are carried out to illustrate our procedure, evaluate the performances and compare with other methods. It shows that our procedure can control the genome-wide error rates at the target levels, provide appropriate thresholds for correlated data and is comparable to the methods using individual-level data in hotspot detection. Depending on the thresholds used, more than 100 hotspots are detected in GRAMENE rice database. We also perform a genome-wide comparative analysis of the detected hotspots and the known genes collected in the Rice Q-TARO database. The comparative analysis reveals that the hotspots and genes are conformable in the sense that they co-localize closely and are functionally related to relevant traits. Our statistical procedure can provide a framework for exploring the networks among QTL hotspots, genes and quantitative traits in biological studies. The R codes that produce both numerical and graphical outputs of QTL hotspot detection in the genome are available on the worldwide web http://www.stat.sinica.edu.tw/~chkao/.
]]></description>
<dc:creator>Kao, C.-H.</dc:creator>
<dc:creator>Yang, M.-H.</dc:creator>
<dc:creator>Wu, D.-H.</dc:creator>
<dc:date>2018-11-27</dc:date>
<dc:identifier>doi:10.1101/479725</dc:identifier>
<dc:title><![CDATA[A Statistical Procedure for Genome-wide Detection of QTL Hotspots Using Public Databases with Application to Rice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-11-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/489278v1?rss=1">
<title>
<![CDATA[
The dynamic association of SPO11-1 with conformational changes of meiotic axial elements in maize 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/489278v1?rss=1</link>
<description><![CDATA[
Meiotic double-strand breaks (DSBs) are generated by the evolutionarily conserved SPO11 complex in the context of chromatin loops that are organized along axial elements (AEs) of chromosomes. However, how DSBs are formed with respect to chromosome axes and the SPO11 complex remains unclear in plants. Here, we confirm that DSB and bivalent formation are defective in maize spo11-1 mutants. Super-resolution microscopy demonstrates dynamic localization of SPO11-1 during recombination initiation, with variable numbers of SPO11-1 foci being distributed in nuclei but similar numbers of SPO11-1 foci being found on AEs. Notably, cytological analysis of spo11-1 meiocytes revealed an aberrant AE structure. At leptotene, AEs of wild-type and spo11-1 meiocytes were similarly curly and discontinuous. However, during early zygotene, wild-type AEs become uniform and exhibit shortened axes, whereas the elongated and curly AEs persisted in spo11-1 mutants, suggesting that loss of SPO11-1 compromised AE structural maturation. Our results reveal an interesting relationship between SPO11-1 loading onto AEs and the conformational remodeling of AEs during recombination initiation.

Author SummaryMeiosis is essential during sexual reproduction to produce haploid gametes. Recombination is the most crucial step during meiotic prophase I. It enables pairing of homologous chromosomes prior to their reductional division and generates new combinations of genetic alleles for transmission to the next generation. Meiotic recombination is initiated by generating DNA double-strand breaks (DSBs) via SPO11, a topoisomerase-related enzyme. The activity, timing and location of this DSB machinery must be controlled precisely, but how this is achieved remains obscure. Here, we show dynamic localization of SPO11-1 on chromatin during meiotic initiation in maize, yet a similar number of SPO11-1 is able to load onto axial elements (AEs), which accompanies a structural change of the AEs of wild-type meiotic chromosomes. Interestingly, loss of SPO11-1 not only affects DSB formation but also impairs structural alterations of AEs, resulting in abnormally long and curly AEs during early meiosis. Our study provides new insights into SPO11-1 localization during recombination initiation and suggests an intimate relationship between DSB formation and AE structural changes.
]]></description>
<dc:creator>Ronceret, A.</dc:creator>
<dc:creator>Golubovskaya, I.</dc:creator>
<dc:creator>Ku, J.-C.</dc:creator>
<dc:creator>Lee, D. H.</dc:creator>
<dc:creator>Timofejeva, L.</dc:creator>
<dc:creator>Angoa, A. K. G.</dc:creator>
<dc:creator>Kao, Y.-H.</dc:creator>
<dc:creator>Kremling, K.</dc:creator>
<dc:creator>Williams-Carrier, R.</dc:creator>
<dc:creator>Meeley, R.</dc:creator>
<dc:creator>Barkan, A.</dc:creator>
<dc:creator>Cande, W. Z.</dc:creator>
<dc:creator>Wang, C.-J. R.</dc:creator>
<dc:date>2018-12-06</dc:date>
<dc:identifier>doi:10.1101/489278</dc:identifier>
<dc:title><![CDATA[The dynamic association of SPO11-1 with conformational changes of meiotic axial elements in maize]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-12-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/503474v1?rss=1">
<title>
<![CDATA[
Mitochondrial cristae biogenesis coordinates with ETC complex IV assembly during Drosophila maturation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/503474v1?rss=1</link>
<description><![CDATA[
Mitochondrial cristae contain electron transport chain (ETC) complexes and are distinct from the inner boundary membrane (IBM) in both protein composition and function. While many details of mitochondrial membrane structure are known, the processes governing cristae biogenesis, including the organization of lipid membranes and assembly of proteins encoded by both nuclear and mitochondrial DNA, remain obscure. We followed cristae biogenesis in situ upon Drosophila eclosion using serial-section electron tomography and revealed that the morphogenesis of lamellar cristae coordinates with ETC complex IV assembly. The membrane morphogenesis and gain-of-function were intricately co-evolved during cristae biogenesis. Marf-knockdown flies formed lamellar cristae containing ATP synthase and functional COX. However, OPA1-knockdown flies showed impaired cristae biogenesis. Overall, this study revealed the multilevel coordination of protein-coupled membrane morphogenesis in building functional cristae.
]]></description>
<dc:creator>Jiang, Y.-f.</dc:creator>
<dc:creator>Lin, H.-l.</dc:creator>
<dc:creator>Wang, L.-j.</dc:creator>
<dc:creator>Hsu, T.</dc:creator>
<dc:creator>Fu, C.</dc:creator>
<dc:date>2018-12-21</dc:date>
<dc:identifier>doi:10.1101/503474</dc:identifier>
<dc:title><![CDATA[Mitochondrial cristae biogenesis coordinates with ETC complex IV assembly during Drosophila maturation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-12-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/513408v1?rss=1">
<title>
<![CDATA[
Reference genome for the WHO reference strain for Mycobacterium bovis BCG Danish, the present tuberculosis vaccine 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/513408v1?rss=1</link>
<description><![CDATA[
Mycobacterium bovis bacillus Calmette-Guerin (M. bovis BCG) is the only vaccine available against tuberculosis (TB). This study reports on an integrated genome analysis workflow for BCG, resulting in the completely assembled genome sequence of BCG Danish 1331 (07/270), one of the WHO reference strains for BCG vaccines. We demonstrate how this analysis workflow enables the resolution of genome duplications and of the genome of engineered derivatives of this vaccine strain.
]]></description>
<dc:creator>Borgers, K.</dc:creator>
<dc:creator>Ou, J.-Y.</dc:creator>
<dc:creator>Zheng, P.-X.</dc:creator>
<dc:creator>Tiels, P.</dc:creator>
<dc:creator>Van Hecke, A.</dc:creator>
<dc:creator>Plets, E.</dc:creator>
<dc:creator>Michielsen, G.</dc:creator>
<dc:creator>Festjens, N.</dc:creator>
<dc:creator>Callewaert, N.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:date>2019-01-07</dc:date>
<dc:identifier>doi:10.1101/513408</dc:identifier>
<dc:title><![CDATA[Reference genome for the WHO reference strain for Mycobacterium bovis BCG Danish, the present tuberculosis vaccine]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-01-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/519546v1?rss=1">
<title>
<![CDATA[
Dominant coral bacterium Endozoicomonas acroporae metabolizes DMSP 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/519546v1?rss=1</link>
<description><![CDATA[
Dominant coral-associated Endozoicomonas bacteria species are hypothesized to play a role in the coral-sulfur cycle by metabolizing Dimethylsulfoniopropionate (DMSP) into Dimethylsulfide (DMS); however, no sequenced genome to date harbors genes for this process. In this study, we assembled high-quality (>95% complete) genomes of strains of a recently added species Endozoicomonas acroporae (Acr-14T, Acr-1 and Acr-5) isolated from the coral Acropora muricata and performed comparative genomic analysis on genus Endozoicomonas. We identified the first DMSP CoA-transferase/lyase--a dddD gene homolog found in all E. acroporae strains--and functionally characterized bacteria capable of metabolizing DMSP into DMS via the DddD cleavage pathway using RT-qPCR and gas chromatography (GC). Furthermore, we demonstrated that E. acroporae strains can use DMSP as the sole carbon source and have genes arranged in an operon-like manner to link DMSP metabolism to the central carbon cycle. This study confirms the role of Endozoicomonas in the coral sulfur cycle.
]]></description>
<dc:creator>Tandon, K.</dc:creator>
<dc:creator>Chiang, P.-W.</dc:creator>
<dc:creator>Lu, C.-Y.</dc:creator>
<dc:creator>Yang, S.-H.</dc:creator>
<dc:creator>Chen, Y.-F.</dc:creator>
<dc:creator>Wada, N.</dc:creator>
<dc:creator>Chen, P.-Y.</dc:creator>
<dc:creator>Chang, H.-Y.</dc:creator>
<dc:creator>Chou, M.-S.</dc:creator>
<dc:creator>Chen, W.-M.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:date>2019-01-17</dc:date>
<dc:identifier>doi:10.1101/519546</dc:identifier>
<dc:title><![CDATA[Dominant coral bacterium Endozoicomonas acroporae metabolizes DMSP]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-01-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/521054v1?rss=1">
<title>
<![CDATA[
Fine-mapping of 150 breast cancer risk regions identifies 178 high confidence target genes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/521054v1?rss=1</link>
<description><![CDATA[
Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants (CCVs) in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium, and enriched genomic features to determine variants with high posterior probabilities (HPPs) of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of potentially causal variants, using gene expression (eQTL), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways, were over-represented among the 178 highest confidence target genes.
]]></description>
<dc:creator>Fachal, L.</dc:creator>
<dc:creator>Aschard, H.</dc:creator>
<dc:creator>Beesley, J.</dc:creator>
<dc:creator>Barnes, D.</dc:creator>
<dc:creator>Allen, J.</dc:creator>
<dc:creator>Kar, S.</dc:creator>
<dc:creator>Pooley, K.</dc:creator>
<dc:creator>Dennis, J.</dc:creator>
<dc:creator>Michailidou, K.</dc:creator>
<dc:creator>Turman, C.</dc:creator>
<dc:creator>Soucy, P.</dc:creator>
<dc:creator>Lemacon, A.</dc:creator>
<dc:creator>Lush, M.</dc:creator>
<dc:creator>Tyrer, J.</dc:creator>
<dc:creator>Ghoussaini, M.</dc:creator>
<dc:creator>Moradi Marjaneh, M.</dc:creator>
<dc:creator>Jiang, X.</dc:creator>
<dc:creator>Agata, S.</dc:creator>
<dc:creator>Aittomaki, K.</dc:creator>
<dc:creator>Alonso, M. R.</dc:creator>
<dc:creator>Andrulis, I.</dc:creator>
<dc:creator>Anton-Culver, H.</dc:creator>
<dc:creator>Antonenkova, N.</dc:creator>
<dc:creator>Arason, A.</dc:creator>
<dc:creator>Arndt, V.</dc:creator>
<dc:creator>Aronson, K.</dc:creator>
<dc:creator>Arun, B.</dc:creator>
<dc:creator>Auber, B.</dc:creator>
<dc:creator>Auer, P.</dc:creator>
<dc:creator>Azzollini, J.</dc:creator>
<dc:creator>Balmana, J.</dc:creator>
<dc:creator>Barkardottir, R.</dc:creator>
<dc:creator>Barrowdale, D.</dc:creator>
<dc:creator>Beeghly-Fadiel, A.</dc:creator>
<dc:creator>Benitez, J.</dc:creator>
<dc:creator>Bermisheva, M.</dc:creator>
<dc:creator>Bialkowska, K.</dc:creator>
<dc:creator>Blanco, A.</dc:creator>
<dc:creator>Blomqvist, C.</dc:creator>
<dc:creator>Blot, W.</dc:creator>
<dc:creator>Bogdanova, N.</dc:creator>
<dc:creator>Bojesen, S.</dc:creator>
<dc:creator>Bolla, M.</dc:creator>
<dc:creator>Bonanni, B.</dc:creator>
<dc:creator>Borg, A.</dc:creator>
<dc:creator>B</dc:creator>
<dc:date>2019-01-15</dc:date>
<dc:identifier>doi:10.1101/521054</dc:identifier>
<dc:title><![CDATA[Fine-mapping of 150 breast cancer risk regions identifies 178 high confidence target genes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-01-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/523936v1?rss=1">
<title>
<![CDATA[
A next generation approach to species delimitation reveals the role of hybridization in a cryptic species complex of corals 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/523936v1?rss=1</link>
<description><![CDATA[
BackgroundOur ability to investigate processes shaping the evolutionary diversification of corals (Cnidaria: Anthozoa) is limited by a lack of understanding of species boundaries. Discerning species has been challenging due to a multitude of factors, including homoplasious and plastic morphological characters and the use of molecular markers that are either not informative or have not completely sorted. Hybridization can also blur species boundaries by leading to incongruence between morphology and genetics. We used traditional DNA barcoding and restriction-site associated DNA sequencing combined with coalescence-based and allele-frequency methods to elucidate species boundaries and simultaneously examine the potential role of hybridization in a speciose genus of octocoral, Sinularia.nnResultsSpecies delimitations using two widely used DNA barcode markers, mtMutS and 28S rDNA, were incongruent with one another and with the morphospecies identifications, likely due to incomplete lineage sorting. In contrast, 12 of the 15 morphospecies examined formed well-supported monophyletic clades in both concatenated RAxML phylogenies and SNAPP species trees of >6,000 RADSeq loci. DAPC and Structure analyses also supported morphospecies assignments, but indicated the potential for two additional cryptic species. Three morphologically distinct species pairs could not, however, be distinguished genetically. ABBA-BABA tests demonstrated significant admixture between some of those species, suggesting that hybridization may confound species delimitation in Sinularia.nnConclusionsA genomic approach can help to guide species delimitation while simultaneously elucidating the processes generating diversity in corals. Results support the hypothesis that hybridization is an important mechanism in the evolution of Anthozoa, including octocorals, and future research should examine the contribution of this mechanism in generating diversity across the coral tree of life.
]]></description>
<dc:creator>Quattrini, A. M.</dc:creator>
<dc:creator>Wu, T.</dc:creator>
<dc:creator>Soong, K.</dc:creator>
<dc:creator>Jeng, M.-S.</dc:creator>
<dc:creator>Benayahu, Y.</dc:creator>
<dc:creator>McFadden, C. S.</dc:creator>
<dc:date>2019-01-17</dc:date>
<dc:identifier>doi:10.1101/523936</dc:identifier>
<dc:title><![CDATA[A next generation approach to species delimitation reveals the role of hybridization in a cryptic species complex of corals]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-01-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/526079v1?rss=1">
<title>
<![CDATA[
Assessing chromatin accessibility in maize using ATAC-seq 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/526079v1?rss=1</link>
<description><![CDATA[
Background: Maize is an important crop that has a complex genome. A better understanding of maize chromatin architecture provides great opportunities for crop improvement, because chromatin accessibility influences gene expression, thereby affecting agricultural traits. The newly developed method for chromatin profiling, Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq), has been developed to investigate chromatin accessibility. Result: We adapt this method by testing parameters of several key steps and generate the first ATAC-seq protocol for maize. We demonstrate that purification of maize nuclei to eliminate organelles can be achieved without the need for cell sorting, and that only a standard bench-top centrifuge is required for sample preparation. Finally, our sequence analyses confirm that our protocol of ATAC-seq can be successfully used to assess the chromatin landscape in maize. Conclusion: The ATAC-seq provides a useful technique to study the chromatin accessibility. Given the parameters tested in our study, it can be a simple and practical method for maize and may be a foundation for similar studies in other crop species.
]]></description>
<dc:creator>Lee, Y.-J.</dc:creator>
<dc:creator>Chang, P.</dc:creator>
<dc:creator>Lu, J.-H.</dc:creator>
<dc:creator>Chen, P.-Y.</dc:creator>
<dc:creator>Wang, C.-J. R.</dc:creator>
<dc:date>2019-01-22</dc:date>
<dc:identifier>doi:10.1101/526079</dc:identifier>
<dc:title><![CDATA[Assessing chromatin accessibility in maize using ATAC-seq]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-01-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/527671v1?rss=1">
<title>
<![CDATA[
Glial response to hypoxia in trachealess mutants induces synapse remodeling. 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/527671v1?rss=1</link>
<description><![CDATA[
Synaptic structure and activity are sensitive to environmental alterations. Modulation of synaptic morphology and function is often induced by signals from glia. However, the process by which glia mediate synaptic responses to environmental perturbations such as hypoxia remains unknown. Here, we report that, in the Drosophila trachealess (trh) mutant, smaller synaptic boutons form clusters named bunch boutons appear at larval neuromuscular junctions (NMJs), which is induced by the reduction of internal oxygen levels due to defective tracheal branches. Thus, the bunch bouton phenotype in the trh mutant is suppressed by hyperoxia, and recapitulated in wild-type larvae raised under hypoxia. We further show that hypoxia-inducible factor (HIF)-1/Similar (Sima) is critical in mediating hypoxia-induced bunch bouton formation. Sima upregulates the level of the Wnt/Wingless (Wg) signal in glia, leading to reorganized microtubule structures within presynaptic sites. Finally, hypoxia-induced bunch boutons maintain normal synaptic transmission at the NMJs, which is crucial for coordinated larval locomotion.

Author summaryOxygen is essential for animals to maintain their life such as growth, metabolism, responsiveness, and movement. It is therefore important to understand how animal cells trigger hypoxia response and adapt to hypoxia thereafter. Both mammalian vascular and insect tracheal branches are induced to enhance the oxygen delivery. However, the study of hypoxia response in the nervous system remains limited. In this study, we assess the morphology of Drosophila neuromuscular junctions (NMJs), a model system to study development and function of synapses, in two hypoxia conditions, one with raising wild-type larvae in hypoxia, and the other in the trachealess (trh) mutant in which the trachea is defective, causing insufficient oxygen supply. Interestingly, glia, normally wrapping the axons of NMJs, invade into synapse and trigger Wg signals to reconstitute the synaptic structure under hypoxia. This synaptic remodeling maintains the synaptic transmission of synapse, which associate the locomotor behavior of larvae.
]]></description>
<dc:creator>Chien, C.-T.</dc:creator>
<dc:creator>Chen, P.-Y.</dc:creator>
<dc:creator>Tsai, Y.-W.</dc:creator>
<dc:creator>Giangrande, A.</dc:creator>
<dc:date>2019-01-22</dc:date>
<dc:identifier>doi:10.1101/527671</dc:identifier>
<dc:title><![CDATA[Glial response to hypoxia in trachealess mutants induces synapse remodeling.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-01-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/547554v1?rss=1">
<title>
<![CDATA[
Glia-derived exosomal miR-274 targets Sprouty in trachea and synaptic boutons to modulate growth and responses to hypoxia 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/547554v1?rss=1</link>
<description><![CDATA[
Secreted exosomal miRNAs mediate inter-organ/tissue communication by downregulating gene expression, thereby modulating developmental and physiological functions. However, the source, route, and function have not been formally established for specific miRNAs. Here, we show that glial miR-274 non-cell autonomously modulates the growth of synaptic boutons and tracheal branches. Whereas precursor miR-274 was expressed in glia, mature miR-274 was secreted. miR-274 secretion to circulating hemolymph was detected in exosomes, a process requiring ESCRT components in exosome biogenesis and Rab11 and Syx1A in exosome release. miR-274 downregulated Sprouty to activate MAPK in synaptic boutons and tracheal branches, thereby promoting their growth. Expression of miR-274 solely in glia of a mir-274 null mutant reset normal levels of Sprouty and MAPK, and hemolymphatic exosomal miR-274. mir-274 mutant larvae were hypersensitive to hypoxia, which was suppressed by increasing tracheal branches. Thus, glia-derived miR-274 coordinates growth of synaptic boutons and tracheal branches to modulate larval hypoxia responses.
]]></description>
<dc:creator>Tsai, Y.-W.</dc:creator>
<dc:creator>Sung, H.-H.</dc:creator>
<dc:creator>Li, J.-C.</dc:creator>
<dc:creator>Yeh, C.-Y.</dc:creator>
<dc:creator>Chen, P.-Y.</dc:creator>
<dc:creator>Cheng, Y.-J.</dc:creator>
<dc:creator>Chen, C.-H.</dc:creator>
<dc:creator>Tsai, Y.-C.</dc:creator>
<dc:creator>Chien, C.-T.</dc:creator>
<dc:date>2019-02-12</dc:date>
<dc:identifier>doi:10.1101/547554</dc:identifier>
<dc:title><![CDATA[Glia-derived exosomal miR-274 targets Sprouty in trachea and synaptic boutons to modulate growth and responses to hypoxia]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-02-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/553503v1?rss=1">
<title>
<![CDATA[
Divergence in Thermostability of Arabidopsis Mitochondrial Nucleotide Exchange Factors Encoded by Duplicate Genes, MGE1 and MGE2 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/553503v1?rss=1</link>
<description><![CDATA[
The divergence of duplicate genes links to organismic adaptation. In Arabidopsis thaliana two nuclear genes encode mitochondrial GrpEs, MGE1 and MGE2, the nucleotide exchange factors of DnaK/HSP70 chaperone. MGE1 and MGE2 are duplicate genes originated from a whole genome duplication event. They respond differentially to high temperature; MGE2 is heat-inducible and is required for Arabidopsis seedlings to tolerate prolonged heat stress, while MGE1 is constitutively expressed. Heterologous expression of MGE2 but not MGE1 restored the growth of E. coli grpE mutant cells at elevated temperatures, suggesting that MGE2 is more thermostable than MGE1. In this study, we directly compared the thermostability of the purified recombinant MGE1 and MGE2 by circular dichroism spectroscopy. The temperature midpoints of the unfolding transition (Tm) of MGE1 and MGE2 were about 38 and 46 {degrees}C, respectively, indicating that MGE2 is remarkably more stable than MGE1 at higher temperature. Domain swapping between the two homologous proteins showed that the N-terminal region, including an unstructured sequence and a long -helix domain, is the major determinant of the thermostability. Although MGE2 contains a conserved sequence derived from an exonized intron within the N-terminus unstructured region, deletion of this sequence did not substantially affect protein thermostability in vitro and complementation of E. coli and Arabidopsis heat sensitive mutants. Taken together, our results suggest that Arabidopsis MGE1 and MGE2 had diverged not only in transcriptional response but also in the thermostability of the encoded proteins, which may contribute to adaptation of plants to higher temperatures.
]]></description>
<dc:creator>Chen, Z.-t.</dc:creator>
<dc:creator>Hung, M.-J.</dc:creator>
<dc:creator>Yu, S.-J.</dc:creator>
<dc:creator>Liao, T.-Y.</dc:creator>
<dc:creator>Lin, Y.-P.</dc:creator>
<dc:creator>Chen, R. P.- Y.</dc:creator>
<dc:creator>Yang, C.-C.</dc:creator>
<dc:creator>Charng, Y.-y.</dc:creator>
<dc:date>2019-02-18</dc:date>
<dc:identifier>doi:10.1101/553503</dc:identifier>
<dc:title><![CDATA[Divergence in Thermostability of Arabidopsis Mitochondrial Nucleotide Exchange Factors Encoded by Duplicate Genes, MGE1 and MGE2]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-02-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/556712v1?rss=1">
<title>
<![CDATA[
Effector loading onto VgrG spike proteins is critical for the assembly of the type VI secretion system in Agrobacterium tumefaciens 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/556712v1?rss=1</link>
<description><![CDATA[
The type VI secretion system (T6SS) is used by many bacteria to engage in social behaviors with others and can directly or indirectly affect the health of plants and animals. Because activities associated with T6SS are often costly, the assembly and activation of the T6SS must be highly regulated. However, our knowledge regarding how T6SS assembly and contraction are regulated remains limited. Here we show that the loading of effectors onto their cognate carriers is critical for the assembly of a functional T6SS in Agrobacterium tumefaciens. A. tumefaciens strain C58 encodes one T6SS and two Tde DNase toxin effectors used as major weapons for interbacterial competition. We found that loading of Tde effectors onto their cognate carrier, the VgrG spike, is required for active T6SS secretion. Our data also suggest the assembly of the TssBC contractile sheath occurs only after Tde effectors are loaded onto the VgrG spike. The requirement of effector loading for efficient T6SS secretion was also validated in other A. tumefaciens strains. Such a mechanism may be used by bacteria as a strategy for efficacious T6SS firing. Given the prevalence of T6SS-encoding loci in host-associated bacteria, these findings inform on mechanisms that influence the composition of microbial communities and the services provided to hosts.
]]></description>
<dc:creator>Lien, Y.-W.</dc:creator>
<dc:creator>Wu, C.-F.</dc:creator>
<dc:creator>Bondage, D.</dc:creator>
<dc:creator>Lin, J.-S.</dc:creator>
<dc:creator>Shih, Y.-L.</dc:creator>
<dc:creator>Chang, J.</dc:creator>
<dc:creator>Lai, E.-M.</dc:creator>
<dc:date>2019-02-21</dc:date>
<dc:identifier>doi:10.1101/556712</dc:identifier>
<dc:title><![CDATA[Effector loading onto VgrG spike proteins is critical for the assembly of the type VI secretion system in Agrobacterium tumefaciens]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-02-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/574319v1?rss=1">
<title>
<![CDATA[
Phytoplasma SAP11 effector destabilization of TCP transcription factors differentially impact development and defence of Arabidopsis versus maize 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/574319v1?rss=1</link>
<description><![CDATA[
Phytoplasmas are insect-transmitted bacterial pathogens that colonize a wide range of plant species, including vegetable and cereal crops, and herbaceous and woody ornamentals. Phytoplasma-infected plants often show dramatic symptoms, including proliferation of shoots (witchs brooms), changes in leaf shapes and production of green sterile flowers (phyllody). Aster Yellows phytoplasma Witches Broom (AY-WB) infects dicots and its effector, secreted AYWB protein 11 (SAP11), was shown to be responsible for the induction of shoot proliferation and leaf shape changes of plants. SAP11 acts by destabilizing TEOSINTE BRANCHED 1-CYCLOIDEA-PROLIFERATING CELL FACTOR (TCP) transcription factors, particularly the class II TCPs of the CYCLOIDEA/TEOSINTE BRANCHED 1 (CYC/TB1) and CINCINNATA (CIN)-TCP clades. SAP11 homologs are also present in phytoplasmas that cause economic yield losses in monocot crops, such as maize, wheat and coconut. Here we show that a SAP11 homolog of Maize Bushy Stunt Phytoplasma (MBSP), which has a range primarily restricted to maize, destabilizes only TB1/CYC TCPs. SAP11MBSP and SAP11AYWB both induce axillary branching and SAP11AYWB also alters leaf development of Arabidopsis thaliana and maize. However, only in maize, SAP11MBSP prevents female inflorescence development, phenocopying maize tb1 lines, whereas SAP11AYWB prevents male inflorescence development and induces feminization of tassels. SAP11AYWB promotes fecundity of the AY-WB leafhopper vector on A. thaliana and modulates the expression of A. thaliana leaf defence response genes that are induced by this leafhopper, in contrast to SAP11MBSP. Neither of the SAP11 effectors promote fecundity of AY-WB and MBSP leafhopper vectors on maize. These data provide evidence that class II TCPs have overlapping but also distinct roles in regulating development and defence in a dicot and a monocot plant species that is likely to shape SAP11 effector evolution depending on the phytoplasma host range.nnAuthor summaryPhytoplasmas are parasites of a wide range of plant species and are transmitted by sap-feeding insects, such as leafhoppers. Phytoplasma-infected plants are often easily recognized because of their dramatic symptoms, including shoot proliferations (witchs brooms) and altered leaf shapes, leading to severe economic losses of crops, ornamentals and trees worldwide. We previously found that the virulence protein SAP11 of aster yellows witches broom phytoplasma (AY-WB) interferes with a specific group of plant transcription factors, named TCPs, leading to witches brooms and leaf shape changes of the model plant Arabidopsis thaliana. SAP11 has been characterized in a number of other phytoplasmas. However, it is not known how phytoplasmas and their SAP11 proteins modulate processes in crops, including cereals such as maize. We identified a SAP11 homolog in Maize bushy stunt phytoplasma (MBSP), a pathogen that can cause severe yield losses of maize. We found that SAP11 interactions with TCPs are conserved between maize and Arabidopsis, and that MBSP SAP11 interferes with less TCPs compared to AY-WB SAP11. This work provides new insights into how phytoplasmas change maize architecture and corn production. Moreover, we found that TCPs regulate leaf defence responses to phytoplasma leafhopper vectors in Arabidopsis, but not in maize.
]]></description>
<dc:creator>Pecher, P.</dc:creator>
<dc:creator>Moro, G.</dc:creator>
<dc:creator>Canale, M. C.</dc:creator>
<dc:creator>Capdevielle, S.</dc:creator>
<dc:creator>Singh, A.</dc:creator>
<dc:creator>MacLean, A.</dc:creator>
<dc:creator>Sugio, A.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:creator>Lopes, J. R. S.</dc:creator>
<dc:creator>Hogenhout, S. A.</dc:creator>
<dc:date>2019-03-12</dc:date>
<dc:identifier>doi:10.1101/574319</dc:identifier>
<dc:title><![CDATA[Phytoplasma SAP11 effector destabilization of TCP transcription factors differentially impact development and defence of Arabidopsis versus maize]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-03-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/576488v1?rss=1">
<title>
<![CDATA[
Characterization of coral-associated microbial aggregates (CAMAs) within tissues of the coral Acropora hyacinthus 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/576488v1?rss=1</link>
<description><![CDATA[
Bacterial diversity associated with corals has been studied extensively, however, localization of bacterial associations within the holobiont is still poorly resolved. Here we provide novel insight into the localization of coral-associated microbial aggregates (CAMAs) within tissues of the coral Acropora hyacinthus. In total, 318 and 308 CAMAs were characterized via histological and fluorescent in situ hybridization (FISH) approaches respectively, and shown to be distributed extensively throughout coral tissues collected from five sites in Japan and Australia. The densities of CAMAs within the tissues were negatively correlated with the distance from the coastline (i.e. lowest densities at offshore sites). CAMAs were randomly distributed across the six coral tissue regions investigated. Within each CAMA, bacterial cells had similar morphological characteristics, but bacterial morphologies varied among CAMAs, with at least five distinct types identified. Identifying the location of microorganisms associated with the coral host is a prerequisite for understanding their contributions to fitness. Localization of tissue-specific communities housed within CAMAs is particularly important, as these communities are potentially important contributors to vital metabolic functions of the holobiont.
]]></description>
<dc:creator>Wada, N.</dc:creator>
<dc:creator>Ishimochi, M.</dc:creator>
<dc:creator>Matsui, T.</dc:creator>
<dc:creator>Pollock, F. J.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:creator>Ainsworth, T. D.</dc:creator>
<dc:creator>Willis, B. L.</dc:creator>
<dc:creator>Mano, N.</dc:creator>
<dc:creator>Bourne, D. G.</dc:creator>
<dc:date>2019-03-14</dc:date>
<dc:identifier>doi:10.1101/576488</dc:identifier>
<dc:title><![CDATA[Characterization of coral-associated microbial aggregates (CAMAs) within tissues of the coral Acropora hyacinthus]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-03-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/577411v1?rss=1">
<title>
<![CDATA[
Population histories of the United States revealed through fine-scale migration and haplotype analysis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/577411v1?rss=1</link>
<description><![CDATA[
The population of the United States is shaped by centuries of migration, isolation, growth, and admixture between ancestors of global origins. Here, we assemble a comprehensive view of recent population history by studying the ancestry and population structure of over 32,000 individuals in the US using genetic, ancestral birth origin, and geographic data from the National Geographic Genographic Project. We identify migration routes and barriers that reflect historical demographic events. We also uncover the spatial patterns of relatedness in subpopulations through the combination of haplotype clustering, ancestral birth origin analysis, and local ancestry inference. Examples of these patterns include substantial substructure and heterogeneity in Hispanics/Latinos, isolation-by-distance in African Americans, elevated levels of relatedness and homozygosity in Asian immigrants, and fine-scale structure in European descents. Taken together, our results provide detailed insights into the genetic structure and demographic history of the diverse US population.
]]></description>
<dc:creator>Dai, C. L.</dc:creator>
<dc:creator>Vazifeh, M. M.</dc:creator>
<dc:creator>Yeang, C.-H.</dc:creator>
<dc:creator>Tachet, R.</dc:creator>
<dc:creator>Vilar, M. G.</dc:creator>
<dc:creator>Daly, M. J.</dc:creator>
<dc:creator>Ratti, C.</dc:creator>
<dc:creator>Martin, A. R.</dc:creator>
<dc:date>2019-03-14</dc:date>
<dc:identifier>doi:10.1101/577411</dc:identifier>
<dc:title><![CDATA[Population histories of the United States revealed through fine-scale migration and haplotype analysis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-03-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/578823v1?rss=1">
<title>
<![CDATA[
Selection of a Malignant Subpopulation from a Colorectal Cancer Cell Line 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/578823v1?rss=1</link>
<description><![CDATA[
Colorectal cancer (CRC) is a leading cause of death from cancer worldwide. Thus, there is an emerging need for new experimental models that allow identification and validation of biomarkers for CRC-specific progression. In this study, we propose a repeated sphere-forming assay as a strategy to select a malignant subpopulation from a CRC line, HCT116. We validated our assay by confirming that three canonical stemness markers, Nanog, Oct4, and Lgr5, were up-regulated in the sphere state at every generation of the selection assay. The resulting line, after eight rounds of selection, exhibited an increased sphere-forming capacity in vitro and tumorgenicity in vivo. Furthermore, dipeptidase 1 (DPEP1) was identified as the major differentially expressed gene in the selected clone, and depletion of DPEP1 suppressed the elevated sphere-forming capacity in vitro and tumorgenicity in vivo. Overall, we have established an experimental strategy for the isolation of a malignant subpopulation from a CRC cell line. Results from our model also suggested that DPEP1 can serve as a promising prognostic biomarker for CRC.
]]></description>
<dc:creator>Lai, P.-L.</dc:creator>
<dc:creator>Chen, T.-C.</dc:creator>
<dc:creator>Feng, C.-Y.</dc:creator>
<dc:creator>Lin, H.</dc:creator>
<dc:creator>Wu, N.</dc:creator>
<dc:creator>Chen, Y.</dc:creator>
<dc:creator>Hsiao, M.</dc:creator>
<dc:creator>Lu, J.</dc:creator>
<dc:creator>Huang, H.-C.</dc:creator>
<dc:date>2019-03-15</dc:date>
<dc:identifier>doi:10.1101/578823</dc:identifier>
<dc:title><![CDATA[Selection of a Malignant Subpopulation from a Colorectal Cancer Cell Line]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-03-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/579870v1?rss=1">
<title>
<![CDATA[
Evidence of extensive intraspecific noncoding reshuffling in a 169-kb mitochondrial genome of a basidiomycetous fungus 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/579870v1?rss=1</link>
<description><![CDATA[
Comparative genomics of fungal mitochondrial genomes (mitogenomes) have revealed a remarkable pattern of rearrangement between and within major phyla owing to horizontal gene transfer (HGT) and recombination. The role of recombination was exemplified at a finer evolutionary time scale in basidiomycetes group of fungi as they display a diversity of mitochondrial DNA (mtDNA) inheritance patterns. Here, we assembled mitogenomes of six species from the Hymenochaetales order of basidiomycetes and examined 59 mitogenomes from two genetic lineages of Pyrrhoderma noxium. Gene order is largely colinear while intergene regions are major determinants of mitogenome size variation. Substantial sequence divergence was found in shared introns consistent with high HGT frequency observed in yeasts, but we also identified a rare case where an intron was retained in five species since speciation. In contrast to the hyperdiversity observed in nuclear genomes of P. noxium, mitogenomes intraspecific polymorphisms at protein coding sequences are extremely low. Phylogeny based on introns revealed turnover as well as exchange of introns between two lineages. Strikingly, some strains harbor a mosaic origin of introns from both lineages. Analysis of intergenic sequence indicated substantial differences between and within lineages, and an expansion may be ongoing as a result of exchange between distal intergenes. These findings suggest that the evolution in mtDNAs is usually lineage specific but chimeric mitotypes are frequently observed, thus capturing the possible evolutionary processes shaping mitogenomes in a basidiomycete. The large mitogenome sizes reported in various basidiomycetes appear to be a result of interspecific reshuffling of intergenes.
]]></description>
<dc:creator>Lee, H.-H.</dc:creator>
<dc:creator>Ke, H.-M.</dc:creator>
<dc:creator>Lin, C.-Y. I.</dc:creator>
<dc:creator>Lee, J. J.</dc:creator>
<dc:creator>Chung, C.-L.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2019-03-16</dc:date>
<dc:identifier>doi:10.1101/579870</dc:identifier>
<dc:title><![CDATA[Evidence of extensive intraspecific noncoding reshuffling in a 169-kb mitochondrial genome of a basidiomycetous fungus]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-03-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/580803v1?rss=1">
<title>
<![CDATA[
Selection and gene flow shape niche-associated copy-number variation of pheromone receptor genes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/580803v1?rss=1</link>
<description><![CDATA[
From quorum sensing in bacteria to pheromone signaling in social insects, chemical communication mediates interactions among individuals in a local population. In Caenorhabditis elegans, ascaroside pheromones can dictate local population density, in which high levels of pheromones inhibit the reproductive maturation of individuals. Little is known about how natural genetic diversity affects the pheromone responses of individuals from diverse habitats. Here, we show that a niche-associated copy-number variation (CNV) of pheromone receptor genes contributes to natural differences in pheromone responses. We found putative loss-of-function deletions that reduce copy number of duplicated pheromone receptor genes (srg-36 and srg-37), which were shown previously to be selected in population-dense laboratory cultures. A common natural deletion in the less functional copy (srg-37) arose from a single ancestral population that spread throughout the world and underlies reduced pheromone sensitivity across the global C. elegans population. This deletion is enriched in wild strains that were isolated from a rotting fruit niche, where proliferating populations are often found. Taken together, these results demonstrate that selection and gene flow together shape the copy number of pheromone receptor genes in natural C. elegans populations to facilitate local adaptation to diverse niches.
]]></description>
<dc:creator>Lee, D.</dc:creator>
<dc:creator>Zdraljevic, S.</dc:creator>
<dc:creator>Cook, D. E.</dc:creator>
<dc:creator>Frezal, L.</dc:creator>
<dc:creator>Hsu, J.-C.</dc:creator>
<dc:creator>Sterken, M. G.</dc:creator>
<dc:creator>Riksen, J. A. G.</dc:creator>
<dc:creator>Wang, J.</dc:creator>
<dc:creator>Kammenga, J. E.</dc:creator>
<dc:creator>Braendle, C.</dc:creator>
<dc:creator>Felix, M.-A.</dc:creator>
<dc:creator>Schroeder, F. C.</dc:creator>
<dc:creator>Andersen, E. C.</dc:creator>
<dc:date>2019-03-18</dc:date>
<dc:identifier>doi:10.1101/580803</dc:identifier>
<dc:title><![CDATA[Selection and gene flow shape niche-associated copy-number variation of pheromone receptor genes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-03-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/591479v1?rss=1">
<title>
<![CDATA[
Rule-governed Dynamic Stochastic Equilibration of Multicellular Motion In Vivo During Olfactory Neurogenesis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/591479v1?rss=1</link>
<description><![CDATA[
The complexity of patterning during organ-wide stem cell migration and differentiation can be challenging to interpret quantitatively. Here, we track neural crest (NC) and ectodermal placode-derived progenitor movements in vivo, for hundreds of cells, implement unbiased algorithmic approaches to extract biologically meaningful information, and discover cell-cell and lineage-lineage coordination between progenitors that form olfactory sensory neurons (OSNs) during zebrafish embryogenesis. Our approach discriminates between NC- and placode-derived contributions and segregates ingressing NC cells into two previously unidentified subtypes termed  trend and  dispersed lineages. Our analyses indicate that NC and placodal progenitor migration and intercalation are coordinated by at least two types of collective behavior: spatiotemporal exclusion and elastic tethering, akin to a push-pull mechanism. A stochastic equilibrium model accurately represents the interactions of NC and placode-derived lineages. Our approach provides insights into the coordination of dual-origin lineages during vertebrate olfactory neurogenesis and offers an algorithmic toolkit for probing multicellular coordination in vivo.nnO_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY Graphical Abstract C_FIG_DISPLAY
]]></description>
<dc:creator>Warrier, V.</dc:creator>
<dc:creator>Cluzeau, C.</dc:creator>
<dc:creator>Chen, B.-C.</dc:creator>
<dc:creator>Green-Saxena, A.</dc:creator>
<dc:creator>Bergey, D. E.</dc:creator>
<dc:creator>Betzig, E.</dc:creator>
<dc:creator>Saxena, A.</dc:creator>
<dc:date>2019-03-28</dc:date>
<dc:identifier>doi:10.1101/591479</dc:identifier>
<dc:title><![CDATA[Rule-governed Dynamic Stochastic Equilibration of Multicellular Motion In Vivo During Olfactory Neurogenesis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-03-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/621037v1?rss=1">
<title>
<![CDATA[
Structural basis for the differential regulatory roles of the PDZ domain in C-terminal processing proteases 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/621037v1?rss=1</link>
<description><![CDATA[
Carboxyl (C)-terminal processing proteases (CTPs) participate in protective and regulatory proteolysis in bacteria. The PDZ domain is central to the activity of CTPs but plays inherently different regulatory roles. For example, the PDZ domain inhibits the activity of the signaling protease CtpB by blocking the active site but is required for the activation of Prc (or Tsp), a tail-specific protease that degrades the ssrA-tagged proteins. Here, by structural and functional analysis we show that in the unliganded resting state of Prc, the PDZ domain is docked inside the bowl-shaped scaffold without contacting the active site, which is kept in a default misaligned conformation. In Prc, a hydrophobic substrate sensor distinct from CtpB engages substrate binding to the PDZ domain and triggers a structural remodeling to align the active site residues. Therefore, this work reveals the structural basis for understanding the contrasting roles of the PDZ domain in the regulation of CTPs.
]]></description>
<dc:creator>Chueh, C.-K.</dc:creator>
<dc:creator>Som, N.</dc:creator>
<dc:creator>Ke, L.-C.</dc:creator>
<dc:creator>Ho, M.-R.</dc:creator>
<dc:creator>Reddy, M.</dc:creator>
<dc:creator>Chang, C.-I.</dc:creator>
<dc:date>2019-04-27</dc:date>
<dc:identifier>doi:10.1101/621037</dc:identifier>
<dc:title><![CDATA[Structural basis for the differential regulatory roles of the PDZ domain in C-terminal processing proteases]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-04-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/622696v1?rss=1">
<title>
<![CDATA[
Plant A20/AN1 proteins coordinate different immune responses including RNAi pathway for antiviral immunity 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/622696v1?rss=1</link>
<description><![CDATA[
Salicylic acid (SA)-mediated immunity plays important roles in combating virus in plants. Two plant stress associated protein (SAPs) containing dual A20/AN1 zinc-finger domain were found to play important roles in SA-mediated immunity; however, detailed mechanisms remain elusive. In this study, another orchid homolog gene of Pha13, Pha21, was analyzed. Pha21 confers antiviral immunity in both transgenic orchid and Arabidopsis overexpressing Pha21. Expression of Pha21 is early-induced by SA treatment, and is involved in the expression of the orchid homolog of the master regulator NPR1. Pha21 but not Pha13 is involved in the expression of key RNAi-related genes, Dicer-like nuclease 4 (DCL4) and Argonaut 1 (AGO1) in orchids. The involvement of SAPs in expression of orchid DCL4 and AGO1 is not limited to orchid, as AtSAP5 also plays essential role in the expression of Arabidopsis DCL4 and AGO1. However, unlike Pha13 and AtSAP5, Pha21 does not play positive role in the expression of orchid homolog gene of RNA-dependent RNA polymerase 1 (RdR1), an important gene in RNAi pathway. Pha21 can be found localized in the nucleus, and confers self-E3 ligase and ubiquitin binding activities. Functional domain analysis revealed that both A20 and AN1 domains of Pha21 are required for decreasing virus accumulation, and the AN1 domain plays a more important role in the expression of orchid DCL4. Collectively, our data suggests SA regulated SAPs play important roles in antiviral immunity and is involved in delicate regulation of key genes in RNAi-mediated pathway.nnIMPORTANCESalicylic acid (SA)-mediated antiviral immunity plays an important role to protect plants from virus infection; however, the detailed mechanisms remain elusive. We previously demonstrated that two plant A20/AN1 proteins, orchid Pha13 and Arabidopsis AtSAP5, function similarly and serve as an important hub to regulate SA-mediated antiviral immunity. In this study, we identified another orchid A20/AN1 protein, Pha21, which is involved in SA-mediated antiviral immunity. In contrast to Pha13 and AtSAP5, Pha21 plays minor negative roles in the expression of PhaRdR1 (orchid homolog of RNA-dependent RNA polymerase 1). However, Pha21 and AtSAP5, but not Pha13, are involved in the expression of important players in RNAi pathway, Dicer-like nuclease 4 (DCL4) and Argonaut 1 (AGO1), in orchid and Arabidopsis. Our data demonstrates that plant A20/AN1 proteins are conserved players in SA-mediated antiviral resistance among plants, and provide links between the A20/AN1 proteins and the RNAi pathway.
]]></description>
<dc:creator>Chang, L.</dc:creator>
<dc:creator>Chang, H.-H.</dc:creator>
<dc:creator>Chiu, Y.-S.</dc:creator>
<dc:creator>Chang, J.-C.</dc:creator>
<dc:creator>Hsu, D.-W.</dc:creator>
<dc:creator>Tzean, Y.</dc:creator>
<dc:creator>Cheng, A.-P.</dc:creator>
<dc:creator>Lu, H.-C.</dc:creator>
<dc:creator>Yeh, H.-H.</dc:creator>
<dc:date>2019-04-29</dc:date>
<dc:identifier>doi:10.1101/622696</dc:identifier>
<dc:title><![CDATA[Plant A20/AN1 proteins coordinate different immune responses including RNAi pathway for antiviral immunity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-04-29</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/625533v1?rss=1">
<title>
<![CDATA[
Sonogenetic modulation of cellular activities using an engineered auditory-sensing protein 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/625533v1?rss=1</link>
<description><![CDATA[
Biomolecules that respond to different external stimuli enable the remote control of genetically modified cells. Chemogenetics and optogenetics, two tools that can control cellular activities via synthetic chemicals or photons, respectively, have been widely used to elucidate underlying physiological processes. These methods are, however, very invasive, have poor penetrability, or low spatiotemporal precision, attributes that hinder their use in therapeutic applications. We report herein a sonogenetic approach that can manipulate target cell activities by focused ultrasound stimulation. This system requires an ultrasound-responsive protein derived from an engineered auditory-sensing protein prestin. Heterogeneous expression of mouse prestin containing two parallel amino acid substitutions, N7T and N308S, that frequently exist in prestins from echolocating species endowed transfected mammalian cells with the ability to sense ultrasound. An ultrasound pulse of low frequency and low pressure efficiently evoked cellular calcium responses after transfecting with prestin(N7T, N308S). Moreover, pulsed ultrasound can also non-invasively stimulate target neurons expressing prestin(N7T, N308S) in deep regions of mice brains. Our study delineates how an engineered auditory-sensing protein can cause mammalian cells to sense ultrasound stimulation. Moreover, owing to the great penetration of low-frequency ultrasound ([~]400 mm in depth), our sonogenetic tools will serve as new strategies for non-invasive therapy in deep tissues of large animals like primates.
]]></description>
<dc:creator>Huang, Y.-S.</dc:creator>
<dc:creator>Fan, C.-H.</dc:creator>
<dc:creator>Hsu, N.</dc:creator>
<dc:creator>Wu, C.-Y.</dc:creator>
<dc:creator>Chang, C.-Y.</dc:creator>
<dc:creator>Hong, S.-R.</dc:creator>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Wu, A. Y.-T.</dc:creator>
<dc:creator>Guo, V.</dc:creator>
<dc:creator>Chiang, Y.-C.</dc:creator>
<dc:creator>Hsu, W.-C.</dc:creator>
<dc:creator>Chiu, N.-H.</dc:creator>
<dc:creator>Chen, L.</dc:creator>
<dc:creator>Lai, C. P.-K.</dc:creator>
<dc:creator>Yeh, C.-K.</dc:creator>
<dc:creator>LIN, Y. C.</dc:creator>
<dc:date>2019-05-03</dc:date>
<dc:identifier>doi:10.1101/625533</dc:identifier>
<dc:title><![CDATA[Sonogenetic modulation of cellular activities using an engineered auditory-sensing protein]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-05-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/627794v1?rss=1">
<title>
<![CDATA[
Successive passaging of a plant-associated microbiome reveals robust habitat and host genotype-dependent selection 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/627794v1?rss=1</link>
<description><![CDATA[
There is increasing interest in the plant microbiome as it relates to both plant health and agricultural sustainability. One key unanswered question is whether we can select for a plant microbiome that is robust after colonization of target hosts. We used a successive passaging experiment to address this question by selecting upon the tomato phyllosphere microbiome. Beginning with a diverse microbial community generated from field-grown tomato plants, we inoculated replicate plants across five plant genotypes for four eight-week long passages, sequencing the microbial community at each passage. We observed consistent shifts in both the bacterial (16S amplicon sequencing) and fungal (ITS amplicon sequencing) communities across replicate lines over time, as well as a general loss of diversity over the course of the experiment suggesting that much of the naturally observed microbial community in the phyllosphere is likely transient or poorly adapted. We found that both host genotype and environment shape microbial composition, but the relative importance of genotype declines through time. Furthermore, using a community coalescence experiment, we found that the bacterial community from the end of the experiment was robust to invasion by the starting bacterial community. These results highlight that selecting for a stable microbiome that is well adapted to a particular host environment is indeed possible, emphasizing the great potential of this approach in agriculture and beyond.nnSignificance StatementThere is great interest in selecting for host-associated microbiomes that confer particular functions to their host, and yet it remains unknown whether selection for a robust and stable microbiome is possible. Here, we use a microbiome passaging approach to measure the impact of host-mediated selection on the tomato phyllosphere (above ground) microbiome. We find robust community selection across replicate lines that is shaped by plant host genotype in early passages, but changes in a genotype-independent manner in later passages. Work such as ours is crucial to understanding the general principles governing microbiome assembly and adaptation, and is widely applicable to both sustainable agriculture and microbiome-related medicine.
]]></description>
<dc:creator>Morella, N. M.</dc:creator>
<dc:creator>Weng, F. C.-H.</dc:creator>
<dc:creator>Joubert, P. M.</dc:creator>
<dc:creator>Metcalf, C. J. E.</dc:creator>
<dc:creator>Lindow, S.</dc:creator>
<dc:creator>Koskella, B.</dc:creator>
<dc:date>2019-05-05</dc:date>
<dc:identifier>doi:10.1101/627794</dc:identifier>
<dc:title><![CDATA[Successive passaging of a plant-associated microbiome reveals robust habitat and host genotype-dependent selection]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-05-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/641258v1?rss=1">
<title>
<![CDATA[
Characterization of Single Protein Dynamics in Cell Plasma Membrane Derived Polymer Cushioned Lipid Bilayers 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/641258v1?rss=1</link>
<description><![CDATA[
Native cell membrane derived supported lipid bilayers (SLBs) are emerging platforms that have broad applications ranging from fundamental research to next-generation biosensors. Central to the success of the platform is proper accommodation of membrane proteins so that their dynamics and functions are preserved. Polymer cushions have been commonly employed to avoid direct contact of the bilayer membrane to the supporting substrate, and thus the mobility of transmembrane proteins is maintained. However, little is known about how the polymer cushion affects the absolute mobility of membrane molecules. Here, we characterized the dynamics of single membrane proteins in polymer-cushioned lipid bilayers derived from cell plasma membranes and investigated the effects of polymer length. Three membrane proteins of distinct structures, i.e., GPI-anchored protein, single-pass transmembrane protein CD98 heavy chain, and seven-pass transmembrane protein SSTR3, were fused with green fluorescence proteins (GFPs) and their dynamics were measured by fluorescence single-molecule tracking. An automated data acquisition was implemented to study the effects of PEG polymer length to protein dynamics with large statistics. Our data showed that increasing the PEG polymer length (molecular weight from 1,000 to 5,000) enhanced the mobile fraction of the membrane proteins. Moreover, the diffusion coefficients of transmembrane proteins were raised by increasing the polymer length, whereas the diffusion coefficient of GPI-anchored protein remained almost identical with different polymer lengths. Importantly, the diffusion coefficients of the three membrane proteins became identical (2.5 m2/s approximately) in the cushioned membrane with the longest polymer length (molecular weight of 5,000), indicating that the SLBs were fully suspended from the substrate by the polymer cushion at the microscopic length scale. Transient confinements were observed from all three proteins, and increasing the polymer length reduced the tendency of transient confinements. The measured dynamics of membrane proteins were found to be nearly unchanged after depletion of cholesterol, suggesting that the observed immobilization and transient confinement were not due to cholesterol-enriched membrane nanodomains (lipid rafts). Our single-molecule dynamics elucidate the biophysical properties of polymer cushioned plasma membrane bilayers that are potentially useful for future developments of membrane-based biosensors and analytical assays.
]]></description>
<dc:creator>Wong, W. C.</dc:creator>
<dc:creator>Juo, J.-Y.</dc:creator>
<dc:creator>Liao, Y.-H.</dc:creator>
<dc:creator>Cheng, C.-Y.</dc:creator>
<dc:creator>Lin, C.-H.</dc:creator>
<dc:creator>Hsieh, C.-L.</dc:creator>
<dc:date>2019-05-17</dc:date>
<dc:identifier>doi:10.1101/641258</dc:identifier>
<dc:title><![CDATA[Characterization of Single Protein Dynamics in Cell Plasma Membrane Derived Polymer Cushioned Lipid Bilayers]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-05-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/644443v1?rss=1">
<title>
<![CDATA[
Two different pathways for initiation of Trichoderma reesei Rad51-only meiotic recombination 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/644443v1?rss=1</link>
<description><![CDATA[
BackgroundMeiotic recombination is mainly, but not exclusively, initiated by Spo11-induced double strand breaks (DSBs) in some sexual eukaryotes. DSBs are repaired by one or two RecA-like recombinases (ubiquitous Rad51 and meiosis-specific Dmc1). In yeast and mammals, Dmc1 is superior to Rad51 in tolerating mismatched sequences during highly polymorphic hybrid meiosis. The mechanisms underlying Rad51-only meiotic recombination remain less studied.nnResultsThe Rad51-only filamentous fungus Trichoderma reesei has only one spo11 gene. Removal of spo11 from T. reesei genome does not affect normal sexual development, meiosis or chromosome synapsis, but results in decrease of interhomolog recombination products to 70%, crossover homeostasis and lower genetic interference. Our results also suggest that T. reesei Rad51, like yeast and mammalian Dmc1 (but not Rad51), can tolerate mismatched sequences during meiotic recombination. Moreover, Topoisomerase II might act redundantly (and predominantly) with Spo11 to initiate meiotic recombination.nnConclusionWe suggest that T. reesei is an emerging model for studying Spo11-independent and Rad51-only meiosis.
]]></description>
<dc:creator>Li, W.-C.</dc:creator>
<dc:creator>Chuang, Y.-C.</dc:creator>
<dc:creator>Chen, C.-L.</dc:creator>
<dc:creator>Wang, C.-L.</dc:creator>
<dc:creator>Chen, Y.-J.</dc:creator>
<dc:creator>Timofejeva, L.</dc:creator>
<dc:creator>Pong, W.-L.</dc:creator>
<dc:creator>Wang, T.-F.</dc:creator>
<dc:date>2019-05-21</dc:date>
<dc:identifier>doi:10.1101/644443</dc:identifier>
<dc:title><![CDATA[Two different pathways for initiation of Trichoderma reesei Rad51-only meiotic recombination]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-05-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/656140v1?rss=1">
<title>
<![CDATA[
Predicting the prognosis of non-small cell lung cancer by integrating microarray and clinical data with deep learning 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/656140v1?rss=1</link>
<description><![CDATA[
AO_SCPLOWBSTRACTC_SCPLOWNon-small cell lung cancer (NSCLC) is one of the most common lung cancers worldwide. Accurate prognostic stratification of NSCLC can become an important clinical reference when designing therapeutic strategies for cancer patients. With this clinical application in mind, we developed a deep neural network (DNN) combining heterogeneous data sources of gene expression and clinical data to accurately predict the prognosis of NSCLC patients. Based on microarray data from a cohort set (614 patients), seven well-known NSCLC markers were used to group patients into marker- and marker+ subgroups. Using a systems biology approach, prognosis relevance values (PRV) were then calculated to select eight additional novel prognostic gene markers. Gene markers along with clinical data were then used to develop an integrative DNN via bimodal learning to predict the 5-year survival rate of NSCLC patients with tremendously high accuracy (AUC: 0.8163, accuracy: 75.44%), which is superior to all other existing methods based on AUC. Using the capability of deep learning, we believe that our predicted cancer prognosis can be a promising index helping oncologists and physicians develop personalized therapy and build the foundation of precision medicine in the future.
]]></description>
<dc:creator>Lai, Y.-H.</dc:creator>
<dc:creator>Chen, W.-N.</dc:creator>
<dc:creator>Hsu, T.-C.</dc:creator>
<dc:creator>Lin, C.</dc:creator>
<dc:creator>Tsao, Y.</dc:creator>
<dc:creator>Wu, S.</dc:creator>
<dc:date>2019-06-11</dc:date>
<dc:identifier>doi:10.1101/656140</dc:identifier>
<dc:title><![CDATA[Predicting the prognosis of non-small cell lung cancer by integrating microarray and clinical data with deep learning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-06-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/659672v1?rss=1">
<title>
<![CDATA[
Fungal Feature Tracker (FFT): A tool for quantitatively characterizing the morphology and growth of filamentous fungi 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/659672v1?rss=1</link>
<description><![CDATA[
Filamentous fungi are ubiquitous in nature and serve as important biological models in various scientific fields including genetics, cell biology, ecology, evolution, and chemistry. A significant obstacle in studying filamentous fungi is the lack of tools for characterizing their growth and morphology in an efficient and quantitative manner. Consequently, assessments of the growth of filamentous fungi are often subjective and imprecise. In order to remedy this problem, we developed Fungal Feature Tracker (FFT), a user-friendly software comprised of different image analysis tools to automatically quantify different fungal characteristics, such as spore number, spore morphology, and measurements of total length, number of hyphal tips and the area covered by the mycelium. In addition, FFT can recognize and quantify specialized structures such as the traps generated by nematode-trapping fungi, which could be tuned to quantify other distinctive fungal structures in different fungi. We present a detailed characterization and comparison of a few fungal species as a case study to demonstrate the capabilities and potential of our software. Using FFT, we were able to quantify various features at strain and species level, such as mycelial growth over time and the length and width of spores, which would be difficult to track using classical approaches. In summary, FFT is a powerful tool that enables quantitative measurements of fungal features and growth, allowing objective and precise characterization of fungal phenotypes.nnAuthor SummaryOne of the main obstacles to study filamentous fungi is the lack of tools for characterizing fungal phenotypes in an efficient and quantitative manner. Assessment of cell growth and numbers rely on tedious manual techniques that often result in subjective and imprecise measurements. In response to those limitations, we developed Fungal Feature Tracker (FFT), a user-friendly software that allows researchers to characterize different phenotypic features of filamentous fungi such as sporulation, spore morphology and mycelial growth. In addition, FFT can recognize and quantify other fungal structures including the fungal traps developed by nematode-trapping fungi. In order to show the capabilities and potential of our software, we conducted a detailed characterization and comparison of different fungal species. Our comparison relies on a series of experimental set-ups using standard and easily accessible equipment to ensure reproducibility in other laboratories. In summary, FFT is an easy to use and powerful tool that can quantitatively characterize fungal morphology, cell number and quantitatively measures the filamentous growth, which will allow advance our understanding of the growth and biology of filamentous fungi.
]]></description>
<dc:creator>Vidal-Diez de Ulzurrun, G.</dc:creator>
<dc:creator>Huang, T.-Y.</dc:creator>
<dc:creator>Chang, C.-W.</dc:creator>
<dc:creator>Lin, H.-C.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:date>2019-06-04</dc:date>
<dc:identifier>doi:10.1101/659672</dc:identifier>
<dc:title><![CDATA[Fungal Feature Tracker (FFT): A tool for quantitatively characterizing the morphology and growth of filamentous fungi]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-06-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/672881v1?rss=1">
<title>
<![CDATA[
Working out Classic Examples of Metabolic Networks Structural Analysis with Wolfram Language 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/672881v1?rss=1</link>
<description><![CDATA[
Metabolic reaction networks usually include a large number of enzymatic reaction steps. Nowadays, people desire to work on larger and larger metabolic networks, in the research fields of for example systems or synthetic biology. With the growing sizes of the metabolic networks considered, it is more and more tedious and cumbersome for a human to perform routine processing and analysis of the networks. Computer programs that automate metabolic analysis will be beneficial. In this work, the use of Wolfram Language to automate metabolic analysis is demonstrated. Although there are many different analyses to perform in a metabolic network analysis project, the analysis of metabolic network structure may be the most common first step and one of the most troublesome tasks. Therefore, instead of demonstrating a lot of different analyses, the structures of a few important examples from one chapter in the classic textbook by Professor Gregory Stephanopoulos are analyzed with a program written in Wolfram Language and the models are book-kept in JSON format.
]]></description>
<dc:creator>Liang, K. K.</dc:creator>
<dc:date>2019-06-18</dc:date>
<dc:identifier>doi:10.1101/672881</dc:identifier>
<dc:title><![CDATA[Working out Classic Examples of Metabolic Networks Structural Analysis with Wolfram Language]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-06-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/685172v1?rss=1">
<title>
<![CDATA[
Identification of type 2 diabetes loci in 433,540 East Asian individuals 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/685172v1?rss=1</link>
<description><![CDATA[
Meta-analyses of genome-wide association studies (GWAS) have identified >240 loci associated with type 2 diabetes (T2D), however most loci have been identified in analyses of European-ancestry individuals. To examine T2D risk in East Asian individuals, we meta-analyzed GWAS data in 77,418 cases and 356,122 controls. In the main analysis, we identified 298 distinct association signals at 178 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 56 loci newly implicated in T2D predisposition. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. New associations include signals in/near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect muscle and adipose differentiation. At another locus, eQTLs at two overlapping T2D signals act through two genes, NKX6-3 and ANK1, in different tissues. Association studies in diverse populations identify additional loci and elucidate disease genes, biology, and pathways.nnType 2 diabetes (T2D) is a common metabolic disease primarily caused by insufficient insulin production and/or secretion by the pancreatic {beta} cells and insulin resistance in peripheral tissues1. Most genetic loci associated with T2D have been identified in populations of European (EUR) ancestry, including a recent meta-analysis of genome-wide association studies (GWAS) of nearly 900,000 individuals of European ancestry that identified >240 loci influencing the risk of T2D2. Differences in allele frequency between ancestries affect the power to detect associations within a population, particularly among variants rare or monomorphic in one population but more frequent in another3,4. Although smaller than studies in European populations, a recent T2D meta-analysis in almost 200,000 Japanese individuals identified 28 additional loci4. The relative contributions of different pathways to the pathophysiology of T2D may also differ between ancestry groups. For example, in East Asian (EAS) populations, T2D prevalence is greater than in European populations among people of similar body mass index (BMI) or waist circumference5. We performed the largest meta-analysis of East Asian individuals to identify new genetic associations and provide insight into T2D pathogenesis.
]]></description>
<dc:creator>Spracklen, C. N.</dc:creator>
<dc:creator>Horikoshi, M.</dc:creator>
<dc:creator>Kim, Y. J.</dc:creator>
<dc:creator>Lin, K.</dc:creator>
<dc:creator>Bragg, F.</dc:creator>
<dc:creator>Moon, S.</dc:creator>
<dc:creator>Suzuki, K.</dc:creator>
<dc:creator>Tam, C.</dc:creator>
<dc:creator>Tabara, Y.</dc:creator>
<dc:creator>Kwak, S.-H.</dc:creator>
<dc:creator>Takeuchi, F.</dc:creator>
<dc:creator>Long, J.</dc:creator>
<dc:creator>Lim, V.</dc:creator>
<dc:creator>Chai, J.-F.</dc:creator>
<dc:creator>Chen, C.-H.</dc:creator>
<dc:creator>Nakatochi, M.</dc:creator>
<dc:creator>Yao, J.</dc:creator>
<dc:creator>Choi, H. S.</dc:creator>
<dc:creator>Iyengar, A. K.</dc:creator>
<dc:creator>Perrin, H. J.</dc:creator>
<dc:creator>Brotman, S. M.</dc:creator>
<dc:creator>van de Bunt, M.</dc:creator>
<dc:creator>Gloyn, A. L.</dc:creator>
<dc:creator>Below, J. L.</dc:creator>
<dc:creator>Boehnke, M.</dc:creator>
<dc:creator>Bowden, D. W.</dc:creator>
<dc:creator>Chambers, J. C.</dc:creator>
<dc:creator>Mahajan, A.</dc:creator>
<dc:creator>McCarthy, M. I.</dc:creator>
<dc:creator>Ng, M. C.</dc:creator>
<dc:creator>Petty, L. E.</dc:creator>
<dc:creator>Zhang, W.</dc:creator>
<dc:creator>Morris, A. P.</dc:creator>
<dc:creator>Adair, L. S.</dc:creator>
<dc:creator>Bian, Z.</dc:creator>
<dc:creator>Chan, J.</dc:creator>
<dc:creator>Chang, L.-C.</dc:creator>
<dc:creator>Chee, M.-L.</dc:creator>
<dc:creator>Chen, Y.-D. I.</dc:creator>
<dc:creator>Chen, Y.-T.</dc:creator>
<dc:creator>Chen, Z.</dc:creator>
<dc:creator>Chuang, L.-M.</dc:creator>
<dc:creator>Du, S.</dc:creator>
<dc:creator>Gordon-Larsen, P.</dc:creator>
<dc:creator>Gross, M.</dc:creator>
<dc:creator>Guo, X.</dc:creator>
<dc:creator>Guo</dc:creator>
<dc:date>2019-06-28</dc:date>
<dc:identifier>doi:10.1101/685172</dc:identifier>
<dc:title><![CDATA[Identification of type 2 diabetes loci in 433,540 East Asian individuals]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-06-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/710707v1?rss=1">
<title>
<![CDATA[
Genome analysis of the steroid-degrading denitrifying Denitratisoma oestradiolicum DSM 16959 and Denitratisoma sp. strain DHT3 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/710707v1?rss=1</link>
<description><![CDATA[
Steroid hormones (androgens and estrogens) are crucial for development, reproduction, and communication of multicellular eukaryotes. The ubiquitous distribution and persistence of steroid hormones in our ecosystems have become an environmental issue due to the adverse effects on wildlife and humans upon long-term exposure. Microbial degradation is critical for the removal of steroid hormones from ecosystems. The aerobic degradation pathways for androgens and estrogens and the anaerobic degradation pathway for androgen have been studied into some details; however, the mechanism for anaerobic estrogen degradation remains completely unknown. Here, we presented the circular genomes of D. oestradiolicum DSM 16959 and Denitratisoma sp. strain DHT3, two betaproteobacteria capable of anaerobic estrogen degradation. We identified the genes involved in steroid transformation and in the anaerobic 2,3-seco pathway in both genomes. Additionally, the comparative genomic analysis revealed that genes exclusively represented in estrogen-degrading anaerobes might play a role in anaerobic estrogen catabolism.
]]></description>
<dc:creator>Chen, Y.-L.</dc:creator>
<dc:creator>Wei, S.</dc:creator>
<dc:creator>Chiang, Y.-R.</dc:creator>
<dc:date>2019-07-22</dc:date>
<dc:identifier>doi:10.1101/710707</dc:identifier>
<dc:title><![CDATA[Genome analysis of the steroid-degrading denitrifying Denitratisoma oestradiolicum DSM 16959 and Denitratisoma sp. strain DHT3]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-07-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/712331v1?rss=1">
<title>
<![CDATA[
Genome-wide, integrative analysis implicates circular RNA dysregulation in autism and the corresponding circular RNA-microRNA-mRNA regulatory axes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/712331v1?rss=1</link>
<description><![CDATA[
Circular RNAs (circRNAs), a class of long non-coding RNAs, are known to be enriched in mammalian brain and neural tissues. While the effects of regulatory genetic variants on gene expression in autism spectrum disorder (ASD) have been widely reported, the role of circRNAs in ASD remains largely unknown. Here, we performed genome-wide circRNA expression profiling in post-mortem brains from individuals with ASD and controls and identified 60 circRNAs and three co-regulated modules that were perturbed in ASD. By integrating circRNA, microRNA, and mRNA dysregulation data derived from the same cortex samples, we identified 8,170 ASD-associated circRNA-microRNA-mRNA interactions. Putative targets of the axes were enriched for ASD risk genes and genes encoding inhibitory postsynaptic density (PSD) proteins, but not for genes implicated in monogenetic forms of other brain disorders or genes encoding excitatory PSD proteins. This result reflects the previous observation that ASD-derived organoids exhibit overproduction of inhibitory neurons. We further confirmed that some ASD risk genes (NLGN1, STAG1, HSD11B1, VIP, and UBA6) were indeed regulated by an upregulated circRNA (circARID1A) via sponging a downregulated microRNA (miR-204-3p) in human neuronal cells. We provided a systems-level view of landscape of circRNA regulatory networks in ASD cortex samples. We also provided multiple lines of evidence for the functional role of ASD for circRNA dysregulation and a rich set of ASD-associated circRNA candidates and the corresponding circRNA-miRNA-mRNA axes, particularly those involving ASD risk genes. Our findings thus support a role for circRNA dysregulation and the corresponding circRNA-microRNA-mRNA axes in ASD pathophysiology.
]]></description>
<dc:creator>Chen, Y.-J.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Mai, T.-L.</dc:creator>
<dc:creator>Chuang, C.-F.</dc:creator>
<dc:creator>Gupta, S. K.</dc:creator>
<dc:creator>Yen, L.</dc:creator>
<dc:creator>Wang, Y.-D.</dc:creator>
<dc:creator>Chuang, T.-J.</dc:creator>
<dc:date>2019-07-24</dc:date>
<dc:identifier>doi:10.1101/712331</dc:identifier>
<dc:title><![CDATA[Genome-wide, integrative analysis implicates circular RNA dysregulation in autism and the corresponding circular RNA-microRNA-mRNA regulatory axes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-07-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/714501v1?rss=1">
<title>
<![CDATA[
Retroconversion of estrogens into androgens by bacteria via a cobalamin-mediated methylation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/714501v1?rss=1</link>
<description><![CDATA[
Steroid estrogens modulate physiology and development of vertebrates. Biosynthesis of C18 estrogens from C19 androgens by the O2-dependent aromatase is thought to be irreversible. Here, we report a denitrifying Denitratisoma sp. strain DHT3 capable of catabolizing estrogens or androgens anaerobically. Strain DHT3 genome contains a polycistronic gene cluster emtABCD differentially transcribed under estrogen-fed conditions. emtABCD encodes a cobalamin-dependent methyltransferase system conserved among estrogen-utilizing anaerobes; emtA-disrupted strain DHT3 can catabolize androgens but not estrogens. These data, along with the observed androgen production in estrogen-fed strain DHT3 cultures, indicate the occurrence of a cobalamin-mediated estrogen methylation to form androgens. Consistently, the estrogen conversion into androgens in strain DHT3 cell-extracts requires methylcobalamin and is inhibited by propyl-iodide, a specific inhibitor of cobalamin-dependent enzymes. The identification of the cobalamin-mediated estrogen methylation thus represents an unprecedented metabolic link between cobalamin and steroid metabolism and suggests that retroconversion of estrogens into androgens occurs in the biosphere.
]]></description>
<dc:creator>Wang, P.-H.</dc:creator>
<dc:creator>Chen, Y.-L.</dc:creator>
<dc:creator>Wei, S. T.-S.</dc:creator>
<dc:creator>Wu, K.</dc:creator>
<dc:creator>Lee, T.-H.</dc:creator>
<dc:creator>Wu, T.-Y.</dc:creator>
<dc:creator>Chiang, Y.-R.</dc:creator>
<dc:date>2019-07-25</dc:date>
<dc:identifier>doi:10.1101/714501</dc:identifier>
<dc:title><![CDATA[Retroconversion of estrogens into androgens by bacteria via a cobalamin-mediated methylation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-07-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/714949v1?rss=1">
<title>
<![CDATA[
Experimental evolution reveals a general role for the methyltransferase Hmt1 in noise buffering 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/714949v1?rss=1</link>
<description><![CDATA[
Cell-to-cell heterogeneity within an isogenic population has been observed in prokaryotic and eukaryotic cells. Such heterogeneity often manifests at the level of individual protein abundance and may have evolutionary benefits, especially for organisms in fluctuating environments. Although general features and the origins of cellular noise have been revealed, details of the molecular pathways underlying noise regulation remain elusive. Here, we used experimental evolution of Saccharomyces cerevisiae to select for mutations that increase reporter protein noise. By combining bulk segregant analysis and CRISPR/Cas9-based reconstitution, we identified the methyltransferase Hmt1 as a general regulator of noise buffering. Hmt1 methylation activity is critical for the evolved phenotype, and noise buffering is primarily achieved via two Hmt1 methylation targets. Hmt1 functions as an environmental sensor to adjust noise levels in response to environmental cues. Moreover, Hmt1-mediated noise buffering is conserved in an evolutionarily distant yeast species, suggesting broad significance of noise regulation.nnAuthor SummaryCell-to-cell heterogeneity within an isogenic population has been observed in prokaryotic and eukaryotic cells. Such heterogeneity often manifests at the level of individual protein abundance and may have evolutionary benefits, especially for organisms in fluctuating environments. Here, we used experimental evolution of Saccharomyces cerevisiae to select for mutations that increase reporter protein noise and identified the methyltransferase Hmt1 as a general regulator of noise buffering. Hmt1 is a central hub protein that is involved in multiple basic cellular pathways, including chromatin remodeling/transcription, translation, ribosome biogenesis, and post-transcriptional regulation. Our results show that Hmt1 constrains the noise level of multiple cellular pathways under normal conditions, so the physiology of individual cells in a population will not deviate too much from optimal peak fitness. However, when cells encounter environmental stresses, HMT1 is quickly down-regulated and expression noise is enhanced to increase the likelihood of population survival. Moreover, the noise buffering function of Hmt1 is conserved in Schizosaccharomyces pombe that diverged from the common ancestor of Saccharomyces cerevisiae more than 400 million years ago. Since the Hmt1 network is conserved from yeast cells to human, it is quite possible that Hmt1-mediated noise buffering also operates in multicellular organisms.
]]></description>
<dc:creator>You, S.-T.</dc:creator>
<dc:creator>Jhou, Y.-T.</dc:creator>
<dc:creator>Kao, C.-F.</dc:creator>
<dc:creator>Leu, J.-Y.</dc:creator>
<dc:date>2019-07-25</dc:date>
<dc:identifier>doi:10.1101/714949</dc:identifier>
<dc:title><![CDATA[Experimental evolution reveals a general role for the methyltransferase Hmt1 in noise buffering]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-07-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/725598v1?rss=1">
<title>
<![CDATA[
It takes two vanilloid ligand bindings per channel to transduce painful capsaicin stimuli 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/725598v1?rss=1</link>
<description><![CDATA[
The capsaicin receptor TRPV1 in mammals evolved the capability of integrating pain arising from combinations of noxious temperature or chemical irritants. Four-fold repetition of TRPV1 subunits makes an ion channel endowed with excellent sensitivity for pain detection, assisting this ionotropic receptor to differentiate graded injuries. We manipulated the stoichiometry and relative steric coordination of capsaicin binding at the molecular level, explicating rules with which a receptor codes pain within a broad range of intensity. The first ligand binding delivers small but clear initiation of channel activation. Maximal agonist action has already been reached in a receptor-in-tandem containing two or three wild-type receptor units, displaying activity comparable to the full liganded all-wild-type tandem tetramers. When the binding sites outnumbered ligands, independent action dominates in each channel. The non-vanilloid agonist 2-APB differs from capsaicin by adopting a distinct open mechanism since it does not demand a vanilloid group to activate. The sharing of the same pore greatly simplifies synergism to transduce relevant inputs by summation for pain signaling. And questions the need to explore deeper into other aspects of nociception.
]]></description>
<dc:creator>Liu, T.-Y.</dc:creator>
<dc:creator>Chu, Y.</dc:creator>
<dc:creator>Mei, H.-R.</dc:creator>
<dc:creator>Chang, D. S.</dc:creator>
<dc:creator>Chuang, H.-h.</dc:creator>
<dc:date>2019-08-12</dc:date>
<dc:identifier>doi:10.1101/725598</dc:identifier>
<dc:title><![CDATA[It takes two vanilloid ligand bindings per channel to transduce painful capsaicin stimuli]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-08-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/732701v1?rss=1">
<title>
<![CDATA[
A single TRPV1 amino acid controls species sensitivity to capsaicin 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/732701v1?rss=1</link>
<description><![CDATA[
Chili peppers produce capsaicin, the principle chemical that accounts for the culinary sensations of heat. Capsaicin activates the transient receptor potential cation channel subfamily V member 1 (TRPV1) on sensory neurons to alter the membrane potential to induce pain. While structural studies have identified residues important for the binding of capsaicin to rat TRPV1, there is still no clear understanding of differential capsaicin sensitivity of TRPV1 between birds and mammals. To determine the residues dictating relative capsaicin sensitivity among species, we have used intracellular Ca2+ imaging to characterize chimeras composed of capsaicin-sensitive rat TRPV1 (rTRPV1) and capsaicin-insensitive chicken TRPV1 (cTRPV1) with a series of capsaicinoids. We find that chimeras containing rat E570-V686 swapped into chicken receptors displays capsaicin sensitivity, and that a single amino acid substitution in the S4-S5 helix, changing the alanine at position 578 in the chick receptor to a glutamate, is sufficient to endow micromolar capsaicin sensitivity. Moreover, introduction of lysine, glutamine or proline at A578 also install capsaicin sensitivity in cTRPV1. Comparing the derivatives Cap-EA and Cap-EMA with capsaicin, these two compounds with the hydrophilic vanilloid-like moiety affect the protein-ligand interaction. The ability of 10 M Cap-EA to activate cTRPV1-A578E and the differential response of mutants to the analogs suggests that chick A578 may participate in vanilloid binding, as does the corresponding rTRPV1 site. The hydrophilic vanilloid agonist zingerone 500 M failed to activate any A578 mutants that retained capsaicin sensitivity, suggesting that the vanilloid group alone is not sufficient for receptor activation. Replacing the rTRPV1-E570 residue with K, Q shows a similar tendency to maintain the receptor capsaicin sensitivity. Our study demonstrates a subtle modification on different species TRPV1 globally alter their capsaicin response.
]]></description>
<dc:creator>Chu, Y.</dc:creator>
<dc:creator>Cohen, B.</dc:creator>
<dc:creator>Chuang, H.-h. A.</dc:creator>
<dc:date>2019-08-12</dc:date>
<dc:identifier>doi:10.1101/732701</dc:identifier>
<dc:title><![CDATA[A single TRPV1 amino acid controls species sensitivity to capsaicin]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-08-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/734046v1?rss=1">
<title>
<![CDATA[
Identification of Escherichia coli ClpAP in regulating susceptibility to type VI secretion system-mediated attack by Agrobacterium tumefaciens 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/734046v1?rss=1</link>
<description><![CDATA[
Type VI secretion system (T6SS) is an effector delivery system used by gram-negative bacteria to kill other bacteria or eukaryotic host to gain fitness. In Agrobacterium tumefaciens, T6SS has been shown to kill other bacteria such as Escherichia coli. Interestingly, the A. tumefaciens T6SS killing efficiency differs when using different E. coli strains as recipient cells. Thus, we hypothesize that a successful T6SS killing not only relies on attacker T6SS activity but also depends on recipient factors. A high-throughput interbacterial competition assay was employed to test the hypothesis by screening for mutants with reduced killing outcomes caused by A. tumefaciens strain C58. From the 3909 E. coli Keio mutants screened, 16 candidate mutants were filtered out. One strain, {Delta}clpP::Kan, showed ten times more resistant to T6SS-mediating killing but restored its susceptibility when complemented with clpP in trans. ClpP is a universal and highly conserved protease that exists in both prokaryotes and eukaryotic organelles. In E. coli, ClpP uses either ClpA or ClpX as an adaptor for substrate specificity. Therefore, the susceptibility of the {Delta}clpA::Kan and {Delta}clpX::Kan was also tested. The T6SS attack susceptibility of {Delta}clpA::Kan is at the same level as {Delta}clpP::Kan, while {Delta}clpX::Kan showed no difference as compared to that of wild-type E. coli BW25113. The data also suggest that ClpA-ClpP interaction, rather than its protease activity, is responsible for enhancing susceptibility to T6SS killing. This study highlights the importance of recipient factors in determining the outcome of T6SS killing.
]]></description>
<dc:creator>Lin, H.-H.</dc:creator>
<dc:creator>Yu, M.</dc:creator>
<dc:creator>Sriramoju, M. K.</dc:creator>
<dc:creator>Hsu, S.-T. D.</dc:creator>
<dc:creator>Liu, C.-T.</dc:creator>
<dc:creator>Lai, E.-M.</dc:creator>
<dc:date>2019-08-14</dc:date>
<dc:identifier>doi:10.1101/734046</dc:identifier>
<dc:title><![CDATA[Identification of Escherichia coli ClpAP in regulating susceptibility to type VI secretion system-mediated attack by Agrobacterium tumefaciens]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-08-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/740209v1?rss=1">
<title>
<![CDATA[
Redundancy and specificity of type VI secretion vgrG loci in antibacterial activity of Agrobacterium tumefaciens 1D1609 strain 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/740209v1?rss=1</link>
<description><![CDATA[
Type VI secretion system (T6SS) is a contractile nanoweapon employed by many Proteobacteria to deliver effectors to kill or inhibit their competitors. One T6SS gene, vgrG, encodes a spike protein for effector translocation and is often present as multiple copies in bacterial genomes. Our phylogenomic analyses sampled 48 genomes across diverse Proteobacteria lineages and found [~]70% of them encode multiple VgrGs, yet only four genomes have nearly identical paralogs. Among these four, Agrobacterium tumefaciens 1D1609 has the highest vgrG redundancy. Compared to A. tumefaciens model strain C58 which harbors two vgrG genes, 1D1609 encodes four vgrG genes (i.e. vgrGa-d) with each adjacent to different putative effector genes. Thus, 1D1609 was selected to investigate the functional redundancy and specificity of multiple vgrG genes and their associated effectors. Secretion assay of single and multiple vgrG deletion mutants demonstrated that these four vgrGs are functionally redundant in mediating T6SS secretion. By analyzing various vgrG mutants, we found that all except for the divergent vgrGb could contribute to 1D1609s antibacterial activity. Further characterizations of putative effector-immunity gene pairs revealed that vgrGa-associated gene 2 (v2a) encodes an AHH family nuclease and serves as the major antibacterial toxin. Interestingly, C58s VgrG2 shares 99% amino acid sequence identity with 1D1609s VgrGa, VgrGc and VgrGd. This high sequence similarity allows 1D1609 to use an exogenous VgrG delivered from C58 to kill another competing bacterium. Taken together, Agrobacterium can use highly similar VgrGs, either produced endogenously or injected from its close relatives, for T6SS-mediated interbacterial competition.

