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	<title>bioRxiv Channel: MPI-CBG/CSBD</title>
	<link>https://biorxiv.org</link>
	<description>
	This feed contains articles for bioRxiv Channel "MPI-CBG/CSBD"
	</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/cgi/content/short/001289v1?rss=1">
<title>
<![CDATA[
An Adaptive Threshold in Mammalian Neocortical Evolution 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/001289v1?rss=1"
</link>
<description><![CDATA[
Expansion of the neocortex is a hallmark of human evolution. However, it remains an open question what adaptive mechanisms facilitated its expansion. Here we show, using gyrencephaly index (GI) and other physiological and life-history data for 102 mammalian species, that gyrencephaly is an ancestral mammalian trait. We provide evidence that the evolution of a highly folded neocortex, as observed in humans, requires the traversal of a threshold of [~]109 neurons, and that species above and below the threshold exhibit a bimodal distribution of physiological and life-history traits, establishing two phenotypic groups. We identify, using discrete mathematical models, proliferative divisions of pro-genitors in the basal compartment of the developing neocortex as evolutionarily necessary and sufficient for generating a fourteen-fold increase in daily prenatal neuron production and thus traversal of the neuronal threshold. Finally, using RNA-seq data from fetal human neocortical germinal zones, we show a genomic correlate to the neuron threshold in the differential conservation of long intergenic non-coding RNA. (see arXiv:1304.5412)
]]></description>
<dc:creator>Eric Lewitus</dc:creator>
<dc:creator>Iva Kelava</dc:creator>
<dc:creator>Alex T Kalinka</dc:creator>
<dc:creator>Pavel Tomancak</dc:creator>
<dc:creator>Wieland B Huttner</dc:creator>
<dc:creator></dc:creator>
<dc:date>2013-12-13</dc:date>
<dc:identifier>doi:10.1101/001289</dc:identifier>
<dc:title><![CDATA[An Adaptive Threshold in Mammalian Neocortical Evolution]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2013-12-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/008938v1?rss=1">
<title>
<![CDATA[
Systematic Imaging Reveals Features of Localized mRNAs and Their Changing Subcellular Destinations in Development 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/008938v1?rss=1"
</link>
<description><![CDATA[
mRNA localization is critical for eukaryotic cells and affects numerous transcripts, yet how cells regulate distribution of many mRNAs to their subcellular destinations is still unknown. We combined transcriptomics and systematic imaging to determine tissue-specific expression and subcellular distribution of 5862 mRNAs during Drosophila oogenesis. mRNA localization is widespread in the ovary, depends on the microtubule cytoskeleton and the mRNAs enriched at the posterior cortex share common localization machinery. Localized mRNAs, in particular the posterior class, have distinct gene features and differ in expression level, 3UTR length and sequence conservation from unlocalized mRNAs. Using cross-tissue comparison we revealed that the localization status of mRNAs differs between epithelial, germline and embryonic cell types and also changes within one cell, the oocyte, over time. This dataset enables the transition from deep mechanistic dissection of singular mRNA localization events towards global understanding of how mRNAs transcribed in the nucleus distribute in cells.