Authors SummarySelective pressure drives bacteria to develop adaptive strategies, which include competitive and cooperative behaviors. Type VI secretion system (T6SS) is one powerful antibacterial and anti-host nanoweapon employed by many Gram-negative bacteria for growth advantages or pathogenesis. A T6SS-harboring bacterium can encode one to multiple VgrG proteins for delivery of cognate effector(s) but the prevalence and biological significance of having sequence redundant vgrGs have not been comprehensively explored. In this study, we investigated the extensiveness of having multicopy vgrG genes for effector delivery among diverse Proteobacteria with T6SS. Moreover, a plant pathogenic bacterium Agrobacterium tumefaciens strain 1D1609 with highest vgrG redundancy was selected for detailed characterization of the roles of multiple VgrGs in T6SS secretion and antibacterial activity. We revealed that the majority of Proteobacterial genomes harbor multiple copies of vgrG and the expansion of vgrG gene clusters contributed to effector diversity and functional redundancy. Furthermore, the near identical VgrG proteins between 1D1609 and its sibling strain C58 can be exchanged for effector delivery in killing another competing bacterium. Such strategy in using exchangeable effector carriers injected from its isogenic sibling or close relatives during T6SS attacks may be a beneficial strategy for agrobacteria to compete in their ecological niche.
]]></description>
<dc:creator>Santos, M. N. M.</dc:creator>
<dc:creator>Cho, S.-T.</dc:creator>
<dc:creator>Wu, C.-F.</dc:creator>
<dc:creator>Chang, C.-J.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:creator>Lai, E.-M.</dc:creator>
<dc:date>2019-08-19</dc:date>
<dc:identifier>doi:10.1101/740209</dc:identifier>
<dc:title><![CDATA[Redundancy and specificity of type VI secretion vgrG loci in antibacterial activity of Agrobacterium tumefaciens 1D1609 strain]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-08-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/751792v1?rss=1">
<title>
<![CDATA[
Parallel Concerted Evolution of Ribosomal Protein Genes in Fungi and Its Adaptive Significance 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/751792v1?rss=1</link>
<description><![CDATA[
Ribosomal proteins (RPs) genes encode structure components of ribosomes, the cellular machinery for protein synthesis. A single functional copy has been maintained in most of 78-80 RP families in animals due to evolutionary constraints imposed by gene dosage balance. Some fungal species have maintained duplicate copies in most RP families. How the RP genes were duplicated and maintained in these fungal species, and their functional significance remains unresolved. To address these questions, we identified all RP genes from 295 fungi and inferred the timing and nature of gene duplication for all RP families. We found that massive duplications of RP genes have independently occurred by different mechanisms in three distantly related lineages. The RP duplicates in two of them, budding yeast and Mucoromycota, were mainly created by whole genome duplication (WGD) events. However, in fission yeasts, duplicate RP genes were likely generated by retroposition, which is unexpected considering their dosage sensitivity. The sequences of most RP paralogs in each species have been homogenized by repeated gene conversion, demonstrating parallel concerted evolution, which might have facilitated the retention of their duplicates. Transcriptomic data suggest that the duplication and retention of RP genes increased RP transcription abundance. Physiological data indicate that increased ribosome biogenesis allowed these organisms to rapidly consuming sugars through fermentation while maintaining high growth rates, providing selective advantages to these species in sugar-rich environments.
]]></description>
<dc:creator>Mullis, A.</dc:creator>
<dc:creator>Lu, Z.</dc:creator>
<dc:creator>Zhan, Y.</dc:creator>
<dc:creator>Wang, T.-Y.</dc:creator>
<dc:creator>Rodriguez, J.</dc:creator>
<dc:creator>Rajeh, A.</dc:creator>
<dc:creator>Chatrath, A.</dc:creator>
<dc:creator>Lin, Z.</dc:creator>
<dc:date>2019-08-31</dc:date>
<dc:identifier>doi:10.1101/751792</dc:identifier>
<dc:title><![CDATA[Parallel Concerted Evolution of Ribosomal Protein Genes in Fungi and Its Adaptive Significance]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-08-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/752394v1?rss=1">
<title>
<![CDATA[
Input dose differentiation by NF-κB 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/752394v1?rss=1</link>
<description><![CDATA[
Cells receive a wide range of dynamic signaling inputs during immune regulation, but how gene regulatory networks measure and interpret such dynamic inputs is not understood. Here, we used microfluidic live-cell analysis and mathematical modeling to study how NF-{kappa}B pathway in single-cells responds to time-varying immune inputs such as increasing, decreasing or fluctuating cytokine signals. Surprisingly, we found that NF-{kappa}B acts as a differentiator, responding strictly to the absolute difference in cytokine concentration, and not to the concentration itself. Our analyses revealed that negative feedbacks by the regulatory proteins A20 and I{kappa}B enable dose differentiation by providing short-term memory of prior cytokine level and continuously resetting kinase cycling and receptor levels. Investigation of NF-{kappa}B target gene expression showed that cells create unique transcriptional responses under different dynamic cytokine profiles. Our results demonstrate how cells use simple network motifs and transcription factor dynamics to efficiently extract information from complex signaling environments.
]]></description>
<dc:creator>Son, M.</dc:creator>
<dc:creator>Wang, A.</dc:creator>
<dc:creator>Tu, H.-L.</dc:creator>
<dc:creator>Metzig, M. O.</dc:creator>
<dc:creator>Patel, P.</dc:creator>
<dc:creator>Husain, K.</dc:creator>
<dc:creator>Lin, J.</dc:creator>
<dc:creator>Murugan, A.</dc:creator>
<dc:creator>Hoffmann, A.</dc:creator>
<dc:creator>Tay, S.</dc:creator>
<dc:date>2019-09-04</dc:date>
<dc:identifier>doi:10.1101/752394</dc:identifier>
<dc:title><![CDATA[Input dose differentiation by NF-κB]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-09-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/755165v1?rss=1">
<title>
<![CDATA[
Engineering recombination between diverged yeast species reveals genetic incompatibilities 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/755165v1?rss=1</link>
<description><![CDATA[
The major cause of the sterility of F1 hybrids formed between Saccharomyces cerevisiae and Saccharomyces paradoxus is anti-recombination. The failure of homologous chromosomes from the different species to recombine causes them to mis-segregate, resulting in aneuploid gametes, most of which are inviable. These effects of anti-recombination have previously impeded the search for other forms of incompatibility, such as negative genetic interactions (Bateson-Dobzhoansky-Muller incompatibilities). By suppressing the meiotic expression of MSH2 and SGS1, we could increase recombination and improve hybrid fertility seventy-fold. This allowed us to recover meiotic tetrads in which all four gametes were viable, ensuring that segregation had occurred properly to produce perfectly haploid, not aneuploid, recombinant hybrid gametes. We sequenced the genomes of 84 such tetrads, and discovered that some combinations of alleles from different species were significantly under-represented, indicating that there are incompatible genes contributing to reproductive isolation.
]]></description>
<dc:creator>Bozdag, G. O.</dc:creator>
<dc:creator>Ono, J.</dc:creator>
<dc:creator>Denton, J. A.</dc:creator>
<dc:creator>Karakoc, E.</dc:creator>
<dc:creator>Hunter, N.</dc:creator>
<dc:creator>Leu, J.-Y.</dc:creator>
<dc:creator>Greig, D.</dc:creator>
<dc:date>2019-09-05</dc:date>
<dc:identifier>doi:10.1101/755165</dc:identifier>
<dc:title><![CDATA[Engineering recombination between diverged yeast species reveals genetic incompatibilities]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-09-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/766022v1?rss=1">
<title>
<![CDATA[
Detection and Classification of Cardiac Arrhythmias by a Challenge-Best Deep Learning Neural Network Model 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/766022v1?rss=1</link>
<description><![CDATA[
BackgroundElectrocardiogram (ECG) is widely used to detect cardiac arrhythmia (CA) and heart diseases. The development of deep learning modeling tools and publicly available large ECG data in recent years has made accurate machine diagnosis of CA an attractive task to showcase the power of artificial intelligence (AI) in clinical applications.nnMethods and FindingsWe have developed a convolution neural network (CNN)-based model to detect and classify nine types of heart rhythms using a large 12-lead ECG dataset (6877 recordings) provided by the China Physiological Signal Challenge (CPSC) 2018. Our model achieved a median overall F1-score of 0.84 for the 9-type classification on CPSC2018s hidden test set (2954 ECG recordings), which ranked first in this latest AI competition of ECG-based CA diagnosis challenge. Further analysis showed that concurrent CAs observed in the same patient were adequately predicted for the 476 patients diagnosed with multiple CA types in the dataset. Analysis also showed that the performances of using only single lead data were only slightly worse than using the full 12 lead data, with leads aVR and V1 being the most prominent. These results are extensively discussed in the context of their agreement with and relevance to clinical observations.nnConclusionsAn AI model for automatic CA diagnosis achieving state-of-the-art accuracy was developed as the result of a community-based AI challenge advocating open-source research. In- depth analysis further reveals the models ability for concurrent CA diagnosis and potential use of certain single leads such as aVR in clinical applications.nnAbbreviationsCA, cardiac arrhythmia; AF, Atrial fibrillation; I-AVB, first-degree atrioventricular block; LBBB, left bundle branch block; RBBB, right bundle branch block; PAC, premature atrial contraction; PVC, premature ventricular contraction; STD, ST-segment depression; STE, ST-segment elevation.
]]></description>
<dc:creator>Chen, T.-M.</dc:creator>
<dc:creator>Huang, C.-H.</dc:creator>
<dc:creator>Shih, E. S. C.</dc:creator>
<dc:creator>Hu, Y.-F.</dc:creator>
<dc:creator>Hwang, M.-J.</dc:creator>
<dc:date>2019-09-19</dc:date>
<dc:identifier>doi:10.1101/766022</dc:identifier>
<dc:title><![CDATA[Detection and Classification of Cardiac Arrhythmias by a Challenge-Best Deep Learning Neural Network Model]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-09-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/776773v1?rss=1">
<title>
<![CDATA[
Nest microbiota and pathogen abundance impact hatching success in sea turtle conservation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/776773v1?rss=1</link>
<description><![CDATA[
Hatchery practices are pivotal to conservation success. In sea turtle hatchery, reusing the same sand has been a norm but remains unclear whether such approach increases the risk of Fusarium solani species complex (FSSC) infection causing huge mortality in sea turtle eggs worldwide. We employed 16S and ITS amplicon sequencing in 123 sand samples and isolated fungal strains from diseased eggs across seven hatcheries and neighboring beaches in Malaysia. FSSC was isolated from all sampled hatcheries where F. solani/falciforme was the predominant species. A distinct microbial composition and higher abundance of FSSC (mean = 5.2 %) was found in all but one hatchery when compared to nesting beaches (mean = 1.3 %). Specifically, an ascomycetous fungus Pseudallescheria boydii consistently appeared in higher abundance (mean = 11.4 %) in FSSC-infected nests and was significantly associated with lower hatching success. The hatchery that maintained the most stringent practice by changing sand every nesting season had a microbiota resembling nesting beaches as well as lowest FSSC and P. boydii abundance. The results of current study imply the need to avoid reusing sand in sea turtle hatchery.
]]></description>
<dc:creator>Hoh, D. Z.</dc:creator>
<dc:creator>Lin, Y.-f.</dc:creator>
<dc:creator>Liu, W.-A.</dc:creator>
<dc:creator>Sidique, S. N. M.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2019-09-20</dc:date>
<dc:identifier>doi:10.1101/776773</dc:identifier>
<dc:title><![CDATA[Nest microbiota and pathogen abundance impact hatching success in sea turtle conservation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-09-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/782193v1?rss=1">
<title>
<![CDATA[
GSAlign - an efficient sequence alignment tool for intra-species genomes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/782193v1?rss=1</link>
<description><![CDATA[
Personal genomics and comparative genomics are becoming more important in clinical practice and genome research. Both fields require sequence alignment to discover sequence conservation and variation. Though many methods have been developed, some are designed for small genome comparison while some are not efficient for large genome comparison. Moreover, most existing genome comparison tools have not been evaluated the correctness of sequence alignments systematically. A wrong sequence alignment would produce false sequence variants. In this study, we present GSAlign that handles large genome sequence alignment efficiently and identifies sequence variants from the alignment result. GSAlign is an efficient sequence alignment tool for intra-species genomes. It identifies sequence variations from the sequence alignments. We estimate performance by measuring the correctness of predicted sequence variations. The experiment results demonstrated that GSAlign is not only faster than most existing state-of-the-art methods, but also identifies sequence variants with high accuracy.
]]></description>
<dc:creator>Lin, H.-N.</dc:creator>
<dc:creator>Hsu, W.-L.</dc:creator>
<dc:date>2019-09-25</dc:date>
<dc:identifier>doi:10.1101/782193</dc:identifier>
<dc:title><![CDATA[GSAlign - an efficient sequence alignment tool for intra-species genomes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-09-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/783209v1?rss=1">
<title>
<![CDATA[
Perinatal exposure to lead results in altered DNA methylation in adult mouse liver and blood: Implications for target versus surrogate tissue use in environmental epigenetics 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/783209v1?rss=1</link>
<description><![CDATA[
BackgroundDNA methylation is a critical epigenetic mechanism linking early developmental environment to long-term health. In humans, the extent to which toxicant-induced changes in DNA methylation in surrogate tissues, such as blood, mirror those in the target tissues is unclear. The Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription (TaRGET II) consortium was established by the National Institute of Environmental Health Sciences to address the utility of surrogate tissues as proxies for toxicant-induced epigenetic changes in target tissues.nnObjectivesThe objective of this study was to investigate the effects of perinatal exposure to a human environmentally relevant level (32 ppm in maternal drinking water) of lead (Pb) on liver and blood DNA methylation in adult male and female mice. We hypothesized that developmental Pb exposure would lead to persistent changes in DNA methylation, and that a subset of differentially methylated loci would overlap between liver and blood.nnMethodsEnhanced reduced-representation bisulfite sequencing was used to assess DNA methylation in 5 month old Pb-exposed and control mice. Sex-stratified modeling of differential methylation by Pb exposure was conducted using an established bioinformatics pipeline.nnResultsAlthough Pb exposure ceased at 3 weeks of age, we observed thousands of stably modified, sex-specific differentially methylated regions in the blood and liver of Pb-exposed animals, including 44 genomically imprinted loci. In males, we discovered 5 sites that overlapped between blood and liver, and exhibited changes in DNA methylation in the same direction in both tissues.nnConclusionsThese data demonstrate that perinatal exposure to Pb induces sex-specific changes in hepatic DNA methylation in adulthood, some of which are also present in blood. Ongoing studies will provide additional exposure-specific insights, and include other epigenetic marks that will enable further refinement of the design and analysis of human studies where target tissues are inaccessible.
]]></description>
<dc:creator>Svoboda, L. K.</dc:creator>
<dc:creator>Neier, K. E.</dc:creator>
<dc:creator>Cavalcante, R. G.</dc:creator>
<dc:creator>Tsai, Z. T.-Y.</dc:creator>
<dc:creator>Jones, T. R.</dc:creator>
<dc:creator>Liu, S.</dc:creator>
<dc:creator>Goodrich, J. M.</dc:creator>
<dc:creator>Lalancette, C.</dc:creator>
<dc:creator>Colacino, J.</dc:creator>
<dc:creator>Sartor, M.</dc:creator>
<dc:creator>Dolinoy, D. C.</dc:creator>
<dc:date>2019-10-02</dc:date>
<dc:identifier>doi:10.1101/783209</dc:identifier>
<dc:title><![CDATA[Perinatal exposure to lead results in altered DNA methylation in adult mouse liver and blood: Implications for target versus surrogate tissue use in environmental epigenetics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/783605v1?rss=1">
<title>
<![CDATA[
MapCaller - An integrated and efficient tool for short-read mapping and variant calling using high-throughput sequenced data 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/783605v1?rss=1</link>
<description><![CDATA[
With the advance of next-generation sequencing (NGS) technologies, more and more medical and biological researches adopt NGS technologies to characterize the genetic variations between individuals. The identification of personal genome variants using NGS technology is a critical factor for the success of clinical genomics studies. It requires an accurate and consistent analysis procedure to distinguish functional or disease-associated variants from false discoveries due to sequencing errors or misalignments. In this study, we integrate the algorithms for read mapping and variant calling to develop an efficient and versatile NGS analysis tool, called MapCaller. It not only maps every short read onto a reference genome, but it also detects single nucleotide variants, indels, inversions and translocations at the same time. We evaluate the performance of MapCaller with existing variant calling pipelines using three simulated datasets and four real datasets. The result shows that MapCaller can identify variants accurately. Moreover, MapCaller runs much faster than existing methods. It is available at https://github.com/hsinnan75/MapCaller.
]]></description>
<dc:creator>Lin, H.-N.</dc:creator>
<dc:creator>Hsu, W.-L.</dc:creator>
<dc:date>2019-09-26</dc:date>
<dc:identifier>doi:10.1101/783605</dc:identifier>
<dc:title><![CDATA[MapCaller - An integrated and efficient tool for short-read mapping and variant calling using high-throughput sequenced data]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-09-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/789222v1?rss=1">
<title>
<![CDATA[
Differential Effects of SUMO1/2 on Circadian Protein PER2 Stability and Function 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/789222v1?rss=1</link>
<description><![CDATA[
Posttranslational modification (PTM) of core circadian clock proteins, including Period2 (PER2), is required for proper circadian regulation. PER2 function is regulated by casein kinase 1 (CK1)-mediated phosphorylation and ubiquitination but little is known about other PER2 PTMs or their interaction with PER2 phosphorylation. We found that PER2 can be SUMOylated by both SUMO1 and SUMO2; however, SUMO1 versus SUMO2 conjugation had different effects on PER2 turnover and transcriptional suppressor function. SUMO2 conjugation facilitated PER2-{beta}-TrCP interaction leading to PER2 proteasomal degradation. In contrast, SUMO1 conjugation, mediated by E3 SUMO-protein ligase RanBP2, enhanced CK1-mediated PER2S662 phosphorylation and increased PER2 transcriptional suppressor function. PER2 K736 was critical for both SUMO1- and SUMO2-conjugation. A PER2K736R mutation was sufficient to alter circadian periodicity and reduce PER2-mediated transcriptional suppression. Together, our data revealed SUMO1 versus SUMO2 conjugation acts as an upstream determinant of PER2 phosphorylation and thereby affects the circadian regulatory system and circadian periodicity.
]]></description>
<dc:creator>Chen, L.-C.</dc:creator>
<dc:creator>Hsieh, Y.-L.</dc:creator>
<dc:creator>Kuo, T.-Y.</dc:creator>
<dc:creator>Chou, Y.-C.</dc:creator>
<dc:creator>Hsu, P.-H.</dc:creator>
<dc:creator>Hwang-Verslues, W. W.</dc:creator>
<dc:date>2019-10-01</dc:date>
<dc:identifier>doi:10.1101/789222</dc:identifier>
<dc:title><![CDATA[Differential Effects of SUMO1/2 on Circadian Protein PER2 Stability and Function]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-10-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/790519v1?rss=1">
<title>
<![CDATA[
Interplay between Desmoglein2 and hypoxia controls intravasation and circulating tumor cell clustering in breast cancer metastasis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/790519v1?rss=1</link>
<description><![CDATA[
Metastasis is the major cause of cancer death. An increased level of circulating tumor cells (CTCs), metastatic cancer cells that have intravasated into the circulatory system, is particularly associated with colonization of distant organs and poor prognosis. However, the key factors required for tumor cell dissemination and colonization remain elusive. We found that high expression of Desmoglein2 (DSG2), a component of desmosome-mediated intercellular adhesion complexes, promoted tumor growth, increased the prevalence of CTC clusters and facilitated distant organ colonization. The dynamic regulation of DSG2 by hypoxia was key to this process as downregulation of DSG2 in hypoxic regions of primary tumors led to elevated epithelial-mesenchymal transition (EMT) gene expression, allowing cells to detach from the primary tumor and undergo intravasation. Subsequent derepression of DSG2 after intravasation and release of hypoxic stress was associated with an increased ability to colonize distant organs. This dynamic regulation of DSG2 was mediated by Hypoxia-Induced Factor1 (HIF1). In contrast to its more widely observed function to promote expression of hypoxia-inducible genes, HIF1 repressed DSG2 by recruitment of the Polycomb Repressive Complex 2 components, EZH2 and SUZ12, to the DSG2 promoter in hypoxic cells. Consistent with our experimental data, DSG2 expression level correlated with poor prognosis and recurrence risk in breast cancer patients. Together, these results demonstrated the importance of DSG2 expression in metastasis and revealed a new mechanism by which hypoxia drives metastasis.

Significance StatementDuring metastasis, hypoxia is a major force driving primary tumor cells to disseminate into the circulatory system. The key factors that promote circulating tumor cells (CTC) dissemination and allow them to successfully colonize distal sites are still incompletely known. We found that downregulation of DSG2 in hypoxic tumor allowed single tumor cell dissemination while DSG2 expressing tumors generated more CTC clusters. Re-induction of DSG2 expression in single CTCs may contribute to CTC survival and colonization in distant organs. These findings highlight the importance of DSG2 in breast cancer progression and metastasis.
]]></description>
<dc:creator>Chang, P.-H.</dc:creator>
<dc:creator>Chen, M.-C.</dc:creator>
<dc:creator>Tsai, Y.-P.</dc:creator>
<dc:creator>Hsu, P.-H.</dc:creator>
<dc:creator>Jeng, Y.-M.</dc:creator>
<dc:creator>Hwang-Verslues, W. W.</dc:creator>
<dc:date>2019-10-02</dc:date>
<dc:identifier>doi:10.1101/790519</dc:identifier>
<dc:title><![CDATA[Interplay between Desmoglein2 and hypoxia controls intravasation and circulating tumor cell clustering in breast cancer metastasis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/807149v1?rss=1">
<title>
<![CDATA[
StrainPro: a highly accurate Metagenomic strain-level profiling tool 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/807149v1?rss=1</link>
<description><![CDATA[
Characterizing the taxonomic diversity of a microbial community is very important to understand the roles of microorganisms. Next generation sequencing (NGS) provides great potential for investigation of a microbial community and leads to Metagenomic studies. NGS generates DNA fragment sequences directly from microorganism samples, and it requires analysis tools to identify microbial species (or taxonomic composition) and estimate their relative abundance in the studied community. However, only a few tools could achieve strain-level identification and most tools estimate the microbial abundances simply according to the read counts. An evaluation study on metagenomic analysis tools concludes that the predicted abundance differed significantly from the true abundance. In this study, we present StrainPro, a novel metagenomic analysis tool which is highly accurate both at characterizing microorganisms at strain-level and estimating their relative abundances. A unique feature of StrainPro is it identifies representative sequence segments from reference genomes. We generate three simulated datasets using known strain sequences and another three simulated datasets using unknown strain sequences. We compare the performance of StrainPro with seven existing tools. The results show that StrainPro not only identifies metagenomes with high precision and recall, but it is also highly robust even when the metagenomes are not included in the reference database. Moreover, StrainPro estimates the relative abundance with high accuracy. We demonstrate that there is a strong positive linear relationship between observed and predicted abundances.
]]></description>
<dc:creator>Lin, H.-N.</dc:creator>
<dc:creator>Lin, Y.-L.</dc:creator>
<dc:creator>Hsu, W.-L.</dc:creator>
<dc:date>2019-10-16</dc:date>
<dc:identifier>doi:10.1101/807149</dc:identifier>
<dc:title><![CDATA[StrainPro: a highly accurate Metagenomic strain-level profiling tool]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-10-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/823278v1?rss=1">
<title>
<![CDATA[
Dynamic-ultrastructural cell volume (3D) correlative microscopy facilitated by intracellular fluorescent nanodiamonds as multi-modal probes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/823278v1?rss=1</link>
<description><![CDATA[
Three-dimensional correlative light and electron microscopy (3D CLEM) are attaining popularity as a potential technique to explore the functional aspects of a cell together with high-resolution ultrastructural details across the cell volume. In order to perform such a 3D CLEM experiment, there is an imperative requirement for multi-modal probes that are both fluorescent and electron-dense. These multi-modal probes will serve as landmarks in matching up the large full cell volume datasets acquired by different imaging modalities. Fluorescent nanodiamonds (FNDs) are a unique nanosized, fluorescent, and electron-dense material from the nanocarbon family. We hereby propose a novel and straightforward method for executing 3D CLEM using FNDs as multi-modal landmarks. We demonstrate that FNDs is biocompatible and easily identified both in living cell fluorescence imaging and in serial block-face scanning electron microscopy (SB-EM). We illustrate the 3D CLEM method by registering multi-modal datasets.
]]></description>
<dc:creator>Prabhakar, N.</dc:creator>
<dc:creator>Belevich, I.</dc:creator>
<dc:creator>Peurla, M.</dc:creator>
<dc:creator>Heiligenstein, X.</dc:creator>
<dc:creator>Chang, H.-C.</dc:creator>
<dc:creator>Sahlgren, C.</dc:creator>
<dc:creator>Jokitalo, E.</dc:creator>
<dc:creator>Rosenholm, J.</dc:creator>
<dc:date>2019-10-29</dc:date>
<dc:identifier>doi:10.1101/823278</dc:identifier>
<dc:title><![CDATA[Dynamic-ultrastructural cell volume (3D) correlative microscopy facilitated by intracellular fluorescent nanodiamonds as multi-modal probes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-10-29</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/835595v1?rss=1">
<title>
<![CDATA[
The assembly of the Drosophila mushroom body circuit and its regulation by Semaphorin 1a 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/835595v1?rss=1</link>
<description><![CDATA[
The Drosophila mushroom body (MB) is a learning and memory center in the fly brain. It is the most extensively studied brain structure in insects, but we know little about the molecular and cellular mechanisms underlying assembly of its neural circuit. The MB is composed of around 2200 intrinsic Kenyon cells (KCs), whose axons are bundled to form multiple MB lobes. The MB lobes are innervated by a large number of extrinsic neurons. Twenty types of dopaminergic neurons (DANs) and 21 types of MB output neurons (MBONs) have been identified. Each type of these extrinsic neurons innervates specific compartments or zones in the MB lobes. Here, we characterize the assembly of the MB circuit and reveal several intriguing features of the process. The DANs and MBONs innervate zones in the MB vertical lobes in specific sequential orders. Innervation of DAN axons in some zones precedes that of MBON dendrites, and vice versa in other zones. MBON and DAN innervations are largely independent of each other. Removing one type of extrinsic neuron during early development has a limited effect on the MB lobe innervations of the other type of extrinsic neurons. However, KC axons are essential for zonal elaboration of DAN axons and MBON dendrites. Competition also exists between MB zones for some MBONs, so when the cognate zones for these MBONs are missing, their dendrites are misdirected to other zones. Finally, we identify Semaphorin 1a (Sema1a) as a crucial guidance molecule for MBON dendrites to innervate specific MB lobe zones. Ectopic expression of Sema1a in some DANs is sufficient to re-direct their dendrites to those zones, demonstrating a potential to rewire the MB circuit. Taken together, our work provides an initial characterization of the cellular and molecular mechanisms underlying MB circuit assembly.
]]></description>
<dc:creator>Lin, C.-H.</dc:creator>
<dc:creator>Lin, S.</dc:creator>
<dc:date>2019-11-08</dc:date>
<dc:identifier>doi:10.1101/835595</dc:identifier>
<dc:title><![CDATA[The assembly of the Drosophila mushroom body circuit and its regulation by Semaphorin 1a]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-11-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/843698v1?rss=1">
<title>
<![CDATA[
Natural diversity in the predatory behavior facilitates the establishment of a new robust model strain for nematode-trapping fungi 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/843698v1?rss=1</link>
<description><![CDATA[
Nematode-trapping fungi (NTF) are a group of specialized microbial predators that consume nematodes when food sources are limited. Predation is initiated when conserved nematode ascaroside pheromones are sensed, followed by the development of complex trapping devices. To gain insights into the co-evolution of this inter-kingdom predator-prey relationship, we investigated natural populations of nematodes and NTF, that we found to be ubiquitous in soils. Arthrobotrys species were sympatric with various nematode species and behaved as generalist predators. The ability to sense prey amongst wild isolates of A. oligospora varied greatly, as determined by the number of traps after exposure to Caenorhabditis elegans. While some strains were highly sensitive to C. elegans and the nematode pheromone ascarosides, others responded only weakly. Furthermore, strains that were highly sensitive to the nematode prey also developed traps faster. The polymorphic nature of trap formation correlated with competency in prey killing, as well as with the phylogeny of A. oligospora natural strains, calculated after assembly and annotation of the genomes of twenty isolates. A chromosome level genome assembly and annotation was established for one of the most sensitive wild isolate, and deletion of the only G protein {beta} subunit-encoding gene of A. oligospora nearly abolished trap formation, implicating G protein signaling in predation. In summary, our study establishes a highly responsive A. oligospora wild isolate as a novel model strain for the study of fungal-nematode interactions and demonstrates that trap formation is a fitness character in generalist predators of the NTF family.

Significance statementNematode-trapping fungi (NTF) are carnivorous microbes that hold potential to be used as biological control agents due to their ability to consume nematodes. In this work we show that NTF are ubiquitous generalist predators found in sympatry with their prey in soil samples. Wild isolates of NTF displayed a naturally diverse ability to execute their predatory lifestyle. We generated a large whole genome sequencing dataset for many of the fungal isolates that will serve as the basis of future projects isolates. In particular, we establish TWF154, a highly responsive strain of Arthrobotrys oligospora, as a model strain to study the genetics of NTF. Lastly, we provide evidence that G-protein signaling is necessary for trap induction in NTF.
]]></description>
<dc:creator>Yang, C.-T.</dc:creator>
<dc:creator>Vidal-Diez de Ulzurrun, G.</dc:creator>
<dc:creator>Goncalves, A. P.</dc:creator>
<dc:creator>Lin, H.-C.</dc:creator>
<dc:creator>Chang, C.-W.</dc:creator>
<dc:creator>Huang, T.-Y.</dc:creator>
<dc:creator>Chen, S.-A.</dc:creator>
<dc:creator>Lai, C.-K.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:creator>Schroeder, F. C.</dc:creator>
<dc:creator>Stajich, J. E.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:date>2019-11-15</dc:date>
<dc:identifier>doi:10.1101/843698</dc:identifier>
<dc:title><![CDATA[Natural diversity in the predatory behavior facilitates the establishment of a new robust model strain for nematode-trapping fungi]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-11-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/861153v1?rss=1">
<title>
<![CDATA[
Enhancer regulation for induced WNT3A expression during neuronal regeneration 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/861153v1?rss=1</link>
<description><![CDATA[
The treatment of traumatic brain injury (TBI) is limited by a lack of knowledge about the mechanisms underlying neuronal regeneration. WNT family members have been implicated in neurogenesis and aberrant WNT signaling has been associated with neurodegenerative diseases. The current study compared the expression of WNT genes during regeneration of injured cortical neurons. Recombinant WNT3A showed positive effect in promoting neuronal regeneration via in vitro and in vivo TBI models. Intranasal administration of WNT3A protein to TBI mice increased NeuN+ cells compared to control mice as well as retained motor function based on behavior analysis. Since TBI is known to reprogram the epigenome, chromatin immunoprecipitation-sequencing of histone H3K27ac and H3K4me3 was performed to address the transcriptional regulation of WNT3A during neuronal regeneration. We predicted, characterized and proposed that a histone H3K4me1-marked enhancer may undergo topological transformation to regulate the WNT3A gene expression.
]]></description>
<dc:creator>Chang, C.-Y.</dc:creator>
<dc:creator>Hung, J.-H.</dc:creator>
<dc:creator>Wu, C.-C.</dc:creator>
<dc:creator>Liang, M.-Z.</dc:creator>
<dc:creator>Huang, P.-Y.</dc:creator>
<dc:creator>Li, J.</dc:creator>
<dc:creator>Chen, H.-I.</dc:creator>
<dc:creator>Yet, S.-F.</dc:creator>
<dc:creator>Fung, K. S.</dc:creator>
<dc:creator>Kao, C.-F.</dc:creator>
<dc:creator>Chen, L.</dc:creator>
<dc:date>2019-12-02</dc:date>
<dc:identifier>doi:10.1101/861153</dc:identifier>
<dc:title><![CDATA[Enhancer regulation for induced WNT3A expression during neuronal regeneration]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-12-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/870915v1?rss=1">
<title>
<![CDATA[
Astrocytic mechanism of glutamate modulation underlying synchronous bursting in cortical cultures 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/870915v1?rss=1</link>
<description><![CDATA[
Synchronous bursting (SB) is ubiquitous in neuronal networks. It is known for a long time that SB is driven by glutamatergic neurotransmissions but its underlying mechanism is still unclear. Recent studies show that local glutamate recycle by astrocytes can affect neuronal activities nearby. Since SB is independent of network structure, it is conceivable that the local dynamics might also be the origin of SB in networks. We investigated the effects of local glutamate dynamics on SBs in both cultures developed on multi-electrode array (MEA) systems and a tripartite synapse simulation model. In our experiments, local glutamate recycle dynamics are studied by pharmacologically targeting the astrocytic glutamate transporters (GLT-1), while neuronal firing activities and synaptic glutamate level are simultaneously monitored with MEA and glutamate sensor (iGluSnFR) expressed on surface of astrocytes respectively. We found SBs to be synchronized with glutamate transients and the manipulation of local glutamate dynamics can indeed alter the global properties of the SBs. Detailed simulation of a network with astrocytic glutamate uptake and recycle mechanisms conforming with the experimental observations revealed that astrocytes function as a slow negative feedback for the neuronal activities in the network. With this model, SB can be understood as the alternation between the positive and negative feedback in the neurons and astrocytes in the network respectively. An understanding of this glutamate trafficking dynamics is of general application to explain disordered phenomena in neuronal systems, and therefore can provide new insights into the origin of fatal seizure-like behavior.

SignificanceSynchronous bursting (SB) is a hallmark of neuronal circuits. Contrary to the common belief that the SB is governed mainly by neuron-neuron interactions, this study shows that SBs are orchestrated through a generic neuron-astrocyte tripartite interactions. These interactions, identified as glutamate uptake and recycle processes in astrocytes, control the excitability of neuronal networks and shape the overall SB patterns. Our simulation results suggest that astrocytes traffic more glutamate than neurons and actively regulating glutamate proceedings around synapses. A bipartite synapse is a good approximation of a tripartite synapse provided that astrocyte-dependent glutamate content is taken into account. Our findings provide key insights into the ubiquity of SB and the origin of fatal seizure-like behavior in brain arising from astrocytic malfunction.
]]></description>
<dc:creator>Kumar, R.</dc:creator>
<dc:creator>Huang, Y.-T.</dc:creator>
<dc:creator>Chen, C.-C.</dc:creator>
<dc:creator>Tzeng, S.-F.</dc:creator>
<dc:creator>Chan, C.-K.</dc:creator>
<dc:date>2019-12-11</dc:date>
<dc:identifier>doi:10.1101/870915</dc:identifier>
<dc:title><![CDATA[Astrocytic mechanism of glutamate modulation underlying synchronous bursting in cortical cultures]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-12-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.09.11.557259v1?rss=1">
<title>
<![CDATA[
Anemonefish are better taxonomists than humans. 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.09.11.557259v1?rss=1</link>
<description><![CDATA[
The symbiosis between giant sea anemones, photosynthetic algae of the family Symbiodiniaceae, and anemonefish is an iconic example of a mutualistic "menage a 3"1. Patterns of associations among 28 species of anemonefish and 10 species of giant sea anemone hosts are complex: Some anemonefish species are highly specialized to inhabit only one species of sea anemone (e.g., Amphiprion frenatus with Entacmaea quadricolor), whereas others are more generalist and can live in almost any host species (e.g., Amphiprion clarkii)1,2,3. Reasons for host preferences and the mechanisms involved are obscured, among other things, by the lack of resolution of giant sea anemone phylogeny. Recent molecular analyses have shown that giant sea anemones hosting anemonefish belong to three distinct clades: Entacmaea, Stichodactyla, and Heteractis4,5,6. Inside these clades, however, species delimitation has been impeded by morphological variability of the giant sea anemones and is poorly resolved with classical markers4,5. Here, we employed an extensive transcriptomic dataset from 55 sea anemones collected from southern Japan to build a robust phylogeny. With this dataset, we observed that the bubble-tip sea anemone E. quadricolor, currently considered to be a single species, can in fact be separated into at least four distinct cryptic lineages (A-D). Moreover, these lineages can be precisely distinguished by their association with anemonefish: A. frenatus is only found associated with lineage D, whereas A. clarkii lives in the other three lineages.
]]></description>
<dc:creator>Kashimoto, R.</dc:creator>
<dc:creator>Mercader, M.</dc:creator>
<dc:creator>Zwahlen, J.</dc:creator>
<dc:creator>Miura, S.</dc:creator>
<dc:creator>Tanimoto, M.</dc:creator>
<dc:creator>Yanagi, K.</dc:creator>
<dc:creator>Reimer, J. D.</dc:creator>
<dc:creator>Khalturin, K.</dc:creator>
<dc:creator>Laudet, V.</dc:creator>
<dc:date>2023-09-11</dc:date>
<dc:identifier>doi:10.1101/2023.09.11.557259</dc:identifier>
<dc:title><![CDATA[Anemonefish are better taxonomists than humans.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-09-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.09.13.557576v1?rss=1">
<title>
<![CDATA[
Structure and dynamics of the contractile vacuole complex in Tetrahymena thermophila 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.09.13.557576v1?rss=1</link>
<description><![CDATA[
The contractile vacuole complex (CVC) is a dynamic and morphologically complex membrane organelle, comprised of a large vesicle (bladder) linked with a tubular reticulum (spongiome). CVCs provide key osmoregulatory roles across diverse eukaryotic lineages, but probing the mechanisms underlying the structure and function is hampered by the limited tools available for in vivo analysis. In the experimentally tractable ciliate Tetrahymena thermophila, we describe four proteins that, as endogenously tagged constructs, localize specifically to distinct CVC zones. The DOPEY homolog Dop1p and the CORVET subunit Vps8Dp localize both to the bladder and spongiome but with different local distributions that are sensitive to osmotic perturbation, while the lipid scramblase Scr7p co-localizes with Vps8Dp. The H+- ATPase subunit Vma4 is spongiome-specific. The live imaging permitted by these probes revealed dynamics at multiple scales including rapid exchange of CVC-localized and soluble protein pools vs. lateral diffusion in the spongiome, spongiome extension and branching, and CVC formation during mitosis. While the association with DOP1 and VPS8D implicate the CVC in endosomal trafficking, both the bladder and spongiome are isolated from bulk endocytic input.

Summary statementIn the ciliate Tetrahymena thermophila, four proteins are shown to provide markers for different zones of the contractile vacuole complex. They shed light on its formation and maintenance by enabling in vivo analysis of its dynamics.
]]></description>
<dc:creator>Cheng, C.-Y.</dc:creator>
<dc:creator>Romero, D. P.</dc:creator>
<dc:creator>Zoltner, M.</dc:creator>
<dc:creator>Yao, M.-C.</dc:creator>
<dc:creator>Turkewitz, A.</dc:creator>
<dc:date>2023-09-14</dc:date>
<dc:identifier>doi:10.1101/2023.09.13.557576</dc:identifier>
<dc:title><![CDATA[Structure and dynamics of the contractile vacuole complex in Tetrahymena thermophila]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-09-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.09.13.557516v1?rss=1">
<title>
<![CDATA[
The HOMEODOMAIN-Like protein HDL mediates chromatin organization and rewires leaf epidermal patterning 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.09.13.557516v1?rss=1</link>
<description><![CDATA[
The Arabidopsis leaf epidermis is comprised of trichomes, pavement cells, and stomata, originating from versatile precursor cells capable of dividing or differentiating to create unique epidermal patterns. The mechanism governing these transitions and the maintenance of cell heterogeneity remains unclear. In this study, we identified a novel homeodomain-like superfamily protein, HDL, localized in chromocenters and playing a role in chromatin organization. HDL interacts with histone deacetylase 6 (HDA6) and methyltransferases, indicating its function in modulating chromatin accessibility. In hdl mutants, we observed moderately increased chromatin accessibility in the promoter region of protein-coding genes, along with reduced stomatal density and elevated trichome numbers on leaf surfaces. Corresponding to these phenotypes, stomatal-related gene expression decreased, while a transcriptional reporter for GLABRA2, a trichome initiation gene, exhibited higher and more variable expression levels. These findings highlight how HDL-mediated chromatin organization influences epidermal cell fate by modulating gene expression and enhancing cell heterogeneity within the leaf epidermis.

One Sentence SummaryA homeodomain-like protein functions with histone modifiers to regulate chromatin and influence cell fate decisions.
]]></description>
<dc:creator>Ali, A.</dc:creator>
<dc:creator>Kuan, C.</dc:creator>
<dc:creator>Hung, F.-Y.</dc:creator>
<dc:creator>Chen, T.-C.</dc:creator>
<dc:creator>Lee, H.-C.</dc:creator>
<dc:creator>Yang, S.-L.</dc:creator>
<dc:creator>Feng, Y.-R.</dc:creator>
<dc:creator>Wu, K.</dc:creator>
<dc:creator>Ho, C.-M. K.</dc:creator>
<dc:date>2023-09-15</dc:date>
<dc:identifier>doi:10.1101/2023.09.13.557516</dc:identifier>
<dc:title><![CDATA[The HOMEODOMAIN-Like protein HDL mediates chromatin organization and rewires leaf epidermal patterning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-09-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.09.13.557568v1?rss=1">
<title>
<![CDATA[
Comparative analysis of metabolic models of microbial communities reconstructed from automated tools and consensus approaches 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.09.13.557568v1?rss=1</link>
<description><![CDATA[
Genome-scale metabolic models (GEMs) of microbial communities offer valuable insights into the functional capabilities of their members and facilitate the exploration of microbial interactions. These models are generated using different automated reconstruction tools, each relying on different biochemical databases that may affect the conclusions drawn from the in silico analysis. One way to address this problem is to employ a consensus reconstruction method that combines the outcomes of different reconstruction tools. Here, we conducted a comparative analysis of community models reconstructed from three automated tools, i.e. CarveMe, gapseq, and KBase, alongside a consensus approach, utilizing data from two marine bacterial communities. Our analysis revealed that these reconstruction approaches, while based on the same genomes, resulted in GEMs with varying numbers of genes and reactions as well as metabolic functionalities, attributed to the different databases employed. Further, our results indicated that the set of exchanged metabolites was more influenced by the reconstruction approach rather than the specific bacterial community investigated. This observation suggests a potential bias in predicting metabolite interactions using community GEMs. We also showed that consensus models encompassed a larger number of reactions and metabolites while concurrently reducing the presence of dead-end metabolites. Therefore, the usage of consensus models allows making full and unbiased use from aggregating genes from the different reconstructions in assessing the functional potential of metabolic communities.

ImportanceOur study contributes significantly to the field of microbial community modeling through a comprehensive comparison of genome-scale metabolic models (GEMs) generated via various automated tools, including: CarveMe, gapseq, KBase, and a consensus approach. We revealed substantial structural disparities in model outcomes, primarily attributed to variations in the employed databases. A key finding underscored the substantial impact of the reconstruction approach on the set of exchanged metabolites, emphasizing the necessity for enhanced data integration strategies. The consensus models emerge as a powerful solution, exhibiting improved functional capabilities by encompassing a greater number of reactions, metabolites, and genes. This not only offers a more comprehensive representation of metabolic networks within bacterial communities but also shows promise in reducing variability for more accurate predictions of exchange metabolites. Overall, our research provides a critical framework for refining microbial community simulations, impacting fields from ecology to synthetic biology.
]]></description>
<dc:creator>Hsieh, Y. E.</dc:creator>
<dc:creator>Tandon, K.</dc:creator>
<dc:creator>Verbruggen, H.</dc:creator>
<dc:creator>Nikoloski, Z.</dc:creator>
<dc:date>2023-09-17</dc:date>
<dc:identifier>doi:10.1101/2023.09.13.557568</dc:identifier>
<dc:title><![CDATA[Comparative analysis of metabolic models of microbial communities reconstructed from automated tools and consensus approaches]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-09-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.09.14.557670v1?rss=1">
<title>
<![CDATA[
Automatic vocalisation detection delivers reliable, multi-faceted, and global avian biodiversity monitoring 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.09.14.557670v1?rss=1</link>
<description><![CDATA[
Tracking biodiversity and its dynamics at scale is essential if we are to solve global environmental challenges. Detecting animal vocalisations in passively recorded audio data offers a highly automatable, inexpensive, and taxonomically broad way to monitor biodiversity. However, uptake is slow due to the expertise and labour required to label new data and fine-tune algorithms for each deployment. In this study, we applied an off-the-shelf bird vocalisation detection model, BirdNET, to 152,376 hours of audio comprising of datasets from Norway, Taiwan, Costa Rica, and Brazil. We manually listened to a subset of detections for each species in each dataset and found precisions of over 80% for 89 of the 139 species (100% for 57 species). Whilst some species were reliably detected across multiple datasets, the performance of others was dataset specific. By filtering out unreliable detections, we could extract species and community level insight on diel (Brazil) and seasonal (Taiwan) temporal scales, as well as landscape (Costa Rica) and national (Norway) spatial scales. Our findings demonstrate that, with a relatively fast validation step, a single vocalisation detection model can deliver multi-faceted community and species level insight across highly diverse datasets; unlocking the scale at which acoustic monitoring can deliver immediate applied impact.
]]></description>
<dc:creator>Sethi, S. S.</dc:creator>
<dc:creator>Bick, A.</dc:creator>
<dc:creator>Chen, M.-Y.</dc:creator>
<dc:creator>Crouzeilles, R.</dc:creator>
<dc:creator>Hillier, B. V.</dc:creator>
<dc:creator>Lawson, J.</dc:creator>
<dc:creator>Lee, C.-Y.</dc:creator>
<dc:creator>Liu, S.-H.</dc:creator>
<dc:creator>Parruco, C. H. d. F.</dc:creator>
<dc:creator>Rosten, C.</dc:creator>
<dc:creator>Somveille, M.</dc:creator>
<dc:creator>Tuanmu, M.-N.</dc:creator>
<dc:creator>Banks-Leite, C.</dc:creator>
<dc:date>2023-09-17</dc:date>
<dc:identifier>doi:10.1101/2023.09.14.557670</dc:identifier>
<dc:title><![CDATA[Automatic vocalisation detection delivers reliable, multi-faceted, and global avian biodiversity monitoring]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-09-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.09.19.558523v1?rss=1">
<title>
<![CDATA[
The interactome of histone deacetylase HDA19 in dark-grown Arabidopsis seedlings 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.09.19.558523v1?rss=1</link>
<description><![CDATA[
Here, we describe a data set derived from an immunoprecipitation (IP)-based analysis of the histone deacetylase HDA19 interactome in etiolated Arabidopsis seedlings. HISTONE DEACETYLASE 19 (HDA19) belongs to the class 1 of the Reduced Potassium Dependence3/Histone Deacetylase-1 (RPD3/HDA1) superfamily and is possibly the most intensively studied HDA. Here, we describe a data set derived from an immunoprecipitation (IP)-based analysis of the histone deacetylase HDA19 interactome in etiolated Arabidopsis seedlings. We believe that this data set presented here provides a valuable resource for follow-up research on novel interacting partners of this central protein.
]]></description>
<dc:creator>Schmidt, W.</dc:creator>
<dc:creator>Velez Bermudez, I. C.</dc:creator>
<dc:date>2023-09-21</dc:date>
<dc:identifier>doi:10.1101/2023.09.19.558523</dc:identifier>
<dc:title><![CDATA[The interactome of histone deacetylase HDA19 in dark-grown Arabidopsis seedlings]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-09-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.09.25.559365v1?rss=1">
<title>
<![CDATA[
The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.09.25.559365v1?rss=1</link>
<description><![CDATA[
A global genome database of all of Earths species diversity could be a treasure trove of scientific discoveries. However, regardless of the major advances in genome sequencing technologies, only a tiny fraction of species have genomic information available. To contribute to a more complete planetary genomic database, scientists and institutions across the world have united under the Earth BioGenome Project (EBP), which plans to sequence and assemble high-quality reference genomes for all [~]1.5 million recognized eukaryotic species through a stepwise phased approach. As the initiative transitions into Phase II, where 150,000 species are to be sequenced in just four years, worldwide participation in the project will be fundamental to success. As the European node of the EBP, the European Reference Genome Atlas (ERGA) seeks to implement a new decentralised, accessible, equitable and inclusive model for producing high-quality reference genomes, which will inform EBP as it scales. To embark on this mission, ERGA launched a Pilot Project to establish a network across Europe to develop and test the first infrastructure of its kind for the coordinated and distributed reference genome production on 98 European eukaryotic species from sample providers across 33 European countries. Here we outline the process and challenges faced during the development of a pilot infrastructure for the production of reference genome resources, and explore the effectiveness of this approach in terms of high-quality reference genome production, considering also equity and inclusion. The outcomes and lessons learned during this pilot provide a solid foundation for ERGA while offering key learnings to other transnational and national genomic resource projects.
]]></description>
<dc:creator>Mc Cartney, A. M.</dc:creator>
<dc:creator>Formenti, G.</dc:creator>
<dc:creator>Mouton, A.</dc:creator>
<dc:creator>Ciofi, C.</dc:creator>
<dc:creator>Waterhouse, R. M.</dc:creator>
<dc:creator>Mazzoni, C. J.</dc:creator>
<dc:creator>De Panis, D.</dc:creator>
<dc:creator>Schlude Marins, L. S.</dc:creator>
<dc:creator>Leitao, H. G.</dc:creator>
<dc:creator>Diedericks, G.</dc:creator>
<dc:creator>Kirangwa, J.</dc:creator>
<dc:creator>Morselli, M.</dc:creator>
<dc:creator>Salces, J.</dc:creator>
<dc:creator>Escudero, N.</dc:creator>
<dc:creator>Iannucci, A.</dc:creator>
<dc:creator>Natali, C.</dc:creator>
<dc:creator>Svardal, H.</dc:creator>
<dc:creator>Fernandez, R.</dc:creator>
<dc:creator>De Pooter, T.</dc:creator>
<dc:creator>Joris, G.</dc:creator>
<dc:creator>Strazisar, M.</dc:creator>
<dc:creator>Wood, J.</dc:creator>
<dc:creator>Herron, K. E.</dc:creator>
<dc:creator>Seehausen, O.</dc:creator>
<dc:creator>Watts, P. C.</dc:creator>
<dc:creator>Shaw, F.</dc:creator>
<dc:creator>Davey, R. P.</dc:creator>
<dc:creator>Minotto, A.</dc:creator>
<dc:creator>Fernandez Gonzalez, J. M.</dc:creator>
<dc:creator>Bohne, A.</dc:creator>
<dc:creator>Alegria, C.</dc:creator>
<dc:creator>Alioto, T.</dc:creator>
<dc:creator>Alves, P. C.</dc:creator>
<dc:creator>Amorim, I. R.</dc:creator>
<dc:creator>Aury, J.-M.</dc:creator>
<dc:creator>Backstrom, N.</dc:creator>
<dc:creator>Baldrian, P.</dc:creator>
<dc:creator>Ballarin, L.</dc:creator>
<dc:creator>Baltrunaite, L.</dc:creator>
<dc:creator>Barta, E.</dc:creator>
<dc:creator>BedHom, B.</dc:creator>
<dc:creator>Belser, C.</dc:creator>
<dc:creator>B</dc:creator>
<dc:date>2023-09-28</dc:date>
<dc:identifier>doi:10.1101/2023.09.25.559365</dc:identifier>
<dc:title><![CDATA[The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-09-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.09.30.560297v1?rss=1">
<title>
<![CDATA[
Successive responses of three coral holobiont components (coral hosts, symbiotic algae, and bacteria) to daily temperature fluctuations 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.09.30.560297v1?rss=1</link>
<description><![CDATA[
Coral reef ecosystems support over a quarter of the worlds marine life and play important ecological and economic roles. However, the increasingly severe weather events associated with ocean warming and climate change are believed to be rapidly altering the functions of coral reefs and their ecosystems. Corals and their associated microbiota form a "holobiont," which includes symbiotic algae and other associated microbiota dominated by bacteria. These microbiota have a direct relationship with the health of the coral host. Their composition is influenced by various environmental factors, such as increasing sea water temperatures. Previous studies of the effects of temperature changes on coral physiology and associated bacterial communities have been conducted based on stable water temperatures set by mean temperatures, or by slowly increasing/decreasing temperatures. However, the daily temperature fluctuations that corals experience in nature are not stable. Rather, there may be significant differences of up to 6{degrees}C in a single day. The current understanding of the effects of large daily temperature fluctuations on coral and associated bacterial community dynamics is limited. Hence, in this study, we conducted a four-week tank experiment using different large daily temperature fluctuations accompanied by continuous warming conditions to investigate the effects on two common reef-building corals, Stylophora pistillata and Pocillopora acuta, in Taiwan. During the experiment, the activity of coral host catalase was measured, the photosynthetic ability of symbiotic algae was recorded, and the variation in bacterial communities was analyzed using the V6-V8 region of 16S rDNA. According to the results, different parts of the holobionts of different coral species exhibited varying response rates to the continuous warming conditions and diurnal temperature fluctuations. Additionally, it was found that diurnal temperature fluctuations may mitigate the heat stress on the host and reduce the changes in bacterial response to warming. Furthermore, the holobionts of different coral species may adopt different adaptation and survival strategies in response to diurnal temperature fluctuations and warming. Finally, based on the response of these two coral species under the conditions of diurnal temperature fluctuations and continuous warming, Acinetobacter and Rhodobacteraceae were identified as potential indicator coral-associated bacteria. This is the first study to investigate the tripartite dynamic response of coral, symbiotic algae and bacteria to daily temperature fluctuations.
]]></description>
<dc:creator>Hsieh, Y. E.</dc:creator>
<dc:creator>Lu, C.-Y.</dc:creator>
<dc:creator>Liu, P.-Y.</dc:creator>
<dc:creator>Kao, J.-M.</dc:creator>
<dc:creator>Yang, S.-Y.</dc:creator>
<dc:creator>Wu, C.-Y.</dc:creator>
<dc:creator>Wong, J.-W. M.</dc:creator>
<dc:creator>Shikina, S.</dc:creator>
<dc:creator>Fan, T.-Y.</dc:creator>
<dc:creator>Yang, S.-H.</dc:creator>
<dc:date>2023-09-30</dc:date>
<dc:identifier>doi:10.1101/2023.09.30.560297</dc:identifier>
<dc:title><![CDATA[Successive responses of three coral holobiont components (coral hosts, symbiotic algae, and bacteria) to daily temperature fluctuations]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-09-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.10.01.560400v1?rss=1">
<title>
<![CDATA[
Brassinosteroid recruits FERONIA to safeguard cell expansion in Arabidopsis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.10.01.560400v1?rss=1</link>
<description><![CDATA[
Plant cell expansion is driven by turgor pressure and regulated by hormones. How plant cells avoid cell wall rupture during hormone-induced cell expansion remains a mystery. Here we show that brassinosteroid (BR), while stimulating cell elongation, promotes the plasma membrane (PM) accumulation of the receptor kinase FERONIA (FER), which monitors cell wall damage and in turn attenuates BR-induced cell elongation to prevent cell rupture. The GSK3-like kinase BIN2 phosphorylates FER, resulting in reduced FER accumulation and translocation from endoplasmic reticulum to PM. By inactivating BIN2, BR signaling promotes dephosphorylation and increases PM accumulation of FER, thereby enhancing the surveillance of cell wall integrity. Our study reveals a vital signaling circuit that coordinates hormone signaling with mechanical sensing to prevent cell bursting during hormone-induced cell expansion.

One-Sentence SummaryBrassinosteroid recruits a cell wall integrity monitor to prevent growth-induced cell wall damage.
]]></description>
<dc:creator>Chaudhary, A.</dc:creator>
<dc:creator>Hsiao, Y.-C.</dc:creator>
<dc:creator>Yeh, F.-L. J.</dc:creator>
<dc:creator>Wu, H.-M.</dc:creator>
<dc:creator>Cheung, A. Y.</dc:creator>
<dc:creator>Xu, S.-L.</dc:creator>
<dc:creator>Wang, Z.-Y.</dc:creator>
<dc:date>2023-10-02</dc:date>
<dc:identifier>doi:10.1101/2023.10.01.560400</dc:identifier>
<dc:title><![CDATA[Brassinosteroid recruits FERONIA to safeguard cell expansion in Arabidopsis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.10.17.562744v1?rss=1">
<title>
<![CDATA[
The impact of light and thioredoxins on the plant thiol-disulfide proteome 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.10.17.562744v1?rss=1</link>
<description><![CDATA[
Thiol-based redox regulation is a crucial post-translational mechanism to acclimate plants to changing light availability. Here, we conduct a biotin-switch-based redox proteomics study to systematically investigate dynamics of the thiol-redox network in response to temporal changes in light availability and across genotypes lacking parts of the thioredoxin (Trx) or NADPH-Trx-reductase C (NTRC) systems in the chloroplast. Time-resolved dynamics revealed light leading to marked decreases in the oxidation states of many chloroplast proteins with photosynthetic functions during the first 10 min, followed by their partial re-oxidation after 2-6 hours into the photoperiod. This involved f, m and x-type Trx proteins showing similar light-induced reduction-oxidation dynamics, while NTRC, 2-Cys-Prx and Trx y2 showed an opposing pattern, being more oxidized in the light than the dark. In Arabidopsis trxf1f2, trxm1m2 or ntrc mutants, in the light most proteins showed increased oxidation states than wild type, suggesting their light-dependent dynamics being related to the NTRC/Trx networks. While NTRC deficiency had a strong influence in all light conditions, deficiencies in f- or m-type Trxs showed differential impacts on the thiol-redox proteome depending on the light environment, being higher in constant or fluctuating light, respectively. Results indicate plant redox proteomes to be subject to dynamic changes in reductive and oxidative pathways to cooperatively fine-tune photosynthetic and metabolic processes in the light. This involves f-type Trxs and NTRC to play a role in constant medium light, while both m-type Trxs and NTRC being important to balance changes in protein redox-pattern during dynamic alterations in fluctuating light intensities.

One sentence summaryThe plant protein redoxome shows light-dependent reduction and reoxidation dynamics linked to Trxs f1/f2, m1/m2 and NTRC, being of different importance depending on the extent of light variability.
]]></description>
<dc:creator>Hou, L.-Y.</dc:creator>
<dc:creator>Sommer, F. K.</dc:creator>
<dc:creator>Poeker, L.</dc:creator>
<dc:creator>Dziubek, D.</dc:creator>
<dc:creator>Schroda, M.</dc:creator>
<dc:creator>Geigenberger, P.</dc:creator>
<dc:date>2023-10-20</dc:date>
<dc:identifier>doi:10.1101/2023.10.17.562744</dc:identifier>
<dc:title><![CDATA[The impact of light and thioredoxins on the plant thiol-disulfide proteome]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-10-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.10.20.563379v1?rss=1">
<title>
<![CDATA[
Modeling alternative translation initiation sites in plants reveals evolutionarily conserved cis-regulatory codes in eukaryotes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.10.20.563379v1?rss=1</link>
<description><![CDATA[
mRNA translation relies on identifying translation initiation sites (TISs) in mRNAs. Alternative TISs are prevalent across plant transcriptomes, but the mechanisms for their recognition are unclear. Using ribosome profiling and machine learning, we developed models for predicting alternative TISs in Arabidopsis thaliana and tomato (Solanum lycopersicum). Distinct feature sets were predictive of AUG and non-AUG TISs in 5' untranslated regions and coding sequences, including a novel CU-rich sequence that promoted plant TIS activity, a translational enhancer found across dicots and monocots and also in humans and viruses. Our results elucidate the mechanistic and evolutionary basis of TIS recognition, whereby cis-regulatory RNA signatures affect start site selection. The TIS prediction model provides global estimates of TISs to discover neglected protein-coding genes across plant genomes. The prevalence of cis-regulatory signatures across eukaryotes and viruses suggests their broad, critical roles in reprogramming the translational landscape in the plant-virus arms race.

TeaserNew insights into how plant ribosomes distinguish AUG and non-AUG triplets for protein synthesis via a conserved eukaryotic cis-regulatory strategy.
]]></description>
<dc:creator>Wu, T.-Y.</dc:creator>
<dc:creator>Li, Y.-R.</dc:creator>
<dc:creator>Chang, K.-J.</dc:creator>
<dc:creator>Urano, D.</dc:creator>
<dc:creator>Liu, M.-J.</dc:creator>
<dc:date>2023-10-21</dc:date>
<dc:identifier>doi:10.1101/2023.10.20.563379</dc:identifier>
<dc:title><![CDATA[Modeling alternative translation initiation sites in plants reveals evolutionarily conserved cis-regulatory codes in eukaryotes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-10-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.10.23.563533v1?rss=1">
<title>
<![CDATA[
The NRC0 gene cluster of sensor and helper NLR immune receptors is functionally conserved across asterid plants 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.10.23.563533v1?rss=1</link>
<description><![CDATA[
NLR (nucleotide-binding domain and leucine-rich repeat-containing) proteins can form complex receptor networks to confer innate immunity. NRCs are phylogenetically related nodes that function downstream of a massively expanded network of disease resistance proteins that protect against multiple plant pathogens. Here, we used phylogenomic methods to reconstruct the macroevolution of the NRC family. One of the NRCs, we termed NRC0, is the only family member shared across asterid plants, leading us to investigate its evolutionary history and genetic organization. In several asterid species, NRC0 is genetically clustered to other NLRs that are phylogenetically related to NRC-dependent disease resistance genes. This prompted us to hypothesize that the ancestral state of the NRC network is an NLR helper-sensor gene cluster that was present early during asterid evolution. We validated this hypothesis by demonstrating that NRC0 is essential for the hypersensitive cell death induced by its genetically linked sensor NLR partners in four divergent asterid species: tomato, wild sweet potato, coffee and carrot. In addition, activation of a sensor NLR leads to high-order complex formation of its genetically linked NRC0 similar to other NRCs. Our findings map out contrasting evolutionary dynamics in the macroevolution of the NRC network over the last 125 million years from a functionally conserved NLR gene cluster to a massive genetically dispersed network.