]]></description>
<dc:creator>Helena Jambor</dc:creator>
<dc:creator>Vineeth Surendranath</dc:creator>
<dc:creator>Alex T. Kalinka</dc:creator>
<dc:creator>Pavel Mejstrik</dc:creator>
<dc:creator>Stephan Saalfeld</dc:creator>
<dc:creator>Pavel Tomancak</dc:creator>
<dc:creator></dc:creator>
<dc:date>2014-09-09</dc:date>
<dc:identifier>doi:10.1101/008938</dc:identifier>
<dc:title><![CDATA[Systematic Imaging Reveals Features of Localized mRNAs and Their Changing Subcellular Destinations in Development]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2014-09-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/028308v1?rss=1">
<title>
<![CDATA[
A genome-wide resource for the analysis of protein localisation in Drosophila 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/028308v1?rss=1"
</link>
<description><![CDATA[
The Drosophila genome contains >13,000 protein coding genes, the majority of which remain poorly investigated. Important reasons include the lack of antibodies or reporter constructs to visualise these proteins. Here we present a genome-wide fosmid library of {approx}10,000 GFP-tagged clones, comprising tagged genes and most of their regulatory information. For 880 tagged proteins we have created transgenic lines and for a total of 207 lines we have assessed protein expression and localisation in ovaries, embryos, pupae or adults by stainings and live imaging approaches. Importantly, we can visualise many proteins at endogenous expression levels and find a large fraction of them localising to subcellular compartments. Using complementation tests we demonstrate that two-thirds of the tagged proteins are fully functional. Moreover, our clones also enable interaction proteomics from developing pupae and adult flies. Taken together, this resource will enable systematic analysis of protein expression and localisation in various cellular and developmental contexts.
]]></description>
<dc:creator>Mihail Sarov</dc:creator>
<dc:creator>Chritiane Barz</dc:creator>
<dc:creator>Helena Jambor</dc:creator>
<dc:creator>Marco Y Hein</dc:creator>
<dc:creator>Christopher Schmied</dc:creator>
<dc:creator>Dana Suchold</dc:creator>
<dc:creator>Bettina Stender</dc:creator>
<dc:creator>Stephan Janosch</dc:creator>
<dc:creator>Vinay K.J. Vikas</dc:creator>
<dc:creator>R.T. Krisnan</dc:creator>
<dc:creator>K. Aishwarya</dc:creator>
<dc:creator>Irene R.S. Ferreira</dc:creator>
<dc:creator>Radoslaw K. Ejsmont</dc:creator>
<dc:creator>Katja Finkl</dc:creator>
<dc:creator>Susanne Hasse</dc:creator>
<dc:creator>Philipp Kaempfer</dc:creator>
<dc:creator>Nicole Plewka</dc:creator>
<dc:creator>Elisabeth Vinis</dc:creator>
<dc:creator>Siegfried Schloissnig</dc:creator>
<dc:creator>Elisabeth Knust</dc:creator>
<dc:creator>Volker Hartenstein</dc:creator>
<dc:creator>Matthias Mann</dc:creator>
<dc:creator>Mani Ramaswami</dc:creator>
<dc:creator>K. VijayRaghavan</dc:creator>
<dc:creator>Pavel Tomancak</dc:creator>
<dc:creator>Frank Schnorrer</dc:creator>
<dc:creator></dc:creator>
<dc:date>2015-10-04</dc:date>
<dc:identifier>doi:10.1101/028308</dc:identifier>
<dc:title><![CDATA[A genome-wide resource for the analysis of protein localisation in Drosophila]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2015-10-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/045187v1?rss=1">
<title>
<![CDATA[
Light sheet microscopy for everyone? Experience of building an OpenSPIM to study flatworm development 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/045187v1?rss=1"
</link>
<description><![CDATA[
BACKGROUNDSelective plane illumination microscopy (SPIM a type of light-sheet microscopy) involves focusing a thin sheet of laser light through a specimen at right angles to the objective lens. As only the thin section of the specimen at the focal plane of the lens is illuminated, out of focus light is naturally absent and toxicity due to light (phototoxicity) is greatly reduced enabling longer term live imaging. OpenSPIM is an open access platform (Pitrone et al. 2013 and OpenSPIM.org) created to give new users step-by-step instructions on building a basic configuration of a SPIM microscope, which can in principle be adapted and upgraded to each laboratorys own requirements and budget. Here we describe our own experience with the process of designing, building, configuring and using an OpenSPIM for our research into the early development of the polyclad flatworm Maritigrella crozieri - a non-model animal.nnRESULTSOur OpenSPIM builds on the standard design with the addition of two colour laser illumination for simultaneous detection of two probes/molecules and dual sided illumination, which provides more even signal intensity across a specimen. Our OpenSPIM provides high resolution 3d images and time lapse recordings, and we demonstrate the use of two colour lasers and the benefits of two color dual-sided imaging. We used our microscope to study the development of the embryo of the polyclad flatworm Maritigrella crozieri. The capabilities of our microscope are demonstrated by our ability to record the stereotypical spiral cleavage pattern of Maritigrella with high-speed multi-view time lapse imaging. 3D and 4D (3D + time) reconstruction of early development from these data is possible using image registration and deconvolution tools provided as part of the open source Fiji platform. We discuss our findings on the pros and cons of a self built microscope.nnCONCLUSIONSWe conclude that home-built microscopes, such as an OpenSPIM, together with the available open source software, such as MicroManager and Fiji, make SPIM accessible to anyone interested in having continuous access to their own light-sheet microscope. However, building an OpenSPIM is not without challenges and an open access microscope is a worthwhile, if significant, investment of time and money. Multi-view 4D microscopy is more challenging than we had expected. We hope that our gained experience during this project will help future OpenSPIM users with similar ambitions.
]]></description>
<dc:creator>Johannes Girstmair</dc:creator>
<dc:creator>Anne Zakrzewski</dc:creator>
<dc:creator>François Lapraz</dc:creator>
<dc:creator>Mette Handberg-Thorsager</dc:creator>
<dc:creator>Pavel Tomancak</dc:creator>
<dc:creator>Peter Gabriel Pitrone</dc:creator>
<dc:creator>Fraser Simpson</dc:creator>
<dc:creator>Maximilian J Telford</dc:creator>
<dc:creator></dc:creator>
<dc:date>2016-03-23</dc:date>
<dc:identifier>doi:10.1101/045187</dc:identifier>
<dc:title><![CDATA[Light sheet microscopy for everyone? Experience of building an OpenSPIM to study flatworm development]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2016-03-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/112623v1?rss=1">
<title>
<![CDATA[
Reconstruction of cell lineages and behaviors underlying arthropod limb outgrowth with multi-view light-sheet imaging and tracking 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/112623v1?rss=1"
</link>
<description><![CDATA[
During development coordinated cell behaviors orchestrate tissue and organ morphogenesis to suit the lifestyle of the organism. We have used here the crustacean Parhyale hawaiensis to study the cellular basis of limb development. Transgenic Parhyale embryos with fluorescently labeled nuclei were imaged at high spatiotemporal resolution with multi-view light-sheet fluorescence microscopy over several days of embryogenesis spanning appendage morphogenesis from early specification up to late differentiation stages. Cell tracking with a new tool called Massive Multi-view Tracker (MaMuT) enabled the reconstruction of the complete cell lineage of an outgrowing thoracic limb with single-cell resolution. In silico clonal analyses suggested that the limb primordium becomes subdivided from an early stage first into anterior-posterior and then into dorsal-ventral compartments whose boundaries intersect at the distal tip of the growing limb. Limb bud formation is associated with the spatial modulation of cell proliferation, while limb elongation is also driven by the preferential orientation of division of epidermal cells along the proximal-distal axis of growth. Cellular reconstructions were predictive of the expression patterns of limb development genes including the Decapentaplegic (Dpp) morphogen.nnHIGHLIGHTSO_LIMulti-view light-sheet microscopy of crustacean embryos from species Parhyale hawaiensis are ideal for cellular-level analysis of organ morphogenesis.nC_LIO_LILineages of 3-dimensional organs were reconstructed at single-cell resolution with the Fiji/ImageJ plugin Massive Multi-view Tracker.nC_LIO_LIThe Parhyale limb primordium undergoes early lineage restrictions associated with particular cell behaviors and patterns of gene expression.nC_LIO_LIDifferential rates of cell proliferation and oriented cell divisions guide appendage proximal-distal outgrowth.nC_LI
]]></description>
<dc:creator>Wolff, C.</dc:creator>
<dc:creator>Tinevez, J.-Y.</dc:creator>
<dc:creator>Pietzsch, T.</dc:creator>
<dc:creator>Stamataki, E.</dc:creator>
<dc:creator>Harich, B.</dc:creator>
<dc:creator>Preibisch, S.</dc:creator>
<dc:creator>Shorte, S.</dc:creator>
<dc:creator>Keller, P. J.</dc:creator>
<dc:creator>Tomancak, P.</dc:creator>
<dc:creator>Pavlopoulos, A.</dc:creator>
<dc:date>2017-02-28</dc:date>
<dc:identifier>doi:10.1101/112623</dc:identifier>
<dc:title><![CDATA[Reconstruction of cell lineages and behaviors underlying arthropod limb outgrowth with multi-view light-sheet imaging and tracking]]></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/cgi/content/short/115220v1?rss=1">
<title>
<![CDATA[
Control of Hox transcription factor concentration and cell-to-cell variability by an auto-regulatory switch 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/115220v1?rss=1"
</link>