One-sentence summaryNRC0 gene cluster is functionally conserved across divergent asterid species and predates the massively expanded NRC network.
]]></description>
<dc:creator>Sakai, T.</dc:creator>
<dc:creator>Martinez-Anaya, C.</dc:creator>
<dc:creator>Contreras, M. P.</dc:creator>
<dc:creator>Kamoun, S.</dc:creator>
<dc:creator>Wu, C.-H.</dc:creator>
<dc:creator>Adachi, H.</dc:creator>
<dc:date>2023-10-23</dc:date>
<dc:identifier>doi:10.1101/2023.10.23.563533</dc:identifier>
<dc:title><![CDATA[The NRC0 gene cluster of sensor and helper NLR immune receptors is functionally conserved across asterid plants]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-10-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.10.25.563953v1?rss=1">
<title>
<![CDATA[
NRC immune receptor networks show diversified hierarchical genetic architecture across plant lineages 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.10.25.563953v1?rss=1</link>
<description><![CDATA[
Plants developed sophisticated immune systems with nucleotide-binding domain and leucine-rich repeat-containing (NLR) proteins to repel invading pathogens. The NRC (NLR required for cell death) family includes helper NLRs that form a complex genetic network with multiple sensor NLRs to provide resistance against pathogens of solanaceous plants. However, the evolution and function of NRC networks outside solanaceous plants is currently unknown. We conducted phylogenomic and macroevolutionary analyses comparing NLRs identified from different asterids lineages and found that NRC networks expanded significantly in most lamiids but not in Ericales and campanulids. Using transient expression assays in Nicotiana benthamiana, we show that NRC networks are simple in Ericales and campanulids, but are with high complexity in lamiids. Phylogenetic analyses grouped the NRC helper NLRs into three NRC0 subclades that are conserved, and several family-specific NRC subclades of lamiids that show signatures of diversifying selection. Functional analyses revealed that members of the NRC0 subclades are partially interchangeable, whereas family-specific NRC members in lamiids lack interchangeability. Our findings highlight the distinctive evolutionary patterns of the NRC networks in asterids and provide potential insights into transferring disease resistance across plant lineages.
]]></description>
<dc:creator>Goh, F.-J.</dc:creator>
<dc:creator>Huang, C.-Y.</dc:creator>
<dc:creator>Derevnina, L.</dc:creator>
<dc:creator>Wu, C.-H.</dc:creator>
<dc:date>2023-10-27</dc:date>
<dc:identifier>doi:10.1101/2023.10.25.563953</dc:identifier>
<dc:title><![CDATA[NRC immune receptor networks show diversified hierarchical genetic architecture across plant lineages]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-10-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.11.01.564642v1?rss=1">
<title>
<![CDATA[
Chromosome-level genome assemblies of two hemichordates provide new insights into deuterostome origin and chromosome evolution 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.11.01.564642v1?rss=1</link>
<description><![CDATA[
Deuterostomes are an animal superphylum that includes Hemichordata and Echinodermata (together Ambulacraria) and Chordata. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to decipher the genetic changes that drove the diversification of deuterostome lineages. Here, we generate chromosome-level genome assemblies of two hemichordate species, Ptychodera flava and Schizocardium californicum, and use comparative genomic approaches to infer the chromosomal architecture of the deuterostome common ancestor and delineate lineage-specific chromosomal modifications. We show that hemichordate chromosomes (1N=23) exhibit remarkable chromosome-scale macrosynteny when compared to other deuterostomes, and can be derived from 24 deuterostome ancestral linkage groups (ALGs). These deuterostome ALGs in turn match previously inferred bilaterian ALGs, consistent with a relatively short transition from the last common bilaterian ancestor to the origin of deuterostomes. Based on this deuterostome ALG complement, we deduced chromosomal rearrangement events that occurred in different lineages. For example, a fusion-with-mixing event produced an Ambulacraria-specific ALG that subsequently split into two chromosomes in extant hemichordates, while this homologous ALG further fused with another chromosome in sea urchins. Orthologous genes distributed in these rearranged chromosomes are enriched for functions in various developmental processes. We found that the deeply conserved Hox clusters are located in highly rearranged chromosomes but have lower densities of transposable elements within the clusters. We also provide evidence that the deuterostome-specific pharyngeal gene cluster was established via the combination of three pre-assembled microsyntenic blocks. We suggest that since chromosomal rearrangement events and formation of new gene clusters may change the regulatory controls of developmental genes, these events may have contributed to the evolution of diverse body plans among deuterostomes.
]]></description>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Marletaz, F.</dc:creator>
<dc:creator>Perez-Posada, A.</dc:creator>
<dc:creator>Martinez Garcia, P. M.</dc:creator>
<dc:creator>Schloissnig, S.</dc:creator>
<dc:creator>Peluso, P.</dc:creator>
<dc:creator>Conception, G. T.</dc:creator>
<dc:creator>Bump, P.</dc:creator>
<dc:creator>Chen, Y.-C.</dc:creator>
<dc:creator>Chou, C.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Fan, T.-P.</dc:creator>
<dc:creator>Tsai, C.-T.</dc:creator>
<dc:creator>Gomez Skarmeta, J. L.</dc:creator>
<dc:creator>Tena, J. J.</dc:creator>
<dc:creator>Lowe, C. J.</dc:creator>
<dc:creator>Rank, D. R.</dc:creator>
<dc:creator>Rokhsar, D. S.</dc:creator>
<dc:creator>Yu, J.-K.</dc:creator>
<dc:creator>Su, Y.-H.</dc:creator>
<dc:date>2023-11-02</dc:date>
<dc:identifier>doi:10.1101/2023.11.01.564642</dc:identifier>
<dc:title><![CDATA[Chromosome-level genome assemblies of two hemichordates provide new insights into deuterostome origin and chromosome evolution]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-11-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.11.02.564871v1?rss=1">
<title>
<![CDATA[
On the independent irritability of goldfish eggs and embryos -- a living communication on the rhythmic yolk contractions in goldfish 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.11.02.564871v1?rss=1</link>
<description><![CDATA[
Rhythms play an important role in the precise spatiotemporal regulation of biological processes during development and patterning of embryos. We here investigate the rhythmic contractions of the yolk during early development of the goldfish Carassius auratus. We quantify these contractions and record robust and persistent rhythmic yolk movements that are not seen in closely-related species (common carp Cyprinus carpio and zebrafish Danio rerio). We report that yolk contractions are an intrinsic emergent property of the egg, i.e. goldfish eggs are independently irritable / excitable. These contractions do not require sperm entry / fertilization nor cell division, and they notably emerge at a precise time -- suggesting that goldfish eggs are able to measure elapsed time from what we infer to be egg activation. We further show that these rhythmic contractions persist even in yolk in isolation. As the yolk itself is known to confer critical cues for early dorsoventral (DV) patterning of teleost embryos, we hypothesize that its contractions in goldfish may influence the patterning process of this species. Indeed, we find that embryos of the naturally more ventralized twin-tail goldfish strain Oranda display altered yolk contraction dynamics (i.e. faster contractions). We also present that the period of yolk contractions is independent of ChdS, a key gene involved in DV pattening and linked to the twin-tail phenotype, but is instead a trait that is maternal in origin. We aim to uncover whether the yolk contractions happening during early development of domesticated goldfish are the licensing process which permit the emergence of novel patterning phenotypes naturally-observed in this species (e.g. twin-tail and dorsal-finless strains) and which instead have not been found among closely-related species (e.g. common carp) whose yolks do not contract.

This manuscript is here published as a living communication (as described in Gnaiger (2021)). The authors intend to share findings when they are available, encourage feedback and discussion, and invite knowledge exchange and collaboration.
]]></description>
<dc:creator>Sanchez, P. G. L.</dc:creator>
<dc:creator>Wang, C.-Y.</dc:creator>
<dc:creator>Li, I.-J.</dc:creator>
<dc:creator>Ota, K. G.</dc:creator>
<dc:date>2023-11-03</dc:date>
<dc:identifier>doi:10.1101/2023.11.02.564871</dc:identifier>
<dc:title><![CDATA[On the independent irritability of goldfish eggs and embryos -- a living communication on the rhythmic yolk contractions in goldfish]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-11-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.11.07.566145v1?rss=1">
<title>
<![CDATA[
An acidophilic fungus is integral to prey digestion in a carnivorous plant 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.11.07.566145v1?rss=1</link>
<description><![CDATA[
Carnivorous plant leaves, such as those of the spoon-leaved sundew Drosera spatulata, secrete mucilage which hosts microorganisms potentially aiding in prey digestion. We characterised the mucilage microbial communities and identified the acidophilic fungus Acrodontium crateriforme as the ecologically dominant species. The fungus grows and sporulates on sundew glands as its preferred acidic environment. We show that the A. crateriforme has a reduced genome similar to that of other symbiotic fungi. Based on the transcriptomes when encountering prey insects, we revealed a high degree of genes co-option in each species during fungus-plant coexistence and digestion. Expression patterns of the holobiont during digestion further revealed synergistic effects in several gene families including fungal aspartic and sedolisin peptidases, facilitating the digestion of sundews prey, as well as transporters and dose-dependent responses in plant genes involved in jasmonate signalling pathway. This study establishes that botanical carnivory is defined by multidimensional adaptations correlated with interspecies interactions.
]]></description>
<dc:creator>Sun, P.-F.</dc:creator>
<dc:creator>Lu, M. R.</dc:creator>
<dc:creator>Liu, Y.-C.</dc:creator>
<dc:creator>Lin, Y.-f.</dc:creator>
<dc:creator>Hoh, D. Z.</dc:creator>
<dc:creator>Ke, H.-M.</dc:creator>
<dc:creator>Wang, I.-F.</dc:creator>
<dc:creator>Lu, M.-Y. J.</dc:creator>
<dc:creator>Kirschner, R.</dc:creator>
<dc:creator>Lin, Y.-C. J.</dc:creator>
<dc:creator>Chen, Y.-L.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2023-11-08</dc:date>
<dc:identifier>doi:10.1101/2023.11.07.566145</dc:identifier>
<dc:title><![CDATA[An acidophilic fungus is integral to prey digestion in a carnivorous plant]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-11-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.11.13.566949v1?rss=1">
<title>
<![CDATA[
The Velvet transcription factor PnVeA regulates necrotrophic effectors and secondary metabolism in the wheat pathogen Parastagonospora nodorum 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.11.13.566949v1?rss=1</link>
<description><![CDATA[
The fungus Parastagonospora nodorum causes septoria nodorum blotch on wheat. The role of the fungal Velvet-family transcription factor VeA in P. nodorum development and virulence was investigated here. Deletion of the P. nodorum VeA ortholog, PnVeA, resulted in growth abnormalities including pigmentation, abolished asexual sporulation and highly reduced virulence on wheat. Comparative RNA-Seq and RT-PCR analyses revealed that the deletion of PnVeA also decoupled the expression of major necrotrophic effector genes. In addition, the deletion of PnVeA resulted in an up-regulation of four predicted secondary metabolite (SM) gene clusters. Using liquid-chromatography mass-spectrometry, it was observed that one of the SM gene clusters led to an accumulation of the mycotoxin alternariol. PnVeA is essential for asexual sporulation, full virulence, secondary metabolism and necrotrophic effector regulation.
]]></description>
<dc:creator>Morikawa, S.</dc:creator>
<dc:creator>Verdonk, C.</dc:creator>
<dc:creator>John, E.</dc:creator>
<dc:creator>Lenzo, L.</dc:creator>
<dc:creator>Sbaraini, N.</dc:creator>
<dc:creator>Turo, C. J.</dc:creator>
<dc:creator>Li, H.</dc:creator>
<dc:creator>Jiang, D.</dc:creator>
<dc:creator>Chooi, Y.-H.</dc:creator>
<dc:creator>Tan, K.-C.</dc:creator>
<dc:date>2023-11-14</dc:date>
<dc:identifier>doi:10.1101/2023.11.13.566949</dc:identifier>
<dc:title><![CDATA[The Velvet transcription factor PnVeA regulates necrotrophic effectors and secondary metabolism in the wheat pathogen Parastagonospora nodorum]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-11-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.12.03.569830v1?rss=1">
<title>
<![CDATA[
A Whole-Cell Screening Platform to Discover Cell Adhesion Molecules that Enable Programmable Bacterial Cell-Cell Adhesion 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.12.03.569830v1?rss=1</link>
<description><![CDATA[
Developing programmable bacterial cell-cell adhesion is of significant interest due to its versatile applications. Current methods that rely on presenting cell adhesion molecules (CAMs) on bacterial surfaces are limited by the lack of a generalizable strategy to identify such molecules targeting bacterial membrane proteins in their natural states. Here, we introduce a whole-cell screening platform designed to discover CAMs targeting bacterial membrane proteins within a synthetic bacteria-displayed nanobody library. Leveraging the potency of the bacterial type IV secretion system--a contact-dependent DNA delivery nanomachine--we have established a positive feedback mechanism to selectively enrich for bacteria displaying nanobodies that target antigen-expressing cells. Our platform successfully identified functional CAMs capable of recognizing three distinct outer membrane proteins (TraN, OmpA, OmpC), demonstrating its efficacy in CAM discovery. This approach holds promise for engineering bacterial cell-cell adhesion, such as targeted antimicrobial interventions in the microbiome by deploying programmed inhibitor cells.
]]></description>
<dc:creator>Ting, S.-Y.</dc:creator>
<dc:creator>Chen, P.-Y.</dc:creator>
<dc:creator>Chen, Y.-C.</dc:creator>
<dc:creator>Chen, P.-P.</dc:creator>
<dc:creator>Lin, K.-T.</dc:creator>
<dc:creator>Wang, W.-L.</dc:creator>
<dc:creator>Hsia, K.-C.</dc:creator>
<dc:date>2023-12-04</dc:date>
<dc:identifier>doi:10.1101/2023.12.03.569830</dc:identifier>
<dc:title><![CDATA[A Whole-Cell Screening Platform to Discover Cell Adhesion Molecules that Enable Programmable Bacterial Cell-Cell Adhesion]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-12-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.12.06.570338v1?rss=1">
<title>
<![CDATA[
Hybrid Neural Networks of the Olfactory Learning Center in the Drosophila Brain 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.12.06.570338v1?rss=1</link>
<description><![CDATA[
Biological signal encoding is shaped by the underlying neural circuitry. In Drosophila melanogaster, the mushroom body (MB) houses thousands of Kenyon cells (KCs) that process olfactory signals from hundreds of projection neurons (PNs). Previous studies debated the connectivity between PNs and KCs (random vs. structured). Our multiscale analysis of electron microscopic data revealed a hybrid network with diverse synaptic connection preferences and input divergence across different KC classes. Using MB connectome data, our simulation model, validated via functional imaging, accurately predicted distinct chemical sensitivities in the major KC classes. The model suggests that the hybrid network excels in detecting food odors while maintaining precise odor discrimination in different KC classes. These findings underscore the computational advantages of this hybrid network.
]]></description>
<dc:creator>Cheng, L.-S.</dc:creator>
<dc:creator>Charng, C.-C.</dc:creator>
<dc:creator>Chen, R.-H.</dc:creator>
<dc:creator>Feng, K.-L.</dc:creator>
<dc:creator>Chiang, A.-S.</dc:creator>
<dc:creator>Lo, C.-C.</dc:creator>
<dc:creator>Lee, T.-K.</dc:creator>
<dc:date>2023-12-06</dc:date>
<dc:identifier>doi:10.1101/2023.12.06.570338</dc:identifier>
<dc:title><![CDATA[Hybrid Neural Networks of the Olfactory Learning Center in the Drosophila Brain]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-12-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.12.07.570675v1?rss=1">
<title>
<![CDATA[
A chloroplast sulfate transporter modulates glutathione-mediated redox cycling to regulate cell division 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.12.07.570675v1?rss=1</link>
<description><![CDATA[
Glutathione redox cycling is important for cell cycle regulation. However, the underlying mechanisms remain unclear. We previously identified a cell-size mutant, suppressor of mat3 15-1 (smt15-1), that has elevated cellular glutathione, increased number of cell divisions, and small daughter cells. Here, we demonstrated that SMT15 is a chloroplast-associated membrane protein that is capable of transporting sulfate. Reducing expression of{gamma} -GLUTAMYLCYSTEINE SYNTHETASE, which encodes the rate-limiting enzyme required for glutathione biosynthesis, corrected the size defect of smt15-1 cells. Moreover, overexpressing GLUTATHIONE SYNTHETASE recapitulated the small-size phenotype of smt15-1 mutant, confirming the role of glutathione in modulation of the cell division. Hence, SMT15 may regulate chloroplast sulfate concentration to modulate cellular glutathione levels. Interestingly, glutathione was found to accumulate in the cytosol at the G1 phase and its level decreased substantially as cells entered the S/M phase in wild-type cells. Even though cytosolic glutathione of the small-sized mutants, smt15-1 and GSH2 overexpressors, followed the pattern of wild-type cells being accumulated at G1 and declined at the S/M phase, the basal body-specific accumulation of glutathione was associated with only the small-sized mutants. Therefore, we propose that glutathione-mediated redox in the basal bodies may regulate mitotic division number in Chlamydomonas reinhardtii. Our results support the link between glutathione-mediated redox regulation and mitotic cell division and suggest a new mechanism through which glutathione regulates the cell cycle.

One sentence summaryGlutathione-mediated redox regulation in basal bodies is important for cell division control
]]></description>
<dc:creator>Huang, P.-j.</dc:creator>
<dc:creator>Chen, C.-H.</dc:creator>
<dc:creator>Lin, Y.-L.</dc:creator>
<dc:creator>Lin, H.-Y.</dc:creator>
<dc:creator>Fang, S.-C.</dc:creator>
<dc:date>2023-12-08</dc:date>
<dc:identifier>doi:10.1101/2023.12.07.570675</dc:identifier>
<dc:title><![CDATA[A chloroplast sulfate transporter modulates glutathione-mediated redox cycling to regulate cell division]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-12-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.12.26.573376v1?rss=1">
<title>
<![CDATA[
Temporal Transcriptome Analysis Uncovers Regulatory Modules Programming Embryo Development from Embryonic Morphogenesis to Post-Germination 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.12.26.573376v1?rss=1</link>
<description><![CDATA[
We profiled the soybean seed embryo transcriptome across embryonic development to post-germinative development to understand gene activities and regulatory networks promoting these processes. Transcriptomic landscapes feature highly prevalent transcripts which are categorized into early and late groups with major functions of reserve accumulation and energy generation, respectively, and both functions are dominant during late reserve accumulation as the transitioning stage. During the mid-reserve accumulation, regulatory events simultaneously dominate at the transcriptional and chromatin levels, followed by the emergence of distinct mRNA populations during late reserve accumulation throughout germination. We identified diverse functions conducted by sequentially activated genes across developmental stages. Gene coexpression network analysis reveals modules associated with developmental stages, some of which are enriched in genes with functions involved in specific developmental processes. We identified an early-desiccation-associated gene module, containing most transcription factors responsive to abiotic stress, within which one transcription factor is functionally validated to demonstrate increased drought tolerance in Arabidopsis overexpression lines. Finally, we found that a subset of genes is under purifying selection, surpasses the number of their Arabidopsis germination-specific homologs and most are active before germination from embryonic morphogenesis through dormancy, suggesting a potential role in governing physical dormancy in soybean compared to physiological dormancy in Arabidopsis. Our data represent a step toward identifying genes and regulatory networks in the soybean genome facilitating developmental programs across transition phases to bridge embryonic and germinative development.
]]></description>
<dc:creator>Wang, Y.-C.</dc:creator>
<dc:creator>Hsieh, W.-H.</dc:creator>
<dc:creator>Huang, C.-J.</dc:creator>
<dc:creator>Jhan, Y.-T.</dc:creator>
<dc:creator>Zhan, J.</dc:creator>
<dc:creator>Chang, C.-C.</dc:creator>
<dc:creator>Hsieh, T.-F.</dc:creator>
<dc:creator>Lin, J.-Y.</dc:creator>
<dc:date>2023-12-27</dc:date>
<dc:identifier>doi:10.1101/2023.12.26.573376</dc:identifier>
<dc:title><![CDATA[Temporal Transcriptome Analysis Uncovers Regulatory Modules Programming Embryo Development from Embryonic Morphogenesis to Post-Germination]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-12-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2023.12.27.573388v1?rss=1">
<title>
<![CDATA[
Microscopy-guided subcellular proteomic discovery by high-speed ultra-content photo-biotinylation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2023.12.27.573388v1?rss=1</link>
<description><![CDATA[
Microscopy-guided proteomics at an organelle-dimension resolution is desired for revealing unknown protein constituents at specific disease- or functional-associated regions at the molecular-molecular interactions level. Here, we achieve protein spatial purification by introducing a firmware-integrated microscopy platform that triggers in situ subcellular photo-biotinylation of proteins at user-defined regions of interest (ROIs) one field of view (FOV) at a time for thousands of FOVs fully automatically. An illumination pattern at the analogous ROIs of each FOV is calculated on the fly by either machine learning or traditional image processing. Photoactivatable amino acid crosslinkers are activated by a two-photon focal light one spot at a time at a sub-millisecond illumination duration per spot. Imaging, pattern generation, targeted illumination, and FOV movement are coordinated and cycled with high-speed mechatronic control to complete illumination on millions of ROI spots within hours. Once enough proteins are biotinylated in a cell or tissue sample, the sample is scraped and lysed, and avidin pulldown is used to enrich proteins to achieve spatial protein scooping at a 240-nm precision. Subsequent LC-MS/MS is implemented to reveal the subcellular proteome in high sensitivity, specificity, and resolution. Using this technology termed optoproteomics, we have revealed novel stress granule-localized and amyloid {beta}-localized proteins validated by immunostaining. Together, spatial purification by ultra-content, high-speed microscopy-targeted photo-biotinylation enables unprecedented subcellular spatial proteomics discovery in any microscopically recognizable regions.
]]></description>
<dc:creator>Liao, J.-C.</dc:creator>
<dc:creator>Chen, Y.-D.</dc:creator>
<dc:creator>Chang, C.-W.</dc:creator>
<dc:creator>Cheung, C. H. Y.</dc:creator>
<dc:creator>Chang, H.-J.</dc:creator>
<dc:creator>Sie, Y.-D.</dc:creator>
<dc:creator>Chung, C.-W.</dc:creator>
<dc:creator>Huang, C.-K.</dc:creator>
<dc:creator>Huang, C.-C.</dc:creator>
<dc:creator>Chong, W. M.</dc:creator>
<dc:creator>Liu, Y.-P.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Kai, H.-J. J.</dc:creator>
<dc:creator>Wang, P.-J.</dc:creator>
<dc:date>2023-12-27</dc:date>
<dc:identifier>doi:10.1101/2023.12.27.573388</dc:identifier>
<dc:title><![CDATA[Microscopy-guided subcellular proteomic discovery by high-speed ultra-content photo-biotinylation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2023-12-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.01.22.576629v1?rss=1">
<title>
<![CDATA[
Glycolysis-Wnt signaling axis tunes developmental timing of embryo segmentation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.01.22.576629v1?rss=1</link>
<description><![CDATA[
The question of how metabolism impacts development is seeing a renaissance [1, 2]. How metabolism exerts instructive signaling functions is one of the central issues that need to be resolved. We tackled this question in the context of mouse embryonic axis segmentation. Previous studies have shown that changes in central carbon metabolism impact Wnt signaling [3-6] and the period of the segmentation clock [7], which controls the timing of axis segmentation. Here, we reveal that glycolysis tunes the segmentation clock period in an anti-correlated manner: higher glycolytic flux slows down the clock, and vice versa. Transcriptome and gene regulatory network analyses identified Wnt signaling and specifically the transcription factor Tcf7l2, previously associated with increased risk for diabetes [8, 9], as potential mechanisms underlying flux-dependent control of the clock period. Critically, we show that deletion of the Wnt antagonist Dkk1 rescued the slow segmentation clock phenotype caused by increased glycolysis, demonstrating that glycolysis instructs Wnt signaling to control the clock period. In addition, we demonstrate metabolic entrainment of the segmentation clock: periodic changes in the levels of glucose or glycolytic sentinel metabolite fructose 1,6-bisphosphate (FBP) synchronize signaling oscillations. Notably, periodic FBP pulses first entrained Wnt signaling oscillations and subsequently Notch signaling oscillations. We hence conclude that metabolic entrainment has an immediate, specific effect on Wnt signaling. Combined, our work identifies a glycolysis-FBP-Wnt signaling axis that tunes developmental timing, highlighting the instructive signaling role of metabolism in embryonic development.
]]></description>
<dc:creator>Miyazawa, H.</dc:creator>
<dc:creator>Rada, J.</dc:creator>
<dc:creator>Sanchez, P. G. L.</dc:creator>
<dc:creator>Esposito, E.</dc:creator>
<dc:creator>Bunina, D.</dc:creator>
<dc:creator>Girardot, C.</dc:creator>
<dc:creator>Zaugg, J.</dc:creator>
<dc:creator>Aulehla, A.</dc:creator>
<dc:date>2024-01-22</dc:date>
<dc:identifier>doi:10.1101/2024.01.22.576629</dc:identifier>
<dc:title><![CDATA[Glycolysis-Wnt signaling axis tunes developmental timing of embryo segmentation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-01-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.02.15.580425v1?rss=1">
<title>
<![CDATA[
Fusion, fission, and scrambling of the bilaterian genome in Bryozoa 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.02.15.580425v1?rss=1</link>
<description><![CDATA[
Groups of orthologous genes are commonly found together on the same chromosome over vast evolutionary distances. This extensive physical gene linkage, known as macrosynteny, is seen between bilaterian phyla as divergent as Chordata, Echinodermata, Mollusca, and Nemertea. Here, we report a unique pattern of genome evolution in Bryozoa, an understudied phylum of colonial invertebrates. Using comparative genomics, we reconstruct the chromosomal evolutionary history of five bryozoans. Multiple ancient chromosome fusions followed by gene mixing led to the near-complete loss of bilaterian linkage groups in the ancestor of extant bryozoans. A second wave of rearrangements, including chromosome fission, then occurred independently in two bryozoan classes, further scrambling bryozoan genomes. We also discover at least five derived chromosomal fusion events shared between bryozoans and brachiopods, supporting the traditional but highly debated Lophophorata hypothesis. Finally, we show that chromosome fusion and fission processes led to the partitioning of genes from bryozoan Hox clusters onto multiple chromosomes. Our findings demonstrate that the canonical bilaterian genome structure has been lost across all studied representatives of an entire phylum; reveal that linkage group fission can occur very frequently in specific lineages; and provide a powerful source of phylogenetic information.
]]></description>
<dc:creator>Lewin, T. D.</dc:creator>
<dc:creator>Liao, I. J.-Y.</dc:creator>
<dc:creator>Chen, M.-E.</dc:creator>
<dc:creator>Bishop, J. D. D.</dc:creator>
<dc:creator>Holland, P. W. H.</dc:creator>
<dc:creator>Luo, Y.-J.</dc:creator>
<dc:date>2024-02-16</dc:date>
<dc:identifier>doi:10.1101/2024.02.15.580425</dc:identifier>
<dc:title><![CDATA[Fusion, fission, and scrambling of the bilaterian genome in Bryozoa]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-02-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.02.14.580375v1?rss=1">
<title>
<![CDATA[
Human iPSC-derived Committed Cardiac Progenitors Generate Cardiac Tissue Grafts in a Swine Ischemic Cardiomyopathy Model without Triggering Ventricular Arrhythmias 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.02.14.580375v1?rss=1</link>
<description><![CDATA[
BackgroundIntramyocardial injection of human pluripotent stem cell-derived cardiomyocytes following a myocardial infarction (MI) improves cardiac function in large animal models, but associated ventricular arrhythmias are major safety concern. We hypothesized that transendocardial injection of human induced pluripotent stem cell (hiPSC)-derived committed cardiac progenitor cells (CCPs), combined with cardiac fibroblast-derived extracellular matrix (cECM) to enhance cell retention, will generate cardiac tissue grafts improving contractility without triggering ventricular arrhythmias.

MethodshiPSCs were differentiated using bioreactors and small molecules to produce committed cardiac progenitor cells (CCPs). MI was created using a coronary artery balloon occlusion and reperfusion model in Yucatan mini pigs. Four weeks later, epicardial needle injections of CCPs+cECM were performed in a small initial feasibility cohort (n=6), and then transendocardial injections of CCPs+cECM (n=14), CCPs alone (n=14), cECM alone (n=4) or vehicle control (n=13) into the peri-infarct region in a randomized cohort. Arrhythmias were evaluated using implanted event recorders. Magnetic resonance imaging (MRI) and invasive pressure-volume assessment were used to evaluate left ventricular anatomic and functional performance. Detailed histology was performed to detect and characterize human grafts.

ResultsA scalable biomanufacturing protocol was developed generating CCPs which can efficiently differentiate into cardiomyocytes or endothelial cells in vitro. Intramyocardial delivery of CCPs to post-MI porcine hearts resulted in engraftment and differentiation of CCPs to form ventricular cardiomyocyte rich grafts. There was no significant difference in cardiac MRI-based measured cardiac volumes or function between control, CCP and CCP+cECM groups; however, pressure-volume analysis showed an improvement in dobutamine-stimulated functional reserve in CCP and CCP+cECM groups. Delivery of CCPs did not result in tumors or ventricular arrhythmias.

ConclusionsTransendocardial delivery of CCPs with or without cECM into post-MI porcine hearts resulted in comparable human cardiomyocyte grafts which did not improve resting LV function but did improve stress-induced contractile reserve without triggering ventricular arrhythmias.
]]></description>
<dc:creator>Raval, A. N.</dc:creator>
<dc:creator>Schmuck, E. G.</dc:creator>
<dc:creator>Roy, S.</dc:creator>
<dc:creator>Saito, Y.</dc:creator>
<dc:creator>Zhou, T.</dc:creator>
<dc:creator>Conklin, J.</dc:creator>
<dc:creator>Hacker, T. A.</dc:creator>
<dc:creator>Koonce, C.</dc:creator>
<dc:creator>Boyer, M.</dc:creator>
<dc:creator>Stack, K.</dc:creator>
<dc:creator>Hebron, E.</dc:creator>
<dc:creator>Nagle, S. K.</dc:creator>
<dc:creator>Hsieh, P. C. H.</dc:creator>
<dc:creator>Kamp, T. J.</dc:creator>
<dc:date>2024-02-17</dc:date>
<dc:identifier>doi:10.1101/2024.02.14.580375</dc:identifier>
<dc:title><![CDATA[Human iPSC-derived Committed Cardiac Progenitors Generate Cardiac Tissue Grafts in a Swine Ischemic Cardiomyopathy Model without Triggering Ventricular Arrhythmias]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-02-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.02.20.581158v1?rss=1">
<title>
<![CDATA[
Generic rules of lumen nucleation and fusion in epithelial organoids 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.02.20.581158v1?rss=1</link>
<description><![CDATA[
Many internal organs in the body harbor a fluid-filled lumen. The mechanisms of lumens initiation and fusion have been reported as dependent on organ-type during organogenesis. In contrast, the physics of lumen suggests that force balance between luminal pressure and cell mechanics could lead to conserved rules which may unify their self-organisation. However, this hypothesis lacks experimental evidence. Here we compare lumen dynamics for three different systems (MDCK cysts, pancreatic spheres, and epiblast cysts) by using quantitative cell biology, microfabrication and theory. We report that initial cell number determines the maximum number of lumens but does not impact the steady state which is a final single lumen. In addition, lumen numbers exhibit two phases over time, a nucleation phase followed by a fusion phase. In the nucleation phase, lumens form between two cells in pancreatic and MDCK cysts whereas they form at the rosette stage between ten cells in epiblasts. In the second phase, lumens fuse by an increase in lumen volume for pancreatic spheres and MDCK cysts, whereas cell convergent directional motion leads to lumens fusion in epiblasts. We show that these phenomena are associated to the luminal hydrostatic pressure. We support these results with theoretical arguments and numerical simulations. We finally use MDCK cysts to manipulate cell adhesion and lumen volume and we successfully reproduce the fusion dynamics of pancreatic spheres and epiblasts. Our results reveal self-organisation rules of lumens across systems with relevance for morphogenesis during development and for the design of synthetic organs.
]]></description>
<dc:creator>Lu, L.</dc:creator>
<dc:creator>Fuji, K.</dc:creator>
<dc:creator>Guyomar, T.</dc:creator>
<dc:creator>Lieb, M.</dc:creator>
<dc:creator>Tanida, S.</dc:creator>
<dc:creator>Nonomura, M.</dc:creator>
<dc:creator>Hiraiwa, T.</dc:creator>
<dc:creator>Alcheikh, Y.</dc:creator>
<dc:creator>Yennek, S.</dc:creator>
<dc:creator>Petzold, H.</dc:creator>
<dc:creator>Martin-Lemaitre, C.</dc:creator>
<dc:creator>Grapin-Botton, A.</dc:creator>
<dc:creator>Honigmann, A.</dc:creator>
<dc:creator>Sano, M.</dc:creator>
<dc:creator>Riveline, D.</dc:creator>
<dc:date>2024-02-23</dc:date>
<dc:identifier>doi:10.1101/2024.02.20.581158</dc:identifier>
<dc:title><![CDATA[Generic rules of lumen nucleation and fusion in epithelial organoids]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-02-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.03.08.584019v1?rss=1">
<title>
<![CDATA[
Cryo-EM inspired NMR analysis reveals a pH-induced conformational switching mechanism for imparting dynamics to Betanodavirus protrusions 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.03.08.584019v1?rss=1</link>
<description><![CDATA[
Nervous necrosis virus (NNV), a non-enveloped betanodavirus, causes neuropathies and retinopathies in farmed fish, damaging aquaculture worldwide. NNV has 60 conspicuous surface protrusions comprising the protrusion domain (P-domain) of its capsid protein. Although NNV protrusions play critical roles in infectivity, the underlying dynamics remain unclear. Our cryogenic electron microscopy (cryo-EM)-derived structures of Dragon grouper (Epinephelus lanceolatus) NNV reveal that the protrusions undergo low-pH-induced compaction and movement. We show that the P-domain is monomeric in solution at a pH germane to infection (7.0). Moreover, nuclear magnetic resonance (NMR) structures reveal a peptide (amino acids 311-330) that adopts a flexible loop to form an open pocket. NMR spectral analysis at pH 5.0 aided by molecular dynamics (MD) simulations show that this loop switches to a {beta}-strand under acidic conditions, eliciting pocket closure and P-domain trimerization, highlighting a unique pH-sensing feature. Our docking analysis revealed the N-terminal moiety of sialic acid inserted into and interacting with conserved residues in the pocket. Additionally, a low-pH-induced conformational change in the linker region via peptide bond isomerization conferred malleability on the protrusions. Our work uncovers the protrusion dynamics of a betanodavirus governing its infectivity through a pH-dependent conformational switching mechanism, providing insights into complex virus-host interactions.
]]></description>
<dc:creator>Sterbova, P.</dc:creator>
<dc:creator>Wang, C.-H.</dc:creator>
<dc:creator>Carillo, K. J. D.</dc:creator>
<dc:creator>Lou, Y.-C.</dc:creator>
<dc:creator>Kato, T.</dc:creator>
<dc:creator>Namba, K.</dc:creator>
<dc:creator>Tzou, D.-L. M.</dc:creator>
<dc:creator>Chang, W.-H.</dc:creator>
<dc:date>2024-03-08</dc:date>
<dc:identifier>doi:10.1101/2024.03.08.584019</dc:identifier>
<dc:title><![CDATA[Cryo-EM inspired NMR analysis reveals a pH-induced conformational switching mechanism for imparting dynamics to Betanodavirus protrusions]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-03-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.03.12.584570v1?rss=1">
<title>
<![CDATA[
Border-zone cardiomyocytes and macrophages contribute to remodeling of the extracellular matrix to promote cardiomyocyte invasion during zebrafish cardiac regeneration 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.03.12.584570v1?rss=1</link>
<description><![CDATA[
Despite numerous advances in our understanding of zebrafish cardiac regeneration, an aspect that remains less studied is how regenerating cardiomyocytes invade, and eventually replace, the collagen-containing fibrotic tissue following injury. Here, we provide an in-depth analysis of the process of cardiomyocyte invasion using live-imaging and histological approaches. We observed close interactions between protruding cardiomyocytes and macrophages at the wound border zone, and macrophage-deficient irf8 mutant zebrafish exhibited defects in extracellular matrix (ECM) remodeling and cardiomyocyte protrusion into the injured area. Using a resident macrophage ablation model, we show that defects in ECM remodeling at the border zone and subsequent cardiomyocyte protrusion can be partly attributed to a population of resident macrophages. Single-cell RNA-sequencing analysis of cells at the wound border revealed a population of cardiomyocytes and macrophages with fibroblast-like gene expression signatures, including the expression of genes encoding ECM structural proteins and ECM-remodeling proteins. The expression of mmp14b, which encodes a membrane-anchored matrix metalloproteinase, was restricted to cells in the border zone, including cardiomyocytes, macrophages, fibroblasts, and endocardial/endothelial cells. Genetic deletion of mmp14b led to a decrease in 1) macrophage recruitment to the border zone, 2) collagen degradation at the border zone, and 3) subsequent cardiomyocyte invasion. Furthermore, cardiomyocyte-specific overexpression of mmp14b was sufficient to enhance cardiomyocyte invasion into the injured tissue and along the apical surface of the wound. Altogether, our data shed important insights into the process of cardiomyocyte invasion of the collagen-containing injured tissue during cardiac regeneration. They further suggest that cardiomyocytes and resident macrophages contribute to ECM remodeling at the border zone to promote cardiomyocyte replenishment of the fibrotic injured tissue.
]]></description>
<dc:creator>Constanty, F.</dc:creator>
<dc:creator>Wu, B.</dc:creator>
<dc:creator>Wei, K.-H.</dc:creator>
<dc:creator>Lin, I.-T.</dc:creator>
<dc:creator>Dallmann, J.</dc:creator>
<dc:creator>Guenther, S.</dc:creator>
<dc:creator>Lautenschlaeger, T.</dc:creator>
<dc:creator>Priya, R.</dc:creator>
<dc:creator>Lai, S.-L.</dc:creator>
<dc:creator>Stainier, D. Y. R.</dc:creator>
<dc:creator>Beisaw, A.</dc:creator>
<dc:date>2024-03-13</dc:date>
<dc:identifier>doi:10.1101/2024.03.12.584570</dc:identifier>
<dc:title><![CDATA[Border-zone cardiomyocytes and macrophages contribute to remodeling of the extracellular matrix to promote cardiomyocyte invasion during zebrafish cardiac regeneration]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-03-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.03.15.585140v1?rss=1">
<title>
<![CDATA[
Clostridium innocuum, an opportunistic gut pathogen, inactivates host gut progesterone and arrests ovarian follicular development 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.03.15.585140v1?rss=1</link>
<description><![CDATA[
HighlightsO_LIWe identified Clostridium innocuum as a key player in gut progesterone metabolism.
C_LIO_LIProgesterone is converted into epipregnanolone with negligible progestogenic activity.
C_LIO_LIWe identified the enzyme and mechanisms of microbial epipregnanolone production.
C_LIO_LIC. innocuum caused decreased serum progesterone and follicular arrest in female mice.
C_LIO_LIC. innocuum is a causal factor of progesterone resistance in women taking progesterone.
C_LI



O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/585140v1_ufig1.gif" ALT="Figure 1">
View larger version (33K):
org.highwire.dtl.DTLVardef@14cceaborg.highwire.dtl.DTLVardef@1946432org.highwire.dtl.DTLVardef@13e46d2org.highwire.dtl.DTLVardef@19b9a25_HPS_FORMAT_FIGEXP  M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG In briefChen et al. identified Clostridium innocuum as a major species involved in gut progesterone metabolism, with epipregnanolone as the main product, and elucidated the molecular mechanisms. C. innocuum inactivates gut progesterone in female mice, leading to decreased circulating progesterone levels. C. innocuum is also a causal factor of follicular arrest.

Levels of progesterone, an endogenous female hormone, increase after ovulation; progesterone is crucial in the luteal phase to maintain successful pregnancy and prevent early miscarriage. Both endogenous and exogenous progesterone are recycled between the liver and gut; thus, the gut microbiota regulate host progesterone levels by inhibiting enterohepatic progesterone circulation. Our data indicated Clostridium innocuum as a major species involved in gut progesterone metabolism in women with infertility. C. innocuum converts progesterone into the neurosteroid epipregnanolone (with negligible progestogenic activity). We purified and characterized the corresponding enzyme, namely NADPH-dependent 5{beta}-dihydroprogesterone reductase, which is highly oxygen sensitive and whose corresponding genes are prevalent in C. innocuum. Moreover, C. innocuum-administered female C57BL/6 mice (aged 7 weeks) exhibited decreased serum progesterone levels ([~]35%). Clostridium-specific antibiotics (metronidazole) restored low serum progesterone levels in these mice. Furthermore, prolonged C. innocuum administration (12 weeks) arrested ovarian follicular development in female mice. Cytological and histological analyses indicated that C. innocuum may cause luteal phase insufficiency and affect menstrual regularity. Our findings suggest C. innocuum as a causal factor of progesterone resistance in women taking progesterone.
]]></description>
<dc:creator>Chen, M.-J.</dc:creator>
<dc:creator>Chou, C.-H.</dc:creator>
<dc:creator>Hsiao, T.-H.</dc:creator>
<dc:creator>Wu, T.-Y.</dc:creator>
<dc:creator>Li, C.-Y.</dc:creator>
<dc:creator>Chen, Y.-L.</dc:creator>
<dc:creator>Chao, K.-H.</dc:creator>
<dc:creator>Lee, T.-H.</dc:creator>
<dc:creator>Gicana, R.</dc:creator>
<dc:creator>Shih, C.-J.</dc:creator>
<dc:creator>Brandon-Mong, G.-J.</dc:creator>
<dc:creator>Lai, Y.-L.</dc:creator>
<dc:creator>Li, P.-T.</dc:creator>
<dc:creator>Tseng, Y.-L.</dc:creator>
<dc:creator>Wang, P.-H.</dc:creator>
<dc:creator>Chiang, Y.-R.</dc:creator>
<dc:date>2024-03-15</dc:date>
<dc:identifier>doi:10.1101/2024.03.15.585140</dc:identifier>
<dc:title><![CDATA[Clostridium innocuum, an opportunistic gut pathogen, inactivates host gut progesterone and arrests ovarian follicular development]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-03-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.03.16.585365v1?rss=1">
<title>
<![CDATA[
Neurosphere culture derived from aged hippocampal dentate gyrus 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.03.16.585365v1?rss=1</link>
<description><![CDATA[
The neurosphere assay is the gold standard for determining proliferative and differentiation potential of neural progenitor cells (NPCs) in neurogenesis studies1-3. While several in vitro assays have been developed to model the process of neurogenesis, they have predominantly used embryonic and early postnatal NPCs derived from the dentate gyrus (DG). A limitation of these approaches is that they do not provide insight into adult-born NPCs, which are modeled to affect hippocampal function and diseases later in life. Here, we show a novel free-floating neurosphere culture system using NPCs isolated from the DG of mature adult and aged mice.

The protocol outlines detailed steps on the isolation, propagation, and maintenance of neurospheres from adult and aged (>12 months old) mouse brain and how to differentiate cultured neurospheres into neurons and astrocytes. Culturing adult and aged NPCs provides an important in vitro model to (1) investigate cellular and molecular properties of this unique cell population and (2) expand the understanding of plasticity in the adult and aging brain. This protocol requires [~]2 hours to complete dissection, dissociation and culture plating, while differentiation to neuronal and astrocytic lineages takes 9 days.

By focusing on neurospheres obtained from animals at later ages this model facilitates investigation of important biological questions related to development and differentiation of hippocampal neurons generated throughout adult life.
]]></description>
<dc:creator>Vafaeva, O.</dc:creator>
<dc:creator>Namchaiw, P.</dc:creator>
<dc:creator>Murray, K. D.</dc:creator>
<dc:creator>Diaz, E.</dc:creator>
<dc:creator>Cheng, H.-J.</dc:creator>
<dc:date>2024-03-17</dc:date>
<dc:identifier>doi:10.1101/2024.03.16.585365</dc:identifier>
<dc:title><![CDATA[Neurosphere culture derived from aged hippocampal dentate gyrus]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-03-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.03.23.586378v1?rss=1">
<title>
<![CDATA[
Development of a tightly regulated copper-inducible transient gene expression system in Nicotiana benthamiana incorporating suicide exon and Cre recombinase 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.03.23.586378v1?rss=1</link>
<description><![CDATA[
Chemical-inducible gene expression systems have been frequently used to regulate gene expression for functional genomics in various plant species. However, a convenient chemical-inducible system that can tightly regulate transgene expression in Nicotiana benthamiana is still missing. In this study, we developed a tightly regulated copper-inducible system that can be used to regulate transgene expression and perform cell death assays in N. benthamiana. We tested several chemical-inducible systems using Agrobacterium-mediated transient expression and found that the copper-inducible system showed the least concerns of leakiness issues. Using the MoClo-based synthetic biology approach, we optimized the design of the copper-inducible system and incorporated the use of the suicide exon HyP5SM/OsL5 and Cre/LoxP as additional regulatory elements to enhance the tightness of the regulation. This new design allowed us to tightly control the hypersensitive cell death induced by several tested NLRs and their matching AVRs, and it can also be easily applied to regulate the expression of other transgenes in transient expression assays. Our findings provide new approaches for both fundamental and translational studies in plant functional genomics.
]]></description>
<dc:creator>Chiang, B.-J.</dc:creator>
<dc:creator>Lin, K.-Y.</dc:creator>
<dc:creator>Chen, Y.-F.</dc:creator>
<dc:creator>Huang, C.-Y.</dc:creator>
<dc:creator>Goh, F.-J.</dc:creator>
<dc:creator>Huang, L.-T.</dc:creator>
<dc:creator>Chen, L.-H.</dc:creator>
<dc:creator>Wu, C.-H.</dc:creator>
<dc:date>2024-03-27</dc:date>
<dc:identifier>doi:10.1101/2024.03.23.586378</dc:identifier>
<dc:title><![CDATA[Development of a tightly regulated copper-inducible transient gene expression system in Nicotiana benthamiana incorporating suicide exon and Cre recombinase]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-03-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.03.26.586198v1?rss=1">
<title>
<![CDATA[
MOS4-Associated Complex subunits 3A and 3B modulate FLM splicing to repress photoperiod-dependent floral transition 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.03.26.586198v1?rss=1</link>
<description><![CDATA[
Plants adjust their flowering time by integrating environmental cues through complex regulatory networks. RNA splicing plays a crucial role in modulating gene expression in response to flowering signals. The MOS4-associated complex (MAC), consisting of the evolutionarily conserved E3 ubiquitin ligases MAC3A and MAC3B, is pivotal in splicing regulation. However, their involvement in floral transition remained unclear. This study observed that mac3a/mac3b mutants flowered significantly earlier under short-day (SD) conditions, a phenotype absent under long-day (LD) conditions. This early flowering correlated with upregulation of FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1) compared to wild-type plants. Transcriptomic analysis revealed alterations in transcript levels and splicing profiles of key floral regulators across different flowering pathways. Further investigation identified the thermosensory flowering regulator FLOWERING LOCUS M (FLM) as being influenced by MAC3A and MAC3B. Subsequently, we found that MAC3A and MAC3B exhibited higher expression and were associated with FLM transcripts to modulate their splicing in SD. This study elucidates how the MAC complex, through RNA splicing regulation, integrates environmental signals to modulate flowering, unveiling a new layer of complexity in flowering pathways crosstalk under non-inductive photoperiods.
]]></description>
<dc:creator>Huang, Y.-W.</dc:creator>
<dc:creator>Tseng, C.-Y.</dc:creator>
<dc:creator>Tu, Y.-T.</dc:creator>
<dc:creator>Hsieh, H.-Y.</dc:creator>
<dc:creator>Wang, Y.-S.</dc:creator>
<dc:creator>Chen, Y.-Z.</dc:creator>
<dc:creator>Ly, Y.-T.</dc:creator>
<dc:creator>Tu, S.-L.</dc:creator>
<dc:creator>Lee, C.-M.</dc:creator>
<dc:date>2024-03-27</dc:date>
<dc:identifier>doi:10.1101/2024.03.26.586198</dc:identifier>
<dc:title><![CDATA[MOS4-Associated Complex subunits 3A and 3B modulate FLM splicing to repress photoperiod-dependent floral transition]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-03-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.03.28.587275v1?rss=1">
<title>
<![CDATA[
PREDICT: Advancing Accurate Gene Expression Prediction and Motif Identification in Plant Stress Responses 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.03.28.587275v1?rss=1</link>
<description><![CDATA[
Cells respond to environmental stimuli through transcriptional responses, orchestrated by transcription factors (TFs) that interpret the gene cis-regulatory DNA sequences, determining gene expression dynamics timing and locations. Diversification in TFs and cis-regulatory element (CRE) interactions result in unique gene regulatory networks (GRNs) that underpin plant adaptation. A primary challenge is identifying Transcription Factor Binding Motifs (TFBMs) for temporal and condition-specific gene expressions in plants. While the Multiple EM for Motif Elicitation (MEME) suite identifies stress-responsive CREs in Arabidopsis, its predictive power for gene expression remains uncertain. Alternatively, the k-mer approach identifies CRE sites and consensus TF motifs, thereby improving gene expression prediction models. In this study, we harnessed the power of a k-mer pipeline to address sequence-to-expression prediction problems across diverse abiotic stresses, in both bryophytic and vascular plants, including monocots and dicots. Moreover, we characterized both un-gapped and gapped CREs and, coupled with GRN analyses, pinpointed key TFs within transcriptional cascades. Lastly, we developed the Predictive Regulatory Element Database for Identifying Cis-regulatory elements and Transcription factors (PREDICT), a web tool for efficient k-mer identification. This advancement will enrich our understanding of the cis-regulatory code landscape that shapes gene regulation in plant adaptation. PREDICT web tool is available at [http://predict.southerngenomics.org/kmers/kmers.php].
]]></description>
<dc:creator>Wu, T.-Y.</dc:creator>
<dc:creator>Liu, M.-J.</dc:creator>
<dc:creator>Thalimaraw, L.</dc:creator>
<dc:creator>Eo, W. X. H.</dc:creator>
<dc:date>2024-03-31</dc:date>
<dc:identifier>doi:10.1101/2024.03.28.587275</dc:identifier>
<dc:title><![CDATA[PREDICT: Advancing Accurate Gene Expression Prediction and Motif Identification in Plant Stress Responses]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-03-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.04.02.587698v1?rss=1">
<title>
<![CDATA[
Chromosome-level genome assembly of the loach goby, Rhyacichthys aspro, reveals mechanisms underlying Gobioidei diversification 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.04.02.587698v1?rss=1</link>
<description><![CDATA[
The percomorph fish clade Gobioidei are a suborder that comprises over 2,200 species distributed in nearly all aquatic habitats. To understand the genetics underlying their diversification, we sequenced and annotated the genome of the loach goby, Rhyacichthys aspro, the basal most group, and compared it with nine additional Gobioidei species. Within Gobioidei, the loach goby possesses the smallest genome at 607 Mb, and a rise in species diversity from basal to derived lineages is mirrored by enlarged genomes and a higher presence of repeat elements (REs), particularly DNA transposons. These transposons are enriched in coding and regulatory regions and their copy number increase is strongly correlated with mutation rate, suggesting that DNA repair after transposon excision/insertion leads to nearby mutations. Consequently, the proliferation of DNA transposons might be the crucial driver of Gobioidei diversification and adaptability. The loach goby genome also points to mechanisms of ecological adaptation. It contains relatively few genes for lateral line development but an over representation of synaptic function genes, with genes putatively under selection linked to synapse organization and calcium signaling, suggesting a sensory system distinct from other Gobioidei species. We also see an overabundance of genes involved in neurocranium development and renal function, adaptations likely connected to its flat morphology suited for strong currents and an amphidromous life cycle. Comparative analyses with hill-stream loaches and the European eel reveal convergent adaptations in body shape and saltwater balance. These findings shed light on the loach gobys survival mechanisms and the broader evolutionary trends within Gobioidei.
]]></description>
<dc:creator>Wang, T.-Y.</dc:creator>
<dc:creator>Lu, H.-J.</dc:creator>
<dc:creator>Wu, Y.-W.</dc:creator>
<dc:creator>Liao, T.-Y.</dc:creator>
<dc:creator>Huang, S.-P.</dc:creator>
<dc:creator>Wang, F.-Y.</dc:creator>
<dc:creator>Ting, C.-T.</dc:creator>
<dc:creator>Chaw, S.-M.</dc:creator>
<dc:creator>Wang, H.-Y.</dc:creator>
<dc:date>2024-04-03</dc:date>
<dc:identifier>doi:10.1101/2024.04.02.587698</dc:identifier>
<dc:title><![CDATA[Chromosome-level genome assembly of the loach goby, Rhyacichthys aspro, reveals mechanisms underlying Gobioidei diversification]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-04-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.04.03.587896v1?rss=1">
<title>
<![CDATA[
A robust platform for BaEVRless-lentiviral synthesis and primary natural killer cell transduction 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.04.03.587896v1?rss=1</link>
<description><![CDATA[
Lentiviral vectors are invaluable tools for genetic modification in human cells for research, biotechnological and clinical applications. However, certain cell types, such as primary human natural killer (NK) cells, present challenges in lentiviral transduction. Overcoming this limitation requires specific pseudotype modifications. BaEVRless-pseudotyped lentivirus (BaEVRless-LV) has shown promise in efficiently transducing human NK cells, B cells, and hematopoietic stem cells (HSCs). BaEVRless, a modified envelope protein derived from Baboon endogenous retrovirus, targets ASCT receptors in human cells. While effective for several immune cell types, BaEVRless-LV production in standard HEK293T cells is challenging. During lentiviral synthesis, BaEVRless protein induces hyper cell fusion, leading to rapid HEK293T cell death and reduced BaEVRless-LV titers. To solve this problem, we used CRISPR genome editing to knockout (KO) the ASCT2 gene in HEK293T cells, thereby abolishing BaEVRless-induced cell fusion. Using the ASCT2-KO cells and an optimized viral production protocol, we efficiently packaged high titers of BaEVRless-LV encoding various transgenes, including turbogfp, chimeric antigen receptor (CAR), and a pooled CRISPR sgRNA library. Our robust BaEVRless-LV synthesis platform is readily adaptable for manufacturing cell therapeutics and enables advanced research techniques such as CRISPR genetic screens in primary NK cells.
]]></description>
<dc:creator>Lan, Y.-J.</dc:creator>
<dc:creator>Nguyen, Q. V.</dc:creator>
<dc:creator>Chao, T.-L.</dc:creator>
<dc:creator>Yeh, K.-L.</dc:creator>
<dc:creator>Lin, S.</dc:creator>
<dc:date>2024-04-04</dc:date>
<dc:identifier>doi:10.1101/2024.04.03.587896</dc:identifier>
<dc:title><![CDATA[A robust platform for BaEVRless-lentiviral synthesis and primary natural killer cell transduction]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-04-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.04.03.587938v1?rss=1">
<title>
<![CDATA[
Zebrafish Foxl2l suppresses stemness and directs feminization of germline progenitors 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.04.03.587938v1?rss=1</link>
<description><![CDATA[
Zebrafish is an important organism for genetic studies, but its germ cell types and the mechanism of sex differentiation remain elusive. Here, we conducted a single-cell transcriptomic profiling and charted a developmental trajectory going from germline stem cells, through early, committed, and late progenitors, to pre-meiotic and meiotic cells. A transcription factor, Foxl2l, is expressed in the progenitors committed to the ovary fate. CRISPR-Cas9-mediated mutation of foxl2l produced 100% male fish with normal fertility. Another single-cell profiling of foxl2l-/- germ cells reveals the arrest of early progenitors. Concomitantly the expression of nanos2 (stem cell marker) and id1 (transcription repressor in stem cells) was elevated together with an increase of nanos2+ germ cell in foxl2l mutants, indicating the reversion to the stem cell state. Thus, we have identified developmental stages of germ cells in juvenile zebrafish and demonstrated that Foxl2l drives zebrafish germ cell progenitors toward feminization and prevents them from reverting back to the stem cell state.
]]></description>
<dc:creator>Hsu, C.-w.</dc:creator>
<dc:creator>Ho, H.</dc:creator>
<dc:creator>Yang, C.-H.</dc:creator>
<dc:creator>Wang, Y.-W.</dc:creator>
<dc:creator>Li, K.-C.</dc:creator>
<dc:creator>Chung, B.-c.</dc:creator>
<dc:date>2024-04-04</dc:date>
<dc:identifier>doi:10.1101/2024.04.03.587938</dc:identifier>
<dc:title><![CDATA[Zebrafish Foxl2l suppresses stemness and directs feminization of germline progenitors]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-04-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.04.08.588570v1?rss=1">
<title>
<![CDATA[
RGF1 controls PLT2 protein stability through ROS-dependent regulation of a cysteine residue in root meristem development 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.04.08.588570v1?rss=1</link>
<description><![CDATA[
The protein concentration gradients of the master regulators of the root meristem, named the PLETHORA proteins, modulate the root meristem size. Root meristem growth factor 1 (RGF1) peptide extends the PLETHORA2 (PLT2) protein gradients by altering reactive oxygen species (ROS) distributions. However, the underlying mechanism through which the ROS alterations regulate PLT2 remains unknown. Here, we demonstrate that the 212th cysteine of the PLT2 protein plays a pivotal role in modulating PLT2 stability through the ROS altered by RGF1. The substitution of the 212th cysteine of PLT2 with serine (PLT2C212S) enhanced the PLT2 protein stability upon RGF1 and resulted in robust resistance to ROS relative to the native PLT2. Accordingly, PLT2C212S modulated expressions of certain specific root development-related genes to a greater extent than native PLT2. In summary, these findings show that the PLT2 concentration gradient formation through ROS, modulated by RGF1, is dependent on a mechanism involving the 212th cysteine of PLT2.
]]></description>
<dc:creator>Hsiao, Y.-C.</dc:creator>
<dc:creator>Shiue, S.-Y.</dc:creator>
<dc:creator>Yen, M.-R.</dc:creator>
<dc:creator>Lai, J.-K.</dc:creator>
<dc:creator>YAMADA, M.</dc:creator>
<dc:date>2024-04-11</dc:date>
<dc:identifier>doi:10.1101/2024.04.08.588570</dc:identifier>
<dc:title><![CDATA[RGF1 controls PLT2 protein stability through ROS-dependent regulation of a cysteine residue in root meristem development]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-04-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.04.10.587378v1?rss=1">
<title>
<![CDATA[
Coupling of cell growth modulation to asymmetric division and cell cycle regulation in Caulobacter crescentus 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.04.10.587378v1?rss=1</link>
<description><![CDATA[
In proliferating bacteria, growth rate is often assumed to be similar between daughter cells. However, most of our knowledge of cell growth derives from studies on symmetrically dividing bacteria. In many -proteobacteria, asymmetric division is a normal part of the life cycle, with each division producing daughter cells with different sizes and fates. Here, we demonstrate that the functionally distinct swarmer and stalked daughter cells produced by the model -proteobacterium Caulobacter crescentus have different average growth rates despite sharing an identical genome and environment. The discrepancy in growth rate is due to a growth slowdown during the cell cycle stage preceding DNA replication (the G1 phase), which is predominantly associated with swarmer cell functionality. We also provide evidence that the second messenger (p)ppGpp extends the timing of the G1/swarmer cell stage by slowing growth specifically during the beginning of the cell cycle. Our data further show that cells factor the amount and rate of their growth to control the G1/S transition, allowing them to adjust the time they spend with ecologically important G1-specific traits.

Significance statementBacterial growth rate modulation is generally associated with changes in genetic make-up or environmental condition. This study demonstrates that the rate of cell growth can also vary between daughter cells and across cell cycle stages under invariant and unstressed environmental conditions. This is illustrated by the asymmetrically dividing -proteobacterium Caulobacter crescentus, which, at each division, produces two functionally distinct daughter cells that differ in average growth rate. This growth rate difference arises from a G1 phase-specific growth slowdown mediated, in part, by the (p)ppGpp alarmone. Altogether, this study showcases the coupling of cell growth modulation to asymmetric division and cell cycle regulation, which may have implications for other -proteobacteria given their cell cycle similarities with C. crescentus.
]]></description>
<dc:creator>Glenn, S.</dc:creator>
<dc:creator>Lin, W.-H.</dc:creator>
<dc:creator>Papagiannakis, A.</dc:creator>
<dc:creator>Kato, S.</dc:creator>
<dc:creator>Jacobs-Wagner, C.</dc:creator>
<dc:date>2024-04-10</dc:date>
<dc:identifier>doi:10.1101/2024.04.10.587378</dc:identifier>
<dc:title><![CDATA[Coupling of cell growth modulation to asymmetric division and cell cycle regulation in Caulobacter crescentus]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-04-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.04.10.588845v1?rss=1">
<title>
<![CDATA[
Multiplexed Assays of Human Disease-relevant Mutations Reveal UTR Dinucleotide Composition as a Major Determinant of RNA Stability 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.04.10.588845v1?rss=1</link>
<description><![CDATA[
UTRs contain crucial regulatory elements for RNA stability, translation and localization, so their integrity is indispensable for gene expression. Approximately 3.7% of genetic variants associated with diseases occur in UTRs, yet a comprehensive understanding of UTR variant functions remains limited due to inefficient experimental and computational assessment methods. To systematically evaluate the effects of UTR variants on RNA stability, we established a massively parallel reporter assay on 6,555 UTR variants reported in human disease databases. We examined the RNA degradation patterns mediated by the UTR library in two cell lines, and then applied LASSO regression to model the influential regulators of RNA stability. We found that UA dinucleotides and UA-rich motifs are the most prominent destabilizing element. Gain of UA dinucleotide outlined mutant UTRs with reduced stability. Studies on endogenous transcripts indicate that high UA-dinucleotide ratios in UTRs promote RNA degradation. Conversely, elevated GC content and protein binding on UA dinucleotides protect high-UA RNA from degradation. Further analysis reveals polarized roles of UA- dinucleotide-binding proteins in RNA protection and degradation. Furthermore, the UA- dinucleotide ratio of both UTRs is a common characteristic of genes in innate immune response pathways, implying a coordinated stability regulation through UTRs at the transcriptomic level. We also demonstrate that stability-altering UTRs are associated with changes in biobank-based health indices, underscoring the importance of precise UTR regulation for wellness. Our study highlights the importance of RNA stability regulation through UTR primary sequences, paving the way for further exploration of their implications in gene networks and precision medicine.
]]></description>
<dc:creator>Su, J.-Y.</dc:creator>
<dc:creator>Wang, Y.-L.</dc:creator>
<dc:creator>Hsieh, Y.-T.</dc:creator>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Yang, C.-H.</dc:creator>
<dc:creator>Kang, Y.</dc:creator>
<dc:creator>Huang, Y.-T.</dc:creator>
<dc:creator>Lin, C.-L.</dc:creator>
<dc:date>2024-04-10</dc:date>
<dc:identifier>doi:10.1101/2024.04.10.588845</dc:identifier>
<dc:title><![CDATA[Multiplexed Assays of Human Disease-relevant Mutations Reveal UTR Dinucleotide Composition as a Major Determinant of RNA Stability]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-04-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.04.10.588860v1?rss=1">
<title>
<![CDATA[
Worldwide soundscape ecology patterns across realms 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.04.10.588860v1?rss=1</link>
<description><![CDATA[
Abstract and keywordsO_ST_ABSAimC_ST_ABSThe urgency for remote, reliable, and scalable biodiversity monitoring amidst mounting human pressures on ecosystems has sparked worldwide interest in Passive Acoustic Monitoring (PAM), which can track life underwater and on land. However, we lack a unified methodology to report this sampling effort and a comprehensive overview of PAM coverage to gauge its potential as a global research and monitoring tool. To remediate this, we created the Worldwide Soundscapes project, a collaborative network and growing database comprising metadata from 409 datasets across all realms (terrestrial, marine, freshwater, and subterranean).

LocationWorldwide, 12 200 sites, all ecosystems.

Time period1991 to present.

Major taxa studiedAll soniferous taxa.

MethodsWe synthesise sampling coverage across spatial, temporal, and ecological scales using metadata describing sampling locations, deployment schedules, focal taxa, and recording parameters. We explore global trends in biological, anthropogenic, and geophysical sounds based on 168 recordings from twelve ecosystems across all realms.

ResultsTerrestrial sampling is spatially denser (45 sites/Mkm2) than aquatic sampling (0.3 and 1.8 sites/Mkm2 in oceans and fresh water) with only two subterranean datasets. Although diel and lunar cycles are well-covered in all realms, only marine datasets (56%) comprehensively sample all seasons. Across twelve ecosystems, biological sounds show contrasting diel patterns, decline with distance from the equator and negatively correlate with anthropogenic sounds.

Main conclusionsPAM can inform macroecology studies as well as global conservation and phenology syntheses, but representation can be improved by expanding terrestrial taxonomic scope, sampling coverage in the high seas and subterranean ecosystems, and spatio-temporal replication in freshwater habitats. Overall, this global PAM network holds promise to support global biodiversity research and monitoring efforts.
]]></description>
<dc:creator>Darras, K. F.</dc:creator>
<dc:creator>Rountree, R.</dc:creator>
<dc:creator>Van Wilgenburg, S.</dc:creator>
<dc:creator>Dong, L.</dc:creator>
<dc:creator>Gasc, A.</dc:creator>
<dc:creator>Chen, Y.</dc:creator>
<dc:creator>Lin, T.-H.</dc:creator>
<dc:creator>Diaz, P. M.</dc:creator>
<dc:creator>Wu, S.-H.</dc:creator>
<dc:creator>Salton, M.</dc:creator>
<dc:creator>Marley, S.</dc:creator>
<dc:creator>Cord, A. F.</dc:creator>
<dc:creator>Aparecido Do Nascimento, L.</dc:creator>
<dc:creator>Astaras, C.</dc:creator>
<dc:creator>Barbaro, L.</dc:creator>
<dc:creator>Bellisario, K.</dc:creator>
<dc:creator>Ben David, A.</dc:creator>
<dc:creator>Berger-Tal, O.</dc:creator>
<dc:creator>Bhalla, I.</dc:creator>
<dc:creator>Bolgan, M.</dc:creator>
<dc:creator>Bradfer-Lawrence, T.</dc:creator>
<dc:creator>Briers, R. A.</dc:creator>
<dc:creator>Budka, M.</dc:creator>
<dc:creator>Cerezo-Araujo, M.</dc:creator>
<dc:creator>Cerwen, G.</dc:creator>
<dc:creator>Desjonqueres, C.</dc:creator>
<dc:creator>Diniz, P.</dc:creator>
<dc:creator>Duarte, A.</dc:creator>
<dc:creator>Enari, H.</dc:creator>
<dc:creator>Enari, H. S.</dc:creator>
<dc:creator>Freitas, B.</dc:creator>
<dc:creator>Friedman, N.</dc:creator>
<dc:creator>Froidevaux, J.</dc:creator>
<dc:creator>Gogoleva, S.</dc:creator>
<dc:creator>Goodale, E.</dc:creator>
<dc:creator>Greenhalgh, J.</dc:creator>
<dc:creator>Hagge, J.</dc:creator>
<dc:creator>Jacot, A.</dc:creator>
<dc:creator>Jahn, O.</dc:creator>
<dc:creator>Kepfer Rojas, S.</dc:creator>
<dc:creator>Lloyd, K. J.</dc:creator>
<dc:creator>Mammides, C.</dc:creator>
<dc:creator>Marcacci, G.</dc:creator>
<dc:creator></dc:creator>
<dc:date>2024-04-14</dc:date>
<dc:identifier>doi:10.1101/2024.04.10.588860</dc:identifier>
<dc:title><![CDATA[Worldwide soundscape ecology patterns across realms]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-04-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.04.11.589132v1?rss=1">
<title>
<![CDATA[
Massively Parallel Polyribosome Profiling Reveals Translation Defects of Human Disease-Relevant UTR Mutations 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.04.11.589132v1?rss=1</link>
<description><![CDATA[
The untranslated regions (UTRs) of mRNAs harbor regulatory elements influencing translation efficiency. Although 3.7% of disease-relevant human mutations occur in UTRs, their exact role in pathogenesis remains unclear. Through metagene analysis, we mapped pathogenic UTR mutations to regions near coding sequences, with a focus on the upstream open reading frame (uORF) initiation site. Subsequently, we utilized massively parallel poly(ribo)some profiling to compare the ribosome associations of 6,555 pairs of wildtype and mutant UTR fragments. We identified 46 UTR variants that altered polysome profiles, with enrichment in pathogenic mutations. Both univariate analysis and the elastic net regression model highlighted the significance of motifs of short repeated sequences, including SRSF2 binding sites, as mutation hotspots that lead to aberrant translation. Furthermore, these polysome-shifting mutations exhibited considerable impact on RNA secondary structures, particularly for upstream AUG-containing 5 UTRs. Integrating these features, our model achieved high accuracy (AUROC > 0.8) in predicting polysome-shifting mutations in the test dataset. Additionally, several lines of evidence indicate that changes in uORF usage underlie the translation deficiency arising from these mutations. Illustrating this, we demonstrate that a pathogenic mutation in the IRF6 5 UTR suppresses translation of the primary open reading frame by creating a uORF. Remarkably, site- directed ADAR editing of the mutant mRNA rescued this translation deficiency. Overall, our study provides insights into the molecular mechanisms of UTR mutations and their links to clinical impacts through translation defects.



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]]></description>
<dc:creator>Li, W.-P.</dc:creator>
<dc:creator>Su, J.-Y.</dc:creator>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Wang, Y.-L.</dc:creator>
<dc:creator>Chiang, H.-L.</dc:creator>
<dc:creator>Hsieh, Y.-T.</dc:creator>
<dc:creator>Chiang, Y.-H.</dc:creator>
<dc:creator>Ko, Y.-L.</dc:creator>
<dc:creator>Chiang, B.-J.</dc:creator>
<dc:creator>Yang, C.-H.</dc:creator>
<dc:creator>Huang, Y.-T.</dc:creator>
<dc:creator>Lin, C.-L.</dc:creator>
<dc:date>2024-04-13</dc:date>
<dc:identifier>doi:10.1101/2024.04.11.589132</dc:identifier>
<dc:title><![CDATA[Massively Parallel Polyribosome Profiling Reveals Translation Defects of Human Disease-Relevant UTR Mutations]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-04-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.04.18.589993v1?rss=1">
<title>
<![CDATA[
Evolution engineering of methylotrophic E. coli enables faster growth than native methylotrophs 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.04.18.589993v1?rss=1</link>
<description><![CDATA[
As methanol can be derived from either CO2 or methane, methanol economy may play a role in combating climate change. In this scenario, rapid utilization of methanol by an industrial microorganism is the first and crucial step for efficient utilization of the C1 feedstock chemical. Here, we report the development of a methylotrophic E. coli strain (SM6) with a doubling time of 3.5 hours, outpacing that of common native methylotrophs. We accomplish this using evolution engineering with dynamic copy number variation (CNV). We developed a bacterial artificial chromosome (BAC) with dynamic CNV to facilitate overcoming the formaldehyde-induced DNA-protein cross-linking (DPC) problem in the evolution process. The growth rate of the organism in methanol minimal medium improved significantly after it acquired a loss-of-function mutation in mutS. We tracked the genome variations of 72 cultures along the evolution process by next-generation sequencing, and identified the metabolic features of the fast-growing strain. This study illustrates the potential of dynamic CNV as an evolution tool and synthetic methylotrophs as a platform for sustainable biotechnological applications.
]]></description>
<dc:creator>Nieh, L.-Y.</dc:creator>
<dc:creator>Chen, F. Y.- H.</dc:creator>
<dc:creator>Jung, H.-W.</dc:creator>
<dc:creator>Su, K.-Y.</dc:creator>
<dc:creator>Tsuei, C.-Y.</dc:creator>
<dc:creator>Lin, C. T.</dc:creator>
<dc:creator>Lee, Y.-Q.</dc:creator>
<dc:creator>Liao, J. C.</dc:creator>
<dc:date>2024-04-18</dc:date>
<dc:identifier>doi:10.1101/2024.04.18.589993</dc:identifier>
<dc:title><![CDATA[Evolution engineering of methylotrophic E. coli enables faster growth than native methylotrophs]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-04-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.04.18.590004v1?rss=1">
<title>
<![CDATA[
Genetic purging of strongly deleterious mutations underlies black-necked crane's unusual escape from an extinction vortex 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.04.18.590004v1?rss=1</link>
<description><![CDATA[
Many species are undergoing rapid demographic declines, necessitating an examination of the resulting genetic impacts. The prevailing small population paradigm posits an elevated genetic load and extinction risk. However, instances of fast recovery from severe population bottlenecks suggest alternative outcomes. To investigate this issue, we performed a population genomic analysis on the black-necked crane, analyzing 42 modern and 11 historical genomes. This study revealed substantial evidence of large-effect allele purging underlying the unexpectedly rapid population recovery following an abrupt bottleneck during the 1980s. Nevertheless, forward simulations supposing a prolonged bottleneck (e.g., five generations) predicted a reversion with negative prospects, implying that rapid population recovery served as both the cause and consequence of the species escaping from an extinction vortex. These findings shed light on a potential positive microevolutionary response to current widespread population collapses and underscore the urgency of implementing active and effective conservation strategies to reverse this trend before it becomes irreversible.
]]></description>
<dc:creator>Cui, N.</dc:creator>
<dc:creator>Ma, X.</dc:creator>
<dc:creator>Wu, H.</dc:creator>
<dc:creator>Chen, X.</dc:creator>
<dc:creator>Hung, C.-M.</dc:creator>
<dc:creator>Zhang, L.</dc:creator>
<dc:creator>Lei, F.</dc:creator>
<dc:creator>Yang, L.</dc:creator>
<dc:creator>Yan, D.</dc:creator>
<dc:creator>Yang, X.</dc:creator>
<dc:creator>Dong, F.</dc:creator>
<dc:date>2024-04-21</dc:date>
<dc:identifier>doi:10.1101/2024.04.18.590004</dc:identifier>
<dc:title><![CDATA[Genetic purging of strongly deleterious mutations underlies black-necked crane's unusual escape from an extinction vortex]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-04-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.04.24.590919v1?rss=1">
<title>
<![CDATA[
StomaVision: stomatal trait analysis through deep learning 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.04.24.590919v1?rss=1</link>
<description><![CDATA[
StomaVision is an automated tool designed for high-throughput detection and measurement of stomatal traits, such as stomatal number, pore size, and closure rate. It provides insights into plant responses to environmental cues, streamlining the analysis of micrographs from field-grown plants across various species, including monocots and dicots. Enhanced by a novel collection method that utilizes video recording, StomaVision increases the number of captured images for robust statistical analysis. Accessible via an intuitive web interface at <https://stomavision.streamlit.app/> and available for local use in a containerized environment at <https://github.com/YaoChengLab/StomaVision>, this tool ensures long-term usability by minimizing the impact of software updates and maintaining functionality with minimal setup requirements. The application of StomaVision has provided significant physiological insights, such as variations in stomatal density, opening rates, and total pore area under heat stress. These traits correlate with critical physiological processes, including gas exchange, carbon assimilation, and water use efficiency, demonstrating the tools utility in advancing our understanding of plant physiology. The ability of StomaVision to identify differences in responses to varying durations of heat treatment highlights its value in plant science research.