<description><![CDATA[
The variability in transcription factor concentration among cells is an important developmental determinant, yet how variability is controlled remains poorly understood. Studies of variability have focused predominantly on monitoring mRNA production noise. Little information exists about transcription factor protein variability, since this requires the use of quantitative methods with single-molecule sensitivity. Using Fluorescence Correlation Spectroscopy (FCS), we characterized the concentration and variability of 14 endogenously tagged TFs in live Drosophila imaginal discs. For the Hox TF Antennapedia we investigated whether protein variability results from random stochastic events or is developmentally regulated. We found that Antennapedia transitioned from low concentration/high variability early, to high concentration/low variability later, in development. FCS and temporally resolved genetic studies uncovered that Antennapedia itself is necessary and sufficient to drive a developmental regulatory switch from auto-activation to auto-repression, thereby reducing variability. This switch is controlled by progressive changes in relative concentrations of preferentially activating and repressing Antennapedia isoforms, which bind chromatin with different affinities. Mathematical modelling demonstrated that the experimentally supported auto-regulatory circuit can explain the increase of Antennapedia concentration and suppression of variability over time.
]]></description>
<dc:creator>Papadopoulos, D. K.</dc:creator>
<dc:creator>Skouloudaki, K.</dc:creator>
<dc:creator>Engstrom, Y.</dc:creator>
<dc:creator>Terenius, L.</dc:creator>
<dc:creator>Rigler, R.</dc:creator>
<dc:creator>Vukojevic, V.</dc:creator>
<dc:creator>Tomancak, P.</dc:creator>
<dc:date>2017-03-14</dc:date>
<dc:identifier>doi:10.1101/115220</dc:identifier>
<dc:title><![CDATA[Control of Hox transcription factor concentration and cell-to-cell variability by an auto-regulatory switch]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-03-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/117515v1?rss=1">
<title>
<![CDATA[
Cadherin Fat2 directs cellular mechanics to promote epithelial rotation 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/117515v1?rss=1"
</link>
<description><![CDATA[
Left and right symmetry breaking is involved in many developmental processes that are important to form bodies and organs. One of them is the epithelial rotation of developing organs. However, how epithelial cells move, how they break symmetry to define common direction of their collective movement and what function rotational epithelial motions have in morphogenesis remain elusive. Here, we identified a dynamic actomyosin network with preferred retrograde contractility at the basal side of the rotating follicle epithelium in Drosophila oogenesis. We provide evidence that unidirectional epithelial rotation is a result of actomyosin asymmetry cue transmission onto a tissue plane synchronized by the atypical cadherin Fat2, a key planar cell polarity regulator in Drosophila oogenesis. We found that Fat2 directs actomyosin contractility to move the epithelial tissue in order to provide directed elongation of follicle cells. In contrast, loss of Fat2 results in anisotropic non-muscle Myosin II pulses that are disorganized in plane and deform cell shape, tissue and Drosophila eggs. Our data indicate that directed elongation of follicle cells is critical for proper Drosophila egg morphogenesis. Together, we demonstrate the importance of atypical cadherins in the control of cell mechanics, left/right symmetry breaking and its propagation onto the tissue scale to facilitate proper organ morphogenesis. This process may be evolutionarily conserved in rotating animal organs.