Plain language summaryStomaVision is a tool that automatically counts and measures tiny openings on plant leaves, helping us learn how plants deal with their surroundings. It is easy to use and works well with various plant species. This tool helps scientists see how plants change under stress, making plant research easier and more accurate.
]]></description>
<dc:creator>Wu, T.-L.</dc:creator>
<dc:creator>Chen, P.-Y.</dc:creator>
<dc:creator>Du, X.</dc:creator>
<dc:creator>Wu, H.</dc:creator>
<dc:creator>Ou, J.-Y.</dc:creator>
<dc:creator>Zheng, P.-X.</dc:creator>
<dc:creator>Wu, Y.-L.</dc:creator>
<dc:creator>Wang, R.-S.</dc:creator>
<dc:creator>Hsu, T.-C.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Lin, W.-Y.</dc:creator>
<dc:creator>Chang, P.-L.</dc:creator>
<dc:creator>Ho, C.-M. K.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:date>2024-04-28</dc:date>
<dc:identifier>doi:10.1101/2024.04.24.590919</dc:identifier>
<dc:title><![CDATA[StomaVision: stomatal trait analysis through deep learning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-04-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.04.30.591943v1?rss=1">
<title>
<![CDATA[
Proteomic Dynamics and Heat Stress Response in Arabidopsis Seedlings 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.04.30.591943v1?rss=1</link>
<description><![CDATA[
Global warming poses a grave threat to plant survival, adversely affecting growth and agricultural productivity. To develop thermotolerant crops, a profound comprehension of plant responses to heat stress at the molecular level is imperative. Leveraging a novel fusion of 15N-stable isotope labeling and the ProteinTurnover algorithm, we meticulously investigated proteome dynamics in Arabidopsis thaliana seedlings subjected to moderate heat stress (30{degrees}C). This innovative approach facilitated a comprehensive analysis of proteomic changes across diverse cellular fractions. Our study unveiled significant turnover rate alterations in 571 proteins, with a median increase of 1.4-fold, indicative of accelerated protein dynamics under heat stress. Notably, root soluble proteins exhibited more subdued changes, suggesting tissue-specific adaptations. Moreover, we observed noteworthy turnover variations in proteins associated with redox signaling, stress response, and metabolism, underscoring the complexity of the response network. Conversely, proteins involved in carbohydrate metabolism and mitochondrial ATP synthesis displayed minimal turnover changes, signifying their stability. This exhaustive examination sheds light on the proteomic adjustments of Arabidopsis seedlings to moderate heat stress, elucidating the delicate balance between proteome stability and adaptability. These findings significantly augment our understanding of plant thermal resilience and offer crucial insights for the development of crops endowed with enhanced thermotolerance.
]]></description>
<dc:creator>Fan, K.-T.</dc:creator>
<dc:creator>Xu, Y.</dc:creator>
<dc:date>2024-04-30</dc:date>
<dc:identifier>doi:10.1101/2024.04.30.591943</dc:identifier>
<dc:title><![CDATA[Proteomic Dynamics and Heat Stress Response in Arabidopsis Seedlings]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-04-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.05.03.592329v1?rss=1">
<title>
<![CDATA[
Syngeneic natural killer cell therapy activates dendritic and T cells in metastatic lungs and effectively treat low-burden metastases 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.05.03.592329v1?rss=1</link>
<description><![CDATA[
Natural killer (NK) cells can control metastasis through cytotoxicity and IFN-{gamma} production independently of T cells in experimental metastasis mouse models. The inverse correlation between NK activity and metastasis incidence supports a critical role for NK cells in human metastatic surveillance. However, autologous NK cell therapy has shown limited benefit in treating patients with metastatic solid tumors. Using a spontaneous metastasis mouse model of MHC-I+ breast cancer, we found that transfer of IL-15/IL-12-conditioned syngeneic NK cells after primary tumor resection promoted long-term survival of mice with low metastatic burden and induced a tumor-specific protective T cell response that is essential for the therapeutic effect. Furthermore, NK cell transfer augments activation of conventional dendritic cells (cDCs), Foxp3-CD4+ T cells and stem cell-like CD8+ T cells in metastatic lungs, to which IFN-{gamma} of the transferred NK cells contributes significantly. These results imply direct interactions between transferred NK cells and endogenous cDCs to enhance T cell activation. We conducted an investigator-initiated clinical trial of autologous NK cell therapy in six patients with advanced cancer and observed that the NK cell therapy was safe and showed signs of effectiveness. These findings indicate that autologous NK cell therapy is effective in treating established low burden metastases of MHC-I+ tumor cells by activating the cDC-T cell axis at metastatic sites.
]]></description>
<dc:creator>Huang, S.-W.</dc:creator>
<dc:creator>Lai, Y.-G.</dc:creator>
<dc:creator>Liao, H.-T.</dc:creator>
<dc:creator>Chang, C.-L.</dc:creator>
<dc:creator>Ma, R.-Y.</dc:creator>
<dc:creator>Chen, Y.-H.</dc:creator>
<dc:creator>Liou, Y.-H.</dc:creator>
<dc:creator>Wu, Z.-Q.</dc:creator>
<dc:creator>Wu, Y.-C.</dc:creator>
<dc:creator>Liu, K.-J.</dc:creator>
<dc:creator>Huang, Y.-T.</dc:creator>
<dc:creator>Yang, J.-L.</dc:creator>
<dc:creator>Dai, M.-S.</dc:creator>
<dc:creator>Liao, N.-S.</dc:creator>
<dc:date>2024-05-05</dc:date>
<dc:identifier>doi:10.1101/2024.05.03.592329</dc:identifier>
<dc:title><![CDATA[Syngeneic natural killer cell therapy activates dendritic and T cells in metastatic lungs and effectively treat low-burden metastases]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-05-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.05.09.583166v1?rss=1">
<title>
<![CDATA[
Naa10 regulates hippocampal neurite outgrowth via Btbd3 N-α-acetylation-mediated actin dynamics 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.05.09.583166v1?rss=1</link>
<description><![CDATA[
Protein N--acetylation is widespread in eukaryotes, yet its neuronal role remains unclear. Mutations in human N--acetyltransferase 10 (NAA10) lead to developmental defects affecting brain function, such as intellectual disability and autism. We found that hippocampal CA1-specific Naa10-knockout mice exhibit anxiety and reduced hippocampal dendritic complexity. Mechanistically, Naa10 promotes neurite outgrowth by acetylating BTB/POZ domain-containing protein 3 (Btbd3), crucial for the interaction of Btbd3 with filamentous actin (F-actin)-capping protein subunit beta (CapZb). Disrupting the Btbd3/CapZb interaction, either through Naa10 knockout or by expressing an N--acetylation-defective Btbd3 mutant, diminishes CapZb binding to F-actin and reduces neurite outgrowth. Moreover, cytochalasin D, a compound like CapZb in capping the barbed end of F-actin, rescues the Naa10 knockout-induced neurite reduction in hippocampal primary neurons. These findings unveil the role of Naa10 in enhancing hippocampal neurite outgrowth through the Btbd3-CapZb-F-actin axis, shedding light on potential mechanisms underlying X-linked Ogden syndrome resulting from human NAA10 mutations.

eTOCChou et al. demonstrate that Naa10 promotes neurite outgrowth by N-acetylating Btbd3, facilitating the binding of the filamentous actin capping protein subunit beta (CapZb) to F-actin. Their study establishes a connection between protein N--acetylation and neuronal function, providing insight into the mechanism underlying brain disorders associated with human NAA10 mutations.

HIGHLIGHTSO_LIHippocampal CA1-specific Naa10 KO leads to anxiety
C_LIO_LIHippocampal CA1-specific Naa10 KO reduces hippocampal dendritic complexity
C_LIO_LINaa10 promotes neurite outgrowth by N-acetylating Btbd3
C_LIO_LINaa10-mediated Btbd3 N--acetylation promotes CapZb binding to F-actin
C_LI

Graphical Abstract

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]]></description>
<dc:creator>Chou, C.-T.</dc:creator>
<dc:creator>Kang, M.-L.</dc:creator>
<dc:creator>Lee, C.-C.</dc:creator>
<dc:creator>Hsu, P.-H.</dc:creator>
<dc:creator>Juan, L.-J.</dc:creator>
<dc:date>2024-05-10</dc:date>
<dc:identifier>doi:10.1101/2024.05.09.583166</dc:identifier>
<dc:title><![CDATA[Naa10 regulates hippocampal neurite outgrowth via Btbd3 N-α-acetylation-mediated actin dynamics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-05-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.05.14.594062v1?rss=1">
<title>
<![CDATA[
Predation by nematode-trapping fungus triggers mechanosensory-dependent quiescence in C. elegans 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.05.14.594062v1?rss=1</link>
<description><![CDATA[
Predation can induce behavioral changes in prey, yet the molecular and neuronal mechanisms underlying prey responses remain poorly understood. Here, we investigated how the nematode Caenorhabditis elegans responds to predation by the nematode-trapping fungus, Arthrobotrys oligospora. We found that A. oligospora predation induced quiescence in C. elegans showing rapid cessation of pharyngeal pumping and movement. Calcium imaging revealed that this quiescence was regulated by the activation of sleep-promoting neurons, ALA and RIS. Genetic analyses demonstrated that ALA were essential for pharyngeal pumping inhibition, whereas both ALA and RIS contributed to movement cessation. Transcriptomic analysis in C. elegans showed the upregulation of immune defense genes in response to A. oligospora predation. We demonstrated that mechanosensation was required for pumping inhibition and transcriptomic regulation upon A. oligospora trapping. These findings suggest that physical constraints imposed by fungal traps trigger a stress-induced quiescence and the upregulation of defense genes in C. elegans. We suggest that trapping-induced quiescence might be a predation strategy used by sessile predators to prevail in the evolutionary arms race.
]]></description>
<dc:creator>Lin, T.-H.</dc:creator>
<dc:creator>Chang, H.-W.</dc:creator>
<dc:creator>Tay, R. J.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:date>2024-05-14</dc:date>
<dc:identifier>doi:10.1101/2024.05.14.594062</dc:identifier>
<dc:title><![CDATA[Predation by nematode-trapping fungus triggers mechanosensory-dependent quiescence in C. elegans]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-05-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.05.15.594278v1?rss=1">
<title>
<![CDATA[
Cathepsin X is a conserved cell death protein involved in algal response to environmental stress 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.05.15.594278v1?rss=1</link>
<description><![CDATA[
Phytoplankton play a crucial role in global primary production and can form vast blooms in aquatic ecosystems. Bloom demise and the rapid turnover of phytoplankton are suggested to involve programmed cell death (PCD) induced by diverse environmental stressors. However, fundamental knowledge of the PCD molecular components in algae and protists in general remains elusive. Previously, we revealed that early oxidation in the chloroplast predicted subsequent cell death or survival in isogenic subpopulations that emerged following H2O2 treatment in the diatom Phaeodactylum tricornutum. Here, we performed transcriptome analysis of sorted sensitive oxidized cells and resilient reduced cells, to discover genes linked to their contrasting fates. By cross-comparison with a large-scale mutant screen in the green alga Chlamydomonas reinhardtii, we identified functionally relevant conserved PCD gene candidates, including the cysteine protease cathepsin X/Z (CPX). CPX mutants in P. tricornutum CPX1 and C. reinhardtii CEP12 both exhibited profound resilience to oxidative stress, supporting a conserved function in algal PCD. P. tricornutum cpx1 mutants, generated using CRISPR-Cas9, also exhibited resilience to the toxic diatom-derived infochemical cyanogen bromide. Phylogenetic and predictive structural analyses show that CPX is highly conserved in eukaryotes, and algae of the green and red lineages exhibit strong structural similarity to human cathepsin CTSZ. CPX is expressed by diverse algae across the oceans and during toxic Pseudo-nitzschia blooms, supporting its ecological importance. Elucidating PCD components in algae sheds light on the evolutionary origin of PCD in unicellular organisms, and on the cellular strategies employed by the population to cope with stressful conditions.
]]></description>
<dc:creator>Mizrachi, A.</dc:creator>
<dc:creator>Sadeh, M.</dc:creator>
<dc:creator>Ben-Dor, S.</dc:creator>
<dc:creator>Dym, O.</dc:creator>
<dc:creator>Ku, C.</dc:creator>
<dc:creator>Feldmesser, E.</dc:creator>
<dc:creator>Zarfin, A.</dc:creator>
<dc:creator>Brunson, J. K.</dc:creator>
<dc:creator>Allen, A. E.</dc:creator>
<dc:creator>Jinkerson, R. E.</dc:creator>
<dc:creator>Schatz, D.</dc:creator>
<dc:creator>Vardi, A.</dc:creator>
<dc:date>2024-05-15</dc:date>
<dc:identifier>doi:10.1101/2024.05.15.594278</dc:identifier>
<dc:title><![CDATA[Cathepsin X is a conserved cell death protein involved in algal response to environmental stress]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-05-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.05.15.594353v1?rss=1">
<title>
<![CDATA[
Annelid comparative genomics and the evolution of massive lineage-specific genome rearrangement in bilaterians 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.05.15.594353v1?rss=1</link>
<description><![CDATA[
The organization of genomes into chromosomes is critical for processes such as genetic recombination, environmental adaptation, and speciation. All animals with bilateral symmetry inherited a genome structure from their last common ancestor that has been highly conserved in some taxa but seemingly unconstrained in others. However, the evolutionary forces driving these differences and the processes by which they emerge have remained largely uncharacterized. Here we analyze genome organization across the phylum Annelida using 23 chromosome-level annelid genomes. We find that while most annelids have maintained the conserved bilaterian genome structure, a group containing leeches and earthworms possesses completely scrambled genomes. We develop a rearrangement index to quantify the extent of genome structure evolution and show leeches and earthworms to have the most highly rearranged genomes of any currently sampled bilaterian. We further show that bilaterian genomes can be classified into two distinct categories--high and low rearrangement--largely influenced by the presence or absence, respectively, of chromosome fission events. Our findings demonstrate that animal genome structure can be highly variable within a phylum and reveal that genome rearrangement can occur both in a gradual, stepwise fashion or as rapid, all-encompassing changes over short evolutionary timescales.
]]></description>
<dc:creator>Lewin, T. D.</dc:creator>
<dc:creator>Liao, I. J.-Y.</dc:creator>
<dc:creator>Luo, Y.-J.</dc:creator>
<dc:date>2024-05-18</dc:date>
<dc:identifier>doi:10.1101/2024.05.15.594353</dc:identifier>
<dc:title><![CDATA[Annelid comparative genomics and the evolution of massive lineage-specific genome rearrangement in bilaterians]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-05-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.05.20.594799v1?rss=1">
<title>
<![CDATA[
A Sap Peptide Conserved across Flowering Plants Positively Regulates Lignin Biosynthesis, Biomass and Immunity 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.05.20.594799v1?rss=1</link>
<description><![CDATA[
Signaling peptides act as hormones to deliver short- or long-distance intercellular signals to govern complex developmental processes. Identifying endogenous signaling peptides is challenging due to their low abundance and the unknown cleavage sites required for release from precursor proteins, not to mention the investigation of their evolutionary roles across species. Consequently, very few peptides were evolutionarily characterized in vivo, especially long-distance signaling peptides. Here we present current largest peptidomic datasets from six species (maize, camphor tree, tomato, rose gum, soybean and poplar), totaling 12,242 peptides, selected from all representative evolutionary clades of angiosperms, including monocots, magnoliids, rosid eudicots, and asterid eudicots. A sap peptide was found to be identical across all six species and named as ASAP (angiosperm sap peptide), emerging as the most conserved peptide family discovered thus far. ASAP rapidly induces a series of protein phosphorylation involved in a signaling cascade previously reported to regulate lignin biosynthesis, plant growth and plant immunity. Functional assays on ASAP activity demonstrated its capability on the induction of monolignol biosynthesis and lignin deposition. High-throughput phenomic analyses showed that ASAP significantly increased plant above- and below-ground biomass. In addition, ASAP treatment enhanced plant immunity and reduced the number of galls and egg masses against nematode invasion. This study provides insights into the conservation and functional significance of plant long-distance mobile signaling peptides, offering potential applications in crop improvement and disease management strategies.
]]></description>
<dc:creator>Chen, C.-H.</dc:creator>
<dc:creator>Liou, P.-C.</dc:creator>
<dc:creator>Hsu, Y.-F.</dc:creator>
<dc:creator>Wang, I.-F.</dc:creator>
<dc:creator>Kuo, C.-Y.</dc:creator>
<dc:creator>Huang, K.-H.</dc:creator>
<dc:creator>Yu, J.-H.</dc:creator>
<dc:creator>Chen, C.-W.</dc:creator>
<dc:creator>Wu, C.-C.</dc:creator>
<dc:creator>Lin, D.-G.</dc:creator>
<dc:creator>Li, C.-B.</dc:creator>
<dc:creator>Tu, Y.-K.</dc:creator>
<dc:creator>Hsu, C.-C.</dc:creator>
<dc:creator>Su, J.-C.</dc:creator>
<dc:creator>Xia, K.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:creator>Lin, Y.-C. J.</dc:creator>
<dc:creator>Chen, Y.-L.</dc:creator>
<dc:date>2024-05-21</dc:date>
<dc:identifier>doi:10.1101/2024.05.20.594799</dc:identifier>
<dc:title><![CDATA[A Sap Peptide Conserved across Flowering Plants Positively Regulates Lignin Biosynthesis, Biomass and Immunity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-05-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.05.29.596462v1?rss=1">
<title>
<![CDATA[
Control of lumen geometry and topology by cell proliferation rate and pressure 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.05.29.596462v1?rss=1</link>
<description><![CDATA[
Many internal organs in multicellular organisms comprise epithelia which enclose fluid-filled cavities. These are referred to as lumens and their formation is regulated by a wide range of processes, including epithelial polarization, secretion, exocytosis and actomyosin contractility [1, 2]. While these mechanisms have shed light on lumen growth, what controls lumen morphology remains enigmatic. Here we use pancreas organoids to explore how lumens acquire either a spherical shape or a branched topology [3]. Combining computational simulations based on a phase field model with experimental measurements we reveal that lumen morphology arises from the balance between the cell cycle duration and lumen pressure, with more complex lumen at low pressure and fast proliferation rates. Moreover, the manipulation of proliferation and lumen pressure in silico and in vitro is sufficient to alter and reverse the morphological trajectories of the lumens. Increasing epithelial permeability of spherical lumens lead to lower lumen pressure and converts their morphology to complex lumen shapes, highlighting its crucial role. In summary, the study underscores the importance of balancing cell proliferation, lumen pressure, and epithelial permeability in determining lumen morphology, providing insights relevant to other organs, for tissue engineering and cystic disease understanding and treatment [4].
]]></description>
<dc:creator>Lee, B. H.</dc:creator>
<dc:creator>Fuji, K.</dc:creator>
<dc:creator>Petzold, H.</dc:creator>
<dc:creator>Seymour, P. A.</dc:creator>
<dc:creator>Yennek, S.</dc:creator>
<dc:creator>Schewin, C.</dc:creator>
<dc:creator>Lewis, A.</dc:creator>
<dc:creator>Riveline, D.</dc:creator>
<dc:creator>Hiraiwa, T.</dc:creator>
<dc:creator>Sano, M.</dc:creator>
<dc:creator>Grapin-Botton, A.</dc:creator>
<dc:date>2024-05-30</dc:date>
<dc:identifier>doi:10.1101/2024.05.29.596462</dc:identifier>
<dc:title><![CDATA[Control of lumen geometry and topology by cell proliferation rate and pressure]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-05-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.05.28.596352v1?rss=1">
<title>
<![CDATA[
Brachiopod genome unveils the evolution of the BMP-Chordin network in bilaterian body patterning 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.05.28.596352v1?rss=1</link>
<description><![CDATA[
Bone morphogenetic protein (BMP) signalling is crucial in regulating dorsal-ventral patterning and cell fate determination during early development in bilaterians. Interactions between BMP ligands and their main antagonist, Chordin, establish BMP gradients, subdivide embryos into distinct territories and organise body plans. However, the molecular control and evolutionary origins of dorsal-ventral patterning within spiralians, one of the three major bilaterian groups, have been obscured by their unique embryonic development. Here we present the chromosome-level genome of a spiralian with deuterostome-like development, the brachiopod Lingula anatina, and apply functional transcriptomics to study dorsal-ventral patterning under the control of BMP signalling. We uncover the presence of a dorsal-ventral BMP signalling gradient in the L. anatina gastrula with bmp2/4 and chordin expressed at its dorsal and ventral sides, respectively. Using small-molecule drugs, exogenous recombinant BMP proteins and RNA sequencing, we show that a high level of BMP pathway activation inhibits the expression of neural genes during gastrula and larval stages. We also show that BMP signalling splits the developing larval shell field into two valves. The discovery of a BMP-mediated dorsal-ventral patterning system in a spiralian, similar to those observed in deuterostomes and non-spiralian protostomes, suggests deep conservation of this mechanism across all three major bilaterian clades. This is further supported by striking similarities in the gene sets regulated by BMP signalling in brachiopods and the vertebrate model Xenopus. We argue that the spiralian ancestor retained the basal bilaterian mechanism of dorsal-ventral patterning, although downstream components of the BMP-Chordin network have undergone dynamic evolutionary changes.
]]></description>
<dc:creator>Lewin, T. D.</dc:creator>
<dc:creator>Shimizu, K.</dc:creator>
<dc:creator>Liao, I. J.-Y.</dc:creator>
<dc:creator>Chen, M.-E.</dc:creator>
<dc:creator>Endo, K.</dc:creator>
<dc:creator>Satoh, N.</dc:creator>
<dc:creator>Holland, P. W. H.</dc:creator>
<dc:creator>Wong, Y. H.</dc:creator>
<dc:creator>Luo, Y.-J.</dc:creator>
<dc:date>2024-06-02</dc:date>
<dc:identifier>doi:10.1101/2024.05.28.596352</dc:identifier>
<dc:title><![CDATA[Brachiopod genome unveils the evolution of the BMP-Chordin network in bilaterian body patterning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-06-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.05.31.596824v1?rss=1">
<title>
<![CDATA[
The tumor-maintaining function of UTX/KDM6A in DNA replication and the PARP1-dependent repair pathway 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.05.31.596824v1?rss=1</link>
<description><![CDATA[
Histone H3K27 demethylase UTX (aka KDM6A) is mutated in many human cancers, suggesting its tumor suppressive role during cancer development. However, most tumors still express wild-type UTX/KDM6A and its function is not always linked to tumor suppression. Here, we present evidence of UTX/KDM6As role in sustaining tumor growth, revealing its function in tumor maintenance. We find that UTX/KDM6A sustains tumor cell cycling and survival via regulating DNA replication-associated transcriptional programs in a demethylase-independent manner. UTX/KDM6A can also interact with PARP1 and facilitate its recruitment to DNA lesions. Therefore, UTX/KDM6A depletion disrupts DNA replication and repair pathways, activating ATM-CHK2 and ATR-CHK1 signaling pathways and triggering S and G2/M checkpoints, leading to a pronounced defect in tumor growth. Analysis of human cancer xenograft models further demonstrates that knockdown of UTX/KDM6A by RNA-interference, rather than inhibition of its enzymatic activity via GSK-J4, shows potent anticancer effects. Dual inhibition of UTX/KDM6A and ATR further demonstrates synergistic anticancer activities. Our work highlights UTX/KDM6A as a potential therapeutic target for cancer treatment, especially when combined with ATR inhibition.

HighlightsO_LIUTX/KDM6A contributes to tumor maintenance by promoting the growth and survival of tumor cells
C_LIO_LITumor cells rely on UTX/KDM6A to maintain DNA replication, cell cycling, and DNA damage repair
C_LIO_LIUTX/KDM6A depletion triggers S and G2/M checkpoints via activating ATM-CHK2 and ATR-CHK1 signaling pathways
C_LIO_LITargeting UTX/KDM6A may prove to be an innovative strategy for cancer therapy, whether employed independently or in conjunction with ATR inhibitors.
C_LI

The Paper ExplainedO_ST_ABSProblemC_ST_ABSThe aggressive growth of tumors relies significantly on heightened proliferation rates and genomic instability, which necessitate robust DNA replication machinery and efficient DNA damage repair mechanisms for tumor cell survival and proliferation. UTX/KDM6A, a histone demethylase central to chromatin and epigenetic regulation, is commonly mutated in various human cancers. However, its role as a tumor suppressor or promoter remains unclear across different cancer contexts. This study delves into the potential tumor-maintaining role of UTX/KDM6A in cancer progression and tumorigenesis, establishing the mechanistic foundation for its tumor-promoting function.

ResultsWe uncover UTX/KDM6As crucial role in tumor maintenance via its participation in DNA replication and repair pathways. Surprisingly, we find that its histone demethylase activity is dispensable for these functions, implying an alternative role as a scaffold protein. Consequently, our findings suggest that targeting the entire UTX/KDM6A gene or protein, rather than inhibiting its enzymatic activity, holds promise as a therapeutic strategy for tumors dependent on its tumor-maintaining function.

ImpactThis study unveils UTX/KDM6As multifaceted role in cancer progression, shedding light on its diverse contributions to tumorigenesis. Our findings suggest promising therapeutic strategies for cancer treatment, highlighting the importance of targeting UTX/KDM6A and its impact on DNA replication and repair pathways. These discoveries set the stage for further exploration of UTX/KDM6A-mediated mechanisms in clinical settings, indicating potential applications in future clinical trials and combination therapy strategies.
]]></description>
<dc:creator>Wang, S.-P.</dc:creator>
<dc:creator>Yeh, L.-W.</dc:creator>
<dc:creator>Chen, J.-W.</dc:creator>
<dc:creator>Yeh, J.-Y.</dc:creator>
<dc:creator>Kao, M.-H.</dc:creator>
<dc:creator>Hong, H.-C.</dc:creator>
<dc:creator>Wu, S.</dc:creator>
<dc:creator>Cheung, W.-M.</dc:creator>
<dc:creator>Liu, T.-Y.</dc:creator>
<dc:creator>Aberin, M. A. E.</dc:creator>
<dc:creator>Paas-Oliveros, E.</dc:creator>
<dc:creator>Escajeda, A.</dc:creator>
<dc:creator>Shih, E.</dc:creator>
<dc:creator>Tarn, W.-Y.</dc:creator>
<dc:creator>Chang, Y.-M.</dc:creator>
<dc:creator>Wang, L.-H.</dc:creator>
<dc:date>2024-06-03</dc:date>
<dc:identifier>doi:10.1101/2024.05.31.596824</dc:identifier>
<dc:title><![CDATA[The tumor-maintaining function of UTX/KDM6A in DNA replication and the PARP1-dependent repair pathway]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-06-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.06.03.597082v1?rss=1">
<title>
<![CDATA[
Evolutionary Insights into Muscle Fiber Distribution in the Twin Tails of Ornamental Goldfish 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.06.03.597082v1?rss=1</link>
<description><![CDATA[
Twin-tail ornamental goldfish have a bifurcated caudal fin with a morphology that is extremely diverged from the conventional body plan of the vertebrates. Here, we investigate the muscu-loskeletal histology of this bifurcated caudal fin. From some of the investigated twin-tail goldfish, we found a twin-tail goldfish specific muscle (hereafter referred to as the "medial caudal muscle") between left and right bifurcated caudal fin skeletons. Our immunohistochemical analyses revealed that the medial caudal muscle showed laterally biased distribution patterns of the slow and fast muscle fibers. Similar distribution patterns were also commonly observed in several deep muscles of wild-type goldfish as well as zebrafish, suggesting that these muscle fiber distribution patterns are formed by the same molecular developmental mechanisms even though their morphologies are highly diverged. These findings provide empirical evidence to consider how the histological features of a newly emerged morphology are influenced by selective pressures and pre-existing developmental mechanisms.
]]></description>
<dc:creator>Ota, K.</dc:creator>
<dc:creator>Abe, G.</dc:creator>
<dc:creator>Wang, C.-Y.</dc:creator>
<dc:creator>Li, I.-J.</dc:creator>
<dc:creator>Sanchez, P. G. L.</dc:creator>
<dc:creator>Chi, T.-C.</dc:creator>
<dc:date>2024-06-04</dc:date>
<dc:identifier>doi:10.1101/2024.06.03.597082</dc:identifier>
<dc:title><![CDATA[Evolutionary Insights into Muscle Fiber Distribution in the Twin Tails of Ornamental Goldfish]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-06-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.06.10.596762v1?rss=1">
<title>
<![CDATA[
Thymic self-recognition-mediated TCR signal strength modulates antigen-specific CD8+ T cell pathogenicity in non-obese diabetic mice 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.06.10.596762v1?rss=1</link>
<description><![CDATA[
Our understanding of autoimmune diabetes underscores the critical involvement of CD8+ T cells recognizing islet-specific antigens. However, the influence of thymic positive selection on diabetogenic CD8+ T cell development remains unclear. Using CD5 marker representing T-cell receptor (TCR) signal strength, we illustrated that naive CD5hiCD8+ T cells of non-obese diabetic (NOD) mice with enhanced TCR signals displayed predisposed differentiated/memory T cell traits with increased activation and proliferation upon TCR stimulation, compared to CD5lo counterparts. Additionally, CD5hiCD8+ T cells exhibited gene expression landscape similar to effector T cells and exacerbated disease in transfer model. Interestingly, the protective effects of transgenic phosphatase Pep expression, which lowers TCR signaling and diabetes incidence, were abolished in NOD strain 8.3 with high CD5 expression linked to increased thymic positive selection. Strikingly, TCR repertoire analysis identified higher frequencies of autoimmune disease-related clonotypes in naive CD5hiCD8+ cells, supporting that distinct effector functions arise from intrinsic TCR repertoire differences. Overall, CD5hiCD8+ clones may be potential targets for autoimmune diabetes treatment.
]]></description>
<dc:creator>Ho, C.-L.</dc:creator>
<dc:creator>Yeh, L.-T.</dc:creator>
<dc:creator>Liu, Y.-W.</dc:creator>
<dc:creator>Dong, J.-L.</dc:creator>
<dc:creator>Sytwu, H.-K.</dc:creator>
<dc:date>2024-06-12</dc:date>
<dc:identifier>doi:10.1101/2024.06.10.596762</dc:identifier>
<dc:title><![CDATA[Thymic self-recognition-mediated TCR signal strength modulates antigen-specific CD8+ T cell pathogenicity in non-obese diabetic mice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-06-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.06.25.600713v1?rss=1">
<title>
<![CDATA[
Cytokinin-inducible DIRIGENT13 involved in lignan synthesis and ROS accumulation promotes root growth and abiotic stress tolerance in Arabidopsis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.06.25.600713v1?rss=1</link>
<description><![CDATA[
Dirigent (DIR) proteins mediate regio- and stereoselectivity of phenoxy radical coupling of monolignols for (neo)lignan or lignin synthesis. However, the role of DIR proteins and lignans in plant development and response to environmental stresses remains elusive. Here, we provide a functional characterization of the cytokinin-responsive DIRIGENT13 (DIR13) in Arabidopsis thaliana. DIR13 was localized to the root endodermis and at the margins of lateral root primordia and lateral roots. While not necessary for Casparian strip formation, DIR13 promoted both main and lateral root growth. Untargeted metabolomics and imaging mass spectrometry analyses unveiled the role of DIR13 in facilitating (neo)lignan synthesis in primary and lateral roots. Interestingly, DIR13 activated the production of putative oxomatairesinol and matairesinol-cysteine which are oxidative derivatives of the lignan matairesinol. Our data also identified DIR13 as an enhancer of salt and drought tolerance. Particularly, DIR13 attenuated salt stress-mediated inhibition of germination and root growth. Moreover, DIR13 activated reactive oxygen species (ROS) accumulation both under control and salt stress conditions, and cytokinin further enhanced the salt-induced ROS production specifically in the DIR13 overexpressing line. Our results uncover a role for DIR13-produced lignans in the priming of ROS accumulation, mediating both abiotic stress tolerance and the control of root architecture.
]]></description>
<dc:creator>Melnikava, A.</dc:creator>
<dc:creator>Perreau, F.</dc:creator>
<dc:creator>Paniagua, C.</dc:creator>
<dc:creator>Cheng, S.-C.</dc:creator>
<dc:creator>Huang, L.-M.</dc:creator>
<dc:creator>Ubogoeva, E.</dc:creator>
<dc:creator>Zemlyanskaya, E.</dc:creator>
<dc:creator>Yang, Y.-L.</dc:creator>
<dc:creator>Mouille, G.</dc:creator>
<dc:creator>Arnaud, D.</dc:creator>
<dc:creator>Hejatko, J.</dc:creator>
<dc:date>2024-06-29</dc:date>
<dc:identifier>doi:10.1101/2024.06.25.600713</dc:identifier>
<dc:title><![CDATA[Cytokinin-inducible DIRIGENT13 involved in lignan synthesis and ROS accumulation promotes root growth and abiotic stress tolerance in Arabidopsis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-06-29</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.06.30.601456v1?rss=1">
<title>
<![CDATA[
CoPR: Collective Pattern Recognition-a Framework for Microbial Community Activity Analysis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.06.30.601456v1?rss=1</link>
<description><![CDATA[
BackgroundMicrobial community activities provide essential information on understanding bacterial communities. Unfortunately, they are generally not directly observable. We rely on longitudinal abundance profiles to get insight into microbial community activities. Often datasets do not have sufficient longitudinal sampling points to successfully apply our algorithms. Hence, in this paper, we are interested in analysing multiple datasets from similar environments to alleviate the aforementioned problem. Furthermore, we wish to see whether collective pattern recognition would enhance our understanding of microbial community activities.

ResultsIn this paper, we present CoPR, a framework for collective microbial longitudinal abundance data. Our visualisation shows that a single pattern for temporal abundance variation does not exist. However, it also indicates that even complete individuality does not exist. Consequently, our visualisation highlights the individuality and conformity in the temporal variation of abundance profiles of similar host environments. We also identify different characteristics in the TVAP (Temporal Variation of Abundance Profile) patterns with regards to cohesion and separation.

ConclusionsCoPR helps gain essential insights into the microbial communities and their heterogeneity through visualisation tools. This paper also highlights the choice between individuality and conformity in microbial community data analysis.
]]></description>
<dc:creator>Vidanaarachchi, R.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:creator>Halgamuge, S. K.</dc:creator>
<dc:date>2024-07-02</dc:date>
<dc:identifier>doi:10.1101/2024.06.30.601456</dc:identifier>
<dc:title><![CDATA[CoPR: Collective Pattern Recognition-a Framework for Microbial Community Activity Analysis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-07-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.07.30.605757v1?rss=1">
<title>
<![CDATA[
Zebrafish Foxl2l functions in proliferating germ cells for female meiotic entry 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.07.30.605757v1?rss=1</link>
<description><![CDATA[
AbstractZebrafish sex differentiation is a complicated process and the detailed mechanism has not been fully understood. Here we characterized a transcription factor, Foxl2l, that participates in female oogenesis. We show that it is expressed specifically in proliferating germ cells in juvenile gonads and mature ovaries. We have used CRISPR-Cas9 to generate zebrafish deficient in foxl2l expression. Zebrafish with foxl2l-/- are all males, and this female-to-male sex reversal cannot be reversed by tp53 mutation, indicating this sex reversal is unrelated to cell death. We have generated transgenic fish expressing GFP under the control of foxl2l promoter to track the development of foxl2l+-germ cells, which failed to enter meiosis and were accumulated as cystic cells. Our RNA-seq analysis also showed the reduced expression of genes in meiosis and oogenesis among other affected pathways. All together, we show that zebrafish Foxl2l is a nuclear factor controlling the expression of meiotic and oogenic genes, and its deficiency leads to defective meiotic entry and the accumulation of premeiotic germ cells.

HighlightsO_LIZebrafish foxl2l is expressed only in proliferating germ cells in juvenile gonads and mature ovaries.
C_LIO_LIFoxl2l is a nuclear factor that promotes expression of genes involved in meiosis and oogenesis.
C_LIO_LIZebrafish depleted of foxl2l lack meiotic oocytes in juveniles and become all males in adults.
C_LIO_LIMutation of foxl2l leads to the accumulation of premeiotic germ cells.
C_LI
]]></description>
<dc:creator>Yang, C.-H.</dc:creator>
<dc:creator>Wang, Y.-W.</dc:creator>
<dc:creator>Hsu, C.-w.</dc:creator>
<dc:creator>Pan, Y.-J.</dc:creator>
<dc:creator>Chung, B.-c.</dc:creator>
<dc:date>2024-07-31</dc:date>
<dc:identifier>doi:10.1101/2024.07.30.605757</dc:identifier>
<dc:title><![CDATA[Zebrafish Foxl2l functions in proliferating germ cells for female meiotic entry]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-07-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.08.20.608638v1?rss=1">
<title>
<![CDATA[
Endophytic pyrroloquinoline quinone enhances banana growth and immunity against Fusarium wilt for plant-microbe mutualisms 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.08.20.608638v1?rss=1</link>
<description><![CDATA[
Fusarium wilt has a substantial impact on global banana production, posing a threat to food security worldwide. However, breeding new Fusarium-resistant cultivars is difficult and time-consuming. Alternatively, endophytic biostimulants that could combat such pervasive plant diseases provide possible novel solutions. Our prior research demonstrated that a pyrroloquinoline quinone (PQQ)-producing endophytic bacterium, Burkholderia seminalis 869T2, can enhance the growth of various plant species and protect bananas from Fusarium wilt in the field. PQQ is a peptide-derived redox cofactor known to stimulate mitochondrial biogenesis and metabolism in animals, but its molecular roles, especially in plants, remain to be elucidated. In this study, multi-omics approaches were employed to explore the potential mechanisms through which PQQ influences banana plants. The result of in situ imaging mass spectrometry revealed that the endophytic metabolite PQQ does not function through direct antagonism against Fusarium. The follow-up transcriptomic profiling shows it could regulate plant respiration, TCA cycle, oxidative phosphorylation, NAD/NADP-dependent dehydrogenases, MAPK signalling, and various phytohormone signalling pathways. Furthermore, PQQ appeared to trigger plant systemic immunity, thereby enhancing plant health and resistance to biotic stress. Beyond that, the complete genome of 869T2 was determined for follow-up comparative genomics analyses, revealing its genetic contexts, potential evolutionary events of PQQ operons among the Burkholderia species, and the absence of human virulence-facilitating genes within those PQQ-producing agricultural isolates. In summary, this study facilitates our understanding of PQQ in plant-microbe mutualisms and provides scientific evidence for its future application in agriculture.

Significance StatementFusarium wilt is caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), a notorious soil-borne pathogen that attacks bananas vascular system, which critically threatens global banana production and food security. A potential PQQ-producing endophytic strain has been confirmed to protect bananas through in planta biocontrol, reducing the morbidity of Banana Fusarium Wilt (BFW) disease in the field and promoting the growth of banana plants simultaneously. Our results revealed that the endophytic metabolite PQQ does not function through direct antagonism but triggers plant systemic immunity and coordinates energetic metabolisms, thereby improving the overall health of host plants and enhancing their resistance against Fusarium wilt.
]]></description>
<dc:creator>Hung, S.-H. W.</dc:creator>
<dc:creator>Yu, M.-Y.</dc:creator>
<dc:creator>Liu, C.-H.</dc:creator>
<dc:creator>Huang, T.-C.</dc:creator>
<dc:creator>Peng, J.-H.</dc:creator>
<dc:creator>Jang, N.-Y.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:creator>Ho, Y.-N.</dc:creator>
<dc:creator>Chiang, E.-P. I.</dc:creator>
<dc:creator>Hwang, H.-H.</dc:creator>
<dc:creator>Huang, C.-C.</dc:creator>
<dc:date>2024-08-21</dc:date>
<dc:identifier>doi:10.1101/2024.08.20.608638</dc:identifier>
<dc:title><![CDATA[Endophytic pyrroloquinoline quinone enhances banana growth and immunity against Fusarium wilt for plant-microbe mutualisms]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-08-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.08.22.609097v1?rss=1">
<title>
<![CDATA[
Asymmetry of acto-myosin cortices as active fluids shape cells in organoids 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.08.22.609097v1?rss=1</link>
<description><![CDATA[
Cell cortex is a thin sheet of actin cytoskeleton spanning cell boundaries with rich out-of-equilibrium dynamics. A theoretical description of the cortex as an active fluid enables to capture cell shapes dynamics in 3D tissues. However models integrated with calibration of parameters and quantitative experiments are lacking so far. Here we report that cells in organoids and in cysts have conserved apico-basal-lateral asymmetric compositions in actin and in myosin, and we quantify their densities and mechanical properties. This allows to calibrate a new model coupling active fluids with a phase field which reproduces the main features of cell shapes. To test our approach, we successfully predict changes in cell shapes by modulating actin polymerisation in experiments and in simulations. Our study shows how active fluid theory integrated with experiments can determine cell shapes in 3D tissues.
]]></description>
<dc:creator>Guyomar, T.</dc:creator>
<dc:creator>Lu, L.</dc:creator>
<dc:creator>Hiraiwa, T.</dc:creator>
<dc:creator>Riveline, D.</dc:creator>
<dc:date>2024-08-22</dc:date>
<dc:identifier>doi:10.1101/2024.08.22.609097</dc:identifier>
<dc:title><![CDATA[Asymmetry of acto-myosin cortices as active fluids shape cells in organoids]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-08-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.08.22.609105v1?rss=1">
<title>
<![CDATA[
Population genomics of a thermophilic cyanobacterium revealed divergence at subspecies level and possible adaptation genes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.08.22.609105v1?rss=1</link>
<description><![CDATA[
BackgroundCyanobacteria are diverse phototrophic microbes with ecological importance and potential for biotechnology applications. One species of thermophilic cyanobacteria, Thermosynechococcus taiwanensis, has been studied for biomass pyrolysis, estrogen degradation, and the production of bioethanol, monosaccharide, and phycocyanin. To better understand the diversity and evolution of this species, we sampled across different regions in Taiwan for strain isolation and genomic analysis.

ResultsA total of 27 novel strains were isolated from nine of the 12 hot springs sampled and subjected to whole genome sequencing. Including strains studied previously, our genomic analyses encompassed 32 strains from 11 hot springs. Genome sizes among these strains ranged from 2.64 to 2.70 Mb, with an average of 2.66 Mb. Annotation revealed between 2,465 and 2,576 protein-coding genes per genome, averaging 2,537 genes. Core-genome phylogeny, gene flow estimates, and overall gene content divergence consistently supported the within-species divergence into two major populations. While isolation by distance partially explained the within-population divergence, the factors driving divergence between populations remain unclear. Nevertheless, this species likely has a closed pan-genome comprising approximately 3,030 genes, with our sampling providing sufficient coverage of its genomic diversity. To investigate the divergence and potential adaptations, we identified genomic regions with significantly lower nucleotide diversity, indicating loci that may have undergone selective sweeps within each population. We identified 149 and 289 genes within these regions in populations A and B, respectively. Only 16 genes were common to both populations, suggesting that selective sweeps primarily targeted different genes in the two populations. Key genes related to functions such as carbon fixation, photosynthesis, motility, and ion transport were highlighted.

ConclusionsThis work provides a population genomics perspective on a hot spring cyanobacterial species in Taiwan. Beyond advancing our understanding of microbial genomics and evolution, the strains collected and genome sequences generated in this work provide valuable materials for future development and utilization of biological resources.
]]></description>
<dc:creator>Chang, H.-Y.</dc:creator>
<dc:creator>Yen, H.-C.</dc:creator>
<dc:creator>Chu, H.-A.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:date>2024-08-22</dc:date>
<dc:identifier>doi:10.1101/2024.08.22.609105</dc:identifier>
<dc:title><![CDATA[Population genomics of a thermophilic cyanobacterium revealed divergence at subspecies level and possible adaptation genes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-08-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.08.22.608962v1?rss=1">
<title>
<![CDATA[
Cell wall arabinogalactan is responsible for Fungitell(R) cross reactivity in nocardiosis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.08.22.608962v1?rss=1</link>
<description><![CDATA[
Nocardiosis is a serious infection in immunosuppressed patients, especially transplant recipients. The slow-growing phenotype of the bacterium and the variety of symptoms complicate diagnosis and delay antimicrobial therapy, which results in high mortality rates despite effective treatments. Incidentally, some nocardiosis patients test positive in fungal diagnostics that detect (1,3) {beta}-D-glucan (the Fungitell(R) assay), but the basis for this cross-reactivity remains unknown. We demonstrate that nocardial cell wall arabinogalactan is a cryptic antigen responsible for cross reactivity in the Fungitell(R) assay and that this antigen is revealed in vivo following bacterial cell lysis. We further show that the reactivity results from {beta}-glucose substitution of the galactan domain, a modification specific to Nocardia, and identify the optimal antigen as a tetramer of the trisaccharide repeating unit. By providing structural evidence for Fungitell(R) cross-reactivity during nocardiosis, this work paves the way for developing specific diagnostic tools that are presently lacking.
]]></description>
<dc:creator>Mariller, C.</dc:creator>
<dc:creator>Letowski, P.</dc:creator>
<dc:creator>Chang, W.-T.</dc:creator>
<dc:creator>Lowary, T.</dc:creator>
<dc:creator>Ulrich, M.</dc:creator>
<dc:creator>Faure, K.</dc:creator>
<dc:creator>Loridant, S.</dc:creator>
<dc:creator>Sendid, B.</dc:creator>
<dc:creator>Wallet, F.</dc:creator>
<dc:creator>Poulain, D.</dc:creator>
<dc:creator>Hazzan, M.</dc:creator>
<dc:creator>Frimat, M.</dc:creator>
<dc:creator>Guerardel, Y.</dc:creator>
<dc:creator>Titecat, M.</dc:creator>
<dc:date>2024-08-26</dc:date>
<dc:identifier>doi:10.1101/2024.08.22.608962</dc:identifier>
<dc:title><![CDATA[Cell wall arabinogalactan is responsible for Fungitell(R) cross reactivity in nocardiosis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-08-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.08.23.609459v1?rss=1">
<title>
<![CDATA[
Lamellar Schwann cells in the Pacinian corpuscle potentiate vibration perception 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.08.23.609459v1?rss=1</link>
<description><![CDATA[
Pacinian corpuscles are among the most sensitive mechanoreceptors found in vertebrates and they are tuned to vibrations in the highest perceptible frequency range (100-2000Hz). One of their anatomical hallmarks is the onion-like cell layers surrounding the central axon. The innermost layers consist of [~]60 densely packed lamellar Schwann cells (LSCs), whose function remains largely unknown. Using high-resolution 3D electron microscopy we found that LSCs in Pacinian corpuscles of the mouse hindlimb do not form concentric rings, but complex, multilayered and intertwining assemblies that are connected via an estimated 5805.1 desmosomes and 4142.5 gap-junctions. LSCs make multiple converging contacts with the afferent axon and its protrusions with desmosomes. Using optogenetic manipulations of LSCs we demonstrate that their activation does not only drive reliable time-locked spiking in the axon, but that their inactivation significantly elevates the thresholds in-situ and increases perceptual thresholds behaviorally. Together these findings provide evidence that LSCs are a key element of somatosensory processing, actively potentiating mechanosensitivity in Pacinian corpuscles.

HighlightsO_LIHigh-resolution electron microscopy reveals details of the Pacinian corpuscle
C_LIO_LILamellar Schwann cells form claw-like structures with converging axonal contacts
C_LIO_LISchwann-cell modulation bidirectionally affects neural coding of Pacinian afferent
C_LIO_LIInactivation of lamellar Schwann-cells increases perceptual thresholds
C_LI
]]></description>
<dc:creator>Chen, Y.-T.</dc:creator>
<dc:creator>de Thomas Wagner, D.</dc:creator>
<dc:creator>Loutit, A. J.</dc:creator>
<dc:creator>Nourizonoz, A.</dc:creator>
<dc:creator>Croisier-Coeytaux, M.-C.</dc:creator>
<dc:creator>Blanc, J.</dc:creator>
<dc:creator>Knott, G.</dc:creator>
<dc:creator>Lee, K.-S.</dc:creator>
<dc:creator>Huber, D.</dc:creator>
<dc:date>2024-08-26</dc:date>
<dc:identifier>doi:10.1101/2024.08.23.609459</dc:identifier>
<dc:title><![CDATA[Lamellar Schwann cells in the Pacinian corpuscle potentiate vibration perception]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-08-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.08.27.609947v1?rss=1">
<title>
<![CDATA[
Dynamic positioning of a TFIIE-related winged-helix domain in RNA polymerase elongation complex III underpins its multi-functionality 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.08.27.609947v1?rss=1</link>
<description><![CDATA[
The tandem-winged-helix (tWH) domain of RNA polymerase III (Pol III) Rpc34 subunit is a multi-function hub in Pol III apparatus while the structure basis remains elusive. To probe tWH in Pol III elongation complex (EC), we engineered an azide-bearing unnatural amino acid into tWH and implemented a thiol-capping scheme to enable strain- promoted click reaction for selective dye labeling to suit single-molecule Forster resonance energy transfer (smFRET). Our discrete smFRET results and nano-positioning analysis reveal multiple docking sites of Rpc34 WH2 on Pol III EC with characteristic dwell-times, reflecting promiscuous and weak interactions underpinning tWHs multi-functionality. The docking sites include one overlapping with that during initiation and others on transcription bubble and downstream DNA, previously unreported. This work provides mechanistic insights into Pol III transcription re-initiation and elongation, with useful bio-orthogonal strategies for studying structural dynamics of large native protein complexes.
]]></description>
<dc:creator>Wu, J.-S.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Wei, Y.-Y.</dc:creator>
<dc:creator>Lin, H.-H.</dc:creator>
<dc:creator>Liu, Y.-C.</dc:creator>
<dc:creator>Chang, J.-W.</dc:creator>
<dc:creator>Tu, I.-P.</dc:creator>
<dc:creator>Chen, H.-T.</dc:creator>
<dc:creator>Chang, W.-H.</dc:creator>
<dc:date>2024-08-28</dc:date>
<dc:identifier>doi:10.1101/2024.08.27.609947</dc:identifier>
<dc:title><![CDATA[Dynamic positioning of a TFIIE-related winged-helix domain in RNA polymerase elongation complex III underpins its multi-functionality]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-08-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.08.29.610202v1?rss=1">
<title>
<![CDATA[
Guard-cell phytosterol homeostasis is critical for proper stomatal development 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.08.29.610202v1?rss=1</link>
<description><![CDATA[
Stomata regulate gas exchange and control water loss in response to the environmental stimuli and their distribution in the leaf epidermis is tightly regulated during development to ensure proper patterns. Although many studies have focused on the function of early stomatal lineage cells, little is known about the role of mature guard cells (GCs) in maintaining stomatal distribution. Here, we identified a previously uncharacterized enzyme, GDSL-type sterol esterase (GSEase), that is specifically expressed in mature guard cells and catalyzes lipid droplet-stored phytosterol ester degradation. Loss of GSEase decreased the level of free campesterol, a biosynthetic precursor of brassinosteroids (BRs), reduced BR level, and increased stomatal density in leaves, which could be further rescued by increasing the BR signaling. Furthermore, selectively reducing the BR response in GCs by utilizing the GSEase promoter-driven det2-1, a mutation causing BR biosynthesis deficiency, resulted in an elevated stomatal count, as demonstrated in gsease plants. These results indicate that GSEase plays a critical role in maintaining phytosterol homeostasis in GCs and the released phytosterols suppress the initiation of stomatal development in adjacent cells though the BR pathway.
]]></description>
<dc:creator>Yen, C.-C.</dc:creator>
<dc:creator>Hsu, Y.-W.</dc:creator>
<dc:creator>Leu, K.-C.</dc:creator>
<dc:creator>Chen, S.-S.</dc:creator>
<dc:creator>Chen, T.-Y.</dc:creator>
<dc:creator>Juan, C.-T.</dc:creator>
<dc:creator>Kuan, C.</dc:creator>
<dc:creator>Shaw, J.-F.</dc:creator>
<dc:creator>Ho, C.-M. K.</dc:creator>
<dc:creator>Jauh, G.-Y.</dc:creator>
<dc:date>2024-08-30</dc:date>
<dc:identifier>doi:10.1101/2024.08.29.610202</dc:identifier>
<dc:title><![CDATA[Guard-cell phytosterol homeostasis is critical for proper stomatal development]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-08-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.09.11.612468v1?rss=1">
<title>
<![CDATA[
Influenza A virus exploits the motility of membrane cytoskeletal actomyosin filaments for its genome packaging in the host cell 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.09.11.612468v1?rss=1</link>
<description><![CDATA[
Influenza A virus encodes its genome in eight segments of viral ribonucleoproteins (vRNPs) replicated in the host cell nucleus. Our understanding of host factors involved in driving vRNP selective packaging remains incomplete. To address this, we used advanced immuno-freeze-etch electron microscopy to visualise the vRNP packaging process and atomic force live-cell imaging (AFM) to examine the motility of membrane cytoskeletal actin filaments. In the cytoplasm, vRNPs were mainly localised on mottled membrane-like structures, suggesting intracellular trafficking through such structures. After reaching the cytoplasmic side surface of the plasma membrane, vRNPs formed many aggregates while associating with actin filaments. Antibody labelling also detected myosin along actin filaments entangled in vRNPs. Blocking myosin activity with blebbistatin prevented the active movement of membrane cytoskeletal actin filaments just below the plasma membrane visualised by AFM and abrogated proper aggregation of vRNPs. Thus, actomyosin motility appears to be crucial for the selective packaging of vRNPs.
]]></description>
<dc:creator>Wang, I.-H.</dc:creator>
<dc:creator>Usukura, J.</dc:creator>
<dc:creator>Miyake, Y.</dc:creator>
<dc:creator>Usukura, E.</dc:creator>
<dc:creator>Narita, A.</dc:creator>
<dc:creator>Yamauchi, Y.</dc:creator>
<dc:creator>Kawaoka, Y.</dc:creator>
<dc:date>2024-09-12</dc:date>
<dc:identifier>doi:10.1101/2024.09.11.612468</dc:identifier>
<dc:title><![CDATA[Influenza A virus exploits the motility of membrane cytoskeletal actomyosin filaments for its genome packaging in the host cell]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-09-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.09.17.613533v1?rss=1">
<title>
<![CDATA[
Structural insights into terminal arabinosylation biosynthesis of the mycobacterial cell wall arabinan 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.09.17.613533v1?rss=1</link>
<description><![CDATA[
The emergence of drug-resistant strains exacerbates the global challenge of tuberculosis caused by Mycobacterium tuberculosis (Mtb). Central to the pathogenicity of Mtb is its complex cell envelope, which serves as a barrier against both immune system and pharmacological attacks. Two key components of this envelope, arabinogalactan (AG) and lipoarabinomannan (LAM) are complex polysaccharides that contain integral arabinan domains important for cell wall structural and functional integrity. The arabinofuranosyltransferase AftB terminates the synthesis of these arabinan domains by catalyzing the addition of {beta}-(1[-&gt;]2)-linked terminal arabinofuranose residues. Here, we present the cryo-EM structures of Mycobacterium chubuense AftB in its apo and donor substrate analog-bound form, determined to 2.9 [A] and 3.4 [A] resolution, respectively. Our structures reveal that AftB has a GT-C fold transmembrane (TM) domain comprised of eleven TM helices and a periplasmic cap domain. AftB has an irregular tube-shaped cavity that bridges the two proposed substrate binding sites. By integrating structural analysis, biochemical assays, and molecular dynamics simulations, we elucidate the molecular basis of the reaction mechanism of AftB and propose a model for catalysis.
]]></description>
<dc:creator>Liu, Y.</dc:creator>
<dc:creator>Brown, C. M.</dc:creator>
<dc:creator>Erramilli, S.</dc:creator>
<dc:creator>Su, Y.-C.</dc:creator>
<dc:creator>Tseng, P.-S.</dc:creator>
<dc:creator>Wang, Y.-J.</dc:creator>
<dc:creator>Duong, N. H.</dc:creator>
<dc:creator>Tokarz, P.</dc:creator>
<dc:creator>Kloss, B.</dc:creator>
<dc:creator>Han, C.-R.</dc:creator>
<dc:creator>Chen, H.-Y.</dc:creator>
<dc:creator>Rodrigues, J.</dc:creator>
<dc:creator>Archer, M.</dc:creator>
<dc:creator>Lowary, T. L.</dc:creator>
<dc:creator>Kossiakoff, A. A.</dc:creator>
<dc:creator>Stansfeld, P. J.</dc:creator>
<dc:creator>Nygaard, R.</dc:creator>
<dc:creator>Mancia, F.</dc:creator>
<dc:date>2024-09-18</dc:date>
<dc:identifier>doi:10.1101/2024.09.17.613533</dc:identifier>
<dc:title><![CDATA[Structural insights into terminal arabinosylation biosynthesis of the mycobacterial cell wall arabinan]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-09-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.09.16.613176v1?rss=1">
<title>
<![CDATA[
Real-space heterogeneous reconstruction, refinement, and disentanglement of CryoEM conformational states with HetSIREN 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.09.16.613176v1?rss=1</link>
<description><![CDATA[
Single-particle analysis by Cryo-electron microscopy (CryoEM) provides direct access to the conformation of each macromolecule. However, the images signal-to-noise ratio is low, and some form of classification is usually performed at the image processing level to allow structural modeling. Classical classification methods imply the existence of a discrete number of structural conformations. However, new heterogeneity algorithms introduce a novel reconstruction paradigm, where every state is represented by a lower number of particles, potentially just one, allowing the estimation of conformational landscapes representing the different structural states a biomolecule explores. In this work, we present a novel deep learning-based method called HetSIREN. HetSIREN can fully reconstruct or refine a CryoEM volume in real space based on the structural information summarized in a conformational latent space. The unique characteristics that set HetSIREN apart start with the definition of the approach as a real space-based only method, a fact that allows spatially focused analysis, but also the introduction of a novel network architecture specifically designed to make use of meta-sinusoidal activations, with proven high analytics capacities. Continuing with innovations, HetSIREN can also refine the pose parameters of the images at the same time that it conditions the network with prior information/constraints on the maps, such as Total Variation and L1 denoising, ultimately yielding cleaner volumes with high-quality structural features. Finally, but very importantly, HetSIREN addresses one of the most confusing issues in heterogeneity analysis, as it is the fact that real structural heterogeneity estimation is entangled with pose estimation (and to a lesser extent with CTF estimation), in this way, HetSIREN introduces a novel encoding architecture able to decouple pose and CTF information from the conformational landscape, resulting in more accurate and interpretable conformational latent spaces. We present results on computer-simulated data, public data from EMPIAR, and data from experimental systems currently being studied in our laboratories. An important finding is the sensitivity of the structure and dynamics of the SARS-CoV-2 Spike protein on the storage temperature.
]]></description>
<dc:creator>Herreros, D.</dc:creator>
<dc:creator>Mata, C. P.</dc:creator>
<dc:creator>Noddings, C.</dc:creator>
<dc:creator>Irene, D.</dc:creator>
<dc:creator>Krieger, J. M.</dc:creator>
<dc:creator>Agard, D.</dc:creator>
<dc:creator>Tsai, M.-D.</dc:creator>
<dc:creator>Sorzano, C. O. S.</dc:creator>
<dc:creator>Carazo, J. M.</dc:creator>
<dc:date>2024-09-19</dc:date>
<dc:identifier>doi:10.1101/2024.09.16.613176</dc:identifier>
<dc:title><![CDATA[Real-space heterogeneous reconstruction, refinement, and disentanglement of CryoEM conformational states with HetSIREN]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-09-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.09.19.613839v1?rss=1">
<title>
<![CDATA[
A helper NLR targets organellar membranes to trigger immunity 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.09.19.613839v1?rss=1</link>
<description><![CDATA[
Upon activation, plant NLR immune receptors are known to assemble into oligomeric resistosomes that insert into the plasma membrane, forming Ca2+-permeable channels and triggering immunity. Here, we show that the RPW8-like coiled-coil (CCR-) NLR NRG1 primarily targets organelles instead of the plasma membrane. Unlike canonical CC-NLRs, activated NRG1 accumulates at the chloroplast envelope and channels stromal Ca2+ into the cytosol. AlphaFold modeling of the NRG1 resistosome reveals an unusually long N-terminal membrane-insertion structure that would span the double chloroplast membranes. Nanobody-mediated relocalization shows functional membrane specificity: chloroplast trapping abolishes activity of the canonical helper CC-NLR NRC4 but not NRG1. NRG1 orthologs, from non-flowering lineages to angiosperms, target chloroplasts, suggesting that organelle-centered defense dates back to at least [~]360 million years. We propose that coiled-coil NLR diversification has enabled compartment-specific immune signaling to capture diverse Ca2+ stores.
]]></description>
<dc:creator>Ibrahim, T.</dc:creator>
<dc:creator>Yuen, E. L. H.</dc:creator>
<dc:creator>Wang, H.-Y.</dc:creator>
<dc:creator>King, F. J.</dc:creator>
<dc:creator>Toghani, A.</dc:creator>
<dc:creator>Kourelis, J.</dc:creator>
<dc:creator>Vuolo, C.</dc:creator>
<dc:creator>Adamkova, V.</dc:creator>
<dc:creator>Castel, B.</dc:creator>
<dc:creator>Jones, J. D.</dc:creator>
<dc:creator>Wu, C.-H.</dc:creator>
<dc:creator>Kamoun, S.</dc:creator>
<dc:creator>Bozkurt, T. O.</dc:creator>
<dc:date>2024-09-22</dc:date>
<dc:identifier>doi:10.1101/2024.09.19.613839</dc:identifier>
<dc:title><![CDATA[A helper NLR targets organellar membranes to trigger immunity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-09-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.09.20.614103v1?rss=1">
<title>
<![CDATA[
Spatiotemporal dynamics and assembly process differ in fungal communities across contiguous habitats in tropical forests 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.09.20.614103v1?rss=1</link>
<description><![CDATA[
BackgroundThe variation in fungal community composition within a single habitat space has been extensively studied in forest ecosystems. However, the spatial and temporal distribution of fungi across contiguous habitats, particularly at a local scale and in tropical regions, remains underexplored. In this study, we examined the fungal community composition across multiple habitats proximal to each other over two seasons in seven Fagaceae species in Taiwanese broadleaf forests. We tested how local spatial scale and habitat influence community assembly.

ResultsUsing a metabarcoding approach, we sequenced ITS3/ITS4 amplicons from 864 samples collected from four distinct habitats--leaves, twigs, litter, and soil. We identified 11,600 fungal amplicon sequence variants (ASVs), with community composition differing significantly between habitats proximal to each other. Phyllosphere (leaves and twigs) fungi exhibited higher diversity compared to soil. Habitat type and long-term precipitation emerged as the most influential factors driving fungal diversity and composition, with a clear distance-decay relationship observed in leaf and twig but not in soil. Random forest analysis accurately classified habitats based on ASVs relative abundances, with strong predictors were mostly endemic ASVs prevalent in soil. Misclassified samples were due to secondary contact of fungi between adjacent habitats. Co-occurrence network analysis revealed more complex and deterministic networks in leaf and twig habitats, while soil was driven by stochastic processes and contained most endemic ASVs. A Cladosporium sp. emerged as a keystone species, maintaining network stability across forests.

ConclusionThis study reveals how local spatial variation and habitat shape distinct fungal communities in tropical forests, with deterministic processes dominating in some habitats and stochasticity playing a key role in others. We show local fungal taxa were strong habitat predictors and drivers of community cohesion. These findings highlight the importance of studying coexisting habitats to gain a deeper understanding of fungal biogeography and ecosystem function.
]]></description>
<dc:creator>Lin, C.-P.</dc:creator>
<dc:creator>Lin, Y.-F.</dc:creator>
<dc:creator>Liu, Y.-C.</dc:creator>
<dc:creator>Lu, M.-Y. J.</dc:creator>
<dc:creator>Ke, H.-M.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2024-09-24</dc:date>
<dc:identifier>doi:10.1101/2024.09.20.614103</dc:identifier>
<dc:title><![CDATA[Spatiotemporal dynamics and assembly process differ in fungal communities across contiguous habitats in tropical forests]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-09-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.09.23.614382v1?rss=1">
<title>
<![CDATA[
From Genes to Pathways: A Curated Gene Approach to Accurate Pathway Reconstruction in Teleost Fish Transcriptomics 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.09.23.614382v1?rss=1</link>
<description><![CDATA[
Interpreting the vast amounts of data generated by high-throughput sequencing technologies can often present a significant challenge, particularly for non-model organism. While automated approaches like GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses are widely used, they often lack specificity for non-model organisms. To bridge this gap, we present a manually curated gene list tailored for teleost fish transcriptomics. This resource focuses on key biological processes crucial for understanding teleost fish physiology, development, and adaptation, including hormone signaling, various metabolic pathways, appetite regulation, digestion, gastrointestinal function, vision, ossification, osmoregulation, and pigmentation. Developed through collaborative efforts of specialists in diverse fields, the list prioritizes genes with established roles in teleost physiology, experimental evidence, and conservation across species. This curated list aims to provide researchers with a reliable starting point for transcriptomic analyses, offering a carefully evaluated set of genes relevant to current research priorities. By streamlining the process of gene selection and interpretation, this resource supports the broader teleost fish research community in designing and analyzing studies that investigate molecular responses to developmental and environmental changes. We encourage the scientific community to collaboratively expand and refine this list, ensuring its continued relevance and utility for teleost fish research.
]]></description>
<dc:creator>Herrera, M.</dc:creator>
<dc:creator>Vianello, S. D.</dc:creator>
<dc:creator>Mitchell, L.</dc:creator>
<dc:creator>Chamot, Z.</dc:creator>
<dc:creator>Lorin-Nebel, C.</dc:creator>
<dc:creator>Roux, N.</dc:creator>
<dc:creator>Besseau, L.</dc:creator>
<dc:creator>Gibert, Y.</dc:creator>
<dc:creator>Laudet, V.</dc:creator>
<dc:date>2024-09-24</dc:date>
<dc:identifier>doi:10.1101/2024.09.23.614382</dc:identifier>
<dc:title><![CDATA[From Genes to Pathways: A Curated Gene Approach to Accurate Pathway Reconstruction in Teleost Fish Transcriptomics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-09-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.10.01.616160v1?rss=1">
<title>
<![CDATA[
Longhorn Beetles form Structural Colour Using Calcium Phosphate Biominerals 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.10.01.616160v1?rss=1</link>
<description><![CDATA[
Brilliant structural colors originating from diverse photonic crystals are found across many phyla, including the striking iridescent colors of beetles and butterflies, produced by three-dimensional photonic crystal structures in the specialized cuticular scales. However, the precise composition of these structures remains largely unknown, although it is key to unravelling colour production mechanisms and morphogenesis. The longhorn beetle Doliops similis displays vibrant green patterns on its otherwise dark elytra. These patterns are formed by arrays of minute scales that encompass a three-dimensional photonic crystal made of orderly packed nanospheres. We found that these nanospheres are composed of carbonated amorphous calcium phosphate biomineral. By accurately parameterizing the structure and calculating the refractive index deduced from the relative fractions of the organic and inorganic phases, we derived reflection wavelengths that match the observed green hue, demonstrating the biominerals role in colour production. Our study further reveals that biomineralization is widespread in the Lamiinae subfamily, with colour diversity achieved through variations in nanosphere size, packing, and composition. This study opens new avenues for developing bioinspired mineral-based optical devices with high refractive indices and defect-resistance, overcoming the shortcomings of current polymer-based designs.
]]></description>
<dc:creator>Chang, Y.</dc:creator>
<dc:creator>Tseng, H.-H.</dc:creator>
<dc:creator>Masahiko, T.</dc:creator>
<dc:creator>Pohl, D.</dc:creator>
<dc:creator>Rellinghaus, B.</dc:creator>
<dc:creator>Bertinetti, L.</dc:creator>
<dc:creator>Politi, Y.</dc:creator>
<dc:date>2024-10-01</dc:date>
<dc:identifier>doi:10.1101/2024.10.01.616160</dc:identifier>
<dc:title><![CDATA[Longhorn Beetles form Structural Colour Using Calcium Phosphate Biominerals]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-10-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.10.08.617308v1?rss=1">
<title>
<![CDATA[
Evolutionary conserved sap peptides derived from xylem-specific peptide precursors in woody angiosperms 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.10.08.617308v1?rss=1</link>
<description><![CDATA[
Peptides act as long-distance mobile signals, transported through vascular sap to coordinate complex developmental processes. Since the tissue-specificity of peptide precursor gene expression is critical in determining peptide signaling function, we integrated vascular sap peptidomes with tissue-level transcriptomes to investigate the roles of sap peptides in two economically important woody plants, Populus trichocarpa and Eucalyptus grandis. Xylem exhibited the highest ratio of tissue-specific sap peptide precursor genes. Most of the sap peptides derived from xylem-specific precursor genes of P. trichocarpa and E. grandis were highly conserved throughout woody species selected from different clades in angiosperms, including magnoliids, rosids and asterids in eudicots. To further explore the conservation of these peptides, we examined the sap peptidome of Cinnamomum kanehirae (camphor tree), from the ancient clade with three xylem cell types. Approximately 90% of the peptides from xylem-specific precursors that were conserved between P. trichocarpa and E. grandis, were also conserved in the vascular sap of C. kanehirae, demonstrating a remarkably high conservation of these peptides across woody angiosperms. Most of the sap peptides conserved in these three woody species are also highly conserved across land plants, suggesting that these peptides may contribute to plant terrestrialization. Within the sap peptides from xylem- specific precursor genes, a total of 10 peptides were identical across all three woody plants. This substantial enrichment of xylem-specific precursor-derived peptides, along with their high conservation, suggests that these long-distance mobile peptides play a crucial role in secondary xylem development.

One sentence summaryIntegration of sap peptidomic and tissue-level transcriptomic data revealed highly conserved long-distance mobile peptides derived from xylem- specific precursors across woody angiosperms.
]]></description>
<dc:creator>Chen, C.-H.</dc:creator>
<dc:creator>Liou, P.-C.</dc:creator>
<dc:creator>Lin, C.-C.</dc:creator>
<dc:creator>Kuo, S.-C.</dc:creator>
<dc:creator>Wu, C.-C.</dc:creator>
<dc:creator>Lin, Y.-C. J.</dc:creator>
<dc:creator>Chen, Y.-L.</dc:creator>
<dc:date>2024-10-12</dc:date>
<dc:identifier>doi:10.1101/2024.10.08.617308</dc:identifier>
<dc:title><![CDATA[Evolutionary conserved sap peptides derived from xylem-specific peptide precursors in woody angiosperms]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-10-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.10.11.617756v1?rss=1">
<title>
<![CDATA[
Toward Automatic Variant Interpretation: Discordant Genetic Interpretation Across Variant Annotations for ClinVar Pathogenic Variants 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.10.11.617756v1?rss=1</link>
<description><![CDATA[
PurposeHigh-throughput sequencing has revolutionized genetic disorder diagnosis, but variant pathogenicity interpretation is still challenging. Even though the Human Genome Variation Society (HGVS) provides recommendations for variant nomenclature, discrepancies in annotation remain a significant hurdle.

MethodsThis study evaluated the annotation concordance between three tools-- ANNOVAR, SnpEff, and Variant Effect Predictor (VEP)--using 164,549 two-star variants from ClinVar. The analysis used HGVS nomenclature string-match comparisons to assess annotation consistency from each tool, corresponding coding impacts, and associated ACMG criteria inferred from the annotations.

ResultsThe analysis revealed variable concordance rates, with 58.52% agreement for HGVSc, 84.04% for HGVSp, and 85.58% for the coding impact. SnpEff showed the highest match for HGVSc (0.988), while VEP bettered for HGVSp (0.977). The substantial discrepancies were noted in the Loss-of-Function (LoF) category. Incorrect PVS1 interpretations affected the final pathogenicity and downgraded PLP variants (ANNOVAR 55.9%, SnpEff 66.5%, VEP 67.3%), risking false negatives of clinically relevant variants in reports.