]]></description>
<dc:creator>Viktorinova, I.</dc:creator>
<dc:creator>Henry, I.</dc:creator>
<dc:creator>Tomancak, P.</dc:creator>
<dc:date>2017-03-16</dc:date>
<dc:identifier>doi:10.1101/117515</dc:identifier>
<dc:title><![CDATA[Cadherin Fat2 directs cellular mechanics to promote epithelial rotation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-03-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/000570v1?rss=1">
<title>
<![CDATA[
Lipoproteins carry endocannabinoids that inhibit the Hedgehog pathway 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/000570v1?rss=1"
</link>
<description><![CDATA[
Hedgehog proteins are lipid-modified secreted signaling molecules that regulate tissue development and homeostasis. Lipids contained in circulating lipoproteins repress the Hedgehog signaling pathway in the absence of Hedgehog ligand, but the identity of these lipids is unknown. Here, using biochemical fractionation and lipid mass spectrometry, we identify these inhibitory lipids as endocannabinoids. Endocannabinoids are present in lipoproteins of both flies and humans, and repress the pathway in both mammalian signaling assays and Drosophila wing imaginal discs. In Drosophila, endocannabinoids are required in vivo to keep the levels of Smoothened and full-length Cubitus interruptus (Ci155) low in the absence of Hedgehog. Furthermore, elevating their endogenous levels inhibits Hedgehog-dependent accumulation of Smoothened and Ci155. Interestingly, cannabis-derived phytocannabinoids are also potent pathway inhibitors in flies and mammals. These findings constitute a novel link between organismal metabolism and local Hedgehog signaling, and suggest previously unsuspected mechanisms for the broad physiological activities of cannabinoids.
]]></description>
<dc:creator>Helena Khaliullina</dc:creator>
<dc:creator>Mesut Bilgin</dc:creator>
<dc:creator>Julio L. Sampaio</dc:creator>
<dc:creator>Andrej Shevchenko</dc:creator>
<dc:creator>Suzanne Eaton</dc:creator>
<dc:creator></dc:creator>
<dc:date>2013-11-18</dc:date>
<dc:identifier>doi:10.1101/000570</dc:identifier>
<dc:title><![CDATA[Lipoproteins carry endocannabinoids that inhibit the Hedgehog pathway]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2013-11-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/002626v1?rss=1">
<title>
<![CDATA[
Production of systemically circulating Hedgehog by the intestine couples nutrition to growth and development 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/002626v1?rss=1"
</link>
<description><![CDATA[
In Drosophila larvae, growth and developmental timing are regulated by nutrition in a tightly coordinated fashion. The networks that couple these processes are far from understood. Here, we show that the intestine responds to nutrient availability by regulating production of a circulating lipoprotein associated form of the signaling protein Hedgehog (Hh). Levels of circulating Hh tune the rates of growth and developmental timing in a coordinated fashion. Circulating Hh signals to the fat body to control larval growth. It regulates developmental timing by controlling ecdysteroid production in the prothoracic gland. Circulating Hh is especially important during starvation, when it is also required for mobilization of fat body triacylglycerol (TAG) stores. Thus, we demonstrate that Hh, previously known only for its local morphogenetic functions, also acts as a lipoprotein-associated endocrine hormone, coordinating the response of multiple tissues to nutrient availability.