ConclusionsThese findings highlight the critical challenges in accurately interpreting variant pathogenicity due to discrepancies in annotations. To enhance the reliability of genetic variant interpretation in clinical practice, standardizing transcript sets and systematically cross-validating results across multiple annotation tools is essential.

Graphic abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/617756v1_ufig1.gif" ALT="Figure 1">
View larger version (24K):
org.highwire.dtl.DTLVardef@9f6378org.highwire.dtl.DTLVardef@3b9a2corg.highwire.dtl.DTLVardef@106fb58org.highwire.dtl.DTLVardef@15f70c8_HPS_FORMAT_FIGEXP  M_FIG This study examined the consistency of variant annotations produced by three widely used open-source toolsANNOVAR, SnpEff, and VEPagainst 164,549 ClinVar two starts variants. The investigation covers HGVS-based transcript, protein nomenclature and coding impact annotation. The results showed that none of the tools were fully consistent with ClinVar across all coding impact categories, particularly in the LoF category, which exhibited the poorest consistency. This inconsistency may lead to discrepancies in PVS1 interpretation, affecting the final pathogenicity assessment. PVS1 loss resulted in a significant downgrading of PLP variants, potentially leading to the omission of clinically relevant variants in reports.

C_FIG
]]></description>
<dc:creator>Chen, A. Y.-A.</dc:creator>
<dc:creator>Yuan, T.-H.</dc:creator>
<dc:creator>Huang, J.-H.</dc:creator>
<dc:creator>Wang, Y.-B.</dc:creator>
<dc:creator>Hung, T.-M.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Hsu, J. S.</dc:creator>
<dc:creator>Chen, P.-L.</dc:creator>
<dc:date>2024-10-15</dc:date>
<dc:identifier>doi:10.1101/2024.10.11.617756</dc:identifier>
<dc:title><![CDATA[Toward Automatic Variant Interpretation: Discordant Genetic Interpretation Across Variant Annotations for ClinVar Pathogenic Variants]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-10-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.10.14.616932v1?rss=1">
<title>
<![CDATA[
The Taiwan Precision Medicine Initiative: A Cohort for Large-Scale Studies 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.10.14.616932v1?rss=1</link>
<description><![CDATA[
The Taiwan Precision Medicine Initiative (TPMI), a project initiated by the Academia Sinica in collaboration with 16 major medical centers around Taiwan, has recruited 565,390 participants who consented to provide DNA samples for genetic profiling and grant access to their electronic medical records (EMR) for studies to develop precision medicine. Access to the EMR is both retrospective and prospective, allowing researchers to conduct prospective studies over time. Genetic profiling is done with population-optimized SNP arrays for the Han Chinese populations that enable genetic analyses such as genome-wide association, phenome-wide association, and polygenic risk score studies to evaluate common disease risk and pharmacogenetic response. Furthermore, the TPMI participants agree to be contacted for future research opportunities related to their genetic risks and receive personalized genetic risk profiles with health management recommendations. TPMI has established the TPMI Data Access Platform (TDAP), a central database and analysis platform that both safeguards the security of the data and facilitates academic research. The TPMI is the largest non-European cohort that merges genetic profiles with EMR in the world. With a cohort that can be followed over time, it can be utilized to validate genetic risk prediction models, conduct clinical trials to show the efficacy of risk-based health management, and optimize health policies based on genetic risks. In this report, we describe the TPMI study design, the population and genetic characteristics of the TPMI cohort, and the power it provides to conduct crucial studies in developing precision medicine on a population and personal level. As Han Chinese represent almost 20% of the worlds population, the results of TPMI studies will benefit >1.4 billion people around the world and serve as a model for developing population-based precision medicine.
]]></description>
<dc:creator>Yang, H.-C.</dc:creator>
<dc:creator>Kwok, P.-Y.</dc:creator>
<dc:creator>Li, L.-H.</dc:creator>
<dc:creator>Liu, Y.-M.</dc:creator>
<dc:creator>Jong, Y.-J.</dc:creator>
<dc:creator>Lee, K.-Y.</dc:creator>
<dc:creator>Wang, D.-W.</dc:creator>
<dc:creator>Tsai, M.-F.</dc:creator>
<dc:creator>Yang, J.-H.</dc:creator>
<dc:creator>Chen, C.-H.</dc:creator>
<dc:creator>Yeh, E.-C.</dc:creator>
<dc:creator>Wei, C.-y.</dc:creator>
<dc:creator>Fann, C. S.- J.</dc:creator>
<dc:creator>Huang, Y.-T.</dc:creator>
<dc:creator>Chen, C.-W.</dc:creator>
<dc:creator>Lee, Y.-J.</dc:creator>
<dc:creator>Chu, S.-K.</dc:creator>
<dc:creator>Ho, C.-h.</dc:creator>
<dc:creator>Yang, C.-S.</dc:creator>
<dc:creator>Lee, Y. L.</dc:creator>
<dc:creator>Chen, H.-H.</dc:creator>
<dc:creator>Hou, M.-C.</dc:creator>
<dc:creator>Chiou, J.-F.</dc:creator>
<dc:creator>Yang, S.-F.</dc:creator>
<dc:creator>Wang, C.-H.</dc:creator>
<dc:creator>Huang, C.-Y.</dc:creator>
<dc:creator>Chiu, K.-M.</dc:creator>
<dc:creator>Chen, M.</dc:creator>
<dc:creator>Chiang, F.-T.</dc:creator>
<dc:creator>Lee, S.-L.</dc:creator>
<dc:creator>Chen, S.-S.</dc:creator>
<dc:creator>Yao, W.-J.</dc:creator>
<dc:creator>Chien, C.-C.</dc:creator>
<dc:creator>Lin, S.-Y.</dc:creator>
<dc:creator>Chang, F.-P.</dc:creator>
<dc:creator>Ho, H.-L.</dc:creator>
<dc:creator>Yeh, Y.-C.</dc:creator>
<dc:creator>Tseng, W.-C.</dc:creator>
<dc:creator>Lin, M.-H.</dc:creator>
<dc:creator>Chang, H.-T.</dc:creator>
<dc:creator>Tseng, L.-M.</dc:creator>
<dc:creator>Liang, W.-Y.</dc:creator>
<dc:creator>Chen, P. C.-H.</dc:creator>
<dc:creator>Hang, J.-F.</dc:creator>
<dc:creator>Lin, S.-C.</dc:creator>
<dc:creator>Chan, Y.-J.</dc:creator>
<dc:creator>Kuo, Y.</dc:creator>
<dc:date>2024-10-17</dc:date>
<dc:identifier>doi:10.1101/2024.10.14.616932</dc:identifier>
<dc:title><![CDATA[The Taiwan Precision Medicine Initiative: A Cohort for Large-Scale Studies]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-10-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.10.15.618377v1?rss=1">
<title>
<![CDATA[
Stabilization of HSA32, an aggregation-prone protein, by the protein disaggregase HSP101 plays a critical role in maintaining acquired thermotolerance in Arabidopsis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.10.15.618377v1?rss=1</link>
<description><![CDATA[
Heat acclimation confers acquired thermotolerance (AT), and heat-acclimation memory (HAM) is the maintenance of AT for some time. In Arabidopsis and rice, the heat-stress-associated 32-kDa protein (HSA32) and the protein disaggregase heat shock protein101 (HSP101) form a positive feedback loop at the protein level to maintain AT; HSA32 mitigates HSP101 degradation, and HSP101 positively regulates the accumulation of HSA32. Here, we report the underpinning mechanism regarding how HSP101 affects the HSA32 level in Arabidopsis. We found that, without HSP101, nascent HSA32 was rapidly degraded, and the proteasome inhibitor, bortezomib, inhibited the degradation. In response to heat stress, the nascent HSA32-GFP fusion protein was present in liquid condensates and diffused in the cytosol after returning to non-stress temperature. Proximity labeling with HSA32-TurboID identified HSP101 and five other protein chaperones and co-chaperones as the primary interactors. Disturbing the interaction between HSA32 and HSP101 destabilized HSA32 and compromised HAM. HSA32 is predicted as a TIM-barrel protein with three intrinsically disordered regions of high aggregation propensity. Recombinant HSA32 expressed in E. coli was partitioned into insoluble fractions, suggesting that HSA32 is aggregation-prone. Our findings highlight how the interplay between an aggregation-prone protein and a protein disaggregase can maintain plant stress memory.
]]></description>
<dc:creator>Mitra, S.</dc:creator>
<dc:creator>Yu, S.-J.</dc:creator>
<dc:creator>Liu, N.-Y.</dc:creator>
<dc:creator>Hsu, C.-C.</dc:creator>
<dc:creator>Li, H.-Y.</dc:creator>
<dc:creator>Borah, A.</dc:creator>
<dc:creator>Shen, Y.-Y.</dc:creator>
<dc:creator>Hsu, Y.-H.</dc:creator>
<dc:creator>Fu, H.</dc:creator>
<dc:creator>Charng, Y.-y.</dc:creator>
<dc:date>2024-10-17</dc:date>
<dc:identifier>doi:10.1101/2024.10.15.618377</dc:identifier>
<dc:title><![CDATA[Stabilization of HSA32, an aggregation-prone protein, by the protein disaggregase HSP101 plays a critical role in maintaining acquired thermotolerance in Arabidopsis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-10-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.10.16.618758v1?rss=1">
<title>
<![CDATA[
Impact of mutations in the HEADING DATE 1 gene on transcription and cell wall composition of rice 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.10.16.618758v1?rss=1</link>
<description><![CDATA[
Plants utilize environmental information to modify their developmental trajectories for optimal survival and reproduction. Over a century ago, day length (photoperiod) was identified as a major factor influencing developmental transitions, particularly the shift from vegetative to reproductive growth. In rice, exposure to day lengths shorter than a critical threshold accelerates flowering, while longer days inhibit this process. This response is mediated by HEADING DATE 1 (Hd1), a zinc finger transcription factor that is central in the photoperiodic flowering network. Hd1 acts as a repressor of flowering under long days but functions as a promoter of flowering under short days. However, the transcriptional organization of this dual function is still not fully understood. In this study, we utilized RNA-Seq to analyze the transcriptome of hd1 mutants under both long and short day conditions. We identified genes involved in the phenylpropanoid pathway that are deregulated under long days in the mutant. Quantitative profiling of cell wall components and abiotic stress assays suggest that Hd1 is involved in processes considered unrelated to flowering control. This indicates that day length perception and responses are intertwined with physiological processes beyond flowering.
]]></description>
<dc:creator>Biancucci, M.</dc:creator>
<dc:creator>Chirivi, D.</dc:creator>
<dc:creator>Baldini, A.</dc:creator>
<dc:creator>Badenhorst, E.</dc:creator>
<dc:creator>Dobetti, F.</dc:creator>
<dc:creator>Khahani, B.</dc:creator>
<dc:creator>Formentin, E.</dc:creator>
<dc:creator>Eguen, T.</dc:creator>
<dc:creator>Turck, F. K.</dc:creator>
<dc:creator>Moore, J. P.</dc:creator>
<dc:creator>Tavakol, E.</dc:creator>
<dc:creator>Wenkel, S.</dc:creator>
<dc:creator>Lo Schiavo, F. L.</dc:creator>
<dc:creator>Ezquer, I.</dc:creator>
<dc:creator>Brambilla, V.</dc:creator>
<dc:creator>Horner, D. S.</dc:creator>
<dc:creator>Chiara, M.</dc:creator>
<dc:creator>Perrella, G.</dc:creator>
<dc:creator>Betti, C.</dc:creator>
<dc:creator>Fornara, F.</dc:creator>
<dc:date>2024-10-18</dc:date>
<dc:identifier>doi:10.1101/2024.10.16.618758</dc:identifier>
<dc:title><![CDATA[Impact of mutations in the HEADING DATE 1 gene on transcription and cell wall composition of rice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-10-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.11.03.621749v1?rss=1">
<title>
<![CDATA[
Personalized cancer treatment strategies incorporating irreversible and reversible drug resistance mechanisms 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.11.03.621749v1?rss=1</link>
<description><![CDATA[
Despite advances in targeted cancer therapy, the promise of precision medicine has been limited by resistance to these treatments. In this study, we propose a mathematical modelling framework incorporating cellular heterogeneity, genetic evolutionary dynamics, and non-genetic plasticity, accounting for both irreversible and reversible drug resistance. Previously we proposed Dynamic Precision Medicine (DPM), a personalized treatment strategy that designed individualized treatment sequences by simulations of irreversible genetic evolutionary dynamics in a heterogeneous tumor. Here we apply DPM to the joint model of reversible and irreversible drug resistance mechanisms, analyze the simulation results and compare the efficacy of various treatment strategies. The results indicate that this enhanced version of DPM results in superior patient outcomes compared with current personalized medicine treatment approaches. Our results provide insights into cancer treatment strategies for heterogeneous tumors with genetic evolutionary dynamics and non-genetic cellular plasticity, potentially leading to improvements in survival time for cancer patients.
]]></description>
<dc:creator>He, W.</dc:creator>
<dc:creator>McCoy, M. D.</dc:creator>
<dc:creator>Riggins, R. B.</dc:creator>
<dc:creator>Beckman, R. A.</dc:creator>
<dc:creator>Yeang, C.-H.</dc:creator>
<dc:date>2024-11-04</dc:date>
<dc:identifier>doi:10.1101/2024.11.03.621749</dc:identifier>
<dc:title><![CDATA[Personalized cancer treatment strategies incorporating irreversible and reversible drug resistance mechanisms]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-11-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.11.07.622398v1?rss=1">
<title>
<![CDATA[
Elucidating the Mechanism Underlying UBA7-UBE2L6 Disulfide Complex Formation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.11.07.622398v1?rss=1</link>
<description><![CDATA[
We elucidate cryo-EM structure and formation of the ubiquitin-associated bovine UBA7*UBE2L6 disulfide complex, shedding light on a highly specific and evolutionarily conserved mechanism governing ISG15 conjugation, a pivotal process in the immune response. UBA7 displays a unique capacity to recognize UBE2L6, distinct from this latters homolog UBE2L3, highlighting the intricacies of cellular regulation. Inter-species interactions of the resulting complex further underscore its significance. We characterize three crucial factors that influence UBA7*UBE2L6 disulfide complex formation: (1) strong binding affinity and specificity; (2) conformational differences in the catalytic cysteine capping loop (CCL); and (3) increased thiolate/thiol ratios at catalytic cysteines. Modification of any of these factors profoundly impacts complex activation and the ISG15 transfer cascade. This redox-sensitive complex implies a link between oxidative stress and regulation of the immune response, highlighting a potential therapeutic target for modulating immune reactions arising from infections and inflammatory conditions.
]]></description>
<dc:creator>Chen, P.-T.</dc:creator>
<dc:creator>Yeh, J.-Y.</dc:creator>
<dc:creator>Weng, J.-H.</dc:creator>
<dc:creator>Wu, K.-P.</dc:creator>
<dc:date>2024-11-08</dc:date>
<dc:identifier>doi:10.1101/2024.11.07.622398</dc:identifier>
<dc:title><![CDATA[Elucidating the Mechanism Underlying UBA7-UBE2L6 Disulfide Complex Formation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-11-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.11.08.622687v1?rss=1">
<title>
<![CDATA[
Conformational plasticity of mitochondrial VDAC2 controls the kinetics of its interaction with cytosolic proteins 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.11.08.622687v1?rss=1</link>
<description><![CDATA[
The Voltage Dependent Anion Channel (VDAC) is the major conduit of water-soluble metabolites and small ions into and out of the mitochondria. In mammals, VDAC exists in three isoforms, VDAC1, VDAC2, and VDAC3, each characterized by distinct tissue-dependent distribution and physiological role. VDAC2 is the most notable among the three isoforms because its knockout results in embryonic lethality and regulates the BAK/BAX-dependent apoptosis pathways. Yet, understanding of the biophysical underpinnings of VDAC2 functions remains limited. In this study, we reevaluate VDAC2s properties, utilizing recombinant human VDAC2 WT and its three mutants - cysteine-less VDAC2, VDAC2 with truncated first 11 residues, and E84A - to explore the biophysical basis that distinguishes VDAC2 from the other isoforms using single-molecule electrophysiology. We found that contrary to VDAC1 and VDAC3, which are characterized by a unique open state, VDAC2 displays dynamic switching between a few high-conductive anion-selective substates. We employed -synuclein (Syn) - a known potent cytosolic regulator of VDAC1 and VDAC3 - as a sensitive molecular probe to show that it induces characteristic blockage events in all open substates of VDAC2 but with up to ten-fold different on-rates and blockage times. A substate with higher conductance always corresponds to a higher on-rate of the Syn-VDAC2 interaction but proportionally lower blockage times. This gives the same equilibrium constant for all substates, thus resulting in the same affinity of the Syn-VDAC2 interaction. The pronounced difference is limited to the kinetic parameters, suggesting that once the Syn molecule is captured, its physical state and free energy are the same for all substates. These striking results imply that the Syn molecule senses the dynamic structural variations within the channel prior to its final capture by the pore. We propose that the discovered conformational flexibility may allow VDAC2 to recognize a larger number of binding partners, thus explaining the physiological significance of this isoform, namely, its ability to adapt to mitochondrial metabolic conditions in cells dynamically.
]]></description>
<dc:creator>Rosencrans, W. M.</dc:creator>
<dc:creator>Khuntia, H.</dc:creator>
<dc:creator>Larimi, M. G.</dc:creator>
<dc:creator>Mahalakshmi, R.</dc:creator>
<dc:creator>Yu, T.-Y. D.</dc:creator>
<dc:creator>Bezrukov, S. M.</dc:creator>
<dc:creator>Rostovtseva, T. K.</dc:creator>
<dc:date>2024-11-11</dc:date>
<dc:identifier>doi:10.1101/2024.11.08.622687</dc:identifier>
<dc:title><![CDATA[Conformational plasticity of mitochondrial VDAC2 controls the kinetics of its interaction with cytosolic proteins]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-11-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.11.10.622827v1?rss=1">
<title>
<![CDATA[
Living xylem cells encode a large number of conserved gene families responsible for vascular sap peptides 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.11.10.622827v1?rss=1</link>
<description><![CDATA[
Plant long-distance signaling peptides travel through the vascular system to coordinate development and respond to environmental cues, yet their precursor genes and expression origins remain elusive. We characterized 4,804 sap peptide precursor genes in Populus trichocarpa using an integrated approach that combined liquid chromatography tandem mass spectrometry (LC-MS/MS) peptidomics, transcriptomics, and comparative genomics. This study expands the known precursor families from approximately 50 to thousands, the majority of which are conserved across angiosperms. Transcriptome analysis across xylem developmental stages revealed that living xylem cells, typically viewed as precursors to non-living structures, predominantly express these specifically at transitions between primary and secondary growth stages, indicating an active role in plant-wide signaling coordination. The precursor genes show conservation at the transcriptome level and are under strong purifying selection. Our findings provide a comprehensive overview of the gene families encoding sap peptides, redefining xylem as an active participant in plant communication and adaptation.
]]></description>
<dc:creator>Lu, M. R.</dc:creator>
<dc:creator>Tung, C.-C.</dc:creator>
<dc:creator>Huang, C.-E.</dc:creator>
<dc:creator>Chen, C.-H.</dc:creator>
<dc:creator>Liou, P.-C.</dc:creator>
<dc:creator>Lin, C.-Y. I.</dc:creator>
<dc:creator>Yu, J.-H.</dc:creator>
<dc:creator>Chen, Y.-L.</dc:creator>
<dc:creator>Lin, Y.-C. J.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2024-11-11</dc:date>
<dc:identifier>doi:10.1101/2024.11.10.622827</dc:identifier>
<dc:title><![CDATA[Living xylem cells encode a large number of conserved gene families responsible for vascular sap peptides]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-11-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.11.11.623098v1?rss=1">
<title>
<![CDATA[
Salinity impacted microbial carbonate precipitation mechanisms of modern microbialites in peritidal zone 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.11.11.623098v1?rss=1</link>
<description><![CDATA[
Microbialites, ancient records of microbial activity, serve as significant indicators of environmental change. This study examined microbialites from the peritidal zone of three tide pools at Fongchueisha, Hengchun, Taiwan, to investigate the impact of salinity on microbial community composition and carbonate precipitation mechanisms. Microbial samples were collected across varying salinity gradients over multiple timepoints and analyzed using next-generation sequencing of bacterial 16S and eukaryotic 18S rRNA genes. Our findings reveal that the microbial communities in higher salinity environments exhibited significant shifts, with increased relative abundance of ureolytic bacteria and ammonifying microorganisms, such as Myxococcota and Actinobacteriota. This suggests the presence of diverse microbial carbonate precipitation mechanisms beyond photosynthesis, including ureolysis and ammonification. Furthermore, our results show that changes in the composition of cyanobacteria and diatoms were influenced by salinity, with heterocystous cyanobacteria (e.g., Nostocales) dominating low-salinity environments, and non-heterocystous cyanobacteria (e.g., Synechococcales) prevailing in higher salinity environments. Functional predictions reveal that microbial communities in high-salinity environments were enriched in anaerobic metabolic pathways, including pyruvate fermentation and the urea cycle. These findings highlight the significant role of salinity in influencing microbial composition and metabolic pathways, shaping carbonate precipitation processes in microbialites.

ImportanceThe study focuses on the impact of environmental salinity on microbial community composition and carbonate precipitation mechanisms within modern microbialites, based on an analysis of samples from three tide pools with different salinity levels collected at five time points throughout the year. Using next-generation sequencing of bacterial 16S and eukaryotic 18S rRNA genes, we identified key shifts in microbial communities along salinity gradients and explored diverse microbial processes involved in carbonate precipitation. This work enhances our understanding of microbial ecosystems within modern microbialites and their response to environmental changes. Additionally, our study provides insight into ancient biogeochemical processes, with implications for interpreting microbial metabolism in carbonate precipitation across different salinity regimes.
]]></description>
<dc:creator>Hsieh, Y. E.</dc:creator>
<dc:creator>Yang, S.-Y.</dc:creator>
<dc:creator>Liu, S.-L.</dc:creator>
<dc:creator>Wang, S.-W.</dc:creator>
<dc:creator>Wang, W.-L.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:creator>Yang, S.-H.</dc:creator>
<dc:date>2024-11-12</dc:date>
<dc:identifier>doi:10.1101/2024.11.11.623098</dc:identifier>
<dc:title><![CDATA[Salinity impacted microbial carbonate precipitation mechanisms of modern microbialites in peritidal zone]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-11-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.11.22.624729v1?rss=1">
<title>
<![CDATA[
The Bacteria of a Fig Microcommunity 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.11.22.624729v1?rss=1</link>
<description><![CDATA[
Understanding the biotic drivers of diversity is a major goal of microbial ecology. One approach towards tackling this issue is to interrogate relatively simple communities that are easy to observe and perturb. Figs (syconia) of the genus Ficus represent such a system. Here, we describe the microbial communities of Ficus septica figs, which are associated with the nematode Caenorhabditis inopinata (the sister species of the C. elegans genetic model system). In 2019, 38 Ficus septica figs (across 12 plants in Taiwan) were dissected, and metadata such as foundress wasp number and nematode occupancy were collected for each fig. Suspensions derived from interior fig material and fig surface washes were prepared for 16S microbial metabarcoding. Over 3,000 OTUs were detected, and microbial communities were dominated by members of Proteobacteria, Bacteroidota, and Actinobacteriota. Although microbial communities of fig exteriors and interiors can be distinguished, levels of microbial alpha diversity were comparable across these areas of the fig. Nematodes likewise had no detectable impact on microbial alpha diversity, although nematodes were associated with a modest change in microbial community composition. A handful of OTUs (associated with the genera Kosokonia, Ochobactrum, and Stenotrophomonas) revealed potential differential abundance among figs varying in nematode occupancy. Additionally, foundress wasp number was negatively correlated with microbial alpha diversity. These findings set the stage for future studies that directly test the role of nematode and wasp occupancy on microbial communities, as well as investigations that probe nematode-microbe interactions through laboratory experiments. Taken together, these results constitute a fundamental step in characterizing the natural microbial communities of figs and Caenorhabditis nematodes.

ImportanceUnraveling why different species live in different places is a longstanding open question in ecology, and it is clear that interspecific interactions among species are a major contributor to species distributions. Ficus figs are a useful system for ecological studies because they are relatively simple microcosms where characterizing animal community composition of multiple samples is straightforward. Additionally, Caenorhabditis inopinata, a close relative of the C. elegans genetic model system, thrives in Ficus septica figs. Here, we tie 16S microbial metabarcoding to nematode and wasp occupancy data to understand the causes of bacterial community composition in F. septica figs. We found that microbial composition, but not total diversity, varies among fig surface and interiors. Likewise, we found that nematode occupancy impacts microbial composition but not alpha diversity. Moreover, we show that as the number of foundress wasps increases, the microbial alpha diversity decreases. Finally, we identified OTUs that are potentially associated with nematode occupancy. Taken together, these results represent a key step in describing a microcommunity wherein ecological genetic hypotheses can be tested, as well as one that can potentially reveal the roles of uncharacterized genes in established model systems.
]]></description>
<dc:creator>Woodruff, G. C.</dc:creator>
<dc:creator>Moser, K. A.</dc:creator>
<dc:creator>Wang, J.</dc:creator>
<dc:date>2024-11-22</dc:date>
<dc:identifier>doi:10.1101/2024.11.22.624729</dc:identifier>
<dc:title><![CDATA[The Bacteria of a Fig Microcommunity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-11-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.11.22.624040v1?rss=1">
<title>
<![CDATA[
CNV-Finder: Streamlining Copy Number Variation Discovery 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.11.22.624040v1?rss=1</link>
<description><![CDATA[
Copy Number Variations (CNVs) play pivotal roles in the etiology of complex diseases and are variable across diverse populations. Understanding the association between CNVs and disease susceptibility is significant in disease genetics research and often requires analysis of large sample sizes. One of the most cost-effective and scalable methods for detecting CNVs is based on normalized signal intensity values, such as Log R Ratio (LRR) and B Allele Frequency (BAF), from Illumina genotyping arrays. In this study, we present CNV-Finder, a novel pipeline integrating deep learning techniques on array data, specifically a Long Short-Term Memory (LSTM) network, to expedite the large-scale identification of CNVs within predefined genomic regions. This facilitates efficient prioritization of samples for time-consuming or costly subsequent analyses such as Multiplex Ligation-dependent Probe Amplification (MLPA), short-read, and long-read whole genome sequencing. We incorporate four genes to establish our methods--Parkin (PRKN), Leucine Rich Repeat And Ig Domain Containing 2 (LINGO2), Microtubule Associated Protein Tau (MAPT), and alpha-Synuclein (SNCA)--which may be relevant to neurological diseases such as Alzheimers disease (AD), Parkinsons disease (PD), Progressive Supranuclear Palsy (PSP), or related disorders such as essential tremor (ET). By training our models on expert-annotated samples and validating them across diverse cohorts, including those from the Global Parkinsons Genetics Program (GP2) and additional dementia-specific databases, we demonstrate the efficacy of CNV-Finder in accurately detecting deletions and duplications. Our pipeline outputs app-compatible files for visualization within CNV-Finders interactive web application. This interface enables researchers to review predictions and filter displayed samples by model prediction values, LRR range, and variant count in order to explore or confirm results. Our pipeline integrates this human feedback to enhance model performance and reduce false positive rates. Through a series of comprehensive analyses and validations using visual inspection, MLPA, short-read, and long-read sequencing data, we demonstrate the robustness and adaptability of CNV-Finder in identifying CNVs with regions of varied size, probe density, and noise. Our findings highlight the significance of contextual understanding and human expertise in enhancing the precision of CNV identification, particularly in complex genomic regions like 17q21.31. The CNV-Finder pipeline is a scalable, publicly available resource for the scientific community, available on GitHub (https://github.com/GP2code/CNV-Finder; DOI 10.5281/zenodo.14182563). CNV-Finder not only expedites accurate candidate identification but also significantly reduces the manual workload for researchers, enabling future targeted validation and downstream analyses in regions or phenotypes of interest.
]]></description>
<dc:creator>Kuznetsov, N.</dc:creator>
<dc:creator>Daida, K.</dc:creator>
<dc:creator>Makarious, M. B.</dc:creator>
<dc:creator>Al-Mubarak, B.</dc:creator>
<dc:creator>Atterling Brolin, K.</dc:creator>
<dc:creator>Malik, L.</dc:creator>
<dc:creator>Kouam, C.</dc:creator>
<dc:creator>Baker, B.</dc:creator>
<dc:creator>Ostrozovicova, M.</dc:creator>
<dc:creator>Andersh, K. M.</dc:creator>
<dc:creator>Kung, P.-J.</dc:creator>
<dc:creator>Mecheri, Y.</dc:creator>
<dc:creator>Tay, Y.-W.</dc:creator>
<dc:creator>Soundous Malek, B.</dc:creator>
<dc:creator>Al Tassan, N.</dc:creator>
<dc:creator>Teresa Perinan, M.</dc:creator>
<dc:creator>Hong, S.</dc:creator>
<dc:creator>Koretsky, M.</dc:creator>
<dc:creator>Sargeant, L.</dc:creator>
<dc:creator>Levine, K.</dc:creator>
<dc:creator>Blauwendraat, C.</dc:creator>
<dc:creator>Billingsley, K. J.</dc:creator>
<dc:creator>Bandres-Ciga, S.</dc:creator>
<dc:creator>Leonard, H. L.</dc:creator>
<dc:creator>Morris, H. R.</dc:creator>
<dc:creator>Singleton, A. B.</dc:creator>
<dc:creator>Nalls, M. A.</dc:creator>
<dc:creator>Vitale, D.</dc:creator>
<dc:creator>The Global Parkinson's Genetics Program,</dc:creator>
<dc:date>2024-11-23</dc:date>
<dc:identifier>doi:10.1101/2024.11.22.624040</dc:identifier>
<dc:title><![CDATA[CNV-Finder: Streamlining Copy Number Variation Discovery]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-11-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.11.26.625491v1?rss=1">
<title>
<![CDATA[
The effects of early-life ambient temperature on the gut microbiome of a wild bird? an experimental approach 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.11.26.625491v1?rss=1</link>
<description><![CDATA[
Vertebrate gut microbiome has significant effects on host development, health, and fitness. Multiple external factors contribute to gut microbiome variation, and the role of ambient temperature has gained increasing attention. Yet, temperature effects are often tested in extremes and in captive systems. We experimentally studied the effect of subtle temperature decreases during post-natal development on gut microbiome diversity and composition in wild pied flycatchers (Ficedula hypoleuca). We also performed partial cross-fostering to study the relative contribution of genetic and rearing environment on microbiome. Nest-box cold treatment did not influence gut microbiome diversity or composition, which may be due to the small temperature change, ontogenetic stage, or other factors, such as diet, causing large variation in the data. Rearing environment explained more of the variation in gut microbiome than genetic background, but the variance explained was relatively small. Future studies need to further address the drivers of the large intraspecific variation in microbiome in natural populations.
]]></description>
<dc:creator>Ruuskanen, S.</dc:creator>
<dc:creator>Hollmen, L.</dc:creator>
<dc:creator>Stier, A.</dc:creator>
<dc:creator>Hsu, B.-Y.</dc:creator>
<dc:creator>Cossin-Sevrin, N.</dc:creator>
<dc:creator>Marciau, C.</dc:creator>
<dc:creator>Hukkanen, M.</dc:creator>
<dc:creator>Vesterinen, E.</dc:creator>
<dc:date>2024-11-28</dc:date>
<dc:identifier>doi:10.1101/2024.11.26.625491</dc:identifier>
<dc:title><![CDATA[The effects of early-life ambient temperature on the gut microbiome of a wild bird? an experimental approach]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-11-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.11.30.626159v1?rss=1">
<title>
<![CDATA[
Circadian Activity Predicts Breeding Phenology in the Asian Burying Beetle Nicrophorus nepalensis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.11.30.626159v1?rss=1</link>
<description><![CDATA[
Climate change continues to alter breeding phenology in a range of plant and animal species across the globe. Traditional methods for assessing when organisms reproduce often rely on time-intensive field observations or destructive sampling, creating an urgent need for efficient, non-invasive approaches to assess reproductive timing. Here, we examined three populations of the Asian burying beetle Nicrophorus nepalensis from subtropical Okinawa (500 m) and Taiwan mountains (1100-3200 m) that were reared under contrasting photoperiods in order to develop a predictive framework linking circadian activity to breeding phenology. Using automated activity monitors, we quantified adult circadian rhythms and employed machine learning to predict breeding phenology (seasonal versus year-round breeders) from behavior alone. Our model achieved 95% accuracy under long-day conditions using just three behavioural features, and notably, maintained 76% accuracy under short-day conditions when both types are reproductively active, revealing persistent behavioural differences between breeding strategies. These results demonstrate how integrating behavioural monitoring with machine learning can provide both a rapid, scalable method for tracking population responses to climate change and novel insights into species adaptive responses to shifting seasonal cues across different elevational gradients in their native range.
]]></description>
<dc:creator>Chen, H.</dc:creator>
<dc:creator>Rubenstein, D. R.</dc:creator>
<dc:creator>Mai, G.-S.</dc:creator>
<dc:creator>Chang, C.-F.</dc:creator>
<dc:creator>Shen, S.-F.</dc:creator>
<dc:date>2024-12-01</dc:date>
<dc:identifier>doi:10.1101/2024.11.30.626159</dc:identifier>
<dc:title><![CDATA[Circadian Activity Predicts Breeding Phenology in the Asian Burying Beetle Nicrophorus nepalensis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-12-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.12.01.626239v1?rss=1">
<title>
<![CDATA[
Repeated evolution of supergenes on an ancient social chromosome 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.12.01.626239v1?rss=1</link>
<description><![CDATA[
Supergenes are non-recombining chromosomal regions that code for complex polymorphic traits. Advances in population genomics have uncovered supergenes associated with diverse traits, ranging from butterfly wing patterns to floral morphs. In ants, two supergenes on non-homologous "social chromosomes" in Solenopsis and Formica are associated with social polymorphism, with either single queen (monogyne) or multiple queens (polygyne) colonies. We discovered a new supergene associated with similar polymorphism in the desert ant Cataglyphis niger. Despite Cataglyphis being more closely related to Formica than Solenopsis, its social chromosome is homologous to that of Solenopsis, with conservation of synteny in gene content and order. This suggests that the social chromosome is ancient, dating back to the common ancestor of Solenopsis and Cataglyphis, at least 90 million years ago. Low sequence divergence between supergene haplotypes in both Solenopsis and Cataglyphis suggests that the two supergenes evolved recently and independently in the two divergent lineages on this ancient social chromosome. Comparative analysis of hymenopteran genomes further revealed a bee chromosome homologous to the ants social chromosome. The ant social chromosome contains the largest set of genes that are conserved as a linkage group across ant and bee genomes. This conserved gene set is enriched for olfactory functions, most notably a large number of odorant-binding proteins. The conservation of this gene set suggests that this chromosome plays an important role in social behavior across social Hymenoptera. We propose that the conserved gene set in the social chromosome was repeatedly used as a pre-adapted toolkit for the evolution of social traits in general, and specifically in the evolution of polygyne social structure in ants.
]]></description>
<dc:creator>Lajmi, A.</dc:creator>
<dc:creator>Cohen, P.</dc:creator>
<dc:creator>Lee, C.-C.</dc:creator>
<dc:creator>Frenkel, Z.</dc:creator>
<dc:creator>Pellen, Y.</dc:creator>
<dc:creator>Privman, E.</dc:creator>
<dc:date>2024-12-02</dc:date>
<dc:identifier>doi:10.1101/2024.12.01.626239</dc:identifier>
<dc:title><![CDATA[Repeated evolution of supergenes on an ancient social chromosome]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-12-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.11.30.626145v1?rss=1">
<title>
<![CDATA[
Rhizobium rhizogenes A4-derived strains mediate hyper-efficient transient gene expression in Nicotiana benthamiana and other solanaceous plants 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.11.30.626145v1?rss=1</link>
<description><![CDATA[
Agroinfiltration, a method utilizing agrobacteria to transfer DNA into plant cells, is widely used for transient gene expression in plants. Besides the commonly used Agrobacterium strains, Rhizobium rhizogenes can also introduce foreign DNA into host plants for gene expression. While many R. rhizogenes strains have been known for inducing hairy root symptoms, their use for transient expression has not been fully explored. Here, we showed that R. rhizogenes A4 outperformed all other tested agrobacterial strains in agroinfiltration experiments on leaves of Nicotiana benthamiana and other solanaceous plants. By conducting an agroinfiltration screening in N. benthamiana leaves using various agrobacterial strains carrying the RUBY reporter gene cassette, we discovered that A4 mediates the strongest and fastest transient expression. Utilizing the genomic information, we developed a collection of disarmed and modified strains derived from A4. By performing vacuum infiltration assays, we demonstrated that these A4-derived strains efficiently transiently transform 6-week-old N. benthamiana leaves, showing less sensitivity to the age of plants compared to the laboratory strain GV3101. Furthermore, we performed agroinfiltration using AS109, an A4-derived disarmed strain, on the leaves of tomato, pepper, and eggplant. Remarkably, AS109 mediated transient gene expression on tested solanaceous plants more effectively than all the tested commonly used agrobacterial strains. This discovery paves the way for establishing R. rhizogenes A4-derived strains as a new option for enhancing transient expression in N. benthamiana and facilitating the functional study of plant genes in other solanaceous species.
]]></description>
<dc:creator>Lopez-Agudelo, J. C.</dc:creator>
<dc:creator>Goh, F.-J.</dc:creator>
<dc:creator>Tchabashvili, S.</dc:creator>
<dc:creator>Huang, Y.-S.</dc:creator>
<dc:creator>Huang, C.-Y.</dc:creator>
<dc:creator>Lee, K.-T.</dc:creator>
<dc:creator>Wang, Y.-C.</dc:creator>
<dc:creator>Wu, Y.</dc:creator>
<dc:creator>Chang, H.-X.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:creator>Lai, E.-M.</dc:creator>
<dc:creator>Wu, C.-H.</dc:creator>
<dc:date>2024-12-03</dc:date>
<dc:identifier>doi:10.1101/2024.11.30.626145</dc:identifier>
<dc:title><![CDATA[Rhizobium rhizogenes A4-derived strains mediate hyper-efficient transient gene expression in Nicotiana benthamiana and other solanaceous plants]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-12-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.12.12.628285v1?rss=1">
<title>
<![CDATA[
Deep homology of a brachyury regulatory syntax and origin of the notochord 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.12.12.628285v1?rss=1</link>
<description><![CDATA[
The brachyury gene encodes a T-box transcription factor (TF) that is crucial for the development of the notochord, a novel trait of chordates1. Brachyury expression in axial mesodermal cells (notochord progenitors) is regarded as a chordate innovation2, yet it remains unclear how the chordate ancestor acquired this expression domain. By examining the sequences of previously identified notochord enhancers of several chordate brachyury genes3-5, we uncovered a regulatory syntax consisting of binding sites for four TFs (Su(H), Foxh1, Zic, and Ets) with a strict order and orientation. We also identified this syntax, here named SFZE, in potential cis-regulatory modules (CRMs) of brachyury orthologs in various non-chordate animals and even in Capsaspora, a close unicellular relative to animals. Reporter assays demonstrated that SFZE-containing CRMs from non-chordate organisms exhibited regulatory activity in the zebrafish notochord, and mutagenesis of the TF sites reduced the activity. Furthermore, the SFZE syntax in sea urchin confers its endoderm activity, with the TF sites functionally decoupled during gastrulation. These findings indicate that the association of the SFZE syntax with brachyury is ancient, likely predating the origin of animals. The emergence of axial brachyury expression is therefore probably not the result of a newly acquired notochord enhancer, but is instead likely attributed to co-option of upstream signals acting on the conserved SFZE syntax, which facilitates the origin of the notochord from rudimentary endodermal cells.
]]></description>
<dc:creator>Fan, T.-P.</dc:creator>
<dc:creator>Lee, J.-R.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Chen, Y.-C.</dc:creator>
<dc:creator>Cutting, A. E.</dc:creator>
<dc:creator>Cameron, R. A.</dc:creator>
<dc:creator>Yu, J.-K.</dc:creator>
<dc:creator>Su, Y.-H.</dc:creator>
<dc:date>2024-12-13</dc:date>
<dc:identifier>doi:10.1101/2024.12.12.628285</dc:identifier>
<dc:title><![CDATA[Deep homology of a brachyury regulatory syntax and origin of the notochord]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-12-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2024.12.30.630690v1?rss=1">
<title>
<![CDATA[
An Interbacterial Cysteine Protease Toxin Inhibits Cell Growth by Targeting Type II DNA Topoisomerases GyrB and ParE 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2024.12.30.630690v1?rss=1</link>
<description><![CDATA[
Bacteria deploy a diverse arsenal of toxic effectors to antagonize competitors, profoundly influencing the composition of microbial communities. Previous studies have identified an interbacterial toxin predicted to exhibit proteolytic activity that is broadly distributed among Gram-negative bacteria. However, the precise mechanism of intoxication remains unresolved. Here, we demonstrate that one such protease toxin from Escherichia coli, Cpe1, disrupts DNA replication and chromosome segregation by cleaving conserved sequences within the ATPase domain of type II DNA topoisomerases GyrB and ParE. This cleavage effectively inhibits topoisomerase-mediated relaxation of supercoiled DNA, resulting in impaired bacterial growth. Cpe1 belongs to the papain-like cysteine protease family and is associated with toxin delivery pathways, including the type VI secretion system and contact-dependent growth inhibition. The structure of Cpe1 in complex with its immunity protein reveals a neutralization mechanism involving competitive substrate binding rather than active site occlusion, distinguishing it from previously characterized effector-immunity pairs. Our findings unveil a unique mode of interbacterial intoxication and provide insights into how bacteria protect themselves from self-poisoning by protease toxins.
]]></description>
<dc:creator>Song, P.-Y.</dc:creator>
<dc:creator>Tsai, C.-E.</dc:creator>
<dc:creator>Chen, Y.-C.</dc:creator>
<dc:creator>Chen, P.-P.</dc:creator>
<dc:creator>Wang, T.-H.</dc:creator>
<dc:creator>Hu, C.-Y.</dc:creator>
<dc:creator>Chen, P.-Y.</dc:creator>
<dc:creator>Ku, C.</dc:creator>
<dc:creator>Hsia, K.-C.</dc:creator>
<dc:creator>Ting, S.-Y.</dc:creator>
<dc:date>2024-12-31</dc:date>
<dc:identifier>doi:10.1101/2024.12.30.630690</dc:identifier>
<dc:title><![CDATA[An Interbacterial Cysteine Protease Toxin Inhibits Cell Growth by Targeting Type II DNA Topoisomerases GyrB and ParE]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2024-12-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.01.10.632296v1?rss=1">
<title>
<![CDATA[
A cytoskeletal scaffold promotes motile cilia assembly by regulating transition-zone integrity 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.01.10.632296v1?rss=1</link>
<description><![CDATA[
Motile cilia are eukaryotic organelles with essential chemo- and mechano-sensing functions across evolution, from single cell organisms to humans. Motile cilia of the mammalian nervous, respiratory and reproductive systems are characterized by unique motility proteins to generate fluid flow essential for transporting metabolites and removing mucus. The molecular mechanism of motile cilia biogenesis remains unknown. Here, we use mouse genetics, single-molecule motility assays, proteomics, high-resolution imaging, and in situ cryo-tomography to identify mammalian KIF27, a motor protein of the Kinesin-4 family and homologue of the Hedgehog pathway regulator COS2/KIF7, as a key regulator of motile cilia assembly. We show that KIF27 promotes the integrity of the transition zone, a diffusion barrier situated at the cilium base. Loss of KIF27 causes specific and profound defects in axonemal structure and disrupts cilia beating, which collectively lead to organismal phenotypes that recapitulate primary ciliary dyskinesia. We show that the motile properties of KIF27 are dispensable for its function in motile cilia biogenesis. Instead, KIF27 acts as a microtubule scaffold to regulate the transition zone architecture and enable correct ciliary incorporation of motility-generating proteins. Given that KIF27 homologues exist in different evolutionarily lineages, we propose that the ancestral activities of KIF27/KIF7 kinesins were to form a microtubule-associated scaffold for protein-protein interactions pertinent to cilia formation and signaling. The transition-zone associated KIF27 activities may represent a general building principle for motile cilia assembly in diverse species and cell types.
]]></description>
<dc:creator>Park, H.</dc:creator>
<dc:creator>Choi, M.</dc:creator>
<dc:creator>Cheung, H. O.-L.</dc:creator>
<dc:creator>Zhang, Y.</dc:creator>
<dc:creator>Makino, S.</dc:creator>
<dc:creator>Yoshikawa, Y.</dc:creator>
<dc:creator>Qi, H.</dc:creator>
<dc:creator>Liu, Z.</dc:creator>
<dc:creator>Lan, G.</dc:creator>
<dc:creator>Fu, G.</dc:creator>
<dc:creator>Wang, Q.</dc:creator>
<dc:creator>Guo, S. S.</dc:creator>
<dc:creator>Liu, P.</dc:creator>
<dc:creator>Liu, Z.</dc:creator>
<dc:creator>Ti, S.-C.</dc:creator>
<dc:creator>Wang, W.-J.</dc:creator>
<dc:creator>Li, X. D.</dc:creator>
<dc:creator>Ni, T.</dc:creator>
<dc:creator>Hui, C. C.</dc:creator>
<dc:creator>He, M.</dc:creator>
<dc:date>2025-01-10</dc:date>
<dc:identifier>doi:10.1101/2025.01.10.632296</dc:identifier>
<dc:title><![CDATA[A cytoskeletal scaffold promotes motile cilia assembly by regulating transition-zone integrity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-01-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.01.09.632083v1?rss=1">
<title>
<![CDATA[
Plasma membrane mediated GLUT10 mitochondrial targeting regulates intracellular ascorbic acid homeostasis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.01.09.632083v1?rss=1</link>
<description><![CDATA[
Regulation of intracellular ascorbic acid (AA) levels is critical for connective tissue development and maintenance, but the underlying mechanisms remain unclear. In this study, we uncover a novel regulatory role of glucose transporter 10 (GLUT10) in AA homeostasis through a noncanonical trafficking pathway from the endomembrane system to mitochondria, traditionally considered as separate entities. We demonstrate that GLUT10 transit from ER to mitochondria through the plasma membrane (PM) and endosomes increases under stress conditions. This PM localization enhances the transport of dehydroascorbic acid (DHA), the oxidized form of AA, thereby maintaining intracellular AA levels. Disruption of this trafficking impairs AA homeostasis. Our findings reveal a previously unrecognized localization of GLUT10 at the PM and endosomes, highlighting a novel communication between endomembrane system and mitochondria for proetin redistribution, which is essential for maintaining intracellular AA homeostasis and facilitating environmental adaptation.

Graphical abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/632083v1_ufig1.gif" ALT="Figure 1">
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]]></description>
<dc:creator>Jose, A. C.</dc:creator>
<dc:creator>Syu, Y.-W.</dc:creator>
<dc:creator>Lai, H.-W.</dc:creator>
<dc:creator>Tsai, M.-Y.</dc:creator>
<dc:creator>Jiang, Y.-F.</dc:creator>
<dc:creator>Hsu, S.-C.</dc:creator>
<dc:creator>Lin, P.-Y.</dc:creator>
<dc:creator>Huang, W.-C.</dc:creator>
<dc:creator>Chu, W.-C.</dc:creator>
<dc:creator>Fu, C.-Y.</dc:creator>
<dc:creator>Lee, Y.-C.</dc:creator>
<dc:date>2025-01-13</dc:date>
<dc:identifier>doi:10.1101/2025.01.09.632083</dc:identifier>
<dc:title><![CDATA[Plasma membrane mediated GLUT10 mitochondrial targeting regulates intracellular ascorbic acid homeostasis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-01-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.01.13.632666v1?rss=1">
<title>
<![CDATA[
Structural basis of K11/K48-branched ubiquitin chain recognition by the human 26S proteasome 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.01.13.632666v1?rss=1</link>
<description><![CDATA[
Beyond the canonical K48-linked homotypic polyubiquitination for proteasome-targeted proteolysis, K11/K48-branched ubiquitin (Ub) chains are involved in fast-tracking protein turnover during cell cycle progression and proteotoxic stress. Here, we report cryo-EM structures of human 26S proteasome in a complex with a K11/K48-branched Ub chain. The structures revealed a multivalent substrate recognition mechanism involving a hitherto unknown K11-linked Ub binding site at the groove formed by RPN2 and RPN10 in addition to the canonical K48-linkage binding site formed by RPN10 and RPT4/5 coiled-coil. Additionally, RPN2 recognizes an alternating K11-K48 linkage through a conserved motif similar to the K48-specific T1 binding site of RPN1. The insights gleaned from these structures explain the molecular mechanism underlying the recognition of the K11/K48 branched Ub as a priority signal in the ubiquitin-mediated proteasomal degradation.
]]></description>
<dc:creator>Draczkowski, P.</dc:creator>
<dc:creator>Chen, S.-N.</dc:creator>
<dc:creator>Chen, T.</dc:creator>
<dc:creator>Wang, Y.-S.</dc:creator>
<dc:creator>Huang, J. Y. C.</dc:creator>
<dc:creator>Tsai, M.-C.</dc:creator>
<dc:creator>Lin, S.-Y.</dc:creator>
<dc:creator>Viner, R.</dc:creator>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Wu, K.-P.</dc:creator>
<dc:creator>Hsu, S.-T. D.</dc:creator>
<dc:date>2025-01-13</dc:date>
<dc:identifier>doi:10.1101/2025.01.13.632666</dc:identifier>
<dc:title><![CDATA[Structural basis of K11/K48-branched ubiquitin chain recognition by the human 26S proteasome]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-01-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.01.17.633688v1?rss=1">
<title>
<![CDATA[
Comparative genomic analysis of a novel heat-tolerant and euryhaline strain of unicellular marine cyanobacterium Cyanobacterium sp. DS4 from a high-temperature lagoon 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.01.17.633688v1?rss=1</link>
<description><![CDATA[
BackgroundCyanobacteria have diversified through their long evolutionary history and occupy a wide range of environments on Earth. To advance our understanding of their adaption mechanisms in extreme environments, we performed stress tolerance characterizations, whole genome sequencing, and comparative genomic analyses of a novel heat-tolerant and euryhaline strain of the unicellular cyanobacterium Cyanobacterium sp. Dongsha4 (DS4). This strain was isolated from a lagoon on Dongsha Island in the South China Sea, a habitat with fluctuations in temperature, salinity, light intensity, and nutrient supply.

ResultsDS4 cells can tolerate long-term high-temperature up to 50  and salinity from 0 to 6.6 %, which is similar to the results previously obtained for Cyanobacterium aponinum. In contrast, most mesophilic cyanobacteria cannot survive under these extreme conditions. Based on the 16S rRNA gene phylogeny, DS4 is most closely related to Cyanobacterium sp. NBRC 102756 isolated from Iwojima Island, Japan, and Cyanobacterium sp. MCCB114 isolated from Vypeen Island, India. For comparison with strains that have genomic information available, DS4 is most similar to Cyanobacterium aponinum strain PCC 10605 (PCC10605), sharing 81.7% of the genomic segments and 92.9% average nucleotide identity (ANI). Gene content comparisons identified multiple distinct features of DS4. Unlike related strains, DS4 possesses the genes necessary for nitrogen fixation. Other notable genes include those involved in photosynthesis, central metabolisms, cyanobacterial starch metabolisms, stress tolerances, and biosynthesis of novel secondary metabolites.

ConclusionsThese findings promote our understanding of the physiology, ecology, evolution, and stress tolerance mechanisms of cyanobacteria. The information is valuable for future functional studies and biotechnology applications of heat-tolerant and euryhaline marine cyanobacteria.
]]></description>
<dc:creator>Chen, C.-N. N.</dc:creator>
<dc:creator>Lin, K.-M.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Chang, H.-Y.</dc:creator>
<dc:creator>Yong, T. C.</dc:creator>
<dc:creator>Chiu, Y.-F.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:creator>Chu, H.-A.</dc:creator>
<dc:date>2025-01-22</dc:date>
<dc:identifier>doi:10.1101/2025.01.17.633688</dc:identifier>
<dc:title><![CDATA[Comparative genomic analysis of a novel heat-tolerant and euryhaline strain of unicellular marine cyanobacterium Cyanobacterium sp. DS4 from a high-temperature lagoon]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-01-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.01.21.634219v1?rss=1">
<title>
<![CDATA[
A hydrophobic core in the coiled-coil domain essential for NRC resistosome function 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.01.21.634219v1?rss=1</link>
<description><![CDATA[
The nucleotide-binding leucine-rich repeat protein (NLR) required for cell death (NRC) family represents a group of helper NLRs that are required by sensor NLRs to execute hypersensitive cell death during pathogen infection. NRCs contain an N-terminal coiled-coil (CC) domain essential for their function, yet our knowledge of how this domain contributes to NRC function remains limited. Here, we identified a novel hydrophobic feature within the CC domain that contributes to NRC-mediated immunity. We screened for conserved hydrophobic residues among NRCs and identified seven required for NRC4-mediated cell death. Structural analysis revealed that four of these residues form a hydrophobic core in the CC domain. This hydrophobic core is important for NRC4 subcellular localization, oligomerization, and phospholipid association, but not for NRC4 focal accumulation at the extrahaustorial membrane during Phytophthora infestans infection. Sequence analysis and functional assays revealed this core is highly conserved in NRCs and some singleton NLRs but has degenerated in NRC-dependent sensor NLRs. Our study identifies a novel hydrophobic feature in the CC domain of NRCs and reveals its contribution to NLR-mediated immunity.
]]></description>
<dc:creator>Wang, H.-Y.</dc:creator>
<dc:creator>Lee, K.-T.</dc:creator>
<dc:creator>Goh, F.-J.</dc:creator>
<dc:creator>Bozkurt, T. O.</dc:creator>
<dc:creator>Wu, C.-H.</dc:creator>
<dc:date>2025-01-24</dc:date>
<dc:identifier>doi:10.1101/2025.01.21.634219</dc:identifier>
<dc:title><![CDATA[A hydrophobic core in the coiled-coil domain essential for NRC resistosome function]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-01-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.01.23.634641v1?rss=1">
<title>
<![CDATA[
Unravel the start element and promoter architecture across the domain Bacteria 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.01.23.634641v1?rss=1</link>
<description><![CDATA[
Core promoters comprise multiple elements whose interaction with RNA polymerase initiates transcription. Despite decades of research, substantial sequence and length variation of promoter elements has hindered efforts to elucidate their function and the evolutionary diversity of transcriptional regulation. Combining massively parallel assays, biophysical modeling, and functional validation, we systematically dissected the promoter architecture upstream of experimentally determined transcription start sites in 49 phylogenetically diverse bacterial genomes (GC content: 27.8-72.1%). We identified a conserved 3-bp promoter element, termed  start, that dictates transcription start site selection and enhances transcription. We uncovered a four-region organization within the variable spacer element, whose sequence composition modulates transcription by up to 600-fold. We showed that the discriminator element is conserved in Terrabacteria but diverse in Gracilicutes, the two major bacterial clades. High discriminator sequence diversity in Gracilicutes likely reflects diversifying evolution, enabling promoter-encoded regulation to orchestrate global gene expression in response to growth rate changes. Together, our findings reveal broad conservation of bacterial promoter organization while highlighting regulatory divergence of promoter elements and RNA polymerase between Terrabacteria and Gracilicutes. Sequence and functional similarities between bacterial promoter elements and their archaeal and eukaryotic counterparts further suggest a shared evolutionary origin of promoter architecture.
]]></description>
<dc:creator>Kuo, S.-T.</dc:creator>
<dc:creator>Chang, J. K.</dc:creator>
<dc:creator>Chang, C.</dc:creator>
<dc:creator>Shen, W.-Y.</dc:creator>
<dc:creator>Hsu, C.</dc:creator>
<dc:creator>Lai, S.-W.</dc:creator>
<dc:creator>Chou, H.-H. D.</dc:creator>
<dc:date>2025-01-24</dc:date>
<dc:identifier>doi:10.1101/2025.01.23.634641</dc:identifier>
<dc:title><![CDATA[Unravel the start element and promoter architecture across the domain Bacteria]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-01-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.01.30.635671v1?rss=1">
<title>
<![CDATA[
Orthologous transcription factor replacement reveals that stable TFIIIC complexes are required for proper mitotic chromosome segregation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.01.30.635671v1?rss=1</link>
<description><![CDATA[
Transcription factors are speculated to play crucial roles in adaptive evolution. Using ortholog replacement of essential transcription factors (eTFs) from other yeast species, we investigated how eTFs can change. Several orthologs could not fully complement Saccharomyces cerevisiae mutants, indicating that functions or interactions of these eTFs have changed, rendering them incompatible. We further characterized TFIIIC, a fast-evolving protein complex that assists RNA polymerase III-mediated transcription, which exhibited complete or partial incompatibility in several subunits. In the orthologous Tfc7-replacement line, binding of TFIIIC to tRNA genes was reduced, yet tRNA abundance was not severely affected. However, the chromosomes of Tfc7-replacement cells were often mis-segregated during mitosis and their fitness was further reduced in a spindle checkpoint mutant. Our chromatin-immunoprecipitation experiments uncovered that unstable TFIIIC binding results in defective cohesion loading, leading to chromosome mis-segregation. Swapping the highly divergent C-terminal domain of Tfc7 orthologs rescued its interaction with Tfc1 and cell fitness, supporting that incompatibility is caused by altered interactions between complex subunits. Our results reveal distinct essential functions of a well-studied protein complex.
]]></description>
<dc:creator>Gupta, A.</dc:creator>
<dc:creator>Hsu, P.-C.</dc:creator>
<dc:creator>Litan, R. R. R.</dc:creator>
<dc:creator>Leu, J.-Y.</dc:creator>
<dc:date>2025-01-31</dc:date>
<dc:identifier>doi:10.1101/2025.01.30.635671</dc:identifier>
<dc:title><![CDATA[Orthologous transcription factor replacement reveals that stable TFIIIC complexes are required for proper mitotic chromosome segregation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-01-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.02.02.636175v1?rss=1">
<title>
<![CDATA[
Shared Alteration of Whole-Brain Connectivity and Olfactory Deficits in Multiple Autism Mouse Models 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.02.02.636175v1?rss=1</link>
<description><![CDATA[
Autism spectrum disorder (ASD) is a disconnection condition influenced by both heterogeneous genetic and environmental factors, yet it remains unclear whether common connectivity deficits exist. Here, we demonstrate that different ASD-linked mutations lead to distinct circuit abnormalities but share deficits in the piriform cortex and olfactory discrimination. Using advanced artificial intelligence, we developed a whole-brain mapping platform to analyze the distribution of the Thy1-YFP projection neurons in three ASD mouse models (Tbr1+/-, Nf1+/-, Vcp+/R95G). Our analysis revealed changes in axonal patterns and neuronal distribution, indicating deficits in projection neuron differentiation and maintenance. Notably, the piriform cortex consistently exhibited reduced YFP+ cells and signals and impaired functionality across all models. Visual and somatosensory cortices were also affected, but the patterns varied. These findings highlight that the sensory regions, especially the piriform cortex, are susceptible to ASD-related mutations, strengthening the notion that different sensory experiences are common in ASD.

HighlightsO_LIAI-powered whole-mouse brain quantification accelerates neural connectivity study.
C_LIO_LIAutism-linked mutations lead to various circuit abnormalities of Thy1-YFP neurons.
C_LIO_LIMultiple sensory regions all exhibit circuit deficits among the three autism models.
C_LIO_LIAbnormalities of olfaction and piriform cortex circuits are common in autism models.
C_LI
]]></description>
<dc:creator>Hsu, T.-T.</dc:creator>
<dc:creator>Chen, C.-P.</dc:creator>
<dc:creator>Lin, M.-H.</dc:creator>
<dc:creator>Huang, T.-N.</dc:creator>
<dc:creator>Wang, C.-Y.</dc:creator>
<dc:creator>Lee, C.-M.</dc:creator>
<dc:creator>Chen, B.-C.</dc:creator>
<dc:creator>Wang, C.-Y.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:date>2025-02-03</dc:date>
<dc:identifier>doi:10.1101/2025.02.02.636175</dc:identifier>
<dc:title><![CDATA[Shared Alteration of Whole-Brain Connectivity and Olfactory Deficits in Multiple Autism Mouse Models]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-02-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.02.08.636946v1?rss=1">
<title>
<![CDATA[
Mismatch repair and homologous recombination are yin-yang partners in hybrid zygote meiosis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.02.08.636946v1?rss=1</link>
<description><![CDATA[
Rad51 and meiosis-specific Dmc1 catalyze homologous recombination (HR) between maternal and paternal chromosomes during meiosis in many sexual eukaryotes, generating three interhomolog (IH) recombination products: noncrossovers (NCOs), class I crossovers (COs), and class II COs. Some COs form chiasmata, which physically connect homologous chromosomes and ensure proper chromosome segregation during meiosis I. Meiosis is highly relevant to speciation, with the mismatch repair (MMR) system believed to prevent IH-HR, leading to postzygotic isolation between closely related species. We report that several Saccharomyces cerevisiae HR proteins exhibit anti-MMR activities, including Rad51, Rad54, and synapsis-promoting ZMM proteins (Mer3, Zip1, Zip4, and Msh4) in SK1/S288c hybrid zygotes. Srs2 (an ortholog of Escherichia coli helicase UvrD) facilitates MMR by dissembling Rad51-ssDNA presynaptic filaments. Rad51 antagonizes MMR and Srs2 to catalyze D-loop formation. Rad54s anti-MMR activity acts after Srs2 and outcompetes its pro-HR function to promote Rad51-mediated IH-HR in hybrid zygotes. Dmc1 does not possess anti-MMR activity, but exhibits better mismatch tolerability than Rad51. Following D-loop formation mediated by Dmc1 and/or Rad51, ZMM proteins promote class I IH-CO formation while limiting MMR to promote NCO formation by Sgs1 (an ortholog of E. coli RecQ helicase) and prevent class II IH-CO formation by the Mms4*Mus81 endonuclease.

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/636946v2_ufig1.gif" ALT="Figure 1">
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org.highwire.dtl.DTLVardef@db6794org.highwire.dtl.DTLVardef@6d5947org.highwire.dtl.DTLVardef@1004489org.highwire.dtl.DTLVardef@938403_HPS_FORMAT_FIGEXP  M_FIG C_FIG HighlightsO_LIMMR and HR antagonize each other in intraspecies hybrid zygotes.
C_LIO_LIThe HR proteins Rad51, Rad54, and ZMM exhibit anti-MMR activities.
C_LIO_LIMMR overrides HR in hybrid zygotes with anti-MMR mutations, causing hybrid sterility.
C_LI
]]></description>
<dc:creator>Chuang, C.-N.</dc:creator>
<dc:creator>Hung, Y.-L.</dc:creator>
<dc:creator>Kim, H.-X.</dc:creator>
<dc:creator>Yao, J.-S.</dc:creator>
<dc:creator>Liu, H.-C.</dc:creator>
<dc:creator>Chen, S.-Y.</dc:creator>
<dc:creator>Jovanska, L.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:creator>Chen, R.-S.</dc:creator>
<dc:creator>Wang, T.-F.</dc:creator>
<dc:date>2025-02-10</dc:date>
<dc:identifier>doi:10.1101/2025.02.08.636946</dc:identifier>
<dc:title><![CDATA[Mismatch repair and homologous recombination are yin-yang partners in hybrid zygote meiosis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-02-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.02.24.639882v1?rss=1">
<title>
<![CDATA[
Natural Killer Cell Receptor Signaling and Activation Depend on Cell Cycle Stages 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.02.24.639882v1?rss=1</link>
<description><![CDATA[
Receptor signaling in Natural Killer (NK) cells leads to post-translational modification (e.g., phosphorylation) of sub-cellular signaling proteins within minutes of receptor stimulation that eventually give rise to diverse effector functions including cell proliferation. Recent single-cell mass cytometry (i.e., CyTOF) experiments in macrophages showed variations of abundances of phosphorylated signaling proteins across cell cycle states indicating a dependence of cell signaling kinetics on an order of magnitude slower kinetics (~ several hours) of cell cycle transitions. We investigated cell cycle dependence of NKG2D signaling kinetics in NK cells by CyTOF measurements performed on IL-2-treated NKG2D-stimulated primary human CD56dim NK cells. The CyTOF experiments revealed monotonic or semi-monotonic increases of the average protein abundances of the majority of signaling proteins such as pCrkL, pPLC{gamma}2, and pErk, and the degranulation marker protein CD107a with progressing cell cycle states at specific time points post-NKG2D stimulation; however, several proteins such as pVav1, pS6, and pAkt, and early activation marker protein CD69 also showed non-monotonic variations in the average abundances with progressing cell cycle states. We used minimal mathematical and computational models coupling signaling and cell cycle processes to show that non-monotonic variations in the signaling protein abundances with progressing cell cycle stages are likely to arise in situations where protein synthesis and degradation and signaling kinetics are actively regulated by cell cycle processes.
]]></description>
<dc:creator>Wethington, D.</dc:creator>
<dc:creator>Nayak, I.</dc:creator>
<dc:creator>Jensen, H.</dc:creator>
<dc:creator>Stewart, W. C.</dc:creator>
<dc:creator>Aguilar, O. A.</dc:creator>
<dc:creator>Chen, S.-Y.</dc:creator>
<dc:creator>Nolan, G. P.</dc:creator>
<dc:creator>Behbehani, G. K.</dc:creator>
<dc:creator>Lanier, L. L.</dc:creator>
<dc:creator>Das, J.</dc:creator>
<dc:date>2025-02-28</dc:date>
<dc:identifier>doi:10.1101/2025.02.24.639882</dc:identifier>
<dc:title><![CDATA[Natural Killer Cell Receptor Signaling and Activation Depend on Cell Cycle Stages]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-02-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.03.04.641443v1?rss=1">
<title>
<![CDATA[
Assigning Targetable Molecular Pathways to Transdiagnostic Subgroups Across Autism and Related Neurodevelopmental Disorders 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.03.04.641443v1?rss=1</link>
<description><![CDATA[
Significant genetic, behavioural and neuroanatomic heterogeneity is common in autism spectrum- and related- neurodevelopmental disorders (NDDs). This heterogeneity constrains the development of effective therapies for diverse patients in precision medicine paradigms. This has led to the search for subgroups of individuals having common etiologic factors/biology (e.g., genetic pathways), thus creating potential uniformity in prognosis and/or treatment response. Despite NDDs having a strong genetic component, only ~15-20% of individuals will present with a specific rare genetic variant considered clinically pathogenic, and therefore, subtyping efforts tend to focus on using clinical, cognitive, and/or brain imaging phenotypes to group individuals. Here we delineated mechanisms via mouse to human translational neuroscience. Using MRI derived structural neuroanatomy and a spatial transcriptomic comparison, we linked subgroups of 135 NDD relevant mouse models (3,515 individual mice) separately to two human databases, with 1,234 and 1,015 human individuals with NDDs, composed of autism, attention-deficit/hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), other related NDDs, and typically developing controls. Subgroups were significantly linked by consistent neuroanatomy across all three datasets, mouse and human, indicating that direct cross-species subgrouping and translation is consistent and reproducible. Ultimately, four specific neuroanatomical clusters were found and linked to precise molecular mechanisms: two showing a chromatin/transcription motif, with one of those showing specific links to G-protein coupled receptors (GPCR) and Notch signalling, and another two being mainly synaptic in origin, with one off those showing specific connections to axon guidance and Wnt signaling. Assigning molecular pathways, and thus genetic information, from the mouse to individual participants provides an insight into undetected and/or related genetic variants that could be working in combination or interacting with an environmental influence. Moreover, the subgroups found are transdiagnostic, including participants with autism, ADHD, and OCD, which indicates that NDDs as a whole can be subdivided into consistent neuroanatomical clusters with cohesive underlying biological mechanisms. This work allows us to bridge the gap between preclinical models and human disorders, linking previously idiopathic human patients to pertinent genetics, molecular mechanisms, and pathways.
]]></description>
<dc:creator>Ellegood, J.</dc:creator>
<dc:creator>Beauchamp, A.</dc:creator>
<dc:creator>Yee, Y.</dc:creator>
<dc:creator>Devenyi, G.</dc:creator>
<dc:creator>Ziolkowski, J.</dc:creator>
<dc:creator>Qiu, L.</dc:creator>
<dc:creator>Askalan, R.</dc:creator>
<dc:creator>Ayub, M.</dc:creator>
<dc:creator>Suetterlin, P.</dc:creator>
<dc:creator>Donovan, A.</dc:creator>
<dc:creator>Basson, M. A.</dc:creator>
<dc:creator>Quesnel, K. M.</dc:creator>
<dc:creator>Berube, N. G.</dc:creator>
<dc:creator>Woo, T.</dc:creator>
<dc:creator>Beversdorf, D.</dc:creator>
<dc:creator>Bjornsson, H.</dc:creator>
<dc:creator>Blakely, R.</dc:creator>
<dc:creator>Crawley, J.</dc:creator>
<dc:creator>Crosbie, J.</dc:creator>
<dc:creator>Orr, B. O.</dc:creator>
<dc:creator>Davis, G. W.</dc:creator>
<dc:creator>Genestine, M.</dc:creator>
<dc:creator>DiCicco-Bloom, E.</dc:creator>
<dc:creator>Egan, S.</dc:creator>
<dc:creator>Fink, K. D.</dc:creator>
<dc:creator>Asbury, S.</dc:creator>
<dc:creator>Lai, J.</dc:creator>
<dc:creator>Rilett, K.</dc:creator>
<dc:creator>Foster, J. A.</dc:creator>
<dc:creator>Vincent, J. B.</dc:creator>
<dc:creator>Frankland, P.</dc:creator>
<dc:creator>Georgiades, S.</dc:creator>
<dc:creator>Penagarikano, O.</dc:creator>
<dc:creator>Geschwind, D.</dc:creator>
<dc:creator>Giger, R. J.</dc:creator>
<dc:creator>Markx, S.</dc:creator>
<dc:creator>Gogos, J.</dc:creator>
<dc:creator>Golzio, C.</dc:creator>
<dc:creator>Pagani, M.</dc:creator>
<dc:creator>Gozzi, A.</dc:creator>
<dc:creator>Pacey, L. K.</dc:creator>
<dc:creator>Hampson, D.</dc:creator>
<dc:creator>Huang, T.-N.</dc:creator>
<dc:creator>Yen, T.-L.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:date>2025-03-10</dc:date>
<dc:identifier>doi:10.1101/2025.03.04.641443</dc:identifier>
<dc:title><![CDATA[Assigning Targetable Molecular Pathways to Transdiagnostic Subgroups Across Autism and Related Neurodevelopmental Disorders]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-03-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.03.06.641946v1?rss=1">
<title>
<![CDATA[
Unusual Ecofunctional Traits of Endozoicomonas: A Pan-Genomic Perspective 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.03.06.641946v1?rss=1</link>
<description><![CDATA[
BackgroundEndozoicomonas is a widely distributed genus of marine bacteria, associated with various marine organisms, and recognized for its ecological importance in host health, nutrient cycling, and disease dynamics. Despite its significance, genomic features of Endozoicomonas remain poorly characterized due to limited availability of high-quality genome assemblies.

ResultsIn this study, we sequenced 5 novel Endozoicomonas strains and re-sequenced 1 known strain to improve genomic resolution. By integrating these 6 high-quality genomes with 31 others that were publicly available, we identified a distinct, coral-associated clade not recognized by the previous two-clade classification. Pan-genomic analysis revealed significant variation in genetic trait distribution among clades. Notably, Endozoicomonas lacks quorum sensing capabilities, suggesting resistance to quorum quenching mechanisms. It also lacks the ability to synthesize and transport vitamin B12, indicating that it is not a primary source of this nutrient for holobionts. A remarkable feature of Endozoicomonas is its abundance of giant proteins, ranging from 15 to 65 kbp. We identified 92 such proteins, which clustered into three major groups based on amino acid similarity, each associated with specialized functions, such as antimicrobial synthesis, exotoxin production, and cell adhesion. Additionally, we explored prophages and CRISPR-Cas systems. We found that Endozoicomonas acquired prophages from diverse sources via infection or other types of gene transfer. Notably, CRISPR-Cas sequences suggest independent evolutionary trajectories from both prophage acquisition and phylogenetic lineage, implying a potential influence of geographic or environmental pressures.

ConclusionsThis study provides new insights into the genomic diversity of Endozoicomonas and its genetic adaptation to diverse hosts. Identification of novel genomic features, including deficiencies in B12 synthesis and quorum sensing, the presence of giant proteins, prophages, and CRISPR-Cas systems, underscores its ecological roles in various holobionts. These findings open new avenues for research on Endozoicomonas and its ecological interactions.
]]></description>
<dc:creator>Lim, S. L.</dc:creator>
<dc:creator>Chin, C.-H.</dc:creator>
<dc:creator>Chiou, Y.-J.</dc:creator>
<dc:creator>Hsu, M.-T.</dc:creator>
<dc:creator>Chiang, P.-W.</dc:creator>
<dc:creator>Chen, H.-J.</dc:creator>
<dc:creator>Tu, Y.-C.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:date>2025-03-11</dc:date>
<dc:identifier>doi:10.1101/2025.03.06.641946</dc:identifier>
<dc:title><![CDATA[Unusual Ecofunctional Traits of Endozoicomonas: A Pan-Genomic Perspective]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-03-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.03.16.643507v1?rss=1">
<title>
<![CDATA[
Phylogenomic inference suggests differential deep time phylogenetic signals from nuclear and organellar genomes in gymnosperms 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.03.16.643507v1?rss=1</link>
<description><![CDATA[
The living gymnosperms include about 1,100 species in five major groups: cycads, ginkgo, gnetophytes, Pinaceae (conifers I), and cuppressophytes (conifers II). Molecular phylogenetic studies have yet to reach a unanimously agreed relationship among them. Moreover, cytonuclear phylogenetic incongruence has been repeatedly observed in gymnosperms. We collated a comprehensive data set from available genomes and added our own high-quality assembly of a species from Podocarpaceae (the 2nd largest conifer family) to increase sampling width. We used these data to infer reconciled nuclear species phylogenies using two separate methods to ensure robustness of our conclusions. We also reconstructed organelle phylogenomic trees from 41 mitochondrial and 82 plastid genes. Our nuclear phylogeny consistently recovers the Ginkgo-cycads clade as the first lineage split from other gymnosperm clades and the Pinaceae as sister to gnetophytes (the Gnepines hypothesis). In contrast, the mitochondrial tree places cycads as the earliest lineage in gymnosperms and gnetophytes as sister to cupressophytes (the Gne-cup hypothesis) while the plastomic tree supports the Ginkgo-cycads clade and Gnetophytes as the sister to Cupressophytes. We also examined the effect of mitochondrial RNA editing sites on the gymnosperm phylogeny by manipulating the nucleotide and amino acid sequences at these sites. Only complete removal of editing sites has an effect on phylogenetic inference, leading to a closer congruence between mitogenomic and nuclear phylogenies. This suggests that RNA editing sites carry a phylogenetic signal with distinct evolutionary traits.
]]></description>
<dc:creator>Lin, Y.-E.</dc:creator>
<dc:creator>Chaw, S.-M.</dc:creator>
<dc:creator>Wu, C.-S.</dc:creator>
<dc:creator>Wu, Y.-W.</dc:creator>
<dc:date>2025-03-17</dc:date>
<dc:identifier>doi:10.1101/2025.03.16.643507</dc:identifier>
<dc:title><![CDATA[Phylogenomic inference suggests differential deep time phylogenetic signals from nuclear and organellar genomes in gymnosperms]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-03-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.03.20.644374v1?rss=1">
<title>
<![CDATA[
Seal milk oligosaccharides rival human milk complexity and exhibit functional dynamics during lactation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.03.20.644374v1?rss=1</link>
<description><![CDATA[
Breast milk oligosaccharides are crucial for neonatal development and health. Yet most milk research focuses on humans, or domesticated mammals that are historically poor in milk oligosaccharide complexity. Here, we perform an exhaustive mass spectrometry-driven structural characterization of milk oligosaccharides in a wild mammal, Atlantic grey seals (Halichoerus grypus), throughout their lactation period. Characterizing and quantifying 332 milk oligosaccharides, including 166 novel structures, we reveal seals to rival human milk in complexity, with seal free oligosaccharides reaching unprecedented 28 monosaccharides in size. Glycomics and metabolomics time course analysis establishes a concerted regulatory process reshaping the seal milk glycome throughout lactation,similar as in human milk. Functional analysis of herein newly characterized structures reveals anti-biofilm effects and immunomodulatory functions of seal milk oligosaccharides. We envision these findings to overturn long-held assumptions about milk complexity of non-human mammals and enable insights into the functional relevance of complex carbohydrates in breast milk.
]]></description>
<dc:creator>Jin, C.</dc:creator>
<dc:creator>Lundstrom, J.</dc:creator>
<dc:creator>Cori, C. R.</dc:creator>
<dc:creator>Guu, S.-Y.</dc:creator>
<dc:creator>Bennett, A. R.</dc:creator>
<dc:creator>Dannborg, M.</dc:creator>
<dc:creator>Bengtsson-Palme, J.</dc:creator>
<dc:creator>Hevey, R.</dc:creator>
<dc:creator>Khoo, K.-H.</dc:creator>
<dc:creator>Bojar, D.</dc:creator>
<dc:date>2025-03-20</dc:date>
<dc:identifier>doi:10.1101/2025.03.20.644374</dc:identifier>
<dc:title><![CDATA[Seal milk oligosaccharides rival human milk complexity and exhibit functional dynamics during lactation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-03-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.03.22.644710v1?rss=1">
<title>
<![CDATA[
The cellular and behavioral blueprints of chordate rheotaxis. 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.03.22.644710v1?rss=1</link>
<description><![CDATA[
The oceans are filled with life-forms exhibiting complex adaptations to help navigate fluid environments and take advantage of fluid motion to locomote and disperse. However, the neuronal and behavioral underpinnings of navigating in fluid environments outside vertebrates are poorly understood.

We present behavioral and computational modelling-based evidence that the pre-vertebrate chordate Ciona intestinalis actively modulates its heading and angular velocities to counter oncoming flows and perform positive rheotaxis.

We demonstrate that a distributed network of ciliated peripheral sensory neurons is responsible for sensing hydrodynamic information such as flow velocity and direction. Pharmacological removal of sensory cilia impedes rheotactic behavior and reduces stimulus evoked neuronal activity.

Whole-brain calcium imaging experiments reveal that the central nervous system of Ciona can encode the onset and offset of flow, flow direction, and flow velocity, suggesting that miniature chordate brain is capable of surprisingly sophisticated computations.
]]></description>
<dc:creator>Tolstenkov, O.</dc:creator>
<dc:creator>Ozawa, A.</dc:creator>
<dc:creator>Allombert-Blaise, C.</dc:creator>
<dc:creator>Hiraiwa, T.</dc:creator>
<dc:creator>Chatzigeorgiou, M.</dc:creator>
<dc:date>2025-03-24</dc:date>
<dc:identifier>doi:10.1101/2025.03.22.644710</dc:identifier>
<dc:title><![CDATA[The cellular and behavioral blueprints of chordate rheotaxis.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-03-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.03.29.646076v1?rss=1">
<title>
<![CDATA[
Misregulation of the jasmonate signaling pathway leads to altered plant microbiota interaction and plant stress responses 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.03.29.646076v1?rss=1</link>
<description><![CDATA[
The model plant Arabidopsis thaliana hosts diverse microbial communities collectively known as the microbiota. The plant microbiota is generally taxonomically structured. Some of the members can promote plant fitness including growth and stress tolerance. However, microbial imbalance can also result in deleterious effects, a phenomenon known as dysbiosis that was first coined in the gut microbiome field. To unveil the regulatory mechanism to maintain plant homeostatic interaction with microbiota, we performed screening using defined synthetic bacterial communities. We identified an Arabidopsis mutant with altered microbial profiles, an overall increase of microbial load and microbiota-dependent growth defects. Transcriptomic and chemical complementation analyses confirmed that the aforementioned microbiota-dependent phenotypes are contributed by an upregulation of the jasmonate signaling pathway. Upregulation of the jasmonate pathway further promotes microbial growth, possibly forming a positive feedback loop. Even though activation of the jasmonate signaling pathway is known to enhance plant stress tolerance, hyperactivation of the pathway alters plant tolerance or resistance against multiple stressors. Plant association with the microbiota together with proper regulation of the jasmonate signaling pathway are thus essential to maintain plant response to environmental stressors.
]]></description>
<dc:creator>Lu, T.-T.</dc:creator>
<dc:creator>Isip, M.</dc:creator>
<dc:creator>Shih, H.-J. S.</dc:creator>
<dc:creator>Perin, S.</dc:creator>
<dc:creator>Ma, K.-W.</dc:creator>
<dc:date>2025-03-31</dc:date>
<dc:identifier>doi:10.1101/2025.03.29.646076</dc:identifier>
<dc:title><![CDATA[Misregulation of the jasmonate signaling pathway leads to altered plant microbiota interaction and plant stress responses]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-03-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.03.27.645670v1?rss=1">
<title>
<![CDATA[
Targeting Wnt Signaling and DNAJB6/MRJ-L as a Dual Anti-RSV Strategy: Insights into a Positive Regulatory Loop 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.03.27.645670v1?rss=1</link>
<description><![CDATA[
Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections, yet effective treatments are lacking. We found that the molecular chaperon DNAJB6/MRJ plays an essential role in RSV replication. Depletion of the long isoform of MRJ (MRJ-L) suppresses RSV replication. Transcriptomic analysis revealed that MRJ-L depletion downregulates Wnt signaling pathways. A pharmacological inhibitor of Wnt signaling suppressed RSV propagation and unexpectedly reduced MRJ-L expression, suggesting a positive regulatory loop between Wnt signaling and MRJ-L expression. Notably, simultaneous inhibition of Wnt signaling and MRJ-L additively suppressed RSV replication, suggesting that the Wnt-MRJ-L axis may serve as a new therapeutic target. This study provides insights into host-RSV interactions and potential antiviral strategies.

Author SummaryThe molecular chaperone DNAJB6/MRJ has been implicated in the replication of respiratory syncytial virus (RSV), although the precise mechanisms remain unclear. In this study, we discovered that MRJ may influence RSV replication via Wnt signaling pathways. Specifically, we demonstrated that Wnt signaling inhibitor Wnt-C59 significantly reduced RSV replication by suppressing the synthesis of viral mRNA and genome/antigenome. Moreover, a positive feedback loop of the Wnt-MRJ axis may play a critical role in regulating RSV replication. Importantly, RSV replication was suppressed additively by inhibition of Wnt signaling and depletion of MRJ-L. Thus, a dual-targeted therapeutic approach may be effective in combating RSV infections.
]]></description>
<dc:creator>Lu, C.-Y.</dc:creator>
<dc:creator>Lai, P.-Y.</dc:creator>
<dc:creator>Huang, J.-M.</dc:creator>
<dc:creator>Chang, L.-Y.</dc:creator>
<dc:creator>Yen, T.-Y.</dc:creator>
<dc:creator>Tarn, W.-Y.</dc:creator>
<dc:creator>Huang, L.-M.</dc:creator>
<dc:date>2025-04-01</dc:date>
<dc:identifier>doi:10.1101/2025.03.27.645670</dc:identifier>
<dc:title><![CDATA[Targeting Wnt Signaling and DNAJB6/MRJ-L as a Dual Anti-RSV Strategy: Insights into a Positive Regulatory Loop]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-04-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.03.27.645864v1?rss=1">
<title>
<![CDATA[
Natural spider silk enhances mechanical performance of collagen scaffold under stretching conditions 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.03.27.645864v1?rss=1</link>
<description><![CDATA[
Collagen is the most abundant protein in the extracellular matrix, crucial for wound healing and cell proliferation. While it holds promise as a scaffold for tendon, skin, and ligament reconstruction, collagens mechanical strength, particularly under stretch, is poor. Previous attempts to improve collagen strength involved blending it with silkworm or recombinant spider silk. In this study, for the first time, we evaluated whether collagen gel from fish skin could be strengthened by infusing it with native spider silk, specifically the major ampullate (MA) silk of Nephila pilipes, known for superior mechanical properties. MA silk was woven onto a frame, pressed into a PDMS platform, and then used to create a collagen scaffold. Youngs modulus of the infused collagen scaffold, subjected to either stretching or non-stretching treatments, was measured using AFM. After 24 hours of cyclic stretching, collagen infused with silk showed less fragility, higher Youngs modulus, and no bacterial growth. Immunohistochemical staining showed that after stretching, the thickness and architecture of the collagen gel infused with silk were maintained, and the fibers were reorganized in a more compact, aligned, and denser manner. Overall, collagen infused with native spider silk exhibited improved mechanical stability and stiffness under cyclic stretching, suggesting that this combination could serve as a robust matrix for bioengineering applications while preventing bacterial infiltration.
]]></description>
<dc:creator>Tso, I.-M.</dc:creator>
<dc:creator>Tsiareshyna, M.</dc:creator>
<dc:creator>Huang, S. Y. T.</dc:creator>
<dc:creator>Liao, C.-P.</dc:creator>
<dc:creator>Tang, M.-J.</dc:creator>
<dc:creator>Wong, T.-Y.</dc:creator>
<dc:date>2025-04-01</dc:date>
<dc:identifier>doi:10.1101/2025.03.27.645864</dc:identifier>
<dc:title><![CDATA[Natural spider silk enhances mechanical performance of collagen scaffold under stretching conditions]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-04-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.04.01.646729v1?rss=1">
<title>
<![CDATA[
N-glycosylation Enables Smut Fungal Nge1 Orthologs to Prevent the Escape of Maize Evolved-PMEIs 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.04.01.646729v1?rss=1</link>
<description><![CDATA[
Cell wall integrity (CWI) is regulated by the coordinated activity of CW-modifying enzymes, including pectin methylesterases (PMEs) and their inhibitors (PMEIs). PMEs de-methylesterify pectins, making them more susceptible to degradation and loosening the CW, facilitating pathogen invasion. Conversely, PMEIs inhibit PMEs, reinforcing the CWI and enhancing plant defense. However, how biotrophic pathogens overcome PMEI-mediated defense remains unclear. Here, we report that smut fungal effectors have evolved to directly target host specific PMEIs, manipulating cell wall integrity to enhance virulence. N-glycosylated Effector 1 (Nge1) from Ustilago maydis selectively interact with PMEI45 and PMEI46, as well as the auto-inhibitory PRO-domains of PMEs. This interaction disrupts PMEI inhibition, liberating PME19 and PME20, which reduce pectin methylesterification and likely loosen the CW, promoting fungal invasion. Notably, the interaction between Nge1 and PMEI45, but not PMEI46, is N-glycosylation-dependent. Restoring glycosylation in a non-glycosylated Nge1 ortholog allows it to functionally replace U. maydis Nge1, suggesting that smut fungal effectors have evolved through glycan modifications to overcome host-adapted PMEIs that would otherwise escape non-glycosylated effectors and impede fungal infection. Our findings reveal bidirectional host-pathogen strategies in a co-evolutionary arms race to fine-tune molecular interactions in the extracellular space.
]]></description>
<dc:creator>Bhaskar, C.</dc:creator>
<dc:creator>Chau, M.-Q.</dc:creator>
<dc:creator>Tsai, W.-L.</dc:creator>
<dc:creator>Teh, O.-K.</dc:creator>
<dc:creator>Ma, L.-S.</dc:creator>
<dc:date>2025-04-02</dc:date>
<dc:identifier>doi:10.1101/2025.04.01.646729</dc:identifier>
<dc:title><![CDATA[N-glycosylation Enables Smut Fungal Nge1 Orthologs to Prevent the Escape of Maize Evolved-PMEIs]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-04-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.04.01.646383v1?rss=1">
<title>
<![CDATA[
A high-quality chromosome-level genome of an undescribed Meretrix species using Nanopore and Hi-C technologies 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.04.01.646383v1?rss=1</link>
<description><![CDATA[
Meretrix is a commercially valuable bivalve genus in Asia, but only one reference genome has hindered comprehensive genetic studies and germplasm resource evaluation. In this study, we present three reference genomes of Meretrix species: Meretrix sp. MF1, Meretrix sp. MT1, and Meretrix lamarckii JML1. Meretrix sp. MF1 was assembled at the chromosome level using Nanopore sequencing and Hi-C technologies, whereas Meretrix sp. MT1 and Meretrix lamarckii were assembled as scaffold-level assemblies. The chromosome-level genome of Meretrix sp. MF1 consists of 36 contigs, including 19 chromosomes and 17 scaffolds, with a total length of 883.3 Mb and a scaffold N50 of 46.87 Mb. Notably, the genome of Meretrix sp. MF1, a putative novel species, exhibits an Average Nucleotide Identity (ANI) of 94.33% with its closest relative, Meretrix lamarckii. These genomic resources not only provide a crucial foundation for genetic research on Meretrix but also contribute to the development of effective conservation strategies for its sustainable management.
]]></description>
<dc:creator>Chen, C.-C.</dc:creator>
<dc:creator>Hsu, T.-H.</dc:creator>
<dc:creator>Lu, H.-Y.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:creator>Ho, Y.-N.</dc:creator>
<dc:date>2025-04-06</dc:date>
<dc:identifier>doi:10.1101/2025.04.01.646383</dc:identifier>
<dc:title><![CDATA[A high-quality chromosome-level genome of an undescribed Meretrix species using Nanopore and Hi-C technologies]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-04-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.04.05.647352v1?rss=1">
<title>
<![CDATA[
Spatiotemporal differences of GABAergic polarization and shunting during dendritic integration 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.04.05.647352v1?rss=1</link>
<description><![CDATA[
In the adult brain, GABA exerts either depolarizing or hyperpolarizing effects on neuronal membranes, depending on neuron type, subcellular location, and neuronal activity. Depolarizing GABA typically inhibits neurons through shunting, which is characterized by increased membrane conductance upon GABAA receptor activation; however, it can also excite neurons by recruiting voltage-dependent conductances. The net influence of these opposing actions of depolarizing GABA on glutamatergic synaptic inputs remains incompletely understood. Here, we examined the spatiotemporal characteristics of membrane polarization and shunting mediated by GABAA receptors and assessed their functional impact on the integration of GABAergic and glutamatergic inputs along dendrites. Using whole-cell current-clamp recordings in CA1 pyramidal neurons and dentate gyrus granule cells (GCs) from rat hippocampal slices, we mimicked GABAergic and glutamatergic inputs with local GABA puffs and glutamate spot-uncaging, respectively. A mathematical model further quantified the relative effects of local shunting and polarization. Depolarizing GABAergic postsynaptic responses (GPSRs) exhibited biphasic actions, exerting inhibitory effects at the synapse through shunting, and excitatory effects distally, where depolarization predominated. The excitatory component also persisted longer than the shunting inhibition. In contrast, hyperpolarizing GPSRs remained consistently inhibitory across both spatial and temporal dimensions. These findings highlight the complex spatiotemporal interplay between shunting and membrane polarization mediated by GABAergic inputs, providing new insights into dendritic computation and neuronal network dynamics.
]]></description>
<dc:creator>Dembitskaya, Y.</dc:creator>
<dc:creator>Kirsanov, A.</dc:creator>
<dc:creator>Wu, Y.-W.</dc:creator>
<dc:creator>Brazhe, A.</dc:creator>
<dc:creator>Semyanov, A.</dc:creator>
<dc:date>2025-04-07</dc:date>
<dc:identifier>doi:10.1101/2025.04.05.647352</dc:identifier>
<dc:title><![CDATA[Spatiotemporal differences of GABAergic polarization and shunting during dendritic integration]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-04-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.04.23.650082v1?rss=1">
<title>
<![CDATA[
Evolutionary dynamics of FoxQ2 transcription factors across metazoans: A tale of three ancient paralogs 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.04.23.650082v1?rss=1</link>
<description><![CDATA[
FoxQ2 is a highly conserved class of Forkhead-box transcription factors expressed on the anterior side of the body in cnidarians and bilaterians. Despite this conserved expression pattern, recent phylogenetic analyses have revealed a complex and rapid evolution of this class, with several taxon-specific duplications and losses. Until recently, FoxQ2 was thought to be lost in most vertebrate lineages, and its presence and localization in different vertebrate groups remains unclear.

To reconcile these conflicting reports of conservation and divergence, here we present a comprehensive analysis of the phylogenetic relationships and expression patterns of FoxQ2 genes across metazoans. By combining phylogenetics and synteny analyses of FoxQ2 sequences from 21 animal phyla, we uncover the presence of three ancient FoxQ2 paralogs in bilaterians, which we name FoxQ2a, FoxQ2b and FoxQ2c. All three FoxQ2 paralogs are present in the chordate lineage and two are conserved in vertebrates, indicating a richer repertoire of vertebrate Fox genes than previously estimated.

To investigate the expression of FoxQ2 genes across bilaterians, we mined expression data from existing single cell transcriptomic datasets of mollusk, acoel, amphioxus and zebrafish development, and expanded it using fluorescent in situ hybridization in amphioxus, lamprey, skate, zebrafish and chicken. Our analysis demonstrates the conserved anterior expression of FoxQ2a and FoxQ2b paralogs while also revealing a novel domain of FoxQ2c expression within the chordate endoderm, including in amphioxus, lamprey and skate. Finally, we devise a method to predict conserved transcription factor binding sites across the three extant amphioxus genera with specificity to developmental stage and cell-type identity. This suggests conserved regulatory interactions for the expression of FoxQ2a across deuterostomes.

Overall, this work clarifies the complex evolutionary history of FoxQ2 genes and identifies a newly discovered endodermally-expressed Fox gene, FoxQ2c. We further propose that the early duplication of FoxQ2a and FoxQ2b, along with their redundant functions, provided the ideal background for subfunctionalization, contributing to the fast evolutionary rate of FoxQ2 sequences observed in bilaterians.
]]></description>
<dc:creator>Gattoni, G.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>York, J. R.</dc:creator>
<dc:creator>Keitley, D.</dc:creator>
<dc:creator>LaBonne, C.</dc:creator>
<dc:creator>Yu, J.-K.</dc:creator>
<dc:creator>Gillis, A.</dc:creator>
<dc:creator>Benito-Gutierrez, E.</dc:creator>
<dc:date>2025-04-24</dc:date>
<dc:identifier>doi:10.1101/2025.04.23.650082</dc:identifier>
<dc:title><![CDATA[Evolutionary dynamics of FoxQ2 transcription factors across metazoans: A tale of three ancient paralogs]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-04-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.05.01.651651v1?rss=1">
<title>
<![CDATA[
Age-related declines in niche self-renewal factors controls testis aging and spermatogonial stem cell competition through Hairless, Imp, and Chinmo 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.05.01.651651v1?rss=1</link>
<description><![CDATA[
Aging is associated with progressive tissue decline and shifts in stem cell clonality. The role of niche signals in driving these processes remains poorly understood. Using the Drosophila testis, we identify a regulatory axis in which age-related decline of niche signals (BMPs) lead to upregulation of the co-repressor Hairless, which downregulates the RNA-binding protein Imp in aged germline stem cells (GSCs). Reduced Imp causes loss of Chinmo, a key factor in GSC aging and competition. Reduced Chinmo causes ectopic Perlecan secretion which accumulates in the testis lumen and causes GSC loss. Aging of the testis is reversed by increasing BMPs in the niche, or by overexpressing Imp or depleting Hairless in GSCs. Furthermore, GSC clones with reduced Imp or increased Hairless are more competitive, expelling wild-type neighbors and monopolizing the niche. Thus, BMPs regulate testicular niche aging through the Hairless-Imp-Chinmo axis and "winning" GSCs usurp these aging mechanisms.

HighlightsO_LIAged niche cells produce less BMPs, resulting in more Hairless (H) in aged GSCs
C_LIO_LIElevated H represses Imp, resulting in less Chinmo and in ectopic ECM secretion
C_LIO_LIAging is prevented by higher BMP in niche cells, or by higher Imp or lower H in GSCs
C_LIO_LIGSCs with low Imp or high H exploit these aging mechanisms to colonize the GSC pool
C_LI
]]></description>
<dc:creator>Zheng, Y.</dc:creator>
<dc:creator>Lee, Y.-C.</dc:creator>
<dc:creator>Wang, Y.-T.</dc:creator>
<dc:creator>Chiang, P.-K.</dc:creator>
<dc:creator>Chang, S.-L.</dc:creator>
<dc:creator>Hsu, H.-J.</dc:creator>
<dc:creator>Hsu, L.-S.</dc:creator>
<dc:creator>Bach, E.</dc:creator>
<dc:creator>Tseng, C.-Y.</dc:creator>
<dc:date>2025-05-02</dc:date>
<dc:identifier>doi:10.1101/2025.05.01.651651</dc:identifier>
<dc:title><![CDATA[Age-related declines in niche self-renewal factors controls testis aging and spermatogonial stem cell competition through Hairless, Imp, and Chinmo]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-05-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.05.07.652770v1?rss=1">
<title>
<![CDATA[
Floral Stage Optimization and Immune Evasion Enhance Agrobacterium-Mediated Genome Editing in Arabidopsis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.05.07.652770v1?rss=1</link>
<description><![CDATA[
O_LIAgrobacterium-mediated transformation via floral inoculation (AMT-FI) enables genetic engineering without tissue culture. It is widely used in the model plant Arabidopsis thaliana, yet its efficiency and broader applicability remain limited.
C_LIO_LIHere, we used a dual-reporter system (RUBY and hygromycin resistance) to identify key floral stages and engineered Agrobacterium strains to evade plant immunity, leading to enhanced transient expression and genome editing.
C_LIO_LIWe determined that flowers opened at 6 day-post-inoculation (DPI) are optimal for high transformation efficiency, with nearly 100% of siliques harboring transformants. However, Agrobacterium infection induced ovule abortion, particularly in wild-type (Col-0) plants, whereas efr mutants lacking the EF-Tu receptor (EFR)-mediated pattern-triggered immunity (PTI) showed reduced ovule abortion. Notably, efr mutants exhibited more RUBY-positive ovules and significantly enhanced genome editing efficiency. Two engineered stealth Agrobacterium strains (AS201 and AS202) expressing a chimeric EF- Tu for evading recognition by EFR enhanced both transient transformation and genome editing efficiency. Remarkably, genome-edited T1 plants could be recovered based on phenotype or direct sequencing without the need for antibiotic selection when targeting flowers opened at 6 DPI.
C_LIO_LIBy integrating floral stage selection, immune evasion, and Agrobacterium engineering, this study provides a practical and versatile platform to advance plant genome engineering.
C_LI
]]></description>
<dc:creator>Liu, M.-S.</dc:creator>
<dc:creator>Huang, T.-K.</dc:creator>
<dc:creator>Wang, Y.-C.</dc:creator>
<dc:creator>Wang, S.-C.</dc:creator>
<dc:creator>WU, C.-H.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:creator>Lai, E.-M.</dc:creator>
<dc:date>2025-05-08</dc:date>
<dc:identifier>doi:10.1101/2025.05.07.652770</dc:identifier>
<dc:title><![CDATA[Floral Stage Optimization and Immune Evasion Enhance Agrobacterium-Mediated Genome Editing in Arabidopsis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-05-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.05.12.652804v1?rss=1">
<title>
<![CDATA[
Spatial proteomics reveals lipid droplet reorganization in symbiotic Paramecium bursaria cells 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.05.12.652804v1?rss=1</link>
<description><![CDATA[
Endosymbiosis is an important adaptive mechanism allowing organisms to exploit novel niches. The flexible relationship between the ciliate Paramecium bursaria and green algae represents a model system for studying early endosymbiosis evolution. However, the mechanisms underlying how P. bursaria cells maintain this endosymbiotic relationship remain unclear. Here, we use mass spectrometry-based proteomics to generate a spatial proteomic atlas of the host P. bursaria cells with and without endosymbionts. This atlas defines the protein composition of the endosymbiont-containing compartment (perialgal vacuole) and reveals pronounced remodeling of host lipid droplets upon symbiosis. Imaging analyses confirm that lipid droplets change in size, morphology, and positioning, accumulating near intracellular algae. Perturbing symbiotic cells with chemical inhibitors of lipid metabolism reduces endosymbiotic algal numbers, revealing a role for lipid droplets in the host-endosymbiont interaction. Our data provide a comprehensive resource for protein localization in P. bursaria cells and elucidate how those cells remodel an existing cellular compartment to maintain endosymbiosis.
]]></description>
<dc:creator>Chen, Y.-J.</dc:creator>
<dc:creator>Kamal, M. M.</dc:creator>
<dc:creator>Hsu, C.-C.</dc:creator>
<dc:creator>Leu, J.-Y.</dc:creator>
<dc:date>2025-05-12</dc:date>
<dc:identifier>doi:10.1101/2025.05.12.652804</dc:identifier>
<dc:title><![CDATA[Spatial proteomics reveals lipid droplet reorganization in symbiotic Paramecium bursaria cells]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-05-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.05.12.653378v1?rss=1">
<title>
<![CDATA[
An early evolutionary stage of mutualistic endosymbiosis reveals a parasitic aspect of endosymbionts 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.05.12.653378v1?rss=1</link>
<description><![CDATA[
Mutualistic endosymbiosis is a cornerstone of evolutionary innovation, enabling organisms to exploit diverse niches unavailable to individual species. However, our knowledge about the early evolutionary stage of this relationship remains limited. The association between the ciliate Tetrahymena utriculariae and its algal endosymbiont Micractinium tetrahymenae indicates an incipient stage of endosymbiosis. Although T. utriculariae cells rely on endosymbiotic algae to grow in low-oxygen conditions, they gradually lose the endosymbionts in aerobic conditions. Our comparative genomics reveals that the mitochondria-related genes of T. utriculariae are fast-evolving. Symbiotic cells display elongated mitochondria, which interact intimately with endosymbionts. Moreover, inhibiting mitochondrial fatty acid oxidation reduces host fitness but increases the endosymbiont population. Time-series transcriptomics reveal physiological fine-tuning of the host during day and night, underscoring adaptations for nutrient exchange and regulation. Notably, endosymbiotic algae downregulate photosynthesis-related genes compared with free-living cells, correlated with a substantially reduced chlorophyll content. These findings indicate that the endosymbionts exploit host metabolites to supplement reduced photosynthesis. Consistently, symbiotic Tetrahymena cells exhibit lower fitness under aerobic conditions than aposymbiotic cells. Our results support that mutualistic and parasitic relationships between symbiotic organisms are condition-dependent, especially at an early evolutionary stage.
]]></description>
<dc:creator>Kamal, M. M.</dc:creator>
<dc:creator>Cheng, Y.-H.</dc:creator>
<dc:creator>Chu, L.-W.</dc:creator>
<dc:creator>Nguyen, P. T.</dc:creator>
<dc:creator>Jeff Liu, C.-F.</dc:creator>
<dc:creator>Liao, C.-W.</dc:creator>
<dc:creator>Posch, T.</dc:creator>
<dc:creator>Leu, J.-Y.</dc:creator>
<dc:date>2025-05-15</dc:date>
<dc:identifier>doi:10.1101/2025.05.12.653378</dc:identifier>
<dc:title><![CDATA[An early evolutionary stage of mutualistic endosymbiosis reveals a parasitic aspect of endosymbionts]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-05-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.05.14.653126v1?rss=1">
<title>
<![CDATA[
Five new Caenorhabditis species from Indonesia provide exceptions to Haldane's rule and partial fertility of interspecific hybrids 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.05.14.653126v1?rss=1</link>
<description><![CDATA[
Given the interest in the biogeography and diversity of the Caenorhabditis genus, we established a collection of these nematodes from field surveys on four Indonesian islands. We isolated over 60 Caenorhabditis strains belonging to ten species. Five species were previously known from other locations: C. briggsae, which was predominant, C. tropicalis, C. nigoni, C. brenneri and C. elegans. The five other species are new, and we describe them here as Caenorhabditis indonesiana, Caenorhabditis malino, Caenorhabditis ceno, Caenorhabditis brawijaya and Caenorhabditis ubi. RNA sequence analysis of 1,861 orthologous genes placed all species from Indonesia in the Elegans group of Caenorhabditis species. Four of the new species belong to a Sinica subclade of species so far only found in an East Asia-Indo-Pacific world region. The fifth new species, C. indonesiana, appears as the sister of the C. tropicalis-C. wallacei pair, both also found in Indonesia. The present findings are thus consistent with diversification in the Elegans group having occurred in this world region. Crosses between closely related species showed counterexamples to Haldanes "rule": for two pairs of species, in one cross direction we only found hybrid males. In addition, we found a pair of species that could partially interbreed: Caenorhabditis ubi (East Java) with C. sp. 41 (Solomon islands), with the hybrid males in one cross direction being fertile. Such closesly related species pairs are good models for genetic studies of incompatibilities arising during speciation.

SummaryThis work addresses their biodiversity, phylogenetic relationships and genetic incompatibilities of Caenorhabditis nematodes, which are laboratory model organisms. Through field studies, the authors isolated 60 Caenorhabditis strains in Indonesia, representing ten species, including five new. From RNA sequencing and phylogenetic reconstruction, all ten species belong to the Elegans group of Caenorhabditis. In crosses between closely related species, the hybrid progeny can be all females, abiding by Haldanes rule, but in other cases all males. In one species pair, partially fertile hybrids are produced in one cross direction. These closely related species are good models for studying genetic incompatibilities.
]]></description>
<dc:creator>Devi, M. P.</dc:creator>
<dc:creator>Haryoso, E.</dc:creator>
<dc:creator>Rais, E. I.</dc:creator>
<dc:creator>Karuniawan, A.</dc:creator>
<dc:creator>Yahya, M. Q.</dc:creator>
<dc:creator>Richaud, A.</dc:creator>
<dc:creator>Wang, J.</dc:creator>
<dc:creator>Rockman, M. V.</dc:creator>
<dc:creator>Tarno, H.</dc:creator>
<dc:creator>Felix, M.-A.</dc:creator>
<dc:date>2025-05-17</dc:date>
<dc:identifier>doi:10.1101/2025.05.14.653126</dc:identifier>
<dc:title><![CDATA[Five new Caenorhabditis species from Indonesia provide exceptions to Haldane's rule and partial fertility of interspecific hybrids]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-05-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.05.30.650902v1?rss=1">
<title>
<![CDATA[
A Ventromedial Hypothalamic Neuron Subset Encodes a Conspecific-Tuned Behavior State Driving Social Investigation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.05.30.650902v1?rss=1</link>
<description><![CDATA[
The VMHSF1 neurons encode a predator-orientated internal state that drives innate defensive responses. Although neuroanatomical studies show that male mouse VMHSF1 neurons are interconnected with structures in the social behavioral network, how VMHSF1 neurons represent stimulus and behaviors under social context remain elusive. To address the question, we employed fiber photometry and miniscope Ca2+ imaging on VMHSF1 neurons and found that VMHSF1 neurons are strongly responsive to social stimuli with a male-biased sex preference, which requires pheromonal signals and intact BNST-VMH pathway. During social interaction, VMHSF1 neurons are highly tuned to investigative yet strongly silenced by consummatory social behaviors. Notably, VMHSF1 neurons that encode defensive actions and those encoding social investigation are two distinct subpopulations. Lastly, silencing VMHSF1 neurons suppresses social investigation. Altogether, our results suggest the existence of a novel, non-defense driving VMHSF1 neurons subset that encodes conspecific social cues with sex-bias and prompts social investigation of male mice.

HighlightsO_LIA subset of VMHSF1 neurons exhibit preferential response to social cues
C_LIO_LIConspecific sex bias of VMHSF1 neurons requires pheromonal signal and BNST input
C_LIO_LISocial-tuned VMHSF1 neurons functionally encode social investigation
C_LIO_LIPredator defense and social investigation recruits distinct VMHSF1 subgroups
C_LI
]]></description>
<dc:creator>Lin, S.-C. A.</dc:creator>
<dc:creator>Hsu, J.-Y.</dc:creator>
<dc:creator>Su, T.-A.</dc:creator>
<dc:creator>Lee, H.-Z.</dc:creator>
<dc:creator>Yang, S.-B.</dc:creator>
<dc:date>2025-05-30</dc:date>
<dc:identifier>doi:10.1101/2025.05.30.650902</dc:identifier>
<dc:title><![CDATA[A Ventromedial Hypothalamic Neuron Subset Encodes a Conspecific-Tuned Behavior State Driving Social Investigation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-05-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.05.29.656761v1?rss=1">
<title>
<![CDATA[
Abnormal synaptic proteomes, impaired neural ensembles, and defective behaviors in autism mouse models are ameliorated by dietary intervention with nutrient mixtures 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.05.29.656761v1?rss=1</link>
<description><![CDATA[
Autism spectrum disorders (ASD) are a group of heterogeneous, behaviorally defined neurodevelopmental conditions influenced by both genetic and environmental factors. Here, we show that nutrients--an important environmental factor--can modulate synaptic proteomes, reconfigure neural ensembles, and improve social behaviors in ASD mouse genetic models. We analyzed Tbr1+/- mice, a well-established model of ASD, using proteomic approaches and in vivo calcium imaging. Synaptic and metabolic proteomes were found to be sensitive to Tbr1 haploinsufficiency. Our results also revealed that Tbr1 haploinsufficiency promotes hyperactivation and hyperconnectivity of basolateral amygdala (BLA) neurons, enhancing the activity correlation between individual neurons and their corresponding ensembles. Zinc, branched-chain amino acids (BCAA), and serine--all nutrients known to regulate synapse formation and activity--were then combined into supplement cocktails and administered to Tbr1+/- mice. This treatment altered synaptic and metabolic proteomes and normalized the activity and connectivity of the BLA in Tbr1+/- mice during social interactions. We further show that although a low dose of individual nutrients did not alter social behaviors, treatment with supplement cocktails containing low-dose individual nutrients improved social behaviors and associative memory of Tbr1+/- mice, implying a synergistic effect of combining low-dose zinc, BCAA, and serine. Moreover, the supplement cocktails also improved social behaviors in Nf1+/- and Cttnbp2+/M120I mice, two additional ASD mouse models. Thus, our findings reveal aberrant neural connectivity in the BLA of Tbr1+/- mice and indicate that dietary supplementation with zinc, BCAA, and/or serine offers a safe and accessible approach to mitigate neural connectivity and social behaviors across multiple ASD models.
]]></description>
<dc:creator>Huang, T.-N.</dc:creator>
<dc:creator>Lin, M.-H.</dc:creator>
<dc:creator>Hsu, T.-T.</dc:creator>
<dc:creator>Yu, C.-H.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:date>2025-06-01</dc:date>
<dc:identifier>doi:10.1101/2025.05.29.656761</dc:identifier>
<dc:title><![CDATA[Abnormal synaptic proteomes, impaired neural ensembles, and defective behaviors in autism mouse models are ameliorated by dietary intervention with nutrient mixtures]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-06-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.05.29.656861v1?rss=1">
<title>
<![CDATA[
Developmental system drift in dorsoventral patterning is linked to transitions to autonomous development in Annelida 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.05.29.656861v1?rss=1</link>
<description><![CDATA[
The Bone Morphogenetic Protein (BMP) pathway is the ancestral signalling system defining the dorsoventral axis in bilaterally symmetrical animals. However, Spiralia, a large bilaterian clade including molluscs and annelids, uses the Fibroblast Growth Factor pathway and ERK1/2 as the ancestral cue to establish their posterodorsal side. How this profound change in axial patterning evolved and what it implied for BMPs developmental role remains elusive. Here, we studied four annelid species and combined disruption of the BMP and Activin/Nodal pathways with transcriptomics and blastomere deletions to demonstrate that BMP is ancestrally downstream of ERK1/2 and promotes dorsoventral development in Spiralia. Importantly, this signalling hierarchy is lost in annelids that secondarily transitioned into a maternally controlled, autonomous development. While some, like Capitella teleta, use Activin/Nodal, Platynereis dumerilii relies on BMP to establish dorsoventral polarity only in the head.

Unexpectedly, this divergence in upstream axial regulators implied extensive rewiring of downstream targets, as inferred by comparing C. teleta and Owenia fusiformis. Our data clarify the ancestral axial role for BMP in Spiralia, unveiling a potential causal link between parallel shifts to autonomous cell-fate specification in early development and the emergence of developmental system drift, a pervasive yet poorly understood phenomenon in animal embryogenesis.
]]></description>
<dc:creator>Carrillo-Baltodano, A. M.</dc:creator>
<dc:creator>Haillot, E.</dc:creator>
<dc:creator>Meha, S. M.</dc:creator>
<dc:creator>Luqman, I.</dc:creator>
<dc:creator>Pashaj, A.</dc:creator>
<dc:creator>Lee, Y.-J.</dc:creator>
<dc:creator>Lu, T.-M.</dc:creator>
<dc:creator>Ferrier, D. E. K.</dc:creator>
<dc:creator>Schneider, S. Q.</dc:creator>
<dc:creator>Martin-Duran, J. M.</dc:creator>
<dc:date>2025-06-01</dc:date>
<dc:identifier>doi:10.1101/2025.05.29.656861</dc:identifier>
<dc:title><![CDATA[Developmental system drift in dorsoventral patterning is linked to transitions to autonomous development in Annelida]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-06-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.06.16.658187v1?rss=1">
<title>
<![CDATA[
Orphan nuclear receptors recruit TRIM28 to promote telomeric H3K9me3 for the alternative lengthening of telomeres pathway 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.06.16.658187v1?rss=1</link>
<description><![CDATA[
Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism deployed in embryonic stem cells and cancer cells. High levels of the heterochromatin mark H3 lysine 9 trimethylation (H3K9me3) at telomeres are critical for ALT, but how that is achieved remains unclear. Telomeric association of orphan nuclear receptors (NRs)--such as COUP-TF1, COUP-TF2, TR2, and TR4--has been shown previously to promote ALT activation. Here, we show that orphan NRs regulate telomeric H3K9me3 through TRIM28, a corepressor of ZNF transcription factors, to drive ALT. We report that H3K9me3 is induced by telomeric association of orphan NRs in cultured human fibroblast and ALT cancer cell lines. Moreover, TRIM28 is required for the orphan NR-induced H3K9me3 and ALT phenotypes. Importantly, physical interaction of TRIM28 with orphan NRs facilitates a telomeric localization of TRIM28. A TRIM28 variant defective in orphan NR interaction fails to localize to telomeres and is unable to promote H3K9me3 and ALT phenotypes. These findings indicate that telomeric orphan NRs recruit TRIM28, driving telomeric H3K9me3 and ALT activation, emphasizing the role of changes in chromatin structure in ALT activation.
]]></description>
<dc:creator>Tsai, C.-T.</dc:creator>
<dc:creator>Gaela, V. M.</dc:creator>
<dc:creator>Hsia, H.-Y.</dc:creator>
<dc:creator>Huang, Y.-C.</dc:creator>
<dc:creator>Chen, L.-Y.</dc:creator>
<dc:date>2025-06-19</dc:date>
<dc:identifier>doi:10.1101/2025.06.16.658187</dc:identifier>
<dc:title><![CDATA[Orphan nuclear receptors recruit TRIM28 to promote telomeric H3K9me3 for the alternative lengthening of telomeres pathway]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-06-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.06.23.660925v1?rss=1">
<title>
<![CDATA[
Evaluation of Multiplexed Liquid Glycan Array (LiGA) for Serological Detection of Glycan-binding Antibodies 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.06.23.660925v1?rss=1</link>
<description><![CDATA[
We test the performance of the multiplexed liquid glycan array (LiGA) technology in serological assays. Specifically, we use LiGA to detect ABO blood group antibodies in human serum. This LiGA, which we name ABO-LiGA, contains ABO blood group trisaccharide glycans with an ethylazido aglycone conjugated to groups of ten multi-barcoded M13 particles carrying dibenzocyclooctyne (DBCO) on p8 proteins. ELISA clonal binding assays to anti-A/B antibodies confirmed the functional performance of ABO-clones and aligned with next-generation sequencing (NGS) of the mixed clones. Multiple DNA-barcoded technical replicates in LiGA allow for quantification of reproducibility and robustness as determined by the Z-score using NGS. We then tested ABO-LiGA for specific detection of IgG and IgM anti-A and anti-B IgG and IgM antibodies in human serum samples. Comparison of antibody binding responses in sera from 31 healthy donors to ABO-LiGA with an ABO-Luminex-based method revealed consistent responses to LiGA-ABO but also minor deficiencies of ABO-LiGA such as low robustness of the current assay format and a limited ability to detect low intensity antibody responses. Some results point to undesired interactions of serum antibodies with small-footprint glycans conjugated to phage via the bulky DBCO moiety. This report illuminates the path for future development of LiGA-based serological assays and suggests the need to develop alternative methods for conjugating glycans to phage to avoid liabilities of the hydrophobic DBCO moiety.
]]></description>
<dc:creator>Reddy, R.</dc:creator>
<dc:creator>Carpenter, E. J.</dc:creator>
<dc:creator>Halpin, A.</dc:creator>
<dc:creator>Sojitra, M.</dc:creator>
<dc:creator>Peng, C.</dc:creator>
<dc:creator>Lima, G. M.</dc:creator>
<dc:creator>Xue, X.</dc:creator>
<dc:creator>Yan, K.</dc:creator>
<dc:creator>Pearcy, J.</dc:creator>
<dc:creator>Ellis, M.</dc:creator>
<dc:creator>Motyka, B.</dc:creator>
<dc:creator>Lowary, T. L.</dc:creator>
<dc:creator>West, L. J.</dc:creator>
<dc:creator>Derda, R.</dc:creator>
<dc:date>2025-06-27</dc:date>
<dc:identifier>doi:10.1101/2025.06.23.660925</dc:identifier>
<dc:title><![CDATA[Evaluation of Multiplexed Liquid Glycan Array (LiGA) for Serological Detection of Glycan-binding Antibodies]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-06-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.06.27.662017v1?rss=1">
<title>
<![CDATA[
Single-cell-resolved calcium and organelle dynamics in resistosome-mediated cell death 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.06.27.662017v1?rss=1</link>
<description><![CDATA[
Plant nucleotide-binding domain leucine-rich repeat-containing (NLR) proteins act as intracellular immune receptors that assemble into resistosomes to execute immune responses. However, the subcellular processes during cell death following resistosome activation remain unclear. Here, we visualized the changes in calcium signaling and organelle behavior after activation of the NRC4 (NLR-required for cell death 4) resistosome. We found that NRC4 membrane enrichment coincided with calcium influx. This is followed by sequential mitochondria and plastid disruption, endoplasmic reticulum fragmentation and cytoskeleton depolymerization. Subsequent loss of plasma membrane integrity, nuclear shrinkage, and vacuolar collapse mark the terminal stage of cell death. Our findings reveal a spatiotemporally-resolved cascade of subcellular events downstream of resistosome activation, providing new mechanistic insight into the execution phase of plant immune cell death.
]]></description>
<dc:creator>Chen, Y.-F.</dc:creator>
<dc:creator>Lin, K.-Y.</dc:creator>
<dc:creator>Huang, C.-Y.</dc:creator>
<dc:creator>Hou, L.-Y.</dc:creator>
<dc:creator>Yuen, E. L. H.</dc:creator>
<dc:creator>Sun, W.-C. J.</dc:creator>
<dc:creator>Chiang, B.-J.</dc:creator>
<dc:creator>Chang, C.-W.</dc:creator>
<dc:creator>Wang, H.-Y.</dc:creator>
<dc:creator>Bozkurt, T. O.</dc:creator>
<dc:creator>Wu, C.-H.</dc:creator>
<dc:date>2025-07-01</dc:date>
<dc:identifier>doi:10.1101/2025.06.27.662017</dc:identifier>
<dc:title><![CDATA[Single-cell-resolved calcium and organelle dynamics in resistosome-mediated cell death]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.07.02.662275v1?rss=1">
<title>
<![CDATA[
Deconstructing the common anteroposterior organisation of adult bilaterian guts 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.07.02.662275v1?rss=1</link>
<description><![CDATA[
A through-gut is one of the major features of bilaterians. Comparative work among bilaterians has identified common molecular mechanisms during early gut patterning, but the primordial gut later often undergoes different degrees of reorganization in each lineage to form a fully differentiated adult gut with specializations along its anteroposterior (AP) axis. Yet, how the conserved embryonic gut AP pattern relates to the adult guts in diverse bilaterians after metamorphosis is still poorly understood. To unravel the molecular subdivisions of adult guts, we investigated the gut through transcriptomic analyses of five phylogenetically informative species, an annelid, a sea urchin, a hemichordate, a cephalochordate, and a vertebrate. We identified bipartite transcriptional programs defining the AP functional subdivisions. Patterning systems composed of Hox, Parahox, and, surprisingly, other transcription factors (TFs) known to be involved in gut formation in sea urchin larvae are maintained in these adult tissues. Using unbiased analyses, we identified five conserved TF modules corresponding to the AP compartments of the guts that are elaborated or shifted in different species. Our study inferred conserved and modified adult AP patterning modules along bilaterian guts enabling the reconstruction of ancestral bilaterian features with profound implications for the evolution of the bilaterian body plan.
]]></description>
<dc:creator>Vianello, S. D.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Pinem, W. C.</dc:creator>
<dc:creator>Li, H.-R.</dc:creator>
<dc:creator>Li, K.-L.</dc:creator>
<dc:creator>Sonia, G.</dc:creator>
<dc:creator>Lee, S.-H.</dc:creator>
<dc:creator>Wu, S.-K.</dc:creator>
<dc:creator>Laudet, V.</dc:creator>
<dc:creator>Su, Y.-H.</dc:creator>
<dc:creator>Yu, J.-K.</dc:creator>
<dc:creator>Schneider, S. Q.</dc:creator>
<dc:date>2025-07-03</dc:date>
<dc:identifier>doi:10.1101/2025.07.02.662275</dc:identifier>
<dc:title><![CDATA[Deconstructing the common anteroposterior organisation of adult bilaterian guts]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-07-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.07.05.663277v1?rss=1">
<title>
<![CDATA[
Virus-induced upregulation of mitochondrial metabolism modulates cytosolic redox balance and defense responses 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.07.05.663277v1?rss=1</link>
<description><![CDATA[
Plants possess a remarkable capacity to reprogram their metabolism in response to pathogen attacks. However, the mechanisms by which metabolic reprogramming modulates defense signaling remain poorly understood. In this study, we leverage a multifaceted omics approach to investigate the metabolic shifts induced by the Bamboo mosaic virus (BaMV), a positive-sense single-stranded RNA virus that depends on host factors from multiple organelles for its replication. Metabolic profiling revealed an accumulation of hexose phosphates and Krebs cycle intermediates in Nicotiana benthamiana plants following BaMV infection. Fluxomic analysis uncovered an orchestrated redirection of metabolic flux toward glycolysis and the Krebs cycle during infection. Proteomic data further highlighted a concerted upregulation of mitochondrial enzymes, with three mitochondrial proteins showing markedly increased accumulation in BaMV-infected tissues. These integrated omics results suggest that BaMV infection triggers a metabolic shift toward energy-generating pathways. Notably, functional analysis revealed that silencing mitochondrial NAD+-dependent malic enzyme 1 significantly enhanced BaMV accumulation, accompanied by alterations in cytoplasmic NADH-to-NAD+ ratio and changes in the landscape of defense gene expression. Collectively, our findings underscore the pivotal role of mitochondrial metabolism in governing cytoplasmic redox balance, finely tuning defense responses to viral infection.

One sentence summaryBaMV infection enhances mitochondrial metabolism to regulate cytoplasmic redox balance and promote antiviral defense.
]]></description>
<dc:creator>Hou, L.-Y.</dc:creator>
<dc:creator>Wu, C.-H.</dc:creator>
<dc:creator>Lin, N.-S.</dc:creator>
<dc:date>2025-07-06</dc:date>
<dc:identifier>doi:10.1101/2025.07.05.663277</dc:identifier>
<dc:title><![CDATA[Virus-induced upregulation of mitochondrial metabolism modulates cytosolic redox balance and defense responses]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-07-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.07.07.663451v1?rss=1">
<title>
<![CDATA[
Genetic Network Shaping Kenyon Cell Identity and Function in Drosophila Mushroom Bodies 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.07.07.663451v1?rss=1</link>
<description><![CDATA[
Revealing the molecular mechanisms underlying neuronal specification and acquisition of specific functions is key to understanding how the nervous system is constructed. In the Drosophila brain, Kenyon cells (KCs) are sequentially generated to assemble the backbone of the mushroom body (MB). Broad-complex, tramtrack and bric-{square}-brac zinc finger transcription factors (BTBzf TFs) specify early-born KCs, whereas the essential TFs for specifying late-born KCs remain unidentified. Here, we report that Pipsqueak domain-containing TF Eip93F promotes the identity of late-born KCs by reciprocally regulating gene expression in main KC types. Moreover, Eip93F not only regulates the expression of calcium channel Ca-1T in late-born KCs to functionally control animal behavior, but it also forms a genetic network with BTBzf TFs to specify the identities of main KC types. Our study provides crucial information linking KC-type diversification to unique function acquisition in the adult MB.
]]></description>
<dc:creator>Chung, P.-C.</dc:creator>
<dc:creator>Ku, K.-Y.</dc:creator>
<dc:creator>Chu, S.-Y.</dc:creator>
<dc:creator>Chen, C.</dc:creator>
<dc:creator>Yu, H.-H.</dc:creator>
<dc:date>2025-07-09</dc:date>
<dc:identifier>doi:10.1101/2025.07.07.663451</dc:identifier>
<dc:title><![CDATA[Genetic Network Shaping Kenyon Cell Identity and Function in Drosophila Mushroom Bodies]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-07-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.07.10.664269v1?rss=1">
<title>
<![CDATA[
A Hierarchical Robust Linear Model for Cryo-EM Map Analysis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.07.10.664269v1?rss=1</link>
<description><![CDATA[
Cryo-electron microscopy (cryo-EM) has become a pivotal tool for determining the atomic structures of biological macromolecules. In this study, we introduce a robust hierarchical linear (RHL) model to estimate key atom-specific parameters: the amplitude and width of Gaussian functions, which are typically simplified using uniform widths and amplitudes scaled by atomic number in cryo-EM map related studies. Our RHL framework incorporates minimum density power divergence estimation (MDPDE) to account for heteroscedasticity and enhance robustness against outliers. Through both simulation studies and real data analysis, we demonstrate that the proposed method effectively reduces the influence of outliers and yields reliable parameter estimates. When applied to cryo-EM data of human apoferritin (PDB ID: 6Z6U; EMDB ID: 11103), our model reveals that the estimated Gaussian parameters are stable across most amino acids, with nitrogen atoms consistently displaying lower amplitude and width values than predicted by conventional Gaussian modeling. These results underscore the need for a systematic analysis of paired cryo-EM maps and atomic models from the EMDB and PDB to gain deeper insights into atom-specific features embedded in cryo-EM data.
]]></description>
<dc:creator>Tu, I.-P.</dc:creator>
<dc:creator>Zheng, S.-C.</dc:creator>
<dc:creator>Lien, Y.-H.</dc:creator>
<dc:creator>Lin, S. H.</dc:creator>
<dc:creator>Lin, P.-C.</dc:creator>
<dc:creator>Chang, W.-H.</dc:creator>
<dc:date>2025-07-14</dc:date>
<dc:identifier>doi:10.1101/2025.07.10.664269</dc:identifier>
<dc:title><![CDATA[A Hierarchical Robust Linear Model for Cryo-EM Map Analysis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-07-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.07.14.664264v1?rss=1">
<title>
<![CDATA[
A plant pathogen effector blocks stepwise assembly of a helper NLR resistosome 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.07.14.664264v1?rss=1</link>
<description><![CDATA[
Helper NLRs function as central nodes in plant immune networks. Upon activation, they oligomerize into inflammasome-like resistosomes to initiate immune signaling, yet the dynamics of resistosome assembly remain poorly understood. Here, we show that the virulence effector AVRcap1b from the Irish potato famine pathogen Phytophthora infestans suppresses immune activation by directly engaging oligomerization intermediates of the tomato helper NLR SlNRC3. Cryo-EM structures of SlNRC3 in AVRcap1b-bound and unbound states reveal that AVRcap1b bridges multiple protomers, stabilizing a stalled intermediate and preventing formation of a functional resistosome. Leveraging AVRcap1b as a molecular tool, we also capture an additional SlNRC3 resistosome intermediate showing that assembly proceeds in a stepwise manner from dissociated monomers. These findings uncover a previously unrecognized vulnerability in NLR activation and reveal a pathogen strategy that disrupts immune complex assembly. This work advances mechanistic understanding of resistosome formation and uncovers a previously unrecognized facet of pathogen-plant coevolution.
]]></description>
<dc:creator>Seager, B. A.</dc:creator>
<dc:creator>Harant, A.</dc:creator>
<dc:creator>Contreras, M. P.</dc:creator>
<dc:creator>Hou, L.-Y.</dc:creator>
<dc:creator>Wu, C.-H.</dc:creator>
<dc:creator>Kamoun, S.</dc:creator>
<dc:creator>Madhuprakash, J.</dc:creator>
<dc:date>2025-07-14</dc:date>
<dc:identifier>doi:10.1101/2025.07.14.664264</dc:identifier>
<dc:title><![CDATA[A plant pathogen effector blocks stepwise assembly of a helper NLR resistosome]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-07-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.07.14.664838v1?rss=1">
<title>
<![CDATA[
Fine-tuning RIPENING INHIBITOR (RIN) expression by introducing allelic mutations in its promoter using CRISPR/Cas9 multiplex editing 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.07.14.664838v1?rss=1</link>
<description><![CDATA[
Tomato is one of the most produced and consumed vegetables globally due to its nutritional benefits, sensory characteristics, and cultural importance. However, tomato fruit has a short shelf-life, which can be extended by postharvest techniques, but often at the expense of fruit quality, leading to consumer dissatisfaction. To address this challenge, we modified the upstream regulatory regions of Ripening inhibitor (RIN), a master regulator of tomato fruit ripening, utilizing a CRISPR/Cas9 multiplex system. This approach enabled the creation of a population of tomato fruit with mutations of varying severity, which could have far-reaching effects on the RIN-induced gene regulatory network in tomato fruit, leading to downstream changes in fruit traits. We have generated 264 first-generation (T0) transgenic lines of RIN promoter mutants with diverse genetic lesions and RIN transcriptional levels. Our study revealed a non-linear relationship between promoter mutations and gene expression, highlighting the potential roles of certain types of mutations in regulating RIN transcription. Future work will focus on evaluating fruit traits from mutants with pronounced changes in RIN expression, as well as performing transcriptomic analysis to explore the mechanisms underlying fruit quality modifications due to genome editing.
]]></description>
<dc:creator>Zhou, J.</dc:creator>
<dc:creator>Yang, C.-L.</dc:creator>
<dc:creator>Beckles, D. M.</dc:creator>
<dc:date>2025-07-18</dc:date>
<dc:identifier>doi:10.1101/2025.07.14.664838</dc:identifier>
<dc:title><![CDATA[Fine-tuning RIPENING INHIBITOR (RIN) expression by introducing allelic mutations in its promoter using CRISPR/Cas9 multiplex editing]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-07-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.07.21.665930v1?rss=1">
<title>
<![CDATA[
The genome of the early diverged amphioxus, Asymmetron lucayanum, illuminates the evolution of genome architecture and gene repertoires in cephalochordates 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.07.21.665930v1?rss=1</link>
<description><![CDATA[
Cephalochordates (amphioxus or lancelet) are considered as living proxies for ancestral chordates due to their key phylogenetic position and slow evolutionary rate. The genomes of living amphioxus thus can help to reveal the genetic basis shaping the evolutionary transition from invertebrates to vertebrates. To gain a comprehensive understanding of the genome architecture in amphioxus, here we generate a chromosome-anchored genome assembly for Asymmetron lucaynum, representing the earliest diverging cephalochordate genus. Our results show that Asymmetron has an enlarged genome compared to those of the other four cephalochordate genomes decoded so far (all in the genus Branchiostoma), causing by pervasive expansions of inter-genic transposable elements (TEs). Nevertheless, both macrosynteny and microsynteny remain highly conserved between Asymmetron and Branchiostoma, enabling reconstruction of the ancestral genomic architecture of the Cephalochordate lineage for tracing genome evolutionary process during Deuterostome and Chordate diversification. By coupling developmental transcriptomic analyses, we further show that purifying selection and constraints on co-transcriptional regulation may have contributed to the maintenance of the conserved microsynteny blocks among cephalochordate species. We also examine the evolutionary history of Hox cluster in cephalochordates and vertebrates, and identify species-specific inversions and TE invasions at this important locus in both Asymmetron and Branchiostoma. Finally, we survey key gene families involved in both innate and adaptive immunity (e.g., TLR, NLR, MHC, and RAG) and uncover their plausible ancestry and evolutionary dynamics in chordates. Taken together, our findings illuminate the genome and gene evolution of cephalochordates and provide valuable resources for understanding the early evolution of chordates and the origin of vertebrates.
]]></description>
<dc:creator>Ren, Y.</dc:creator>
<dc:creator>Miao, Z.</dc:creator>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Yang, L.</dc:creator>
<dc:creator>Li, H.</dc:creator>
<dc:creator>Holland, L. Z.</dc:creator>
<dc:creator>Cho, S.-J.</dc:creator>
<dc:creator>Yu, J.-K.</dc:creator>
<dc:creator>Yue, J.-X.</dc:creator>
<dc:date>2025-07-22</dc:date>
<dc:identifier>doi:10.1101/2025.07.21.665930</dc:identifier>
<dc:title><![CDATA[The genome of the early diverged amphioxus, Asymmetron lucayanum, illuminates the evolution of genome architecture and gene repertoires in cephalochordates]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-07-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.07.21.666031v1?rss=1">
<title>
<![CDATA[
Temporal coordination of tissue transformation, olfactory sensory neural development and central axon projections through morphogens 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.07.21.666031v1?rss=1</link>
<description><![CDATA[
During development, sensory neurons arise in the peripheral sensory organ in close spatial and temporal coordination with the dynamic morphological transformation of the sensory organ in the central nervous system. Moreover, intricate coordination exists between the peripheral map and the central map. Yet, it remains largely unclear what mechanisms are responsible for orchestrating such coordination and whether these mechanisms might be evolutionarily conserved. Here, we performed a systematic analysis of the sensory organ transformation process, defining the expression patterns of morphogens and their receptors at multiple developmental stages and creating receptor mutants in sensory neurons and projections. These experiments revealed combinatorial codes of morphogens that are utilized to coordinate sensory circuit development. Remarkably, two distinct strategies were likely deployed by different morphogen families, including a two-step strategy (same ligand from different sources at two different stages) and a ligand switch strategy (different ligands at two different stages).

Significance StatementTissue transformation, dissociation and integration occur in all species. However, it remains largely unclear how such transformations are coordinated with cell fate determination, local cell migration and axonal guidance both temporally and spatially. We found Drosophila antennal discs undergo a series of tissue transformation steps to develop a three-dimensional structure from a two-dimensional neuroepithelium. During this tissue transformation, olfactory sensory neurons acquire their distinct cell types and project their axons to specific targets in the antennal lobe. The whole process is temporally and spatially coordinated by combinatorial codes of morphogens.
]]></description>
<dc:creator>Chen, S.-C.</dc:creator>
<dc:creator>Lu, T.-M.</dc:creator>
<dc:creator>Lin, C.-T.</dc:creator>
<dc:creator>Low, I. Z. Q.</dc:creator>
<dc:creator>Chou, Y.-H.</dc:creator>
<dc:date>2025-07-22</dc:date>
<dc:identifier>doi:10.1101/2025.07.21.666031</dc:identifier>
<dc:title><![CDATA[Temporal coordination of tissue transformation, olfactory sensory neural development and central axon projections through morphogens]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-07-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.07.22.666114v1?rss=1">
<title>
<![CDATA[
Regulation of mRNA polyadenylation governs mammalian body plan formation in gastruloids 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.07.22.666114v1?rss=1</link>
<description><![CDATA[
The establishment of the body plan during gastrulation represents a hallmark of animal life. It emerges from the interplay of gene-regulatory programs and positional cues, yet how these signals are integrated post-transcriptionally remains largely unexplored. Here, we combine the scalability of mouse gastruloids with a single-cell CRISPR screening platform to functionally dissect germ layer specification at single-cell transcriptomic resolution. Focusing on post-transcriptional regulation, we systematically map drivers of mesodermal and endodermal fate and identify the deadenylase Cnot8. Loss of Cnot8 leads to widespread poly(A) tail elongation and transcript stabilization, shifting mesoderm differentiation toward ectopic notochord fate, thereby profoundly impacting axial patterning. Collectively, our findings identify mRNA deadenylation as a fundamental mechanism linking cellular identity with morphogenetic signaling during mammalian body plan formation.
]]></description>
<dc:creator>Taborsky, D.</dc:creator>
<dc:creator>Valdivia-Francia, F.</dc:creator>
<dc:creator>Ranjbar, N.</dc:creator>
<dc:creator>Llop-Grau, L.</dc:creator>
<dc:creator>Dure, C.</dc:creator>
<dc:creator>Ghoshdastider, U.</dc:creator>
<dc:creator>Renz, P. F.</dc:creator>
<dc:creator>Weber, R.</dc:creator>
<dc:creator>Yigit, M.</dc:creator>
<dc:creator>Mironov, A.</dc:creator>
<dc:creator>Hyams, K.</dc:creator>
<dc:creator>Vianello, S.</dc:creator>
<dc:creator>Zavolan, M.</dc:creator>
<dc:creator>Lutolf, M. P.</dc:creator>
<dc:creator>Sendoel, A.</dc:creator>
<dc:date>2025-07-22</dc:date>
<dc:identifier>doi:10.1101/2025.07.22.666114</dc:identifier>
<dc:title><![CDATA[Regulation of mRNA polyadenylation governs mammalian body plan formation in gastruloids]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-07-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.07.25.666797v1?rss=1">
<title>
<![CDATA[
The Multifaceted Role of EXOC6A in Ciliogenesis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.07.25.666797v1?rss=1</link>
<description><![CDATA[
Ciliogenesis is a highly ordered process that requires membrane trafficking, fusion, and maturation. In this study, we investigated EXOC6A, a component of the exocyst complex known for secretory vesicle trafficking and fusion, and found that it interacts with myosin-Va (Myo-Va) during ciliogenesis. EXOC6A colocalizes with Myo-Va at various stages of ciliogenesis, including preciliary vesicles, ciliary vesicles (CVs), and ciliary sheath membrane during ciliogenesis. We found that EXOC6A vesicles are actively recruited, integrated, and exit from the CVs and the ciliary sheath, implying that EXOC6A vesicles may facilitate continuous cilia membrane remodeling during ciliogenesis. Importantly, EXOC6A knockout impairs ciliogenesis, arresting most cells at the CV stage and preventing recruitment of NPHP and MKS module components to the transition zone. Furthermore, EXOC6A vesicles are transported to the mother centriole via a dynein-, microtubule-, and actin-dependent mechanism. Our results suggest that EXOC6A functions in both early and late stages of ciliogenesis and is involved in orchestrating vesicle dynamics, cilia membrane remodeling, and formation.
]]></description>
<dc:creator>Tang, T. K.</dc:creator>
<dc:creator>Wu, C.-T.</dc:creator>
<dc:creator>Lin, T.-L.</dc:creator>
<dc:date>2025-07-26</dc:date>
<dc:identifier>doi:10.1101/2025.07.25.666797</dc:identifier>
<dc:title><![CDATA[The Multifaceted Role of EXOC6A in Ciliogenesis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-07-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.07.28.667269v1?rss=1">
<title>
<![CDATA[
A sensitive orange fluorescent calcium ion indicator for imaging neural activity 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.07.28.667269v1?rss=1</link>
<description><![CDATA[
Genetically encoded calcium indicators (GECIs) are vital tools for fluorescence-based visualization of neuronal activity with high spatial and temporal resolution. However, current highest-performance GECIs are predominantly green or red fluorescent, limiting multiplexing options and efficient excitation with fixed-wavelength femtosecond lasers operating at 1030 nm. Here, we introduce OCaMP (also known as O-GECO2), an orange fluorescent GECI engineered from O-GECO1 through targeted substitutions to improve calcium affinity while retaining the favorable photophysical properties of mOrange2. OCaMP exhibits improved two-photon cross-section, responsiveness, photostability, and calcium affinity relative to O-GECO1. In cultured neurons, zebrafish, and mouse cortex, OCaMP outperforms the red GECIs jRCaMP1a and jRGECO1a in sensitivity, kinetics, and signal-to-noise ratio. These properties establish OCaMP as a robust tool for high-fidelity neural imaging optimized for 1030 nm excitation and a compromise-free option within the spectral gap between existing green and red GECIs.
]]></description>
<dc:creator>Aggarwal, A.</dc:creator>
<dc:creator>Baker, H. A.</dc:creator>
<dc:creator>Durst, C. D.</dc:creator>
<dc:creator>Chen, I.-W.</dc:creator>
<dc:creator>de Chambrier, P.</dc:creator>
<dc:creator>Gonzales, J. M.</dc:creator>
<dc:creator>Marvin, J. S.</dc:creator>
<dc:creator>Vandal, M.</dc:creator>
<dc:creator>Lundberg, T.</dc:creator>
<dc:creator>Sakoi, K.</dc:creator>
<dc:creator>Patel, R. H.</dc:creator>
<dc:creator>Wang, C.-Y.</dc:creator>
<dc:creator>Visser, F.</dc:creator>
<dc:creator>Fouad, Y.</dc:creator>
<dc:creator>Sunil, S.</dc:creator>
<dc:creator>Wiens, M.</dc:creator>
<dc:creator>Terai, T.</dc:creator>
<dc:creator>Takahashi-Yamashiro, K.</dc:creator>
<dc:creator>Thompson, R. J.</dc:creator>
<dc:creator>Brown, T. A.</dc:creator>
<dc:creator>Nasu, Y.</dc:creator>
<dc:creator>Nguyen, M. D.</dc:creator>
<dc:creator>Gordon, G. R. J.</dc:creator>
<dc:creator>McFarlane, S.</dc:creator>
<dc:creator>Podgorski, K.</dc:creator>
<dc:creator>Holtmaat, A.</dc:creator>
<dc:creator>Campbell, R. E.</dc:creator>
<dc:creator>Lohman, A. W.</dc:creator>
<dc:date>2025-07-31</dc:date>
<dc:identifier>doi:10.1101/2025.07.28.667269</dc:identifier>
<dc:title><![CDATA[A sensitive orange fluorescent calcium ion indicator for imaging neural activity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-07-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.08.08.669258v1?rss=1">
<title>
<![CDATA[
Two pore domain THIK2 channel is involved in acute and chronic pain signal regulation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.08.08.669258v1?rss=1</link>
<description><![CDATA[
Two-pore domain potassium channels (K2P) regulate neuronal excitability by acting as hyperpolarizing leak channels. Among them, THIK2 remain poorly characterized. Although no study has yet clearly linked them to excitability or pain, their selective expression in nociceptive neurons of the Dorsal Root Ganglia (DRG) suggests a role in nociception and pain regulation. This project investigates THIK2 channels in pain pathophysiology through molecular, electrophysiological, and behavioral approaches. We mapped THIK expression patterns and in THIK2 knock-out mice, we examined DRG neuron excitability and pain sensitivity. Results reveal thermal hypersensitivity under both naive and inflammatory conditions, indicating that THIK2 normally limits neuronal hyperexcitability. These findings position THIK2 as a potential therapeutic target in chronic inflammatory pain, with peripheral inhibition potentially offering analgesia without central opioid side effects.
]]></description>
<dc:creator>Gilbert, N.</dc:creator>
<dc:creator>Chatelain, F. C.</dc:creator>
<dc:creator>Gibaud, S.</dc:creator>
<dc:creator>Lorivel, T.</dc:creator>
<dc:creator>Shen, Y.-L.</dc:creator>
<dc:creator>kerros, M.-E.</dc:creator>
<dc:creator>Feliciangeli, S.</dc:creator>
<dc:creator>Fiore, F.</dc:creator>
<dc:creator>Chen, C.-C.</dc:creator>
<dc:creator>Lesage, F.</dc:creator>
<dc:creator>Delphine, B.</dc:creator>
<dc:date>2025-08-12</dc:date>
<dc:identifier>doi:10.1101/2025.08.08.669258</dc:identifier>
<dc:title><![CDATA[Two pore domain THIK2 channel is involved in acute and chronic pain signal regulation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-08-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.08.08.669265v1?rss=1">
<title>
<![CDATA[
Distinct Flower signaling domains orchestrate cellular fitness via secreted vesicles in Aβ-induced neurodegeneration 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.08.08.669265v1?rss=1</link>
<description><![CDATA[
Cellular fitness surveillance preserves tissue integrity, yet its regulation within the mammalian brain remains poorly understood. We identify a bifurcated mechanism in the transmembrane protein Flower--encoding both survival-promoting ("win") and apoptosis-inducing ("lose") isoforms. We demonstrate that astrocytes secrete specialized extracellular vesicles (EVs), termed "fitness vesicles," carrying Flower to facilitate competitive selection across distal cell populations. The N-terminal Flower domain acts extrinsically via these EVs to drive the elimination of less-fit neighbors. Conversely, the "win"-specific C-terminal domain functions as a cell-intrinsic module; it translocates to the nucleus under stress to repress Caspase-3 and provide resilience. In Alzheimers disease (AD) models and human AD brains, Flower-positive astrocytes accumulate around amyloid-{beta} (A{beta}) plaques. Under A{beta} stress, the "win" isoform reprograms astrocytes toward a neuroprotective state that enhances plaque clearance while ensuring cell-intrinsic survival. Our findings reveal how Flower couples long-range, EV-mediated cellular selection with cell-autonomous protection to coordinate astrocyte quality control and tissue resilience in neurodegeneration.
]]></description>
<dc:creator>Chang, H.-F.</dc:creator>
<dc:creator>Tu, S.-M.</dc:creator>
<dc:creator>Lin, C.-H.</dc:creator>
<dc:creator>Liu, Y.</dc:creator>
<dc:creator>Hohneck, J.</dc:creator>
<dc:creator>Jung, M.</dc:creator>
<dc:creator>Clemenz, A.</dc:creator>
<dc:creator>Rother, S.</dc:creator>
<dc:creator>Schirra, C.</dc:creator>
<dc:creator>Schwarz, Y.</dc:creator>
<dc:creator>Krause, E.</dc:creator>
<dc:creator>Schulz-Schaeffer, W. J.</dc:creator>
<dc:creator>Flockerzi, V.</dc:creator>
<dc:creator>Yao, C.-K.</dc:creator>
<dc:date>2025-08-12</dc:date>
<dc:identifier>doi:10.1101/2025.08.08.669265</dc:identifier>
<dc:title><![CDATA[Distinct Flower signaling domains orchestrate cellular fitness via secreted vesicles in Aβ-induced neurodegeneration]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-08-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.08.20.671209v1?rss=1">
<title>
<![CDATA[
Multigram-scale stereoselective synthesis of neurosteroid isomers by gut microbial isolates using plant biomass-derived medium 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.08.20.671209v1?rss=1</link>
<description><![CDATA[
Neurosteroids are vital therapeutics for mood disorders, with FDA-approved allopregnanolone (Zulresso) for postpartum depression and zuranolone for major depressive disorder representing breakthrough treatments. However, current production methods rely on costly animal-derived sources or non-stereoselective chemical synthesis that require extensive chiral purification steps. Here, we present a sustainable microbial platform utilizing gut bacteria and a completely plant-based medium for stereoselective neurosteroid biosynthesis. Through bioinformatics- and structural biology-guided screening of more than 3000 bacterial isolates, we identified three anaerobic gut strains exhibiting distinct stereospecificities: Holdemania filiformis produces isopregnanolone (3{beta}-hydroxy-5-pregnan-20-one), Clostridium innocuum generates epipregnanolone (3{beta}-hydroxy-5{beta}-pregnan-20-one), and Hungatella effluvii synthesizes pregnanolone (3-hydroxy-5{beta}-pregnan-20-one). We developed Molasses-Okara Medium (MOM), a fully plant-derived composite medium combining sugarcane molasses with enzymatically hydrolyzed okara devoid of animal-derived components. In multigram batch whole-cell biotransformation trials using MOM, we achieved >95% progesterone conversion into target neurosteroid isomers. The inherent stereoselectivity of these whole-cell biotransformations bypasses downstream chiral chromatographic separation, enabling pharmaceutical-grade product recovery through a simple open-column purification. Compared to using peptone-yeast-glucose media for whole-cell biotransformation, MOM reduced production costs by 90% and carbon footprint by 95% that embodies sustainable bioeconomy principles in pharmaceutical biotechnology.