]]></description>
<dc:creator>Jonathan Rodenfels</dc:creator>
<dc:creator>Oksana Lavrynenko</dc:creator>
<dc:creator>Sophie Ayciriex</dc:creator>
<dc:creator>Julio L Sampaio</dc:creator>
<dc:creator>Maria Carvalho</dc:creator>
<dc:creator>Andrej Shevchenko</dc:creator>
<dc:creator>Suzanne Eaton</dc:creator>
<dc:creator></dc:creator>
<dc:date>2014-02-14</dc:date>
<dc:identifier>doi:10.1101/002626</dc:identifier>
<dc:title><![CDATA[Production of systemically circulating Hedgehog by the intestine couples nutrition to growth and development]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2014-02-14</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/059923v1?rss=1">
<title>
<![CDATA[
A temperature-dependent shift in dietary preference alters the viable temperature range of Drosophila 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/059923v1?rss=1"
</link>
<description><![CDATA[
How cold-blooded animals adapt their behaviour and physiology to survive seasonal changes in temperature is not completely understood - even for well-studied model organisms like Drosophila melanogaster. Here, we show that Drosophila can extend their viable temperature range through temperature-dependent changes in feeding behaviour. Above 15{degrees}C, Drosophila feed and lay eggs on yeast. In contrast, below 15{degrees}C, Drosophila prefer to feed and lay eggs on plant material. The different lipids present in yeast and plants improve survival at high and low temperatures, respectively. Yeast lipids promote high tempera-ture survival by increasing systemic insulin signalling. This expands the range over which developmental rate increases with temperature, suggesting that faster nutrient utilization is required to fuel biochemical reactions driven faster by ki-netic energy. In addition to speeding development, yeast lipids increase fertility. Thus, yeast provide cues that could help Drosophila to exploit a transient summer food resource. Plant lipids, on the other hand, are required to maintain mem-brane lipid fluidity at low temperature, and increase cold-resistance of larvae and adults. The cold-resistance and lowered insulin signalling conferred by feeding on plants allows adults to survive for many months at temperatures consistent with overwintering in temperate climates. Thus, temperature-dependent changes in feeding behaviour produce physiological changes that could promote seasonal adaption.
]]></description>
<dc:creator>Marko Brankatschk</dc:creator>
<dc:creator>Theresia Gutmann</dc:creator>
<dc:creator>Michal Grzybek</dc:creator>
<dc:creator>Beate Brankatschk</dc:creator>
<dc:creator>Uenal Coskun</dc:creator>
<dc:creator>Suzanne Eaton</dc:creator>
<dc:creator></dc:creator>
<dc:date>2016-06-20</dc:date>
<dc:identifier>doi:10.1101/059923</dc:identifier>
<dc:title><![CDATA[A temperature-dependent shift in dietary preference alters the viable temperature range of Drosophila]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2016-06-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/140038v1?rss=1">
<title>
<![CDATA[
Cell Dynamics Underlying Oriented Growth Of The Drosophila Imaginal Wing Disc 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/140038v1?rss=1"
</link>
<description><![CDATA[
Quantitative analysis of the dynamic cellular mechanisms shaping the Drosophila wing during its larval growth phase has been limited, impeding our ability to understand how morphogen patterns regulate tissue shape. Such analysis requires imaging explants under conditions that maintain both growth and patterning, as well as methods to quantify how much cellular behaviors change tissue shape. Here, we demonstrate a key requirement for the steroid hormone 20-hydroxyecdysone (20E) in the maintenance of numerous patterning systems in vivo and in explant culture. We find that low concentrations of 20E support prolonged proliferation in explanted wing discs in the absence of insulin, incidentally providing novel insight into the hormonal regulation of imaginal growth. We use 20E-containing media to directly observe growth and apply recently developed methods for quantitatively decomposing tissue shape changes into cellular contributions. We discover that while cell divisions drive tissue expansion along one axis, their contribution to expansion along the orthogonal axis is cancelled by cell rearrangements and cell shape changes. This finding raises the possibility that anisotropic mechanical constraints contribute to growth orientation in the wing disc.