Technology Readiness BoxWe argue that this gut microbiota-derived neurosteroid bioproduction technology has reached a Technology Readiness Level (TRL) of 4, having been validated in laboratory environments with the demonstrated multigram-scale synthesis of high-purity neurosteroids. The platform integrates stereoselective bacterial isolates (Holdemania filiformis, Clostridium innocuum, and Hungatella effluvii) with a sustainable plant-based fermentation medium (molasses-okara medium), achieving >90% progesterone conversion efficiency, >99.9% stereochemical purity, and the successful production of 0.7-0.9 g of neurosteroids per gram of progesterone across multiple 1 L fed-batch fermentations. Compared with conventional chemical synthesis approaches that require expensive chiral catalysts and multi-step purification, this microbial platform offers inherent stereoselectivity while eliminating animal-derived media components. Despite these advantages, several challenges remain for industrial implementation, including scale-up validation beyond laboratory conditions, optimization of anaerobic bioprocess control at pilot scale, and ensuring consistent performance under variable industrial feedstock conditions. Addressing these issues will require pilot-scale demonstration (10-50 L bioreactors), process robustness validation, and supply chain development for plant-based feedstocks. Regulatory pathway development will also be essential for pharmaceutical applications, particularly establishing precedents for gut microbiota-derived therapeutic compounds under existing cGMP frameworks

HighlightsO_LIIdentification of gut bacteria for stereoselective synthesis of neurosteroid isomers (isopregnanolone, epipregnanolone, pregnanolone) with >99% chiral purity
C_LIO_LISustainable plant biomass-based medium replacing animal-derived components for whole-cell progesterone biotransformation
C_LIO_LIMulti-gram scale production of progestogenic neurosteroids and one-step-open-column purification bypassing chiral chromatographic separation
C_LI

Graphical Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/671209v1_ufig1.gif" ALT="Figure 1">
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]]></description>
<dc:creator>Gicana, R. G.</dc:creator>
<dc:creator>Wang, P.-H.</dc:creator>
<dc:creator>Huang, Y.-H.</dc:creator>
<dc:creator>Huang, M.-H.</dc:creator>
<dc:creator>Wu, T.-Y.</dc:creator>
<dc:creator>Lai, Y.-L.</dc:creator>
<dc:creator>Brandon-Mong, G.-J.</dc:creator>
<dc:creator>Wei, Y.</dc:creator>
<dc:creator>Yeo, W. W. Z.</dc:creator>
<dc:creator>Ng, I.-S.</dc:creator>
<dc:creator>Chiang, Y.-R.</dc:creator>
<dc:date>2025-08-24</dc:date>
<dc:identifier>doi:10.1101/2025.08.20.671209</dc:identifier>
<dc:title><![CDATA[Multigram-scale stereoselective synthesis of neurosteroid isomers by gut microbial isolates using plant biomass-derived medium]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-08-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.08.21.671633v1?rss=1">
<title>
<![CDATA[
Cell-cell communication as underlying principle governing color pattern formation in fishes 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.08.21.671633v1?rss=1</link>
<description><![CDATA[
The diverse pigmentation patterns of animals are crucial for predation avoidance and behavioral display, yet mechanisms underlying this diversity remain poorly understood. In zebrafish, Turing models have been proposed to explain stripe patterns, but it is unclear if they apply to other fishes. In anemonefish (Amphiprion ocellaris), we identified gja5b, a gene orthologous to zebrafish leopard and encoding a connexin involved in pigment cell communication, as responsible for the Snowflake phenotype. Using CRISPR/Cas9 and transgenesis, we recapitulate the Snowflake phenotype and show expression of gja5b in iridophores. A matching allele was recovered in zebrafish, revealing complementary requirements in both species. Our findings highlight conserved roles of gap junction mediated communication in pigment patterning across divergent teleosts.
]]></description>
<dc:creator>Klann, M.</dc:creator>
<dc:creator>Miura, S.</dc:creator>
<dc:creator>Lee, S.-H.</dc:creator>
<dc:creator>Vianello, S. D.</dc:creator>
<dc:creator>Ross, R.</dc:creator>
<dc:creator>Watanabe, M.</dc:creator>
<dc:creator>Gairin, E.</dc:creator>
<dc:creator>Liang, Y.</dc:creator>
<dc:creator>Hutto, H. W.</dc:creator>
<dc:creator>McCluskey, B. M.</dc:creator>
<dc:creator>Herrera, M.</dc:creator>
<dc:creator>Solnica-Krezel, L.</dc:creator>
<dc:creator>Besseau, L.</dc:creator>
<dc:creator>Pigolotti, S.</dc:creator>
<dc:creator>Parichy, D. M.</dc:creator>
<dc:creator>Kinoshita, M.</dc:creator>
<dc:creator>Laudet, V.</dc:creator>
<dc:date>2025-08-25</dc:date>
<dc:identifier>doi:10.1101/2025.08.21.671633</dc:identifier>
<dc:title><![CDATA[Cell-cell communication as underlying principle governing color pattern formation in fishes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-08-25</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.08.22.671685v1?rss=1">
<title>
<![CDATA[
CASTLE: a training-free foundation-model pipeline for cross-species behavioral classification 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.08.22.671685v1?rss=1</link>
<description><![CDATA[
Accurately and efficiently quantifying animal behavior at scale without intensive manual labeling is a long-standing challenge for neuroscience and ethology. Keypoint-based tracking emphasizes simplicity and efficiency but loses the richness of posture and context, while emerging foundation models capture pixel-level details, yet often require nontrivial efforts of retraining and can be more sensitive to backgrounds or lighting. Here, we present CASTLE, a training-free pipeline that addresses all these issues by synergistically combining foundation models for segmentation, tracking, and feature extraction. By isolating regions-of-interest (ROI), CASTLE first generates "focused (ROI-masked)" and orientation-invariant latent features, capturing rich postural details in zero-shot, fine-tuning-free manners. Following ROI isolation, CASTLE, through an interactive "Behavior Microscope" module, supports hierarchical clustering, for progressive, human-in-the-loop embedding and clustering. This enables raw-image-assisted discovery of behavioral classes without predefined categories. Across mice, Drosophila and C. elegans, CASTLE matches expert class annotations (>90%), reveals disease-relevant phenotypes in Parkinsonian mouse models. By eliminating purpose-specific model training and providing a raw-image-informed accessible workflow, CASTLE offers a scalable framework for interpretable, cross-species behavioral phenotyping.
]]></description>
<dc:creator>Liu, Y.-S. R.</dc:creator>
<dc:creator>Yeh, H.-Y.</dc:creator>
<dc:creator>Hu, Y.-T.</dc:creator>
<dc:creator>Wu, B.-S.</dc:creator>
<dc:creator>Chen, Y.-F.</dc:creator>
<dc:creator>Yang, J.-B.</dc:creator>
<dc:creator>Jasmin, S.</dc:creator>
<dc:creator>Hsu, C.-L.</dc:creator>
<dc:creator>Lin, S.</dc:creator>
<dc:creator>Chen, C.-H.</dc:creator>
<dc:creator>Wu, Y.-W.</dc:creator>
<dc:date>2025-08-27</dc:date>
<dc:identifier>doi:10.1101/2025.08.22.671685</dc:identifier>
<dc:title><![CDATA[CASTLE: a training-free foundation-model pipeline for cross-species behavioral classification]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-08-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.08.28.672032v1?rss=1">
<title>
<![CDATA[
Pleistocene demographic histories dominate contemporary genomic diversity in a continental radiation of Himalayan-Hengduan songbirds 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.08.28.672032v1?rss=1</link>
<description><![CDATA[
While population genetic theory expects genetic diversity to scale predictably with population size, mounting empirical evidence has challenged this fundamental prediction. This striking inconsistency has prompted a paradigm shift in our understanding of the determinants of genetic diversity, driving increased efforts to disentangle the relative contributions of Pleistocene demography and linked selection. Here, based on systematic sampling and a unified analytical pipeline, we de novo assembled genomes for 120 songbird species breeding in the Himalayas-Hengduan Mountains (HHMs) and conducted population genomic analysis to examine the drivers of their genomic diversity. We observed a 6.5-fold variation in genome-wide heterogeneity and a 16.4-fold variation nucleotide diversity and across species. Notably, these measures of genomic diversity showed no correlation with recent population dynamics, current population size, or other contemporary factors--such as natural selection, elevational distribution, or life-history traits. Instead, historical demography strongly predicted genetic diversity, with ancestral population size during the late Pleistocene emerging as the sole correlate: larger ancestral sizes consistently coincided with higher diversity. These findings underscore the critical influence of historical demography on contemporary genetic diversity in natural populations--an insight essential for designing effective conservation strategies.
]]></description>
<dc:creator>Liu, Y.</dc:creator>
<dc:creator>Hung, C.-M.</dc:creator>
<dc:creator>He, Y.</dc:creator>
<dc:creator>Wu, F.</dc:creator>
<dc:creator>Yan, D.</dc:creator>
<dc:creator>Song, G.</dc:creator>
<dc:creator>Dong, F.</dc:creator>
<dc:date>2025-08-30</dc:date>
<dc:identifier>doi:10.1101/2025.08.28.672032</dc:identifier>
<dc:title><![CDATA[Pleistocene demographic histories dominate contemporary genomic diversity in a continental radiation of Himalayan-Hengduan songbirds]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-08-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.08.31.672925v1?rss=1">
<title>
<![CDATA[
What Large Language Models Know About Plant Molecular Biology 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.08.31.672925v1?rss=1</link>
<description><![CDATA[
Large language models (LLMs) are rapidly permeating scientific research, yet their capabilities in plant molecular biology remain largely uncharacterized. Here, we present MO_SCPLOWOC_SCPLOWBO_SCPLOWIC_SCPLOWPO_SCPLOWLANTC_SCPLOW, the first comprehensive benchmark for evaluating LLMs in this domain, developed by a consortium of 112 plant scientists across 19 countries. MO_SCPLOWOC_SCPLOWBO_SCPLOWIC_SCPLOWPO_SCPLOWLANTC_SCPLOW comprises 565 expert-curated multiple-choice questions and 1,075 synthetically generated questions, spanning core topics from gene regulation to plant-environment interactions. We benchmarked seven leading chat-based LLMs using both automated scoring and human evaluation of open-ended answers. Models performed well on multiple-choice tasks (exceeding 75% accuracy), although most of them exhibited a consistent bias towards option A. In contrast, expert reviews exposed persistent limitations, including factual misalignment, hallucinations, and low self-awareness. Critically, we found that model performance strongly correlated with the citation frequency of source literature, suggesting that LLMs do not simply encode plant biology knowledge uniformly, but are instead shaped by the visibility and frequency of information in their training corpora. This understanding is key to guiding both the development of next-generation models and the informed use of current tools in the everyday work of plant researchers. MO_SCPLOWOC_SCPLOWBO_SCPLOWIC_SCPLOWPO_SCPLOWLANTC_SCPLOW is publicly available online in this link.
]]></description>
<dc:creator>Fernandez Burda, M.</dc:creator>
<dc:creator>Ferrero, L.</dc:creator>
<dc:creator>Gaggion, N.</dc:creator>
<dc:creator>Fonouni-Farde, C.</dc:creator>
<dc:creator>Iglesias, M. J.</dc:creator>
<dc:creator>Fragkostefanakis, S.</dc:creator>
<dc:creator>Tonelli, M. L.</dc:creator>
<dc:creator>Zanetti, M. E.</dc:creator>
<dc:creator>Krapp, A.</dc:creator>
<dc:creator>Mencia, R.</dc:creator>
<dc:creator>Romani, F.</dc:creator>
<dc:creator>Muschietti, J. P.</dc:creator>
<dc:creator>Mansilla, N.</dc:creator>
<dc:creator>Casal, J.</dc:creator>
<dc:creator>Pagnussat, L. A.</dc:creator>
<dc:creator>Ballare, C. L.</dc:creator>
<dc:creator>Mammarella, M. F.</dc:creator>
<dc:creator>Blanco, F. A.</dc:creator>
<dc:creator>Roy, S.</dc:creator>
<dc:creator>Maroniche, G. A.</dc:creator>
<dc:creator>Rivarola, M.</dc:creator>
<dc:creator>Fiol, D. F.</dc:creator>
<dc:creator>Cubas, P.</dc:creator>
<dc:creator>Dezar, C.</dc:creator>
<dc:creator>Casati, P.</dc:creator>
<dc:creator>Ibanez, F.</dc:creator>
<dc:creator>Fernanda, d. C.-N.</dc:creator>
<dc:creator>Staiger, D.</dc:creator>
<dc:creator>Fusari, C. M.</dc:creator>
<dc:creator>Auge, G.</dc:creator>
<dc:creator>Arana, M. V.</dc:creator>
<dc:creator>Parmar, R.</dc:creator>
<dc:creator>Zhang, W.</dc:creator>
<dc:creator>Mathur, S.</dc:creator>
<dc:creator>Verslues, P. E. V.</dc:creator>
<dc:creator>Manavella, P. A.</dc:creator>
<dc:creator>Mateos, J. L.</dc:creator>
<dc:creator>Bouche, N.</dc:creator>
<dc:creator>Lucero, L. E.</dc:creator>
<dc:creator>Drincovich, M. F.</dc:creator>
<dc:creator>Traubenik,</dc:creator>
<dc:date>2025-09-04</dc:date>
<dc:identifier>doi:10.1101/2025.08.31.672925</dc:identifier>
<dc:title><![CDATA[What Large Language Models Know About Plant Molecular Biology]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-09-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.09.09.674793v1?rss=1">
<title>
<![CDATA[
Critical phenomenon underlies de novo luminogenesis during mammalian follicle development 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.09.09.674793v1?rss=1</link>
<description><![CDATA[
A key process during mammalian folliculogenesis is the formation of a fluid-filled antrum around the oocyte. While it is known that the antrum is critical for oocyte maturation and the eventual ovulation, the detailed process underlying de novo luminogenesis remains poorly understood. In this study, we investigated the spatiotemporal dynamics of lumen growth and the cellular mechanism driving this process, using advanced microscopy, molecular perturbations and computational modelling. We found that in secondary follicles, the interstitial gaps exist in a near-critical regime, characterised by a highly dynamic and interconnected fluid network with gap size obeying a power-law distribution. Above a critical size of 180 m, we observed an onset of cell death and the emergence of a stably growing dominant fluid cavity resembling phase separation. By modelling the granulosa cells and the interstitial fluid as a binary fluid, we reproduced the near-critical and phase-separated regimes and found that a spatial gradient of cell-fluid interfacial tension, as observed experimentally, is sufficient to robustly maintain the secondary follicles in a near-critical state. Reducing cell-fluid interfacial tension globally by weakening the cell-cell adhesion between granulosa cells leads to fragmentation of fluid and growth arrest of the dominant cavity, as predicted by the model. Importantly, perturbing the critical state in secondary follicles leads to impaired follicle growth. Altogether, our study reveals how collective spatiotemporal regulation of cell junction mechanics and cell death can contribute to the effective transition between distinct regimes of fluids, which are indispensable for functional maturation of follicles.
]]></description>
<dc:creator>Leong, K. W.</dc:creator>
<dc:creator>Lou, Y.</dc:creator>
<dc:creator>Biswas, A.</dc:creator>
<dc:creator>Tan, J. Y.</dc:creator>
<dc:creator>Ng, B. H.</dc:creator>
<dc:creator>Lu, X.</dc:creator>
<dc:creator>Teo, X. P.</dc:creator>
<dc:creator>Lu, T. B.</dc:creator>
<dc:creator>Bevilacqua, C.</dc:creator>
<dc:creator>Bonne, I.</dc:creator>
<dc:creator>Prevedel, R.</dc:creator>
<dc:creator>Hiraiwa, T.</dc:creator>
<dc:creator>Chan, C. J.</dc:creator>
<dc:date>2025-09-11</dc:date>
<dc:identifier>doi:10.1101/2025.09.09.674793</dc:identifier>
<dc:title><![CDATA[Critical phenomenon underlies de novo luminogenesis during mammalian follicle development]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-09-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.09.12.675939v1?rss=1">
<title>
<![CDATA[
H3N2 influenza virus tropism shifts to glycan receptors on tracheal ciliated cells 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.09.12.675939v1?rss=1</link>
<description><![CDATA[
Human H3N2 influenza viruses, introduced during the 1968 pandemic, have evolved to recognize human-type sialic acid-containing receptors (Neu5Ac2-6Gal) extended with at least three LacNAc (Gal{beta}1-4GlcNAc) repeats. To investigate this restriction in the context of virus attachment to the airway epithelium, we comprehensively analyzed the glycome of human nasal and tracheal epithelial cells. Using a synthetic N-glycan library that reflects the structural diversity of the human airway glycome, we found that only bi-antennary N-glycans with extended human-type receptors on at least one branch serve as receptors for the recent H3 hemagglutinins (HAs). Such receptors are found on tracheal epithelium but are deficient in nasal epithelium. Immunofluorescence analysis on human trachea reveals that recent H3 HAs preferentially attach to ciliated cells, consistent with single-cell RNA sequencing analysis indicating that these cells express glycosyltransferases that produce extended glycan chains. These findings suggest that H3N2 viruses have developed a tropism for tracheal ciliated cells. (146 words)
]]></description>
<dc:creator>Kikuchi, C.</dc:creator>
<dc:creator>Antonopoulos, A.</dc:creator>
<dc:creator>Wang, S.</dc:creator>
<dc:creator>Biyasheva, A.</dc:creator>
<dc:creator>Chien, Y.-C.</dc:creator>
<dc:creator>Bharat, A.</dc:creator>
<dc:creator>McBride, R.</dc:creator>
<dc:creator>Nycholat, C. M.</dc:creator>
<dc:creator>Thompson, A. J.</dc:creator>
<dc:creator>Dell, A.</dc:creator>
<dc:creator>Khoo, K.-H.</dc:creator>
<dc:creator>Schleimer, R.</dc:creator>
<dc:creator>Haslam, S. M.</dc:creator>
<dc:creator>Paulson, J. C.</dc:creator>
<dc:date>2025-09-13</dc:date>
<dc:identifier>doi:10.1101/2025.09.12.675939</dc:identifier>
<dc:title><![CDATA[H3N2 influenza virus tropism shifts to glycan receptors on tracheal ciliated cells]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-09-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.09.09.675276v1?rss=1">
<title>
<![CDATA[
Eco-genomic analysis uncovers precision-conservation targets for the western Pacific's southernmost salmonid 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.09.09.675276v1?rss=1</link>
<description><![CDATA[
Understanding how isolated small populations persist and adapt in adverse environments is instrumental to evolutionary and conservation biology. We combine a chromosome-level genome assembly, population resequencing and forward-time simulations to reconstruct the history and viability of the Formosan landlocked salmon (Oncorhynchus formosanus), now restricted to a handful of high-mountain headwaters in Taiwan. We estimate that this lineage has diverged from Japanese masu salmon over one million years ago and has no detectable gene flow for [~]50,000 years. It has accumulated extensive chromosome fusions and expansions of cold-adaptation gene families, qualifying it as a new species rather than a subspecies of Japanese masu salmon. Whole-stream sampling reveals an overlooked Hehuan-Creek population that retains high heterozygosity and has gained unique alleles. Life-table simulations show that the Hehuan population has a notably lower extinction risk and can persist or even grow under low-to-moderate typhoon frequency, whereas Qijiawan-Creek population would decline precipitously under the same or higher frequency . These findings contradict the notion that peripheral populations are likely genetically depleted and support stream-specific "precision conservation" in place of broad, untargeted translocations that could erode local adaptation potential. Thus, our genomic-ecological analysis has uncovered hidden strong resilience in a critically endangered, climate-threatened salmonid lineage.
]]></description>
<dc:creator>Lee, Y.-C.</dc:creator>
<dc:creator>Shen, Z.-Y.</dc:creator>
<dc:creator>Lin, W.-R.</dc:creator>
<dc:creator>Wang, T.-Y.</dc:creator>
<dc:creator>Liu, M.</dc:creator>
<dc:creator>Yeh, Y.-C.</dc:creator>
<dc:creator>Chan, S.-F.</dc:creator>
<dc:creator>Lu, M.-Y. J.</dc:creator>
<dc:creator>Wang, H.-Y.</dc:creator>
<dc:creator>Liao, L.-Y.</dc:creator>
<dc:creator>Li, W.-H.</dc:creator>
<dc:creator>Huang, J.-P.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:creator>Shen, S.-F.</dc:creator>
<dc:date>2025-09-15</dc:date>
<dc:identifier>doi:10.1101/2025.09.09.675276</dc:identifier>
<dc:title><![CDATA[Eco-genomic analysis uncovers precision-conservation targets for the western Pacific's southernmost salmonid]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-09-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.09.17.676772v1?rss=1">
<title>
<![CDATA[
Genome dynamics across the radiation of a mega-diverse genus 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.09.17.676772v1?rss=1</link>
<description><![CDATA[
Understanding the drivers of species diversity and rapid radiations is a major goal in evolutionary biology. Begonia is one of the most species-rich angiosperm genera with 2,164 species currently identified. This genus exhibits considerable variation in chromosome number and a wide range of genome sizes, allowing us to associate genome dynamics with divergence and speciation at a range of temporal scales. We investigate all main radiations within the Begoniaceae family using five previously published Begonia genomes and seven new genome assemblies. We show that Begonia species show more complex, repetitive and dynamic genomes overall than their close relative, the monotypic Hillebrandia sandwicensis. We identify families of repetitive elements that have recently expanded in species from two different highly speciose Southeast Asian sections and two large Neotropical radiations. Detailed characterisation of genomes from species belonging to two parallel radiations, one in Southeast Asia (Begonia section Coelocentrum) and the other in the Neotropics (Begonia section Gireoudia), revealed recent expansion in LTR retrotransposons (LTR-RTs) and satellite DNA, in contrast to more species-poor closely related clades. We further investigate variation in repetitive elements within species, finding that accessions from a population of the widespread Begonia heracleifolia with unusually large genomes show a markedly higher satellite repeat and Ty3/Gypsy LTR-RT content associated with the expansion of a few abundant repeat lineages. We find that accessions derived from this population show lower seed viability in crosses with other conspecific populations, and thus identify a direct link between expansions of repetitive DNA and the process of genetic isolation. These results show how genome dynamics may promote speciation in one of the most diverse flowering plant genera.
]]></description>
<dc:creator>Campos-Dominguez, L.</dc:creator>
<dc:creator>Kongsted, T. E.</dc:creator>
<dc:creator>Cure, L.</dc:creator>
<dc:creator>Downie, M.</dc:creator>
<dc:creator>Martinez-Martinez, A.</dc:creator>
<dc:creator>Fan, C.</dc:creator>
<dc:creator>Dong, L. N.</dc:creator>
<dc:creator>Tseng, Y. H.</dc:creator>
<dc:creator>Hu, A. Q.</dc:creator>
<dc:creator>Chung, K. F.</dc:creator>
<dc:creator>Pellicer, J.</dc:creator>
<dc:creator>Leitch, I. J.</dc:creator>
<dc:creator>Bombarely, A.</dc:creator>
<dc:creator>Twyford, A. D.</dc:creator>
<dc:creator>Kidner, C. A.</dc:creator>
<dc:date>2025-09-20</dc:date>
<dc:identifier>doi:10.1101/2025.09.17.676772</dc:identifier>
<dc:title><![CDATA[Genome dynamics across the radiation of a mega-diverse genus]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-09-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.10.01.679696v1?rss=1">
<title>
<![CDATA[
Novel Tissue Mechanics-Guided Cellular Flows Enable the Evolution of Feather Follicles 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.10.01.679696v1?rss=1</link>
<description><![CDATA[
Complex tissue architecture is achieved through multiple rounds of morphological transitions. Here, we analyzed cellular flows and tissue mechanics during avian skin development. We showed how novel cellular flows initiate chemo-mechanical circuits that guide epithelial protrusion, folding, invagination, and spatial cell fate specification. In the initial feather bud formation, stiff dermal condensates protrude vertically out of the locally softened epithelial sheet. As the bud elongates, it stretches the epithelial cells at the base, which mechanically activates YAP and causes the epithelial sheet to fold downward and form a stiff cylindrical wall that invaginates into the skin. This stiff epithelial tongue is essential to the compaction and formation of the tightly packed dermal papillae. These topological transformational events are mechanically interconnected, and the completion of the previous circuit initializes the next one. On the contrary, during scale development, its rigid epithelial sheet restricts dermal cell flows, preventing other further topological transformation. We generated a topological transformation model to show how the process enables the novel evolution of feather follicles.
]]></description>
<dc:creator>Harn, H. I.-C.</dc:creator>
<dc:creator>Jiang, T.-X.</dc:creator>
<dc:creator>Huang, C.-H.</dc:creator>
<dc:creator>Juan, W.-T.</dc:creator>
<dc:creator>Liu, T.-Y.</dc:creator>
<dc:creator>Chuang, T.-C.</dc:creator>
<dc:creator>Liao, W.-C.</dc:creator>
<dc:creator>Wang, Y.</dc:creator>
<dc:creator>Weijer, C. J.</dc:creator>
<dc:creator>Wu, P.</dc:creator>
<dc:creator>Guo, C.-L.</dc:creator>
<dc:creator>Chuong, C.-M.</dc:creator>
<dc:date>2025-10-01</dc:date>
<dc:identifier>doi:10.1101/2025.10.01.679696</dc:identifier>
<dc:title><![CDATA[Novel Tissue Mechanics-Guided Cellular Flows Enable the Evolution of Feather Follicles]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-10-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.10.01.676159v1?rss=1">
<title>
<![CDATA[
Ca2+ Plateau Potentials Reflect Cross-Theta Cortico-Hippocampal Input Dynamics and Acetylcholine for Rapid Formation of Efficient Place-Cell Code 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.10.01.676159v1?rss=1</link>
<description><![CDATA[
A central tenet of Systems Neuroscience lies in an understanding of memory and behavior through learning rules, but synaptic plasticity has rarely been shown to create functional single-neuron code in a causal and biophysically rooted manner. Behavioral Time-Scale Synaptic Plasticity (BTSP), identified in vivo, holds a great potential for explaining instantaneous hippocampal selectivity emergence by long-term potentiation (LTP), yet the cellular and endogenous mechanisms are unknown, impeding broader conceptualization of this novel rule for its algorithmic, systems-level and theoretical implications. Here, we addressed this gap by in-vivo, ex-vivo, in-silico and computational approaches to seek neurophysiologically inspired protocols for synaptically evoking Ca2+ plateau potentials and inducing potentiation in the CA1. We found induction of BTSP-LTP is best explained by a theta-oscillation-paced, gradually developed cellular state being supported with precisely timed weak ramping inputs. Remarkably, the previously presumed one-shot LTP for in-vivo place-field formation is possible under the influence of muscarinic activation. Through modeling, the notion of acetylcholine-gated BTSP gave rise to a computational advantage for low-interference continual learning. We further demonstrated that biophysics of Transient Receptor Potential (TRPM) and NMDA receptor (NMDAR) channels powerfully shapes the cross-theta dynamics underlying BTSP. These results which cover pre-, post-synaptic and neuromodulatory factors and their timing suggest fundamental principles for graded plateau potentials and hippocampal LTP induction. Overall, our work dissects cellular mechanisms potentially important for a prominent in-vivo hippocampal plasticity phenomenon, and offers a biological basis for framing BTSP as an input-dynamics-aware, neuromodulation-tuned synaptic algorithm.
]]></description>
<dc:creator>Wang, H.-Y.</dc:creator>
<dc:creator>Hsu, Y.-C.</dc:creator>
<dc:creator>Huang, H.-P.</dc:creator>
<dc:creator>Chen, C.-T.</dc:creator>
<dc:creator>Huang, X.-B.</dc:creator>
<dc:creator>Wang, C.-T.</dc:creator>
<dc:creator>Naud, R.</dc:creator>
<dc:creator>Hsu, C.-L.</dc:creator>
<dc:date>2025-10-02</dc:date>
<dc:identifier>doi:10.1101/2025.10.01.676159</dc:identifier>
<dc:title><![CDATA[Ca2+ Plateau Potentials Reflect Cross-Theta Cortico-Hippocampal Input Dynamics and Acetylcholine for Rapid Formation of Efficient Place-Cell Code]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.10.01.679695v1?rss=1">
<title>
<![CDATA[
Histological divergence underlying globular body shapes in ornamental goldfish 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.10.01.679695v1?rss=1</link>
<description><![CDATA[
Body shape diversity in vertebrates reflects a complex interplay between functional demands, environmental constraints, and internal developmental mechanisms. Various environments have promoted diverse morphological adaptations not only under natural but also domesticated conditions. One of the most remarkable examples of artificially induced morphology is found in the domesticated ornamental goldfish (Carassius auratus), which has diversified into numerous strains with strikingly different body shapes through prolonged human selection. In this study, we compared the body shapes of representative goldfish strains: the single-tail common goldfish (wild-type), Ryukin, Oranda, Pearl scale, and Ranchu. Our analysis revealed that the Ryukin and Pearl scale strains exhibit significantly greater body circularity in dorsal view compared to the other strains. Further anatomical and histological analyses showed that Pearl scale goldfish possess a thicker lateral body wall along with increased adipose tissue accumulation and reduced muscle fiber density, unlike Ryukin goldfish. These findings suggest that similar globular body shapes in different goldfish strains have arisen through distinct developmental pathways, exemplifying morphological convergence accompanied by histological divergence. We further discuss adipose accumulation in Pearl scale goldfish in relation to natural examples, providing insight into how function, morphology, and tissue organization may be interlinked in the evolution of globular body shapes.
]]></description>
<dc:creator>Ota, K. G.</dc:creator>
<dc:creator>Abe, G.</dc:creator>
<dc:creator>Wang, C.-Y.</dc:creator>
<dc:creator>Li, I.-J.</dc:creator>
<dc:creator>Sanchez, P. G. L.</dc:creator>
<dc:date>2025-10-02</dc:date>
<dc:identifier>doi:10.1101/2025.10.01.679695</dc:identifier>
<dc:title><![CDATA[Histological divergence underlying globular body shapes in ornamental goldfish]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.10.11.681280v1?rss=1">
<title>
<![CDATA[
gAIRR-wgs: An Algorithm to Genotype T Cell Receptor Alleles Using Whole Genome Sequencing Data 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.10.11.681280v1?rss=1</link>
<description><![CDATA[
T cell receptor (TR) genes, including variable (TR_V), diversity (TR_D), and joining (TR_J) segments, exhibit allelic diversity that is critical to adaptive immunity. Growing evidence has identified associations between TR genes and immune-related diseases. Germline variants may influence TR gene function and subsequent usage, highlighting the importance of accurate TR allele profiling. However, accurately identifying germline TR from standard WGS data remains challenging due to short read lengths, limited depth, and high sequence similarity. To address these challenges, we developed gAIRR-wgs, for WGS-based TR allele typing. By incorporating novel alleles from HPRC individuals, gAIRR-wgs exhibited excellent performance in allele calling, with F1 scores of 100.0% for TR_D, 99.8% for TR_J, and 98.3% for TR_V. Applying this pipeline to 1,492 individuals from the Taiwan Biobank (TWB), we identified 449 novel TR alleles, 277 of which overlapped with HPRC release 1 data of mixed ethnicity and are absent in the IMGT database. Further population comparison analysis revealed significant TR allele distribution differences across global populations, showing population-specific patterns and diversity variations between ethnic groups. We also discovered TWB-specific deletion polymorphisms affecting contiguous TRGV and TRBV genes, which are not recorded in the gnomAD database and undetected by standard structural variant callers, highlighting the need for tailored approaches to resolve complex immune gene regions. In conclusion, gAIRR-wgs enables accurate TR allele calling from standard WGS data using feasible computational resources and reveals substantial immunogenetic diversity in population cohorts.
]]></description>
<dc:creator>Huang, K.-T.</dc:creator>
<dc:creator>Yang, Y.-H.</dc:creator>
<dc:creator>Lin, M.-J.</dc:creator>
<dc:creator>Lai, S.-K.</dc:creator>
<dc:creator>Chou, T.-H.</dc:creator>
<dc:creator>Lee, C.-Y.</dc:creator>
<dc:creator>Hung, T.-K.</dc:creator>
<dc:creator>Hsu, C.-L.</dc:creator>
<dc:creator>Yang, Y.-C.</dc:creator>
<dc:creator>Chen, C.-Y.</dc:creator>
<dc:creator>Chen, P.-L.</dc:creator>
<dc:creator>Hsu, J. S.</dc:creator>
<dc:date>2025-10-13</dc:date>
<dc:identifier>doi:10.1101/2025.10.11.681280</dc:identifier>
<dc:title><![CDATA[gAIRR-wgs: An Algorithm to Genotype T Cell Receptor Alleles Using Whole Genome Sequencing Data]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-10-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.10.13.681989v1?rss=1">
<title>
<![CDATA[
Pervasive suppressors halt the spread of selfish Segregation Distorter in a natural population 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.10.13.681989v1?rss=1</link>
<description><![CDATA[
Meiotic drivers are selfish genetic elements that subvert Mendelian inheritance to increase their own transmission, yet they are typically found at low frequencies across natural populations. The factors that limit their spread remain unclear. To investigate this paradox, we studied the Segregation Distorter (SD) system, a selfish coadapted gene complex in Drosophila melanogaster. SD biases its transmission by killing sperm carrying a homologous chromosome bearing a target locus, Responder (Rsp), which appear as satellite repeats. Such selfish killing impairs male fertility and imposes selective pressure on the host genome to evolve resistance, either by deleting Rsp copies or acquiring unlinked suppressors. To characterize the spectrum of Rsp alleles and the frequency of segregating suppressors, we surveyed 90 strains from the Drosophila Genome Reference Panel. Rather than loss of Rsp, we found that over half of the strains (52/90) harbor suppressors located on the X chromosome or autosomes, but not the Y chromosome. The widespread presence of strong suppressors limited the resolution of our genome-wide association mapping; however, recombination analysis identified a strong X-linked suppressor to a [~]300 kb interval on the chromosome. Together, our findings suggest that pervasive, multilocus suppression constrains the spread of SD in natural populations.
]]></description>
<dc:creator>Chang, C.-H.</dc:creator>
<dc:creator>Handler, T.</dc:creator>
<dc:creator>Fuda, N.</dc:creator>
<dc:creator>Pascua, D.</dc:creator>
<dc:creator>Mouton, T.</dc:creator>
<dc:creator>Larracuente, A. M.</dc:creator>
<dc:date>2025-10-14</dc:date>
<dc:identifier>doi:10.1101/2025.10.13.681989</dc:identifier>
<dc:title><![CDATA[Pervasive suppressors halt the spread of selfish Segregation Distorter in a natural population]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-10-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.10.17.683024v1?rss=1">
<title>
<![CDATA[
Comparative genomics of a poinsettia-associated phytoplasma and functional validation of its SAP11-homologous effectors that induce plant branching 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.10.17.683024v1?rss=1</link>
<description><![CDATA[
Phytoplasmas are insect-transmitted plant pathogens that manipulate host development through secreted effector proteins. While they are notorious for causing agricultural losses, in the ornamental plant poinsettia (Euphorbia pulcherrima), phytoplasma infection is uniquely harnessed to induce the commercially desirable free-branching trait. However, the effectors responsible for this phenotype have remained unknown. To address this question, we sequenced and analyzed the genome of  Candidatus Phytoplasma pruni PR2021, a strain associated with the high-branching cultivar Princettia Pink. Comparative genomics confirmed its species assignment and revealed an unusual effector repertoire. PR2021 lacks most previously described effectors but encodes two distinct SAP11 homologs, a family of effectors known to induce plant branching. Genomic context analysis showed that one homolog is located within a potential mobile unit (PMU) and is nearly identical to the SAP11 of the distantly related  Ca. P. asteris, while the other is located outside PMU regions and is divergent in sequence and predicted structure. Functional assays using Agrobacterium-mediated transient expression in Nicotiana benthamiana demonstrated that each homolog independently induced significant branching, whereas co-expression did not enhance the phenotype, indicating overlapping functions. These findings establish a direct connection between poinsettia branching and SAP11-homologous effectors, providing the first experimental evidence linking phytoplasma effector activity to this horticulturally important trait. This work expands understanding of phytoplasma effector diversity and mobility, while offering a functional framework for developing pathogen-free strategies to modulate ornamental plant architecture.

IMPACT STATEMENTPhytoplasmas are uncultivated bacterial pathogens that reprogram host development through secreted effectors. While they are notorious for causing agricultural losses, phytoplasma infection is uniquely harnessed to induce the desirable free-branching trait in poinsettia, although the molecular basis has remained unresolved. Through analysis of the complete genome of  Candidatus Phytoplasma pruni PR2021, a strain associated with a high-branching cultivar, we identified two SAP11-homologous effectors with contrasting genomic and evolutionary contexts. One appears vertically inherited and divergent from previously characterized homologs, whereas the other is embedded in a potential mobile unit and likely acquired through horizontal transfer. Importantly, both homologs induce branching despite substantial sequence divergence. Taken together, this work advances understanding of phytoplasma genome evolution and effector diversity, while providing experimental evidence that links effector function to host developmental manipulation. Beyond its horticultural relevance, it illustrates how horizontal gene transfer and lineage-specific retention shape phytoplasma effector complements, offering a foundation for future efforts to dissect and re-engineer effector-host interactions.

DATA SUMMARYAll genome assemblies analyzed in this study were obtained from the National Center for Biotechnology Information (NCBI) Genome Database. The accession numbers are provided in Table S1.
]]></description>
<dc:creator>Pei, S.-C.</dc:creator>
<dc:creator>Li, N.-P.</dc:creator>
<dc:creator>Li, T.-T.</dc:creator>
<dc:creator>Yang, Y.-C.</dc:creator>
<dc:creator>Hung, T.-H.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:date>2025-10-17</dc:date>
<dc:identifier>doi:10.1101/2025.10.17.683024</dc:identifier>
<dc:title><![CDATA[Comparative genomics of a poinsettia-associated phytoplasma and functional validation of its SAP11-homologous effectors that induce plant branching]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-10-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.10.21.683700v1?rss=1">
<title>
<![CDATA[
BMAL2 is a druggable target for ARID1A-wildtype ovarian clear cell carcinoma (OCCC) 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.10.21.683700v1?rss=1</link>
<description><![CDATA[
Ovarian clear cell carcinoma (OCCC) is highly chemo-resistant and has worse clinical outcome at advanced stages than other ovarian cancer subtypes. The most frequent ([~]50%) alterations in OCCC are AT-rich interactive domain 1A gene (ARID1A) mutations which lead to ARID1A deficiency. However, OCCC that retains ARID1A function differs substantially from ARID1A mutated OCCC. Particularly, targeted therapies that sensitize ARID1A-deficient OCCC to DNA damage are largely ineffective against OCCC with wild-type (wt) ARID1A. Thus, it is important to identify druggable targets and develop targeted therapies specifically for ARID1A-wt OCCC. We identified BMAL2 as a critical OCCC oncogene that promotes tumorigenesis by preventing DNA damage from endogenous origins. BMAL2 depletion altered expression of genes in DNA damage repair pathways, including RAD51, a core enzyme of the homologous recombination (HR) pathway. This led to double-stranded break accumulation, decreased cell viability and reduced tumor growth. This dependence on BMAL2 to maintain DNA integrity and cell viability can be a new route to suppress ARID1A-wt OCCC. Consistent with this idea, we found that GW833972A, a cannabinoid receptor agonist, bound BMAL2 with high affinity and facilitated its degradation. This in turn reduced RAD51 expression, leading to an accumulation of DNA damage and decreased cell viability. Xenograft models further demonstrated that GW833972A treatment alone inhibited ARID1A-wt OCCC tumor growth. Together, our findings reveal an essential oncogenic role of BMAL2 and demonstrate that it is an appealing therapeutic target, especially for ARID1A-wt OCCC.

Statement of significanceBMAL2 depletion, or degradation by a small molecule, led to DNA damage accumulation, decreased cell viability and reduced tumorigenesis of ARID1A-wildtype ovarian clear cell carcinoma, indicating that BMAL2 is an appealing therapeutic target for treating this malignant disease.
]]></description>
<dc:creator>Tan, G. Y. T.</dc:creator>
<dc:creator>Lin, P.-Y.</dc:creator>
<dc:creator>Cheng, L.-T.</dc:creator>
<dc:creator>Tsai Yuan, Y.-S.</dc:creator>
<dc:creator>Huang, S.-H.</dc:creator>
<dc:creator>Yu, C.-H.</dc:creator>
<dc:creator>Chen, C.-T.</dc:creator>
<dc:creator>Chi, P.</dc:creator>
<dc:creator>Hwang-Verslues, W. W.</dc:creator>
<dc:date>2025-10-22</dc:date>
<dc:identifier>doi:10.1101/2025.10.21.683700</dc:identifier>
<dc:title><![CDATA[BMAL2 is a druggable target for ARID1A-wildtype ovarian clear cell carcinoma (OCCC)]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-10-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.10.26.684708v1?rss=1">
<title>
<![CDATA[
TRIB2 couples UCP1 degradation to thermogenic adaptation and metabolic health 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.10.26.684708v1?rss=1</link>
<description><![CDATA[
Genetic variation in TRIB2 has been associated with thermogenesis and fat accumulation, yet the underlying molecular mechanisms remain unclear. Uncoupling protein 1 (UCP1) is a key regulator of adaptive thermogenesis and energy expenditure. Here, we identified a human TRIB2 variant associated with migration patterns along latitude and environmental temperature, which destabilized its mRNA and is consistent with enhanced thermogenic capacity. We demonstrate that loss of Trib2 protects mice from diet-induced obesity, alleviates hepatic steatosis, and improves glucose tolerance and insulin sensitivity. Trib2 knockout mice exhibit elevated UCP1 expression in brown adipose tissue, leading to enhanced thermogenesis and increased heat production. Mechanistically, TRIB2 acts as a scaffold that binds UCP1 through its pseudokinase domain and recruits the E3 ligase MYCBP2, thereby promoting UCP1 ubiquitination and proteasomal degradation. Collectively, our findings reveal a previously unrecognized post-translational mechanism that regulates UCP1 stability and link TRIB2 function to both thermogenic adaptation and metabolic health, thereby highlighting TRIB2 as a potential therapeutic target for obesity and metabolic disorders.
]]></description>
<dc:creator>Lee, J. H.</dc:creator>
<dc:creator>Chueh, L.-Y.</dc:creator>
<dc:creator>Tien, S.-C.</dc:creator>
<dc:creator>Lee, H.-l.</dc:creator>
<dc:creator>Lin, K.-R.</dc:creator>
<dc:creator>Lee, T.-Y.</dc:creator>
<dc:creator>Che, T. P.-H.</dc:creator>
<dc:creator>Yen, J. J. Y.</dc:creator>
<dc:creator>Hu, C.-M.</dc:creator>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:date>2025-10-27</dc:date>
<dc:identifier>doi:10.1101/2025.10.26.684708</dc:identifier>
<dc:title><![CDATA[TRIB2 couples UCP1 degradation to thermogenic adaptation and metabolic health]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-10-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.10.29.685309v1?rss=1">
<title>
<![CDATA[
A topologically conserved unstructured region helps positioning the evolutionarily conserved Prp40 WW domains to promote non-canonical intron splicing 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.10.29.685309v1?rss=1</link>
<description><![CDATA[
Newly transcribed introns are immediately identified by early splicing factors that recognize the intron 5 splice site (5SS) and branch site (BS). In the budding yeast, these critical splice-site sequences are generally constrained, whereas degeneracy is the rule in higher eukaryotes. Yet, [~]40% of the yeast introns do diverge, to a certain degree, from the canonical sequences. Exactly how these non-canonical introns are recognized and spliced remains unknown. Here we show that the conserved Prp40 WW domains promote non-canonical intron splicing by enhancing stable U1 snRNP and BBP recruitments. AlphaFold predicts a topologically conserved unstructured region between Prp40 WW and FF domains. Alignment of the AlphaFold Prp40 structure with published U1 snRNP structure positions WW domains adjacent to 5SS and Luc7, which is known to be critical for 5SS recognition. Indeed, deletion of this unstructured region negatively impacts on splicing of the non-canonical 5SS introns. Taken together, our results suggest that the conserved WW domains may have evolved to deal with the highly degenerate 5SS and BS sequences in higher eukaryotes, so as to accommodate increased splicing complexity.

HighlightsO_LIThe evolutionarily conserved Prp40 WW domains promote splicing of introns harboring non-canonical 5 splice site or branch site.
C_LIO_LIPrp40 WW domains enhance stable U1 snRNP and BBP recruitments to nascent transcripts containing non-canonical splice sites.
C_LIO_LIA topologically conserved unstructured region between WW and FF domains helps to position Prp40 WW domains close to the 5 splice site.
C_LIO_LIThe N-terminal WW domain sterically hinders conformational rearrangements required for efficient release of a BBP variant during spliceosome assembly.
C_LIO_LIA reporter assay identified 13 non-canonical introns whose splicing, under various environmental conditions, depend on Prp40 WW domains.
C_LI
]]></description>
<dc:creator>Tung, L.</dc:creator>
<dc:creator>Yeh, C.-S.</dc:creator>
<dc:creator>Lin, H.-H.</dc:creator>
<dc:creator>Tsai, H.-Y.</dc:creator>
<dc:creator>Chang, S.-L.</dc:creator>
<dc:creator>Larson, A.</dc:creator>
<dc:creator>Wang, H.-K.</dc:creator>
<dc:creator>Yeh, F.-L.</dc:creator>
<dc:creator>Hsu, C.-L.</dc:creator>
<dc:creator>Kao, C.-F.</dc:creator>
<dc:creator>Pleiss, J.</dc:creator>
<dc:creator>Chang, W.-H.</dc:creator>
<dc:creator>Chang, T.-H.</dc:creator>
<dc:date>2025-10-30</dc:date>
<dc:identifier>doi:10.1101/2025.10.29.685309</dc:identifier>
<dc:title><![CDATA[A topologically conserved unstructured region helps positioning the evolutionarily conserved Prp40 WW domains to promote non-canonical intron splicing]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-10-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.10.29.685362v1?rss=1">
<title>
<![CDATA[
Bacteriophages of the predominant coral symbiont Endozoicomonas: novel models for coral holobiont interactions 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.10.29.685362v1?rss=1</link>
<description><![CDATA[
Phages are important symbionts in corals that modulate the community and functions of other symbiotic bacteria. Although phages infecting coral pathogens have been reported, no phage targeting beneficial microorganisms in corals has been isolated to date. From seawater near Acropora and Stylophora corals, we isolated the first bacteriophages (designated EmPhiA and EmPhiS) that infect Endozoicomonas montiporae CL-33, a model strain of the coral-prevalent and predominant Endozoicomonas bacteria. Electron microscopic observations of both phages showed Myovirus-like morphology and head sizes characteristic of jumbophages, with cryo-electron microscopy reveals long whiskers unprecedent in known phages. Genetically, these phages shared 99.21% genome similarity and are distant from known prokaryotic viruses, suggesting that they represent a novel viral species, which we name Encorevirus taiwanensis, in a novel family Encoreviridae. The small burst sizes of these phages (13.14 PFU/cell for EmPhiA and 21.4 PFU/cell for EmPhiS) potentially enable continuous coexistence of them with host bacteria within corals, making them putative core members of coral holobionts. Furthermore, host range test showed that EmPhiA and EmPhiS infect both Endozoicomonas bacteria isolated from stony and soft corals, implying their presence in a broad spectrum of host marine invertebrates. Using EmPhiS, we also investigated phage-bacterium interaction during its infection of E. montiporae CL-33. Interestingly, in addition to modulation of host cellular machinery, we found expression of several tellurium resistance proteins by EmPhiS during infection, which may provide the host additional stress resistance. These phages provide a novel model that will greatly advance our understanding of coral-Endozoicomonas-phage interactions.
]]></description>
<dc:creator>Chuang, P.-S.</dc:creator>
<dc:creator>Chen, M.</dc:creator>
<dc:creator>Chiang, P.-W.</dc:creator>
<dc:creator>Chen, H.-J.</dc:creator>
<dc:creator>Wang, F.-Q.</dc:creator>
<dc:creator>Chen, Y.-H.</dc:creator>
<dc:creator>Yu, S.-P.</dc:creator>
<dc:creator>Chen, F.-C.</dc:creator>
<dc:creator>Shih, K.-N.</dc:creator>
<dc:creator>Chang, Y.-P.</dc:creator>
<dc:creator>Lim, S. L.</dc:creator>
<dc:creator>Chang, H.-F.</dc:creator>
<dc:creator>Jane, W.-N.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:date>2025-10-30</dc:date>
<dc:identifier>doi:10.1101/2025.10.29.685362</dc:identifier>
<dc:title><![CDATA[Bacteriophages of the predominant coral symbiont Endozoicomonas: novel models for coral holobiont interactions]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-10-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.11.05.686880v1?rss=1">
<title>
<![CDATA[
MEX3A control of mitochondrial fitness is essential for ovarian clear cell carcinoma tumorigenesis and liver metastasis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.11.05.686880v1?rss=1</link>
<description><![CDATA[
Ovarian cancer (OC) is highly metastatic and chemoresistant. Due to heterogeneity among OC subtypes, the mechanisms underlying OC malignancy and metastasis remain largely unknown. Ovarian clear cell carcinoma (OCCC) accounts for 5-25% of OC and its incidence rate is rising. Liver metastasis is particularly high in OCCC patients and leads to significantly reduced median survival. Why OCCC metastasizes to liver at such high frequency remains elusive. We previously identified MEX3A as a key factor that promotes OCCC tumorigenesis in part by circumventing p53-mediated ferroptosis. Here, we report that MEX3A control of mitochondrial fitness, which occurs independently of p53, is essential for OCCC primary tumor growth and liver metastasis. MEX3A depletion resulted in chronic mitochondrial fragmentation and accumulation of non-functional mitochondria. MEX3A-depleted cells had decreased mitochondrial membrane potential, increased superoxide and decreased NAD+/NADH ratio, resulting in inhibition of oxidative phosphorylation (OXPHOS) and decreased ATP levels. In an environment enriched with mitophagy stressors, such as the liver, MEX3A-depleted OCCC cells had greatly reduced survival due to failure to recover from mitophagy. Consistent with these observations, MEX3A knockdown greatly reduced liver metastasis. Together, these data demonstrate that MEX3A-mediated mitochondrial fitness is a major factor underlying its p53-independent promotion of OCCC tumorigenesis and liver metastasis. Thus, targeting MEX3A will be a promising strategy to inhibit OCCC progression.

Statement of significanceUnexpected effects of MEX3A on mitochondrial fitness indicate that the need for high MEX3A expression is an OCCC vulnerability that can be exploited to uncover new treatment strategies.
]]></description>
<dc:creator>Vinothkumar, P.</dc:creator>
<dc:creator>Lin, P.-Y.</dc:creator>
<dc:creator>Cheng, L.-T.</dc:creator>
<dc:creator>Yu, C.-H.</dc:creator>
<dc:creator>Hsu, P.-H.</dc:creator>
<dc:creator>Chou, Y.-C.</dc:creator>
<dc:creator>Hwang-Verslues, W. W.</dc:creator>
<dc:date>2025-11-07</dc:date>
<dc:identifier>doi:10.1101/2025.11.05.686880</dc:identifier>
<dc:title><![CDATA[MEX3A control of mitochondrial fitness is essential for ovarian clear cell carcinoma tumorigenesis and liver metastasis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-11-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.11.11.687106v1?rss=1">
<title>
<![CDATA[
A Single-Aliquot, Enrichment-Free Workflow for High-Throughput Plasma Proteome and N-Glycoproteome Profiling 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.11.11.687106v1?rss=1</link>
<description><![CDATA[
High cancer mortality rates highlight an urgent need for early detection. Plasma proteomics and glycoproteomics provide minimally invasive routes for biomarker discovery, yet achieving an optimal balance among profiling depth, throughput, and longitudinal reproducibility remains a major challenge for clinical application and translation. To overcome this bottleneck, we present a single-aliquot, enrichment-free, paired-run dual-omics pipeline that concurrently profiles the global plasma proteome and N-glycoproteome from unenriched plasma. Following depletion of top14 abundant plasma proteins, we implemented sequential 23-min narrow-window data-independent acquisition (DIA) and 42-min stepped-collision-energy data-dependent (SCE-DDA) runs from the same plasma digest, delivering a clinical throughput of [~]24 patients/day with deep proteome coverage of 3,756{+/-}413 protein groups (PGs) and 1,226{+/-}78 glycopeptides per sample, including 303 FDA-approved drug targets. Cross-platform benchmarking with a previous generation instrument demonstrated significantly faster (>10-20 fold) profiling speed to achieve 113 PGs/min and high protein abundance reproducibility (Pearson r > 0.9), confirming cross-instrument transferability. Application to a 300-participant lung cohort (cancer, LDCT-detected non-cancer nodules, and controls) revealed differential expression of S100 and annexin family proteins between cancer and nodules. Paired glycoproteomic analysis (n=30) identified site-specific N-glycosylation alterations in FN1, IGHG2, C3, and MET independent of total protein abundance, uncovering additional biomarker candidates for early lung cancer detection. Together, this dual-omics strategy enables deep, scalable, and reproducible plasma analysis, supporting longitudinal biomarker discovery and validation across instruments and laboratories.
]]></description>
<dc:creator>Chang, K.-H.</dc:creator>
<dc:creator>Deyarmin, J.</dc:creator>
<dc:creator>Pradita, T.</dc:creator>
<dc:creator>Chen, Y.-J.</dc:creator>
<dc:creator>Samra, S.</dc:creator>
<dc:creator>Chang, G.-C.</dc:creator>
<dc:creator>Yu, C.-J.</dc:creator>
<dc:creator>Chuang, Y.-S.</dc:creator>
<dc:creator>Arrey, T.</dc:creator>
<dc:creator>Hsu, H.-E.</dc:creator>
<dc:creator>Xuan, Y.</dc:creator>
<dc:creator>Huang, P.-R.</dc:creator>
<dc:creator>Lin, K.-T.</dc:creator>
<dc:creator>Yen, K.-H.</dc:creator>
<dc:creator>Tsai, H.-j.</dc:creator>
<dc:creator>Hermanson, D.</dc:creator>
<dc:creator>Chang, Y.</dc:creator>
<dc:creator>Yu, S.-L.</dc:creator>
<dc:creator>Yang, P.-C.</dc:creator>
<dc:creator>Chen, Y.-J.</dc:creator>
<dc:date>2025-11-12</dc:date>
<dc:identifier>doi:10.1101/2025.11.11.687106</dc:identifier>
<dc:title><![CDATA[A Single-Aliquot, Enrichment-Free Workflow for High-Throughput Plasma Proteome and N-Glycoproteome Profiling]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-11-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.11.12.687945v1?rss=1">
<title>
<![CDATA[
Targeting STING-ATM axis overcomes radiotherapy-induced immune suppression and restores anti-tumor immunity in nasopharyngeal carcinoma 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.11.12.687945v1?rss=1</link>
<description><![CDATA[
BackgroundRadiotherapy (RT) is a standard treatment for nasopharyngeal carcinoma (NPC), however, RT-induced immune suppression and tumor radioresistance limit durable cancer control, with approximately 20% of patients developing recurrence or metastasis after treatment. We investigated the molecular effects of RT on the immune landscape of NPC and identified a key role of the STING-ATM-MPO axis in RT-induced immune suppression, which is associated with regulatory T cell (Treg) expansion and radioresistance.

MethodsWe analyzed leukocyte counts from 653 NPC patients before treatment and at multiple time points (week 1-2, week 3-4, and week 5-6) after RT. Single-cell RNA sequencing (scRNA-seq) was performed on peripheral blood mononuclear cell (PBMC) samples from stage I NPC patients (T1N0M0) treated with RT alone. Blood samples were collected before and after 18 Gy RT (in 2 Gy fractions). A randomized six-arm syngeneic mouse tumor model and in vitro cell studies were used to investigate interactions among STING-ATM signaling, immune modulation, and tumor response.

ResultsIn NPC patients, RT suppressed cGAS-STING signaling in monocytes and dendritic cells but promoted immunosuppressive programs, including PD-1 signaling, checkpoint expression, regulatory T cell expansion, and upregulation of TGF{beta}1, IL-10, VEGF, PDGF, and MDSC-associated pathways. In a syngeneic mouse model, co-treatment with the STING agonist diABZI reversed these effects and improved tumor control. Bulk RNA sequencing confirmed that RT suppressed cGAS-STING and ATM signaling in both spleens and tumors. Combination treatment restored this signaling, enhanced neutrophil degranulation, and inhibited PD-1 signaling and immune checkpoints. Immunohistochemistry showed that diABZI increased ATM activation, MPO expression, and reduced Treg infiltration in spleens and tumors. ATM activation correlated positively with MPO and inversely with FOXP3 immunoreactivity, suggesting that STING-ATM-MPO activation counteracts Treg-mediated immune suppression. In vitro, diABZI activated STING-ATM signaling in PBMCs, THP-1 cells, and Jurkat T cells, while inhibiting NPC cell growth partly via CYLD upregulation.

ConclusionsThese findings link RT-induced suppression to inhibition of cGAS-STING signaling. Activation of STING-ATM-MPO axis counteracts Treg-mediated immune suppression, supporting the therapeutic potential of STING agonists as radiosensitizers in NPC.
]]></description>
<dc:creator>Liu, T.-T.</dc:creator>
<dc:creator>Chang, K.-P.</dc:creator>
<dc:creator>Wang, Y.-N.</dc:creator>
<dc:creator>OuYang, C.-N.</dc:creator>
<dc:creator>Li, M.-H.</dc:creator>
<dc:creator>Tsang, N.-M.</dc:creator>
<dc:creator>Jiang, S. S.</dc:creator>
<dc:creator>Sui, Y.-H.</dc:creator>
<dc:creator>Hu, C.-M.</dc:creator>
<dc:creator>Chou, Y.-C.</dc:creator>
<dc:creator>Chen, H.-C.</dc:creator>
<dc:creator>Liu, S.-C.</dc:creator>
<dc:date>2025-11-13</dc:date>
<dc:identifier>doi:10.1101/2025.11.12.687945</dc:identifier>
<dc:title><![CDATA[Targeting STING-ATM axis overcomes radiotherapy-induced immune suppression and restores anti-tumor immunity in nasopharyngeal carcinoma]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-11-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.11.13.688282v1?rss=1">
<title>
<![CDATA[
Structure and functional analyses of Vaccinia virus entry- fusion complex component J5 protein 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.11.13.688282v1?rss=1</link>
<description><![CDATA[
Vaccinia virus enters host cells through an 11-protein entry fusion complex (EFC) that operates by a mechanism distinct from those of canonical viral fusion systems. Understanding how this multiprotein complex mediates membrane fusion is crucial for elucidating poxvirus entry and identifying potential antiviral targets. Here, we determined the NMR structure of a truncated J5 protein, (J5 2-68). To further dissect the functional determinants of J5, we generated recombinant vaccinia viruses expressing various J5 mutants, including substitutions in conserved residues, alterations of exposed charged residues, and chimeric constructs between vaccinia J5 and its orthologous AMV232 gene from an entomopoxvirus. Functional analyses revealed that residues 90-110 and the conserved P38YYCWY43 motif are indispensable for maintaining EFC integrity and promoting membrane fusion. Together, we define the structural and functional elements of J5 that are essential for poxvirus entry and advance our understanding of the unique membrane fusion mechanism employed by poxviruses.

ImportanceVaccinia virus enters host cells through an eleven-protein entry fusion complex (EFC) that is mechanistically distinct from canonical viral fusion systems. Understanding how this multiprotein machinery mediates membrane fusion is essential for elucidating poxvirus entry mechanisms and for developing antiviral strategies. Here, we determined the NMR structure of the J5 ectodomain and generated a series of recombinant vaccinia viruses carrying J5 mutations. Functional analyses identified two regions, residues 90-110 and the conserved P38YYCWY43 motif, as essential for EFC stability and membrane fusion. These findings provide the first structure-function framework for J5, a core component of the EFC, and reveal key determinants required for complex integrity and viral entry.
]]></description>
<dc:creator>Chang, W.</dc:creator>
<dc:creator>Chiu, H.-J.</dc:creator>
<dc:creator>Tzou, D.-L.</dc:creator>
<dc:creator>Carillo, K. J.</dc:creator>
<dc:creator>Hsieh, L. T.-H.</dc:creator>
<dc:date>2025-11-14</dc:date>
<dc:identifier>doi:10.1101/2025.11.13.688282</dc:identifier>
<dc:title><![CDATA[Structure and functional analyses of Vaccinia virus entry- fusion complex component J5 protein]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-11-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.11.21.689727v1?rss=1">
<title>
<![CDATA[
Establishment of a Congenic Strain for the Oyster mushroom reveals the Structure and Evolution of Mating-Type Loci 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.11.21.689727v1?rss=1</link>
<description><![CDATA[
Pleurotus ostreatus, a widely cultivated edible oyster mushroom, is an ecologically versatile species with applications in biotechnology, agriculture, and food production. It functions as a decomposer and in nutrient-limited conditions it enhances its survival by using a potent toxin to prey on nematodes. Its adaptability is further regulated by sexual reproduction, which follows a tetrapolar mating system governed by two unlinked, multiallelic loci, matA and matB. The two mating-compatible monokaryotic strains PC9 and PC15, derived from the parental dikaryon strain N001, exhibit significant physiological differences. PC9 grows robustly in laboratory conditions, whereas PC15 grows more slowly, making PC9 the preferred strain for research. To advance P. ostreatus as a genetic model, we characterized the mating-type (MAT) loci of both monokaryon strains and developed a congenic strain. We analyzed the MAT loci in multiple P. ostreatus strains, and identified 11 A and 12 B alleles among twelve haplotypes, confirming their multiallelic nature. Using genetic backcrosses, we introgressed the matA and matB loci from PC15 into the PC9 genetic background to generate the congenic strain PC9.15. After sequencing and assembling a high-quality and contiguous genome for PC9.15, we confirmed that the genomes of PC9.15 and PC9 are 99% similar, with the only major difference placed at the matA and matB loci.

Author SummaryMushrooms are not just decomposers-they can also be predators. The oyster mushroom Pleurotus ostreatus is an ecologically adaptable species that thrives by breaking down plant material and preying on nematodes using a potent toxin that triggers rapid paralysis of nematode prey. In addition to its ability to switch from saprophyte to predator, another feature contributing to the ecological success of Pleurotus is its reproductive strategy. P. ostreatus reproduces sexually through a tetrapolar mating-type system, governed by two unlinked mating loci, matA and matB. These loci determine mating compatibility and contribute to genetic diversity, yet their precise structure and allelic diversity remain unclear. In this study, we characterized the matA and matB loci in P. ostreatus strains PC9 and PC15 and analyzed MAT loci across multiple strains, confirming their multiallelic nature. To enhance P. ostreatus as a genetic model, we developed the congenic strain PC9.15 by introgressing MAT alleles from PC15 into the PC9 genetic background through genetic backcrosses. Genome sequencing confirmed that PC9.15 closely matches the genome of PC9, except at the MAT loci. This study expands our understanding of mating-type diversity in P. ostreatus, introduces PC9.15 as a valuable tool for genetic studies and controlled crosses, and facilitates the development of P. ostreatus as a model system for fungal biology.
]]></description>
<dc:creator>Lee, Y.-Y.</dc:creator>
<dc:creator>Vidal-Diez de Ulzurrun, G.</dc:creator>
<dc:creator>Tay, R. J.</dc:creator>
<dc:creator>Hsueh, Y.-P.</dc:creator>
<dc:date>2025-11-21</dc:date>
<dc:identifier>doi:10.1101/2025.11.21.689727</dc:identifier>
<dc:title><![CDATA[Establishment of a Congenic Strain for the Oyster mushroom reveals the Structure and Evolution of Mating-Type Loci]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-11-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.11.24.690302v1?rss=1">
<title>
<![CDATA[
Multi-Omics analyses reveal dynamic interactions between DNA methylation and transcriptional regulation during black raspberry ripening 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.11.24.690302v1?rss=1</link>
<description><![CDATA[
We profiled developmental-series transcriptome, methylome, and metabolome profiling to reveal extensive epigenetic reprogramming during black raspberry (Rubus occidentalis) fruit ripening. Fruit tissues exhibit globally higher DNA methylation than leaves, particularly in CHG and CHH contexts. Local methylation in all cytosine contexts progressively decreases in promoter regions during ripening, whereas CHG and CHH methylation increase in transposon-rich regions. Two primary methylation transitions--promoter hypomethylation and CHH hypermethylation--govern transcriptional shifts in genes involved in ripening processes. Methyl-binding transcription factors with activation potential likely promote CHH hypermethylation-linked transcriptional activation. Multi-omics integration revealed coordinated anthocyanin accumulation parallels expression of biosynthetic and regulatory genes within coherent networks. Elevated non-CG methylation in heterochromatin coincides with increased transcription of histone variants mediating chromatin compaction, suggesting chromatin remodelers fine-tune accessibility for methyltransferases. Our study highlights both genome-wide and locus-specific epigenetic reprogramming and demonstrates a coordinated interplay between DNA methylation and transcriptional regulation during black raspberry fruit ripening.
]]></description>
<dc:creator>Hsieh, W.-H.</dc:creator>
<dc:creator>Hung, Y.-H.</dc:creator>
<dc:creator>Zhang, J.-H.</dc:creator>
<dc:creator>Chen, H.-Y.</dc:creator>
<dc:creator>Lin, L.-P.</dc:creator>
<dc:creator>He, M.-H.</dc:creator>
<dc:creator>Wang, Y.-C.</dc:creator>
<dc:creator>Ho, Y.-Y.</dc:creator>
<dc:creator>Fernandez, G.</dc:creator>
<dc:creator>Perkins-Veazie, P.</dc:creator>
<dc:creator>Le, B.</dc:creator>
<dc:creator>Li, X.</dc:creator>
<dc:creator>Hsieh, T.-F.</dc:creator>
<dc:creator>Lin, J.-Y.</dc:creator>
<dc:date>2025-11-27</dc:date>
<dc:identifier>doi:10.1101/2025.11.24.690302</dc:identifier>
<dc:title><![CDATA[Multi-Omics analyses reveal dynamic interactions between DNA methylation and transcriptional regulation during black raspberry ripening]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-11-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.11.27.690892v1?rss=1">
<title>
<![CDATA[
Host-derived lipid transfer and metabolic reprogramming in a ciliate-algal symbiosis 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.11.27.690892v1?rss=1</link>
<description><![CDATA[
Symbiotic associations enable species to integrate complementary traits and adapt to novel environments. However, how the host and endosymbiont exchange nutrients remains poorly understood in most cases. Previously Paramecium bursaria cells were shown to reorganize lipid droplets to accommodate endosymbiotic Chlorella cells and interfering with lipid metabolism reduced the endosymbiont number. Here, we combined transcriptomics, lipidomics, imaging mass spectrometry, and stable-isotope tracing to investigate organic nutrient exchange in this symbiotic system. Our results reveal that endosymbiotic algae undergo extensive reprogramming of lipid metabolic pathways and accumulate markedly higher levels of triglycerides than free-living algae. Isotope-labeling experiments demonstrate that at least some of these lipids originate from the host, providing direct evidence for organic carbon transfer from Paramecium to its algal endosymbionts. Together, our results show that the establishment of symbiosis fundamentally reshapes algal lipid metabolism and uncover an unexpected host-to-symbiont lipid provisioning mechanism--opposite to the canonical direction of carbon flow observed in most photosynthetic symbioses. This work provides new insight into the metabolic principles that sustain and stabilize endosymbiotic partnerships.
]]></description>
<dc:creator>Chen, Y.-J.</dc:creator>
<dc:creator>Wei, C.-Y.</dc:creator>
<dc:creator>Kamal, M. M.</dc:creator>
<dc:creator>Hsu, C.-W.</dc:creator>
<dc:creator>Hsiao, S.-Y.</dc:creator>
<dc:creator>Lee, D.-C.</dc:creator>
<dc:creator>Wang, P.-L.</dc:creator>
<dc:creator>Leu, J.-Y.</dc:creator>
<dc:date>2025-11-28</dc:date>
<dc:identifier>doi:10.1101/2025.11.27.690892</dc:identifier>
<dc:title><![CDATA[Host-derived lipid transfer and metabolic reprogramming in a ciliate-algal symbiosis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-11-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.11.27.690926v1?rss=1">
<title>
<![CDATA[
Root meristem growth factor (RGF) peptide signaling as a molecular bridge between root development and non-lethal thermal stress adaptation 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.11.27.690926v1?rss=1</link>
<description><![CDATA[
O_LIRoots adapt to temperature ranges that restrict growth but are not lethal. Although lethal heat shock and moderately high temperatures have been studied in detail, the effects of non-lethal high temperatures on root development remain largely unknown.
We defined 31{degrees}C as a non-lethal thermal stress in Arabidopsis thaliana and examined its impact on root growth using phenotypic analyses and developmental-zone-specific transcriptomics.
C_LIO_LICompared to growth at 22{degrees}C, at 31{degrees}C, primary root growth, meristem size, and superoxide (O2-) accumulation were reduced, and the distribution of the meristem master regulator PLETHORA2 (PLT2) became restricted. Transcriptome analysis revealed a strong downregulation of RGFs, RGFRs, and PLT2, rather than activation of heat shock-inducible genes.
C_LIO_LIThese gene mutants were more sensitive to non-lethal thermal stress. In contrast, RGF treatment recovered heat-stress-induced defects. Beyond alleviating the stress in the primary root meristem, RGF treatments promoted lateral root elongation under prolonged non-lethal thermal stress, resulting in a more complex root system.
C_LIO_LIThese results indicate that the RGF-RGF receptor-PLT2 pathway plays a central role in root adaptation to non-lethal heat stress rather than the canonical heat shock response pathway and suggest that manipulating RGF signaling could enhance root thermotolerance and crop resilience under elevated temperatures.
C_LI
]]></description>
<dc:creator>Hsiao, Y.-C.</dc:creator>
<dc:creator>Lai, J.-K.</dc:creator>
<dc:creator>Shiue, S.-Y.</dc:creator>
<dc:creator>YAMADA, M.</dc:creator>
<dc:date>2025-11-28</dc:date>
<dc:identifier>doi:10.1101/2025.11.27.690926</dc:identifier>
<dc:title><![CDATA[Root meristem growth factor (RGF) peptide signaling as a molecular bridge between root development and non-lethal thermal stress adaptation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-11-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.1101/2025.11.27.690639v1?rss=1">
<title>
<![CDATA[
A 3D Amphioxus Brain Atlas Illuminates the Blueprint of the Ancestral Chordate Brain 
]]>
</title>
<link>https://biorxiv.org/content/10.1101/2025.11.27.690639v1?rss=1</link>
<description><![CDATA[
Comparative studies on highly complex vertebrate brains have provided insights into the evolutionary history of morphological diversity. However, a long-standing question in vertebrate brain evolution is how the fundamental blueprint emerged. To probe the cellular and molecular origins of brain architecture in the chordate lineage, we performed single-nucleus RNA-seq combined with spatial transcriptomics and generated a three-dimensional cell atlas of the basal chordate amphioxus central nervous system (CNS). This atlas reveals a tripartite organization along the anterior-posterior axis of the adult amphioxus brain, with a rostral retinal/hypothalamic region followed by a di-mesencephalon and caudally, the hindbrain and spinal cord. Notably, we show that the amphioxus brain contains cell clusters resembling the zona limitans intrathalamica and midbrain-hindbrain boundary, both of which demarcate the major brain compartments. Furthermore, expression profiling and gene ontology enrichment analyses support that the cell clusters located in the rostral part of the amphioxus forebrain correspond to vertebrate retinal primordium and hypothalamic cells. However, the absence of key telencephalic marker expression in the amphioxus anterior forebrain suggests that the telencephalon likely represents a vertebrate innovation. Together, our findings establish a spatial transcriptomic framework for the amphioxus CNS and provide a critical link for understanding the evolution of the complex vertebrate brain.
]]></description>
<dc:creator>Lin, C.-Y.</dc:creator>
<dc:creator>Hsu, W.-H.</dc:creator>
<dc:creator>Lu, M.-Y. J.</dc:creator>
<dc:creator>Chen, Y.-H.</dc:creator>
<dc:creator>Chen, Y.-C.</dc:creator>
<dc:creator>Su, Y.-H.</dc:creator>
<dc:creator>Chou, S.-J.</dc:creator>
<dc:creator>Yu, J.-K.</dc:creator>
<dc:date>2025-11-29</dc:date>
<dc:identifier>doi:10.1101/2025.11.27.690639</dc:identifier>
<dc:title><![CDATA[A 3D Amphioxus Brain Atlas Illuminates the Blueprint of the Ancestral Chordate Brain]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-11-29</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2025.12.01.691703v1?rss=1">
<title>
<![CDATA[
Sperm-specific fertility factors SMZ-1/2 promote FB-MO biogenesis and MSP filament assembly in C. elegans 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2025.12.01.691703v1?rss=1</link>
<description><![CDATA[
In nematode sperm, motility is powered by polymerization of major sperm protein (MSP) into filaments assembled from a specialized organelle (FB-MO), but how filament formation begins is unclear. We identify two sperm-specific PDZ proteins, SMZ-1 and SMZ-2 (SMZ-1/2), that initiate MSP loading into pre-formed membranous organelles in Caenorhabditis elegans. SMZ-1/2 were expressed specifically in spermatogenic germ cells, colocalized with developing FB-MOs from diplotene through spermatid formation, and were redundant for fertility. Loss of SMZ-1/2 abolished MSP filaments, left MOs MSP-negative and morphologically immature, and caused primary spermatocyte arrest. Electron microscopy showed fewer, smaller FB-MOs lacking crystalline FBs, consistent with a defect in assembly initiation rather than late polymerization. SMZ-1/2 cytoplasmic structures were absent in spe-6 casein kinase mutants, placing SMZ-1/2 within a SPE-6-dependent initiation module. These findings identify SMZ-1/2 as PDZ scaffold proteins that initiate MSP assembly and couple kinase signaling to FB-MO biogenesis during nematode spermatogenesis.
]]></description>
<dc:creator>Peng, H.-F.</dc:creator>
<dc:creator>Liu, C.-L.</dc:creator>
<dc:creator>Jane, W.-N.</dc:creator>
<dc:creator>Chen, C.-S.</dc:creator>
<dc:creator>Wang, C.-W.</dc:creator>
<dc:creator>Wu, J.-c.</dc:creator>
<dc:date>2025-12-03</dc:date>
<dc:identifier>doi:10.64898/2025.12.01.691703</dc:identifier>
<dc:title><![CDATA[Sperm-specific fertility factors SMZ-1/2 promote FB-MO biogenesis and MSP filament assembly in C. elegans]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-12-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2025.11.20.689376v1?rss=1">
<title>
<![CDATA[
Deep Mediation Analysis for Multimodal Genotype-Imaging Associations with Disease Phenotypes 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2025.11.20.689376v1?rss=1</link>
<description><![CDATA[
Both genotype and imaging data carry entangled information about the phenotypes. Associations between genotypes and phenotypes can be manifested or absent on biomedical images. While there are abundant multimodal association studies integrating genotype and imaging data, few of them disentangle their direct and indirect effects in associations. We propose GIF (Genotype-Image-Phenotype), a novel modeling framework to predict phenotypes by genotype and imaging data with a mediation structure of these three sets of variables. GIF constitutes a backbone of mediation path genotype[-&gt;]image[-&gt;]phenotype, and direct genotype[-&gt;]phenotype and image[-&gt;]phenotype paths capturing the additional direct associations not explained by the mediation model. To implement the mediation model with a convolutional neural network (CNN), we constructed a CNN to predict genotypes with images and then employed the joint embedding vectors of the CNN to predict phenotypes. The direct links were sequentially augmented to the mediation model to further improve prediction accuracy. We validated GIF on three datasets: (1) a synthetic polygon dataset where the presence or absence of a polygon specie indicates a genotype and selected combinations of multiple polygon species indicate phenotypes, (2) the PASCAL VOL dataset of object detection and action recognition, where the presence or absence of an object class indicates a genotype and the presence or absence of an action class indicates a phenotype, (3) the ADNI dataset of Alzheimers disease diagnosis comprising the genotype and imaging data of subjects with three cognitive states. GIF prediction outcomes on the ADNI data indicate the associations between genotypes and phenotypes are primarily mediated by image features, and images provide additional information about phenotypes which is not attributed to genotype variations.
]]></description>
<dc:creator>Golderzahi, V.</dc:creator>
<dc:creator>Wang, G.-J.</dc:creator>
<dc:creator>Hu, J.</dc:creator>
<dc:creator>Yeang, C.-H.</dc:creator>
<dc:date>2025-12-05</dc:date>
<dc:identifier>doi:10.64898/2025.11.20.689376</dc:identifier>
<dc:title><![CDATA[Deep Mediation Analysis for Multimodal Genotype-Imaging Associations with Disease Phenotypes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-12-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2025.12.07.692860v1?rss=1">
<title>
<![CDATA[
OsIDS3L, a Non-Canonical Dioxygenase Enhancing Iron Homeostasis and Micronutrient Biofortification in Rice 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2025.12.07.692860v1?rss=1</link>
<description><![CDATA[
O_LIGraminaceous plants synthesize some organic compounds known as phytosiderophores (PSs) for iron (Fe) uptake. The first PS, deoxymugineic acid (DMA), is common to all grasses. However, PSs synthesized from DMA, hydroxylated PSs, have higher efficiency for Fe chelation and are species-specific. Hydroxylated PS, mugineic acid (MA) synthesis via the Fe(II)-2-oxoglutarate-dependent dioxygenase enzymes HvIDS2 and HvIDS3 have been reported in barley.
C_LIO_LIHere, we report that IDS3-Like (OsIDS3L), a homolog of the MA biosynthesis gene, is responsive to Fe deficiency in rice. Functional analysis using overexpression (OE) lines demonstrates OsIDS3Ls role in Fe-deficiency tolerance and micronutrient assimilation in seeds. However, MA was not detected, indicating functional divergence of IDS in rice. Increased DMA and NA levels in OE lines support enhanced Fe uptake and homeostasis.
C_LIO_LICRISPR-generated mutants lack an obvious phenotype and show no substrate DMA accumulation. Expression analysis suggests regulation of Fe-responsive genes by both gain- and loss-of-function lines. A computational metabolomics analysis, supported by chemotype justification, suggests a role for OsIDS3l in an enzyme reaction upstream of DMA.
C_LIO_LIThe results not only identified a gene potential for agronomy-specific traits and biofortification, but also shed light on a possible non-canonical PS biosynthesis pathway.
C_LI
]]></description>
<dc:creator>Aggarwal, J.</dc:creator>
<dc:creator>Yeh, K.-C.</dc:creator>
<dc:date>2025-12-09</dc:date>
<dc:identifier>doi:10.64898/2025.12.07.692860</dc:identifier>
<dc:title><![CDATA[OsIDS3L, a Non-Canonical Dioxygenase Enhancing Iron Homeostasis and Micronutrient Biofortification in Rice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-12-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2025.12.08.693002v1?rss=1">
<title>
<![CDATA[
Caenorhabditis briggsae ancestral genomic hyper-diversity contrasts with globally distributed genome-wide haplotypes 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2025.12.08.693002v1?rss=1</link>
<description><![CDATA[
Comparative genomics provides a powerful framework to uncover the molecular and evolutionary mechanisms that shape genetic diversity within and across species, revealing how shared and lineage-specific processes influence their evolutionary trajectories through time. The nematode Caenorhabditis briggsae is distributed world-wide and is a comparative model to Caenorhabditis elegans in the biology of development, cellular mechanisms, neurobiology, genetic mappings of complex traits, and genome evolution. Following massive collection efforts by the nematode research community, we present the isolation of over 2,000 wild strains and analyses of genome sequences that catalog over six million single-nucleotide and insertion-deletion variants. This genome and strain resource provide a powerful means to interrogate the causal genetic bases of phenotypic variation for diverse traits. Additionally, we describe its global population structure and discover new and genetically distinct groups within this primarily self-fertilizing species, including groups of highly related strains that were sampled across different continents. We leverage expansive genetic variation to decipher the effects of linkage and selection on the distribution of genetic diversity across the genome and across geographic regions. Within the species, we find genomic regions with extremely high levels of genetic variation similar to hyper-divergent regions found in C. elegans and other species. These regions harbor new genes and variation enriched for environmental sensing and pathogen responses. In comparison to the outbreeding sister species Caenorhabditis nigoni, we conclude that long-term balancing selection has maintained substantial functional variation since the divergence from their outbreeding ancestor, likely in response to differences in the ecological niche. Overall, this massive strain resource enables future comparative genetics and genomics studies, including genome-wide association studies between Caenorhabditis species.
]]></description>
<dc:creator>Moya, N. D.</dc:creator>
<dc:creator>Wang, B.</dc:creator>
<dc:creator>Tanny, R. E.</dc:creator>
<dc:creator>Sauria, M. E. G.</dc:creator>
<dc:creator>O'Connor, L. M.</dc:creator>
<dc:creator>Khorshidian, A.</dc:creator>
<dc:creator>McKeown, R.</dc:creator>
<dc:creator>Gosse, C.</dc:creator>
<dc:creator>Dilks, C. M.</dc:creator>
<dc:creator>Crombie, T. A.</dc:creator>
<dc:creator>Zhang, G.</dc:creator>
<dc:creator>Rais, E.</dc:creator>
<dc:creator>Frezal, L.</dc:creator>
<dc:creator>Dang, V. D.</dc:creator>
<dc:creator>Haryoso, E.</dc:creator>
<dc:creator>Devi, M. P.</dc:creator>
<dc:creator>Gimond, C.</dc:creator>
<dc:creator>Cook, D. E.</dc:creator>
<dc:creator>Hsu, J.-C.</dc:creator>
<dc:creator>Shaver, A. O.</dc:creator>
<dc:creator>Zdraljevic, S.</dc:creator>
<dc:creator>Richaud, A.</dc:creator>
<dc:creator>Wen, T.</dc:creator>
<dc:creator>Mehraj, A.</dc:creator>
<dc:creator>H, S.</dc:creator>
<dc:creator>Arulprakasam, K. R.</dc:creator>
<dc:creator>Koury, E. J.</dc:creator>
<dc:creator>Roberto, N. M.</dc:creator>
<dc:creator>Schaye, E. S.</dc:creator>
<dc:creator>Singh, V.</dc:creator>
<dc:creator>Tarno, H.</dc:creator>
<dc:creator>Ailion, M.</dc:creator>
<dc:creator>Paaby, A. B.</dc:creator>
<dc:creator>Zhao, Z.</dc:creator>
<dc:creator>Cutter, A. D.</dc:creator>
<dc:creator>Wang, J.</dc:creator>
<dc:creator>Rockman, M. V.</dc:creator>
<dc:creator>Braendle, C.</dc:creator>
<dc:creator>Andersen, E. C.</dc:creator>
<dc:date>2025-12-11</dc:date>
<dc:identifier>doi:10.64898/2025.12.08.693002</dc:identifier>
<dc:title><![CDATA[Caenorhabditis briggsae ancestral genomic hyper-diversity contrasts with globally distributed genome-wide haplotypes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-12-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2025.12.11.693522v1?rss=1">
<title>
<![CDATA[
Retention of a single Cenp-C gene in different syntenic locations in the montium group of Drosophila species 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2025.12.11.693522v1?rss=1</link>
<description><![CDATA[
Chromosome segregation in eukaryotes requires the orchestrated interaction of chromosomes with microtubules, mediated by the kinetochore multiprotein complex that assembles on specific chromosomal regions known as centromeres. In most eukaryotes, two centromeric proteins, CenH3 and Cenp-C, are essential for centromere function. In Drosophila, the localization of CenH3 (referred to as Cid in Drosophila) depends on its chaperone CAL1 and Cenp-C. Previous studies have shown that both Cid and Cenp-C underwent a coincident gene duplication and likely functional specialization in the Drosophila subgenus. Independently, Cid duplications led to Cid1, Cid3, and Cid4 paralogs in the montium group (Sophophora subgenus), but it is unknown whether this group also underwent parallel duplications of Cenp-C. Here, we investigate this possibility by analyzing sequenced genomes of 23 montium group species. We identified Cenp-C genes in five distinct syntenic loci; we named these genes Cenp-C1b, Cenp-C1c, Cenp-C1d, Cenp-C1e and Cenp-C3. Despite their distinct synteny, most montium group species only encode a single Cenp-C; their phylogeny mirrors the species phylogeny, and they appear to have retained Cenp-C protein motifs indicative of function. A closer examination revealed that these Cenp-C genes resulted from gene translocations or alternate retention (duplication followed by loss of the ancestral copy); only one species, D. vulcana, retains two intact Cenp-C paralogs. Therefore, unlike the Drosophila genus, the co-retention of three Cid paralogs in the montium group has not resulted in a coincident Cenp-C paralog co-retention. Our work highlights differences in functional retention and likely specialization of the two most conserved centromeric proteins in eukaryotes.
]]></description>
<dc:creator>Soares, R. F.</dc:creator>
<dc:creator>Chang, C.-H.</dc:creator>
<dc:creator>Koerich, L. B.</dc:creator>
<dc:creator>Malik, H. S.</dc:creator>
<dc:creator>KUHN, G. C. S.</dc:creator>
<dc:date>2025-12-15</dc:date>
<dc:identifier>doi:10.64898/2025.12.11.693522</dc:identifier>
<dc:title><![CDATA[Retention of a single Cenp-C gene in different syntenic locations in the montium group of Drosophila species]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-12-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2025.12.16.694684v1?rss=1">
<title>
<![CDATA[
A novel, fig-associated microbe promotes reproductive success via variable life history mechanisms in C. elegans and C. inopinata 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2025.12.16.694684v1?rss=1</link>
<description><![CDATA[
Variation in life history strategies is among the most striking features of animal diversity. Simultaneously, the microbes an animal interacts with are a critical and dynamic aspect of the host environment that can have profound impacts on their life history traits. As microbial environments diverge across animal lineages, life histories and their responses to such microbial contexts are expected to evolve as a consequence. Caenorhabditis nematodes are bacterivores that exhibit a diversity of life history strategies and fill diverse ecological niches. C. elegans thrives on rotting plants and grows rapidly with high fecundity; C. inopinata thrives in fresh figs and grows more slowly with lower fecundity. To understand how hosts with divergent life histories and ecologies respond to the microbes they interact with, we isolated over forty bacterial species from the natural fig environment of C. inopinata. This microbial survey revealed an isolate, Klebsiella sp. WOUb2, that doubles the population growth rate of C. inopinata. While this isolate also increases the population growth rate of C. elegans, Klebsiella sp. WOUb2 increases individual fecundity and developmental rate in C. elegans, whereas it only increases developmental rate of C. inopinata. Thus, fitness is modulated by variable life history mechanisms in the two species. Comparisons with nucleotide databases reveal Klebsiella sp. WOUb2 is closely related to other Klebsiella isolates known to influence Caenorhabditis nematode fitness. Additionally, the similarity of Klebsiella sp. WOUb2 to microbes associated with fig wasps and figs suggests C. inopinata frequently encounters this microbe in its natural context. Taken together, this shows that different physiological responses can underlie conserved, beneficial interspecific interactions.
]]></description>
<dc:creator>Link, A. C.</dc:creator>
<dc:creator>Moser, K. A.</dc:creator>
<dc:creator>Wang, J.</dc:creator>
<dc:creator>Woodruff, G. C.</dc:creator>
<dc:date>2025-12-19</dc:date>
<dc:identifier>doi:10.64898/2025.12.16.694684</dc:identifier>
<dc:title><![CDATA[A novel, fig-associated microbe promotes reproductive success via variable life history mechanisms in C. elegans and C. inopinata]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-12-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2025.12.16.694779v1?rss=1">
<title>
<![CDATA[
Dynamic evolution of AT-rich isochores shapes the genome of an intertidal fungus Annulohypoxylon annulatoides 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2025.12.16.694779v1?rss=1</link>
<description><![CDATA[
Marine and coastal fungi experience intense environmental variability, yet the genomic mechanisms enabling filamentous fungi to tolerate such conditions remain unclear. From 56 fungal isolates collected along the Lailai rocky shore in northern Taiwan, we selected Annulohypoxylon annulatoides for deeper investigation due to its prevalence and distinctive stress response. Phenotypic assays revealed that this strain exhibits distinct growth and recovery dynamics under salinity, temperature, and UV stress compared to conspecific strains isolated from tree bark. To investigate the genomic basis of its adaptation, we generated a high-quality 41.8 Mbp de novo genome assembly with 11,529 predicted proteins. Across Hypoxylaceae genomes, we identified variably sized and dispersed AT-rich isochores, which in A. annulatoides were enriched in repeats and displayed low gene density. Despite differences in AT content, core gene content and Pfam domain profiles remained conserved. These AT-rich isochores exhibit several sequence and structural features consistent with scaffold/matrix attachment regions (S/MARs), raising the possibility that they influence higher-order genome organisation. Comparative analyses suggest they arose through independent repeat insertions or via ancestral repeat amplifications. Together, our findings point to a role for AT-rich isochores in shaping genome architecture and potentially mediating stress-responsive regulation, supporting the broader environmental flexibility observed in Hypoxylaceae, including adaptation to dynamic coastal habitats.
]]></description>
<dc:creator>Kuo, C.-Y. T.-U.</dc:creator>
<dc:creator>Liu, Y.-C.</dc:creator>
<dc:creator>Yang, C.-J.</dc:creator>
<dc:creator>Lin, C.-P.</dc:creator>
<dc:creator>Chen, H.-W.</dc:creator>
<dc:creator>Hsieh, H.-M.</dc:creator>
<dc:creator>Ju, Y.-M.</dc:creator>
<dc:creator>Liu, T.-H.</dc:creator>
<dc:creator>Lee, Y.-C.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:date>2025-12-19</dc:date>
<dc:identifier>doi:10.64898/2025.12.16.694779</dc:identifier>
<dc:title><![CDATA[Dynamic evolution of AT-rich isochores shapes the genome of an intertidal fungus Annulohypoxylon annulatoides]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-12-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2025.12.17.695032v1?rss=1">
<title>
<![CDATA[
Scube2 Modulates Coronary Vessel Formation during Cardiac Growth and Regeneration in Zebrafish 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2025.12.17.695032v1?rss=1</link>
<description><![CDATA[
Coronary vessel formation is essential for cardiac growth and regeneration, yet the mechanisms regulating these processes remain incompletely defined. In this study, we identified and characterized Scube2 as a novel regulator in coronary vessel formation and heart regeneration. Scube2 is expressed in the epicardium covering the coronary vasculature under homeostatic conditions in adult hearts and is strongly upregulated after cardiac injury. Zebrafish scube2 mutant exhibits reduced coronary vessel coverage during cardiac growth and pronounced myocardial defects, including abnormal vessel morphology, disorganized contractile fibers, and mitochondrial damage. Following injury, scube2 mutant hearts show impaired revascularization and persistent fibrosis, indicating defective regeneration. Mechanistically, transcriptomic profiling of scube2 mutant hearts reveals attenuated expression of angiogenic-related genes, including those mediated by vascular endothelial and platelet-derived growth factors, consistent with reduced proliferation of endothelial cells and cardiomyocytes during repair. In a gain-of-function setting, SCUBE2 enhances platelet-derived growth factor signaling by promoting receptor activation in HEK293 cells. These findings support a novel role for Scube2 in cardiac growth and regeneration by modulating coronary vessel formation.

Graphical Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/695032v1_ufig1.gif" ALT="Figure 1">
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]]></description>
<dc:creator>Lai, S.-L. B.</dc:creator>
<dc:creator>Lee, A. N.</dc:creator>
<dc:creator>Wei, K.-H.</dc:creator>
<dc:creator>Chowdhury, K.</dc:creator>
<dc:creator>Rouf, M. A.</dc:creator>
<dc:creator>Chu, A.-J.</dc:creator>
<dc:creator>Hung, Y.-J.</dc:creator>
<dc:creator>Tsao, K.-C.</dc:creator>
<dc:creator>Chen, Y.-T.</dc:creator>
<dc:creator>Lin, Y.-C.</dc:creator>
<dc:creator>Chang, Y.-M.</dc:creator>
<dc:creator>Marin-Juez, R.</dc:creator>
<dc:creator>Yang, R.-B.</dc:creator>
<dc:date>2025-12-19</dc:date>
<dc:identifier>doi:10.64898/2025.12.17.695032</dc:identifier>
<dc:title><![CDATA[Scube2 Modulates Coronary Vessel Formation during Cardiac Growth and Regeneration in Zebrafish]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-12-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2025.12.27.696724v1?rss=1">
<title>
<![CDATA[
Molecular bases for USP48 cis-activity regulation and hyperactivation by Cushing's disease-associated mutations 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2025.12.27.696724v1?rss=1</link>
<description><![CDATA[
Ubiquitin-specific protease 48 (USP48) is a deubiquitinating enzyme involved in various pathophysiological processes, including DNA repair, tumorigenesis, and inflammation. Somatic mutations in USP48 (M415I/V) are associated with pituitary tumors in Cushings disease. These variants lead to increased USP48 enzyme activity and adrenocorticotropic hormone (ACTH) hypersecretion, a key feature of Cushings disease, indicating a direct link to the condition. Using biochemical experiments and in silico structural analyses, we identified Y414 in the catalytic USP domain as a critical residue for USP48 activity. In the wild-type USP domain, the Y414 side chain was oriented to  closed, which led to catalytic triad misalignment and weak ubiquitin recognition. We also found that the C-terminal region (CTR) of USP48 is a cis-activating region. It interacts with the USP domain and ubiquitin tail, thereby facilitating the alignment of the catalytic triad and enhancing ubiquitin recognition ability. Additionally, genomic analyses of pituitary tumors in Japanese patients with Cushings disease (n=46) confirmed that USP48 M415I/V variants occurred at a frequency of 10%, which is consistent with previous reports. Our structural model suggests that M415I/V sterically interferes with and fixes the closed Y414 side chain to  open, resulting in catalytic triad alignment and increased ubiquitin recognition ability. Furthermore, USP48 with M415I/V showed enhanced CTR-mediated activity, indicating that the open Y414 side chain and CTR can cause hyperactivation. This study provides a molecular basis for the novel cis-activation regulation of USP48 and its hyperactivation by Cushings disease-associated variants.

Significance StatementThe regulatory mechanisms of DUB activity are not yet fully understood. This study identifies the CTR of USP48 as an activity-promoting region, a mechanism also present in USP7 and potentially other closely related DUBs such as USP40 and USP47. Despite the disease association of some DUBs, developing drugs to inhibit specific DUB members or variants remains challenging. The substitutions of USP48 M415 embedded in the USP domain to Ile/Val are associated with Cushings disease, which lacks adequate targeted therapeutics. This study reveals that these variants alter the orientation of Y414, leading to hyperactivation. These findings provide a molecular basis for developing USP48M415I/V-specific inhibitors for Cushings disease therapy.
]]></description>
<dc:creator>Ando, G.</dc:creator>
<dc:creator>Tsujimoto, Y.</dc:creator>
<dc:creator>Moritsugu, K.</dc:creator>
<dc:creator>Kakihara, K.</dc:creator>
<dc:creator>Kidera, A.</dc:creator>
<dc:creator>Yamada, S.</dc:creator>
<dc:creator>Komada, M.</dc:creator>
<dc:creator>Fukuoka, H.</dc:creator>
<dc:creator>Fukushima, T.</dc:creator>
<dc:date>2025-12-28</dc:date>
<dc:identifier>doi:10.64898/2025.12.27.696724</dc:identifier>
<dc:title><![CDATA[Molecular bases for USP48 cis-activity regulation and hyperactivation by Cushing's disease-associated mutations]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-12-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2025.12.30.697121v1?rss=1">
<title>
<![CDATA[
Rescuing Neurodevelopmental Deficits in AMPA Receptor Gain-of-Function Mutant 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2025.12.30.697121v1?rss=1</link>
<description><![CDATA[
AMPA receptors (AMPARs) mediate fast excitatory synaptic transmission and are essential for neuronal development and brain function. We investigated the role of a recurrent variant in the AMPAR GluA1 subunit (GRIA1 p.A636T) identified in individuals with autism spectrum disorder (ASD) and intellectual disability (ID). To test causality and mechanism, we generated a Gria1-A636T knock-in mouse model. Mutant mice exhibited core ASD/ID-like behaviors and a selective hippocampal vulnerability characterized by progressive dendritic atrophy and neuronal loss. Despite reduced GluA1-containing complexes, AMPARs displayed synaptic hyperexcitability and failed to undergo the normal postnatal transition to calcium-impermeable AMPARs, resulting in persistent excitotoxicity. To explore therapeutic intervention, we designed an allele-specific antisense oligonucleotide to specifically silence the mutant transcript. A single neonatal administration of the antisense oligonucleotide entirely prevented hippocampal pathology and ameliorated behavioral deficits. These findings establish GRIA1-A636T as a gain-of-function mutation that drives developmental excitotoxicity and highlight the potential of RNA-targeted precision medicine for neurodevelopmental disorders.
]]></description>
<dc:creator>Chen, C.-M.</dc:creator>
<dc:creator>Huang, Y.-M.</dc:creator>
<dc:creator>Chung, C.-C.</dc:creator>
<dc:creator>Johnson, R. C.</dc:creator>
<dc:creator>Tsai, C.-Y.</dc:creator>
<dc:creator>Chen, Y.-H.</dc:creator>
<dc:creator>Tan, H. L.</dc:creator>
<dc:creator>Hsiao, F.-Y.</dc:creator>
<dc:creator>Huganir, R. L.</dc:creator>
<dc:creator>Chiu, S.-L.</dc:creator>
<dc:date>2025-12-31</dc:date>
<dc:identifier>doi:10.64898/2025.12.30.697121</dc:identifier>
<dc:title><![CDATA[Rescuing Neurodevelopmental Deficits in AMPA Receptor Gain-of-Function Mutant]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2025-12-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.01.18.698864v1?rss=1">
<title>
<![CDATA[
Resilience and reassembly of redox-structured microbial functional networks after rare holomixis in a meromictic lake 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.01.18.698864v1?rss=1</link>
<description><![CDATA[
Abstract-shortLand-locked meromictic lakes are characterized by long-term stratification and steep redox gradients that sustain vertically structured microbial communities and tightly coupled biogeochemical processes. Because complete overturns of the lake are rare, the dynamics of microbial reassembly after redox gradients collapse and subsequently recover remain poorly resolved. We investigated a mixing-restratification transition in Lake Shira (Siberia) with depth-stratified sampling of oxic, chemocline, anoxic, and water-sediment interface layers across four stages: intermittent holomictic (IH), complete holomictic (CH), developing meromictic (DM), and stable meromictic (M). 16S rRNA gene amplicons showed that CH homogenized the water column, dominated by Gamma- and Alphaproteobacteria, Campylobacteria, and Cyanobacteriia. As stratification re-formed (DM-M), communities became strongly depth-partitioned, with Desulfobacterota and other anaerobes re-established in sulfidic deep waters and assemblages concentrating near the redox transition. Nanopore metagenomics reconstructed 401 MAGs, revealing stage- and depth-specific functional repertoires consistent with redox zonation. Core MAGs, including Yoonia spp., persisted across phases, suggesting functional continuity underpinning rapid ecosystem recovery. These data provide a system-wide view of biogeochemical reassembly during collapse and restoration of stratification meromictic lake.
]]></description>
<dc:creator>Chan, Y.-F.</dc:creator>
<dc:creator>Chiang, P.-W.</dc:creator>
<dc:creator>Lim, S. L.</dc:creator>
<dc:creator>Rogozin, D.</dc:creator>
<dc:creator>Zykov, V.</dc:creator>
<dc:creator>Ye, C.-H.</dc:creator>
<dc:creator>Tang, S.-L.</dc:creator>
<dc:date>2026-01-19</dc:date>
<dc:identifier>doi:10.64898/2026.01.18.698864</dc:identifier>
<dc:title><![CDATA[Resilience and reassembly of redox-structured microbial functional networks after rare holomixis in a meromictic lake]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-01-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.01.17.700073v1?rss=1">
<title>
<![CDATA[
Engineering a performance-improved, axon-targeted kalium channelrhodopsin for optogenetic neuropathway inhibition 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.01.17.700073v1?rss=1</link>
<description><![CDATA[
Optogenetic neuropathway inhibition is a powerful approach for dissecting circuit functions. This strategy, however, frequently encounters practical challenges due to insufficient expression or performance of the optogenetic silencer on axonal projections/terminals. HcKCR1, a light-gated potassium-selective channel from Hyphochytrium catenoides, has shown great promise for optogenetic inhibition. Unfortunately, the application of HcKCR1 in neuropathway manipulations is hindered by its unsatisfactory gating properties and poor axonal trafficking. To overcome these hurdles, we first engineered a performance-improved HcKCR1 (piKCR) that allowed more reliable neuronal inhibition at low intensities of green or red light. We next engineered an axon-targeted piKCR (piKCR.AT) that demonstrated long-range axonal trafficking and optical presynaptic inhibition in the mouse hippocampus. When piKCR.AT was expressed in the cerebellar Purkinje Cells (PCs), optical manipulation of PC outputs to the deep cerebellar nuclei robustly disrupted mouse movement on the balance beam. With enhanced performance and axonal distribution, piKCR.AT may provide new opportunities for elucidating neuropathway functions in health and diseases.
]]></description>
<dc:creator>Lopez, S. M. M.</dc:creator>
<dc:creator>Wang, H.-Y.</dc:creator>
<dc:creator>Lee, I.-C.</dc:creator>
<dc:creator>Chen, W.-H.</dc:creator>
<dc:creator>Chen, Y.-C.</dc:creator>
<dc:creator>Lin, Y.-J.</dc:creator>
<dc:creator>Chen, C.-C.</dc:creator>
<dc:creator>Pan, M.-K.</dc:creator>
<dc:creator>Hsu, C.-L.</dc:creator>
<dc:creator>Lin, W.-C.</dc:creator>
<dc:date>2026-01-21</dc:date>
<dc:identifier>doi:10.64898/2026.01.17.700073</dc:identifier>
<dc:title><![CDATA[Engineering a performance-improved, axon-targeted kalium channelrhodopsin for optogenetic neuropathway inhibition]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-01-21</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.01.24.701468v1?rss=1">
<title>
<![CDATA[
Deficiency of miR130a leads to fat hypertrophy, hepatic steatosis, insulin resistance and glucose intolerance in mice 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.01.24.701468v1?rss=1</link>
<description><![CDATA[
Insulin resistance, excessive and ectopic fat accumulation, chronic low-grade inflammation, and pancreatic beta-cell failure are pathological features of type 2 diabetes mellitus.MiR-130a has been demonstrated to suppress the mRNA levels of PPAR{gamma}, NF-{kappa}B, and TNF- in vitro. PPAR{gamma} is a master regulator of systemic fat and glucose metabolism. NF-{kappa}B and TNF- are pivotal modulators of inflammation. Therefore, we aimed to examine the systemic effect of miR130a on fat metabolism, glucose/insulin homeostasis, and inflammation in mice.

We found that mirR130a-deficient mice exhibited larger white fat mass with hypertrophic adipocytes, increased lipogenic gene expression in fat, and elevated serum leptin levels than controls. The white fat pads of mirR130a-deficient mice showed significant macrophage infiltration with enhanced expression of pro-inflammatory genes. In addition, mirR130a-deficient mice had more severe hepatic steatosis and higher hepatic triglycerides content than controls. Similarly, mirR130a-deficient mice had increased macrophage infiltration and lipogenic and inflammatory gene expression in the liver. Consistently, we found that Lepob/ob mice expressed markedly decreased miR130a expression in the liver and white fat compared to controls.

Importantly, mirR130a-deficient mice displayed impaired glucose tolerance and worsened insulin resistance, accompanied with reduced serum adiponectin levels. Furthermore, insulin secretion is reduced in mirR130a-deficient mice compared to controls.

In conclusion, knockout of miR130a in mice results in fat hypertrophy, hepatic steatosis, increased macrophage infiltration in liver and fat, glucose intolerance, and insulin resistance. These data indicate miR130a exert systemic anti-diabetic effects.
]]></description>
<dc:creator>Chang, Y.-C.</dc:creator>
<dc:creator>Chuang, C.-H.</dc:creator>
<dc:creator>Chou, S.-F.</dc:creator>
<dc:creator>Huang, J.-Y.</dc:creator>
<dc:creator>Shih, C.-h.</dc:creator>
<dc:date>2026-01-24</dc:date>
<dc:identifier>doi:10.64898/2026.01.24.701468</dc:identifier>
<dc:title><![CDATA[Deficiency of miR130a leads to fat hypertrophy, hepatic steatosis, insulin resistance and glucose intolerance in mice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-01-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.02.04.703894v1?rss=1">
<title>
<![CDATA[
Time perception follows Weber's law in Drosophila 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.02.04.703894v1?rss=1</link>
<description><![CDATA[
The ability to perceive time is essential for adaptive behavior, enabling organisms to respond to change, coordinate actions, and predict future events in dynamic environments and during social interactions. However, its evolutionary origins and underlying neural mechanisms remain poorly understood. Here, we demonstrate that the fruit fly, Drosophila melanogaster, can perceive time intervals ranging from sub-second to a few seconds and use them to predict the location of potential food sources. Using a behavioral paradigm in which flies learn to associate temporal patterns of sound with food rewards, we show that their ability to discriminate between two time intervals depends on the ratio of their durations rather than their absolute difference. This proportional relationship follows Webers law, a fundamental principle of sensory discrimination. Moreover, flies can generalize learned temporal rules to novel stimuli and across sensory modalities, suggesting they form an abstract representation of time. Finally, we identify the mushroom body as a critical neural circuit for temporal learning. These findings reveal unexpected timing capabilities in Drosophila, providing new insights into the evolutionary origin of temporal cognition and establishing Drosophila as a genetically tractable model for investigating the neural basis of time perception.
]]></description>
<dc:creator>Lo, T.-N.</dc:creator>
<dc:creator>Huang, C.-Y.</dc:creator>
<dc:creator>Lin, S.</dc:creator>
<dc:date>2026-02-07</dc:date>
<dc:identifier>doi:10.64898/2026.02.04.703894</dc:identifier>
<dc:title><![CDATA[Time perception follows Weber's law in Drosophila]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-02-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.02.13.705822v1?rss=1">
<title>
<![CDATA[
A haploid wild yeast resource for exploring the natural ecology of Saccharomyces cerevisiae 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.02.13.705822v1?rss=1</link>
<description><![CDATA[
Saccharomyces cerevisiae predominantly exists as diploid cells in nature, a life-cycle feature that limits classical genetic analyses of wild populations. Here, we establish a stable haploid strain collection derived from 33 diverse Taiwanese S. cerevisiae isolates through targeted disruption of the HO endonuclease gene. This resource spans predomesticated Asian wild lineages and enables systematic analyses of mating compatibility, reproductive isolation, and ecological trait variation. Although all pairwise hybridizations formed zygotes, many produced low spore viabilities, revealing strong postzygotic barriers. Genome analyses show that reduced hybrid fertility is primarily associated with chromosomal inversions and inter-chromosomal rearrangements rather than sequence divergence, indicating that structural variation maintains lineage separation despite geographic coexistence. Phenotypic profiling uncovered marked ecological differentiation, with the most diverged TW1 lineage favoring cooler growth conditions and a naturally occurring hybrid exhibiting heterosis with expanded thermal tolerance. While most wild strains grew poorly on maltose, two anthropogenically associated strains displayed enhanced maltose utilization linked to functional MAL regulatory alleles and maltose-specific transporters. Together, these findings demonstrate how structural genomic variation and metabolic gene divergence drive ecological and reproductive divergence in wild S. cerevisiae and establish this haploid collection as a platform for studying yeast evolution in nature.
]]></description>
<dc:creator>Yang, C.-J.</dc:creator>
<dc:creator>Yeh, Y.-C.</dc:creator>
<dc:creator>Hsiao, C.</dc:creator>
<dc:creator>Liu, Y.-H.</dc:creator>
<dc:creator>Lu, M. R.</dc:creator>
<dc:creator>Liu, Y.-C.</dc:creator>
<dc:creator>Liti, G.</dc:creator>
<dc:creator>Tsai, I. J.</dc:creator>
<dc:creator>Ke, H.-M.</dc:creator>
<dc:date>2026-02-16</dc:date>
<dc:identifier>doi:10.64898/2026.02.13.705822</dc:identifier>
<dc:title><![CDATA[A haploid wild yeast resource for exploring the natural ecology of Saccharomyces cerevisiae]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-02-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.03.08.710424v1?rss=1">
<title>
<![CDATA[
Structure and functional analyses of vaccinia virus J5 protein reveal distinct determinants for entry-fusion complex assembly and activation 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.03.08.710424v1?rss=1</link>
<description><![CDATA[
Vaccinia virus enters host cells through a multi-component entry fusion complex (EFC) that is structurally distinct from canonical viral fusion systems. Understanding how vaccinia virus EFC mediates membrane fusion is crucial for elucidating poxvirus entry and identifying potential antiviral targets. Here, we report the solution NMR structure of a truncated ectodomain of vaccinia J5 protein, residues 2-68. Using recombinant vaccinia viruses expressing J5 mutants, we analyzed substitutions in conserved and surface-exposed residues, as well as chimeric constructs between vaccinia J5 and its entomopoxvirus ortholog AMV232. Functional analyses revealed that the conserved P38YYCWY43 motif is dispensable for EFC assembly but required for membrane fusion activity whereas the flexible region spanning residues 90-110 mediates interactions required for stable incorporation of J5 into the EFC.

ImportanceVaccinia virus enters host cells through membrane fusion mediated by a unique multi-component entry fusion complex (EFC) that is distinct from classical viral fusion proteins. Although J5 has been identified as a central component of the pre-fusion EFC, the structural regions of J5 required for membrane fusion remain unclear. Here, we determined the solution NMR structure of the J5 ectodomain and identified two regions, the conserved P38YYCWY43 motif and residues 90-110, as key determinants of EFC function during vaccinia virus entry.
]]></description>
<dc:creator>Chiu, H.-J.</dc:creator>
<dc:creator>Carillo, K. J. D.</dc:creator>
<dc:creator>Hsieh, L. T.-H.</dc:creator>
<dc:creator>Lou, Y.-C.</dc:creator>
<dc:creator>Lin, C. S.-H.</dc:creator>
<dc:creator>Tzou, D.-L. M.</dc:creator>
<dc:creator>Chang, W.</dc:creator>
<dc:date>2026-03-09</dc:date>
<dc:identifier>doi:10.64898/2026.03.08.710424</dc:identifier>
<dc:title><![CDATA[Structure and functional analyses of vaccinia virus J5 protein reveal distinct determinants for entry-fusion complex assembly and activation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.03.09.710440v1?rss=1">
<title>
<![CDATA[
Robust volumetric multiplex staining of centimeter-scale FFPE tissues guided by neural network-based optimization 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.03.09.710440v1?rss=1</link>
<description><![CDATA[
Neurodegenerative diseases involve structural and morphological alterations in tissue architecture that are difficult to capture in single thin sections. Three-dimensional multiplexed pathology, however, remains limited by the lack of clearing methods applicable to formalin-fixed paraffin-embedded (FFPE) clinical specimens. As the development of tissue-clearing methods requires the optimization of multiple parameters, we employed a neural network-based Complex System Response (CSR) approach to guide the design of FIDELITY, an epoxy-free delipidation and epitope-retrieval pipeline for whole FFPE specimens. FIDELITY preserves tissue rigidity, enhances immunostaining efficiency, and supports at least five rounds of multiplex labeling without deformation. It enables whole-brain atlas registration, quantitative neuronal profiling, and volumetric pathology of archived human Alzheimers and glioma specimens while remaining compatible with routine histology. Altogether, FIDELITY provides accurate 3D metrics and offers translational potential to bridge spatial mapping and conventional pathology.
]]></description>
<dc:creator>Lin, Y.-H.</dc:creator>
<dc:creator>Huang, C.-Y.</dc:creator>
<dc:creator>Chen, Y.-H.</dc:creator>
<dc:creator>Chen, Y.-H.</dc:creator>
<dc:creator>Xu, Z.-W.</dc:creator>
<dc:creator>Ko, P.-L.</dc:creator>
<dc:creator>Hsu, H.-H.</dc:creator>
<dc:creator>Tung, Y.-C.</dc:creator>
<dc:creator>Chen, Y.-F.</dc:creator>
<dc:creator>Chen, H.-C.</dc:creator>
<dc:creator>Chiang, A.-S.</dc:creator>
<dc:creator>Fiock, K. L.</dc:creator>
<dc:creator>Wang, K.-C.</dc:creator>
<dc:creator>Lin, C.-H.</dc:creator>
<dc:creator>Hu, S.-H.</dc:creator>
<dc:creator>Chen, B.-C.</dc:creator>
<dc:creator>Chu, L.-A.</dc:creator>
<dc:date>2026-03-11</dc:date>
<dc:identifier>doi:10.64898/2026.03.09.710440</dc:identifier>
<dc:title><![CDATA[Robust volumetric multiplex staining of centimeter-scale FFPE tissues guided by neural network-based optimization]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.03.11.710967v1?rss=1">
<title>
<![CDATA[
Oxidative Stress-Induced Microglial CD22 Upregulation Impairs Phagocytosis and Exacerbates Huntingtons Disease 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.03.11.710967v1?rss=1</link>
<description><![CDATA[
BackgroundHuntingtons disease (HD) is a neurodegenerative disorder caused by an abnormal polyglutamine expansion in mutant huntingtin (mHTT) and is characterized by movement dysfunction and neuronal loss. Siglecs, a family of sialic acid-binding proteins, are expressed on brain microglia and implicated in Alzheimers disease. Sialic acids are abundant in mammalian brains and cap the termini of the glycocalyx of various brain cells. Alterations in sialoglycans or Siglecs may affect interactions between microglia and other brain cells. However, the roles of Siglecs in HD have not been investigated.

MethodsWe profiled Siglecs in postmortem caudate nucleus samples from HD subjects and in a mouse model of HD (R6/2) using RT-qPCR and mass cytometry analyses. CD22 functions in microglia were evaluated using a microglial cell line (BV2) and primary microglia. Native ligands for microglial CD22 were assessed via glycomic profiling and flow cytometry. Regulation of CD22 ligands in astrocytes was investigated in an astrocytic cell line (C8-D1A) and primary astrocytes. The role of CD22 in HD was examined by genetic deletion in HD mice, followed by behavioral analyses and pathological evaluation with immunofluorescence staining and MRI.

ResultsUpregulation of CD22 in microglia, observed in the brains of patients and mice with HD, impairs microglial phagocytosis via ITIM-ITAM signaling crosstalk. This CD22 upregulation was driven by chronic oxidative stress, as antioxidant treatment (N-acetylcysteine) markedly normalized CD22 levels. CD22 ligand, 2,6-sialylated-6-sulfo-LacNAc, primarily expressed by astrocytes, was significantly reduced in HD mice. mHTT, but not wild-type HTT, suppressed ligand synthesis in astrocytes under elevated oxidative stress, allowing more CD22 on the microglial surface to inhibit phagocytosis. Treatment with a neutralizing antibody or ligand-enriched extracellular vesicles depleted surface CD22 and restored the phagocytic function of microglia. Genetic deletion of CD22 in HD mice improved rotarod performance, reduced mHTT inclusion burden, increased Darpp32 expression, and alleviated brain atrophy, supporting the concept that CD22-mediated inhibition of microglial phagocytosis contributes to HD pathogenesis.

ConclusionOur findings suggest that CD22 acts as a checkpoint-like regulator that restrains microglial phagocytosis and contributes to HD progression when astrocyte-microglia communication is impaired, thereby highlighting CD22 as a promising therapeutic target.
]]></description>
<dc:creator>Lee, Y. H.</dc:creator>
<dc:creator>Siew, J. J.</dc:creator>
<dc:creator>Lee, C.-W.</dc:creator>
<dc:creator>Chen, H.-M.</dc:creator>
<dc:creator>Lu, Y.-T.</dc:creator>
<dc:creator>Sridharan, D.</dc:creator>
<dc:creator>Huang, P.-C. J.</dc:creator>
<dc:creator>Chang, H.-C.</dc:creator>
<dc:creator>Guu, S.-Y.</dc:creator>
<dc:creator>Wang, P.-Y.</dc:creator>
<dc:creator>Wang, Y.-F.</dc:creator>
<dc:creator>Liang, S.-Y.</dc:creator>
<dc:creator>Khoo, K.-H.</dc:creator>
<dc:creator>Angata, T.</dc:creator>
<dc:creator>Chern, Y.</dc:creator>
<dc:date>2026-03-13</dc:date>
<dc:identifier>doi:10.64898/2026.03.11.710967</dc:identifier>
<dc:title><![CDATA[Oxidative Stress-Induced Microglial CD22 Upregulation Impairs Phagocytosis and Exacerbates Huntingtons Disease]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.03.14.711779v1?rss=1">
<title>
<![CDATA[
Calcium modulates intramolecular long-range contacts to form a polymorphic α-synuclein A53T fibril 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.03.14.711779v1?rss=1</link>
<description><![CDATA[
Human -synuclein (aSyn) is an intrinsically disordered protein, and aggregations of its amyloid fibrils are associated with Parkinsons disease (PD). Apart from familial aSyn mutations, accumulated environmental calcium exacerbates aSyn aggregation and accelerates symptoms in aging PD patients. Here, we explored the effects of Ca2+ ions on aSyn A53T, an aggregation-prone mutant variant, from disordered states to fibrillar structures. Paramagnetic nuclear magnetic resonance (NMR) revealed that binding of Ca2+ ions to the aSyn C-terminal (residues 110-140) relaxed the aSyn conformation, resulting in more aggressive fibrillogenesis. Cryo-electron microscopy structures of aSyn A53T with or without Ca2+ ion revealed substantial differences in amyloid folds and fibril assemblies. We characterized N1 (residues 61-66), N2 (residues 69-79), and N3 (residues 89-95) segments in the central non-amyloid {beta} component (NAC) crucial for forming localized structural contacts during early-step aggregation. Our work establishes the contacts governing aSyn misfolding from disordered monomer to aggregated fibril and provides insights into the structural changes elicited by Ca2+ ions.
]]></description>
<dc:creator>Huang, J. Y. C.</dc:creator>
<dc:creator>Wu, K.-P.</dc:creator>
<dc:date>2026-03-17</dc:date>
<dc:identifier>doi:10.64898/2026.03.14.711779</dc:identifier>
<dc:title><![CDATA[Calcium modulates intramolecular long-range contacts to form a polymorphic α-synuclein A53T fibril]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.03.16.712002v1?rss=1">
<title>
<![CDATA[
A Distinct Layer 1 Astrocyte Program Shapes Perisynaptic Structure and Calcium Signaling in Mouse Motor Cortex 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.03.16.712002v1?rss=1</link>
<description><![CDATA[
Although layer-specific molecular and morphological diversity among cortical astrocytes is increasingly well established, how these distinct states are linked to specialized calcium signaling and maintained in the adult cortex remains unclear. Here, combining super-resolution structural imaging, two-photon calcium imaging, and analysis of public single-cell and spatial transcriptomic resources, we identify Layer 1 (L1) astrocytes in mouse primary motor cortex as a distinct superficial astrocyte program. These cells occupy compact territories yet contain dense synapse-associated loop-like structures and display frequent, fast, broadly spreading calcium events that engage a large fraction of the territory. Transcriptomic analyses identify Id1 and Id3 as enriched components of this superficial program. CRISPR-Cas9 deletion of Id1 and Id3 in adult astrocytes selectively disrupts L1 and superficial Layer 2/3 (L2/3) astrocytes, expanding territory size, reducing fine-process complexity, and suppressing calcium activity. Thus, adult layer-specific transcriptional programs maintain specialized astrocyte structure and signaling.

Graphical Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=185 SRC="FIGDIR/small/712002v1_ufig1.gif" ALT="Figure 1">
View larger version (65K):
org.highwire.dtl.DTLVardef@89c916org.highwire.dtl.DTLVardef@1f0d71eorg.highwire.dtl.DTLVardef@bb02f3org.highwire.dtl.DTLVardef@1bedf7e_HPS_FORMAT_FIGEXP  M_FIG C_FIG HighlightsO_LILayer 1 astrocytes in mouse motor cortex have compact, loop-rich nanoarchitecture
C_LIO_LILayer 1 astrocytes show fast, frequent, widespread calcium events
C_LIO_LISingle-cell data define a superficial astrocyte state enriched for Id1 and Id3
C_LIO_LIAdult Id1/Id3 loss selectively disrupts Layer 1 astrocyte structure and calcium
C_LI

In BriefBhattacharjee et al., identify a specialized Layer 1 astrocyte state in mouse motor cortex, defined by compact, loop-rich nanoarchitecture and unusually high calcium signaling. Id1/Id3 deletion selectively disrupts this superficial program, linking layer-specific astrocyte form and function to adult transcriptional control.
]]></description>
<dc:creator>Bhattacharjee, S.</dc:creator>
<dc:creator>Yeh, K.-H.</dc:creator>
<dc:creator>Wu, P.-Y.</dc:creator>
<dc:creator>Pan, M.-X.</dc:creator>
<dc:creator>Liu, T.-H.</dc:creator>
<dc:creator>Tsai, Z.-B.</dc:creator>
<dc:creator>Tong, S.-K.</dc:creator>
<dc:creator>Zhuang, Z.-H.</dc:creator>
<dc:creator>Huang, Y.-M.</dc:creator>
<dc:creator>Chou, S.-J.</dc:creator>
<dc:creator>Chiu, S.-L.</dc:creator>
<dc:creator>Chou, M.-Y.</dc:creator>
<dc:creator>Yu, C.-H.</dc:creator>
<dc:creator>Wu, Y.-W.</dc:creator>
<dc:date>2026-03-17</dc:date>
<dc:identifier>doi:10.64898/2026.03.16.712002</dc:identifier>
<dc:title><![CDATA[A Distinct Layer 1 Astrocyte Program Shapes Perisynaptic Structure and Calcium Signaling in Mouse Motor Cortex]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.03.18.712551v1?rss=1">
<title>
<![CDATA[
IFN-γ-Dependent Macrophage Reprogramming Coordinates Inflammatory Resolution and Matrix Remodeling in Heart Regeneration 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.03.18.712551v1?rss=1</link>
<description><![CDATA[
Heart regeneration requires coordinated immune activation, timely inflammatory resolution, and dynamic extracellular matrix (ECM) remodeling in addition to cardiomyocyte (CM) proliferation. However, the cytokine signals that instruct immune cell functions during cardiac repair remain incompletely understood. Here, we identify interferon-gamma (IFN-{gamma}) as a critical regulator of macrophage plasticity in zebrafish heart regeneration. IFN-{gamma} signaling components are dynamically activated following cardiac injury, with early induction of ifng1 and temporally coordinated receptor expression. Genetic ablation of ifng1 impairs myocardial regeneration, resulting in reduced CM proliferation and persistent fibrotic scarring. Temporal transcriptional profiling reveals sustained inflammatory signatures, impaired efferocytosis, and abolished reparative programs, accompanied by aberrant immune cell dynamics and retention of injury-derived debris in mutant hearts. Transcriptomic analysis of cardiac macrophages further reveals that IFN-{gamma} deficiency disrupts the transition from an inflammatory state to a reparative, ECM-remodeling phenotype, leading to reduced collagen denaturation and diminished CM protrusion at the injury border zone. Inducible- and macrophage-specific blockade of IFN-{gamma} signaling phenocopies defects in global knockout, establishing a cell-autonomous requirement for IFN-{gamma} in coordinating regenerative immune function. Collectively, our findings define an IFN-{gamma}-dependent macrophage reprogramming axis that couples inflammatory resolution to ECM remodeling in heart regeneration, elucidating how cytokine signaling actively instructs tissue repair.

GRAPHICAL ABSTRACT

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/712551v1_ufig1.gif" ALT="Figure 1">
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org.highwire.dtl.DTLVardef@8cb384org.highwire.dtl.DTLVardef@15dd8d6org.highwire.dtl.DTLVardef@46dcc4org.highwire.dtl.DTLVardef@47e2ac_HPS_FORMAT_FIGEXP  M_FIG C_FIG
]]></description>
<dc:creator>Lim, K. L.</dc:creator>
<dc:creator>Chowdhury, K.</dc:creator>
<dc:creator>Hung, Y.-J.</dc:creator>
<dc:creator>Lai, S.-L.</dc:creator>
<dc:date>2026-03-20</dc:date>
<dc:identifier>doi:10.64898/2026.03.18.712551</dc:identifier>
<dc:title><![CDATA[IFN-γ-Dependent Macrophage Reprogramming Coordinates Inflammatory Resolution and Matrix Remodeling in Heart Regeneration]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.03.27.714696v1?rss=1">
<title>
<![CDATA[
Effect of spatial heterogeneities on minimal stochastic models of cell polarity 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.03.27.714696v1?rss=1</link>
<description><![CDATA[
Asymmetric self-organization is a hallmark of cell polarity, yet the diversity of observed polarization patterns is frequently attributed to specialized, complex biochemical mechanisms motifs beyond simple positive feedback. Here, we demonstrate that spatial heterogeneity alone fundamentally reshapes polarization dynamics within minimal stochastic reaction-diffusion processes. We show that weak differences in reaction rates between distinct spatial domains strongly bias polarization timing and determine which region ultimately polarizes. In systems containing two distant favored regions, a "stochastic winner-takes-all" mechanism--driven by long-range competition mediated by a shared cytoplasmic pool--induces stochastic switching that manifests as pole-to-pole oscillations. By relaxing the assumption of a perfectly mixed cytoplasm and incorporating finite cytoplasmic diffusion, we reveal a qualitative shift in this competitive dynamic. Specifically, as the total particle abundance increases, the system transitions from monopolar to bipolar activation, capturing the essence of the New-End Take-Off (NETO) phenomenon during cell growth and provides a physical basis for pole coexistence. These results demonstrate that spatial heterogeneity alone can strongly influence polarization dynamics in minimal models, highlighting the potential importance of quenched spatial variability in biological reaction-diffusion systems.

Author summaryCells often need to choose a specific site for growth, division, or shape change. This process, known as cell polarization, is a fundamental organizing principle in biology. The wide variety of polarization patterns seen in living cells is often explained by proposing complex biochemical mechanisms beyond basic positive feedback among signaling molecules. In this work, we asked whether some of this diversity could instead arise from a simpler source: fixed spatial differences within the cell. Using minimal stochastic reaction-diffusion models, we found that even small local differences can strongly influence where polarization appears and how quickly it develops. When two favored sites are present, they can compete for a shared pool of molecules in cytoplasm, so that one site dominates at a time and the polarized state can switch stochastically between them. We also found that this competition changes when the shared molecular pool does not mix instantly: under these conditions, two polarized sites can start to coexist. This behavior offers a simple physical explanation for phenomena such as the appearance of a new growth site during cell development. Our results show that spatial heterogeneity alone can generate behaviors that might otherwise seem to require much more complicated biochemical mechanisms.
]]></description>
<dc:creator>Anfray, V.</dc:creator>
<dc:creator>Shih, H.-Y.</dc:creator>
<dc:date>2026-03-28</dc:date>
<dc:identifier>doi:10.64898/2026.03.27.714696</dc:identifier>
<dc:title><![CDATA[Effect of spatial heterogeneities on minimal stochastic models of cell polarity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.03.28.714958v1?rss=1">
<title>
<![CDATA[
Root Hydraulic and Metabolic Regulation Drives Drought Tolerance in Napier Grass 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.03.28.714958v1?rss=1</link>
<description><![CDATA[
Napier grass (Cenchrus purpureus syn. Pennisetum purpureum), a perennial C4 forage and bioenergy crop, exhibits strong drought resilience, yet the integrative mechanisms underlying this tolerance remain incompletely understood. This study examined physiological, hydraulic, and metabolic responses of four Napier grass cultivars under PEG-induced osmotic stress and progressive soil water deficit. Drought significantly increased the root-to-shoot ratio, indicating preferential biomass allocation to roots, which supported maintenance of shoot growth and tissue water status. All cultivars showed an approximate twofold increase in water-use efficiency (WUE) under water deficit, with cv2 and cv7 displaying superior performance. Upregulation of aquaporin genes (PIP2;2 and PIP2;3) suggested active hydraulic regulation that sustained carbon assimilation under reduced transpiration. Metabolic profiling revealed pronounced root-centered osmotic adjustment, including accumulation of galactinol, myo-inositol, raffinose family oligosaccharides, proline, and several amino acids. Enhanced expression of the galactinol synthase gene confirmed activation of raffinose biosynthesis pathways. Genotypic variation highlighted cv2 as particularly drought resilient. Rapid post-stress regrowth further underscored the importance of perennial root persistence. In conclusion, drought tolerance in Napier grass arises from coordinated hydraulic resilience, osmotic adjustment, and C4 photosynthetic efficiency, supporting its suitability for forage and bioenergy production in water-limited environments.

SignificantThis study shows drought tolerance in Napier grass relies on root-driven hydraulic and metabolic regulation with efficient water-use efficiency, rather than avoidance, and that PEG responses predict field performance.
]]></description>
<dc:creator>Ko, S.-S.</dc:creator>
<dc:creator>Wu, Y.-C.</dc:creator>
<dc:creator>Cheng, S.-C.</dc:creator>
<dc:creator>Li, M.-J.</dc:creator>
<dc:creator>Li, T.-R.</dc:creator>
<dc:creator>Lin, J.- B.</dc:creator>
<dc:creator>Sun, C.-H.</dc:creator>
<dc:creator>Chou, C. C.- K.</dc:creator>
<dc:creator>Yeh, K.-C.</dc:creator>
<dc:date>2026-03-31</dc:date>
<dc:identifier>doi:10.64898/2026.03.28.714958</dc:identifier>
<dc:title><![CDATA[Root Hydraulic and Metabolic Regulation Drives Drought Tolerance in Napier Grass]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-31</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.03.31.715701v1?rss=1">
<title>
<![CDATA[
Endosymbiotic algal photosynthesis shapes diel transcriptome architecture in its ciliate host Paramecium bursaria 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.03.31.715701v1?rss=1</link>
<description><![CDATA[
How photosynthetic endosymbionts reorganize host daily regulation remains unclear. Paramecium bursaria displays pronounced day-night behaviors, but whether its algal symbionts drive host temporal programs has been unresolved. We compared host gene expressions across a 24-hour light-dark cycle in symbiotic and aposymbiotic cells. Symbiotic cells exhibit an expanded and highly temporally ordered diel transcriptome compared with aposymbiotic cells. These rhythmic programs encompass motility, signaling, metabolism, and growth regulation, consistent with observed behaviors. Symbiosis-associated rhythmic programs recruit gene families encoding post-translational regulatory domains, including kinases, ubiquitin-related factors, WD40 scaffolds, and calcium-binding proteins, despite lacking recognizable canonical clock genes. Disrupting photosynthesis with paraquat altered these temporal profiles, shifting them toward an aposymbiotic-like state. A distantly related ciliate, Tetrahymena utriculariae, with an independently evolved symbiosis, showed similar symbiosis-associated daily programs, suggesting that photosynthetic endosymbionts can act as important organizers of host daily gene regulation in endosymbiotic protists.
]]></description>
<dc:creator>Kamal, M. M.</dc:creator>
<dc:creator>Cheng, Y.-H.</dc:creator>
<dc:creator>Yang, C.-L.</dc:creator>
<dc:creator>Jeff Liu, C.-F.</dc:creator>
<dc:creator>Ku, C.</dc:creator>
<dc:creator>Leu, J.-Y.</dc:creator>
<dc:date>2026-04-01</dc:date>
<dc:identifier>doi:10.64898/2026.03.31.715701</dc:identifier>
<dc:title><![CDATA[Endosymbiotic algal photosynthesis shapes diel transcriptome architecture in its ciliate host Paramecium bursaria]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.04.05.716573v1?rss=1">
<title>
<![CDATA[
Global genomic diversity of the selfing nematode Caenorhabditis tropicalis correlates with geography 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.04.05.716573v1?rss=1</link>
<description><![CDATA[
Self-fertilization reduces genetic diversity compared to outcrossing and hypothetically decreases the ability to adapt to diverse environments. Among Caenorhabditis nematodes, self-fertilization evolved three times independently in Caenorhabditis elegans, Caenorhabditis briggsae, and the more recently discovered Caenorhabditis tropicalis. To survey C. tropicalis genetic relatedness, the influence of geography and niche on species-wide variation, and the signatures of selection, we collected 785 wild strains, sequenced their genomes, and identified 622 distinct genotypes (isotypes). In contrast to C. elegans and C. briggsae, C. tropicalis relatedness shows substantial association with geography and no transcontinental selective sweeps or broadly sampled isotypes. Populations from the Hawaiian Islands or Taiwan harbor more genetic variation than populations from the Caribbean or Americas, suggesting a Pacific species origin similar to other members of the Elegans subclade. Punctuated genomic regions of extreme genetic variation pervade the genome. These hyper-divergent regions (HDRs) comprise less than 6% of the reference genome in any given strain despite harboring 73% of all variant sites and are enriched for genes likely involved in environmental adaptation. HDRs represent a shared genomic feature of self-fertilizing Caenorhabditis nematodes despite their independent evolutionary origins and suggest a mechanism to explain worldwide distributions despite low species-wide levels of genetic variation.
]]></description>
<dc:creator>Wang, B.</dc:creator>
<dc:creator>Moya, N. D.</dc:creator>
<dc:creator>Tanny, R. E.</dc:creator>
<dc:creator>Sauria, M. E. G.</dc:creator>
<dc:creator>O Connor, L. M.</dc:creator>
<dc:creator>Khorshidian, A.</dc:creator>
<dc:creator>McKeown, R.</dc:creator>
<dc:creator>Stevens, L.</dc:creator>
<dc:creator>Buchanan, C.</dc:creator>
<dc:creator>Crombie, T. A.</dc:creator>
<dc:creator>Dilks, C. M.</dc:creator>
<dc:creator>Evans, K. S.</dc:creator>
<dc:creator>Cook, D. E.</dc:creator>
<dc:creator>Zhang, G.</dc:creator>
<dc:creator>Stinson, L. A.</dc:creator>
<dc:creator>Roberto, N. M.</dc:creator>
<dc:creator>Lee, D.</dc:creator>
<dc:creator>Zdraljevic, S.</dc:creator>
<dc:creator>Gosse, C.</dc:creator>
<dc:creator>Gimond, C.</dc:creator>
<dc:creator>Chen, M.-E.</dc:creator>
<dc:creator>Dang, V. D.</dc:creator>
<dc:creator>Wang, J.</dc:creator>
<dc:creator>Cutter, A. D.</dc:creator>
<dc:creator>Rockman, M. V.</dc:creator>
<dc:creator>Felix, M.-A.</dc:creator>
<dc:creator>Braendle, C.</dc:creator>
<dc:creator>Andersen, E. C.</dc:creator>
<dc:date>2026-04-08</dc:date>
<dc:identifier>doi:10.64898/2026.04.05.716573</dc:identifier>
<dc:title><![CDATA[Global genomic diversity of the selfing nematode Caenorhabditis tropicalis correlates with geography]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.04.16.718233v1?rss=1">
<title>
<![CDATA[
Evolutionary landscapes of zygotic genome activation across animals 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.04.16.718233v1?rss=1</link>
<description><![CDATA[
During early animal embryogenesis, control over gene expression transitions from maternally deposited products to newly transcribed zygotic RNA. This process, termed zygotic genome activation (ZGA), is universal and essential but remains poorly characterized beyond a handful of model species 1. Here, we generated a comprehensive transcriptomic atlas of early embryogenesis from 61 animal species, spanning 13 phyla. By applying a unified computational framework, we systematically inferred the timing of ZGA across species. We uncover a large variation in ZGA timing, but find that a proxy for nuclear-to-cytoplasmic (N/C) ratio robustly predicts the onset of genome activation. Comparative analyses of the properties of zygotic genes showed that they are shorter and with fewer introns, enriched in functions related to RNA processing and gene expression, and phylogenetically younger than maternal genes. Altogether, our findings suggest that ZGA is universally timed by the stoichiometry between DNA content and specific maternally deposited factors, and this activation involves a highly flexible transcriptomic program that follows a deeply conserved molecular logic.
]]></description>
<dc:creator>Campo-Bes, I.</dc:creator>
<dc:creator>Mantica, F.</dc:creator>
<dc:creator>Permanyer, J.</dc:creator>
<dc:creator>Rodriguez-Marin, C.</dc:creator>
<dc:creator>Guynes, K.</dc:creator>
<dc:creator>Senar-Serra, T.</dc:creator>
<dc:creator>Quiroga-Artigas, G.</dc:creator>
<dc:creator>Liang, Y.</dc:creator>
<dc:creator>Carrillo-Baltodano, A. M.</dc:creator>
<dc:creator>Cruz, J.</dc:creator>
<dc:creator>Annunziata, R.</dc:creator>
<dc:creator>Chevalier, S.</dc:creator>
<dc:creator>Iglesias, M.</dc:creator>
<dc:creator>Sugahara, F.</dc:creator>
<dc:creator>Luo, Y.-J.</dc:creator>
<dc:creator>Schoenauer, A.</dc:creator>
<dc:creator>Corbacho, J.</dc:creator>
<dc:creator>Paganos, P.</dc:creator>
<dc:creator>Caccavale, F.</dc:creator>
<dc:creator>Sepe, R. M.</dc:creator>
<dc:creator>Iniguez, L. P.</dc:creator>
<dc:creator>Handberg-Thorsager, M.</dc:creator>
<dc:creator>Zakas, C.</dc:creator>
<dc:creator>Sommer, R. J.</dc:creator>
<dc:creator>Arnone, M. I.</dc:creator>
<dc:creator>McGregor, A. P.</dc:creator>
<dc:creator>Martinez-Morales, J. R.</dc:creator>
<dc:creator>Satoh, N.</dc:creator>
<dc:creator>Escriva, H.</dc:creator>
<dc:creator>Bertrand, S.</dc:creator>
<dc:creator>Sebe-Pedros, A.</dc:creator>
<dc:creator>D'Aniello, E.</dc:creator>
<dc:creator>Pascual-Anaya, J.</dc:creator>
<dc:creator>Houliston, E.</dc:creator>
<dc:creator>Franch-Marro, X.</dc:creator>
<dc:creator>Martin, D.</dc:creator>
<dc:creator>Somorjai, I. M. L.</dc:creator>
<dc:creator>Almudi, I.</dc:creator>
<dc:creator>Martin-</dc:creator>
<dc:date>2026-04-17</dc:date>
<dc:identifier>doi:10.64898/2026.04.16.718233</dc:identifier>
<dc:title><![CDATA[Evolutionary landscapes of zygotic genome activation across animals]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.04.17.719174v1?rss=1">
<title>
<![CDATA[
An N-degron proteolytic pathway modulates recipient susceptibility to T6SS DNase effectors 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.04.17.719174v1?rss=1</link>
<description><![CDATA[
The type VI secretion system (T6SS) is a contractile nanoweapon widely employed by Gram-negative bacteria to gain competitive advantages by injecting effector proteins into recipient cells. Although the biochemical activities of T6SS effectors have been well characterized, how recipient factors modulate effector toxicity remains poorly understood. Using Agrobacterium C58 as a model, previous work identified the Escherichia coli ClpAP protease as a recipient susceptibility (RS) factor that enhances T6SS-mediated interbacterial competition. Agrobacterium C58 deploys two DNase effectors, Tde1 and Tde2, as the major antibacterial weapon. Here, we demonstrate that the recipient ClpAP protease and its adaptor ClpS enhanced C58-mediated interbacterial competition in a Tde2-dependent manner in both intra- and interspecies competition. Ectopic expression of Tde2 in E. coli caused growth inhibition and DNA cleavage in the presence of a functional ClpAPS protease complex, but not in any of the clpP, clpA or clpS mutants. Notably, Tde2 accumulated in these mutants but not in wild-type cells, whereas a catalytic variant accumulated regardless of ClpAPS status, suggesting that Tde2 is not directly degraded by ClpAPS. Instead, Tde2 depends on ClpAPS for full toxicity, likely through degradation of inhibitory N-degron substrate(s). Affinity purification of His-tagged Tde2 in a clpP mutant background, followed by mass spectrometry, identified eight N-degron substrate candidates. Tde2-mediated interbacterial competition was significantly reduced by overexpression of three candidates. Among them, the Tde2 DNase domain directly associated with guanosine 5-monophosphate reductase GuaC, supporting a model in which Tde2 toxicity is blocked by binding of GuaC. Collectively, our findings reveal an unanticipated layer of recipient-mediated regulation in T6SS competition and highlight proteolytic control of inhibitory substrates as a determinant of bacterial susceptibility during interbacterial conflict.
]]></description>
<dc:creator>Wen, Y.-H. V.</dc:creator>
<dc:creator>Lin, H.-H.</dc:creator>
<dc:creator>Zheng, X.-T.</dc:creator>
<dc:creator>Hwang, H.-H.</dc:creator>
<dc:creator>Lai, E.-M.</dc:creator>
<dc:date>2026-04-19</dc:date>
<dc:identifier>doi:10.64898/2026.04.17.719174</dc:identifier>
<dc:title><![CDATA[An N-degron proteolytic pathway modulates recipient susceptibility to T6SS DNase effectors]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/content/10.64898/2026.04.20.719558v1?rss=1">
<title>
<![CDATA[
A broad-host-range Rhizobium rhizogenes strain enables transient expression across diverse crops and establishes functional assays in faba bean 
]]>
</title>
<link>https://biorxiv.org/content/10.64898/2026.04.20.719558v1?rss=1</link>
<description><![CDATA[
Agrobacterium-mediated transient expression has revolutionized plant research, enabling numerous landmark discoveries across diverse areas of plant biology. Yet this powerful approach remains largely confined to solanaceous species, leaving most economically important crop families without a comparable rapid assay platform. Here, we show that an engineered Rhizobium rhizogenes strain, AS109, mediates efficient transient expression across diverse dicot species spanning multiple taxonomic families, consistently outperforming commonly used laboratory agrobacterial strains. Leveraging the broad host range of AS109, we establish a suite of functional assays in faba bean (Vicia faba), including protein localisation, RNA interference-mediated gene silencing, cell-surface elicitor recognition screens, nucleotide-binding leucine-rich repeat receptor (NLR) activation, and infection cell biology at the host-pathogen interface. We further demonstrate that both singleton NLRs and sensor-helper NLR pairs from Solanaceae retain effector recognition and cell death activity when transferred into faba bean, establishing a rapid platform for evaluating cross-family transferability of disease-resistance genes. AS109 thus provides an accessible and versatile chassis for functional genomics in non-model crops, bridging the widening gap between hypothesis generation and experimental validation across diverse plant species.
]]></description>
<dc:creator>King, F.</dc:creator>
<dc:creator>Lopez-Agudelo, J. C.</dc:creator>
<dc:creator>Stephens, C.</dc:creator>
<dc:creator>Aung, M. H.</dc:creator>
<dc:creator>Ibrahim, T.</dc:creator>
<dc:creator>Yuen, E. L. H.</dc:creator>
<dc:creator>Chen, A.</dc:creator>
<dc:creator>Eilmann, N. M.</dc:creator>
<dc:creator>Jenkins, S.</dc:creator>
<dc:creator>Vuolo, C.</dc:creator>
<dc:creator>Swee, Y.-N.</dc:creator>
<dc:creator>Liu, W.-J.</dc:creator>
<dc:creator>Bruty, S.</dc:creator>
<dc:creator>Toghani, A.</dc:creator>
<dc:creator>Kuo, C.-H.</dc:creator>
<dc:creator>Lai, E.-M.</dc:creator>
<dc:creator>Kourelis, J.</dc:creator>
<dc:creator>Derevnina, L.</dc:creator>
<dc:creator>Wu, C.-H.</dc:creator>
<dc:creator>Bozkurt, T. O.</dc:creator>
<dc:date>2026-04-22</dc:date>
<dc:identifier>doi:10.64898/2026.04.20.719558</dc:identifier>
<dc:title><![CDATA[A broad-host-range Rhizobium rhizogenes strain enables transient expression across diverse crops and establishes functional assays in faba bean]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-22</prism:publicationDate>
<prism:section></prism:section>
</item>
</rdf:RDF>