]]></description>
<dc:creator>Dye, N. A.</dc:creator>
<dc:creator>Popovic, M.</dc:creator>
<dc:creator>Spannl, S.</dc:creator>
<dc:creator>Etournay, R.</dc:creator>
<dc:creator>Kainmueller, D.</dc:creator>
<dc:creator>Myers, E. W.</dc:creator>
<dc:creator>Julicher, F.</dc:creator>
<dc:creator>Eaton, S.</dc:creator>
<dc:date>2017-05-19</dc:date>
<dc:identifier>doi:10.1101/140038</dc:identifier>
<dc:title><![CDATA[Cell Dynamics Underlying Oriented Growth Of The Drosophila Imaginal Wing Disc]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-05-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/238634v1?rss=1">
<title>
<![CDATA[
Phenotype loss is associated with widespread divergence of the gene regulatory landscape in evolution 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/238634v1?rss=1"
</link>
<description><![CDATA[
Detecting the genomic changes underlying phenotypic changes between species is a main goal of evolutionary biology and genomics. Evolutionary theory predicts that changes in cis-regulatory elements are important for morphological changes. Here, we combine genome sequencing and functional genomics with genome-wide comparative analyses to investigate the fate of regulatory elements in lineages that lost morphological traits. We first show that limb loss in snakes is associated with widespread divergence of limb regulatory elements. We next show that eye degeneration in subterranean mammals is associated with widespread divergence of eye regulatory elements. In both cases, sequence divergence results in an extensive loss of relevant transcription factor binding sites. Importantly, diverged regulatory elements are associated with key genes required for normal limb patterning or normal eye development and function, suggesting that regulatory divergence contributed to the loss of these phenotypes. Together, our results provide the first evidence that genome-wide decay of the phenotype-specific cis-regulatory landscape is a hallmark of lost morphological traits.
]]></description>
<dc:creator>Roscito, J. G.</dc:creator>
<dc:creator>Sameith, K.</dc:creator>
<dc:creator>Parra, G.</dc:creator>
<dc:creator>Langer, B.</dc:creator>
<dc:creator>Petzold, A.</dc:creator>
<dc:creator>Rodrigues, M. T.</dc:creator>
<dc:creator>Hiller, M.</dc:creator>
<dc:date>2017-12-22</dc:date>
<dc:identifier>doi:10.1101/238634</dc:identifier>
<dc:title><![CDATA[Phenotype loss is associated with widespread divergence of the gene regulatory landscape in evolution]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-12-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/225722v1?rss=1">
<title>
<![CDATA[
Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/225722v1?rss=1"
</link>
<description><![CDATA[
To understand the molecular basis underlying the expansion of the neocortex during primate, and notably human, evolution, it is essential to identify the genes that are particularly active in the neural stem and progenitor cells of developing neocortex. Here, we have used existing transcriptome datasets to carry out a comprehensive screen for protein-coding genes preferentially expressed in progenitors of fetal human neocortex. In addition to the previously studied gene ARHGAP11B, we show that ten known and two newly identified human-specific genes exhibit such expression, however with distinct neural progenitor cell-type specificity compared to their ancestral paralogs. Furthermore, we identify 41 additional human genes with progenitor-enriched expression which have orthologs only in primates. Our study not only provides a resource of genes that are candidates to exert specific, and novel, roles in neocortical development, but also reveals that distinct mechanisms gave rise to these genes during primate, and notably human, evolution.
]]></description>
<dc:creator>Florio, M.</dc:creator>
<dc:creator>Heide, M.</dc:creator>
<dc:creator>Brandl, H.</dc:creator>
<dc:creator>Pinson, A.</dc:creator>
<dc:creator>Winkler, S.</dc:creator>
<dc:creator>Wimberger, P.</dc:creator>
<dc:creator>Huttner, W. B.</dc:creator>
<dc:creator>Hiller, M.</dc:creator>
<dc:date>2017-11-28</dc:date>
<dc:identifier>doi:10.1101/225722</dc:identifier>
<dc:title><![CDATA[Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-11-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/006916v1?rss=1">
<title>
<![CDATA[
Products of the Parkinson’s-disease related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/006916v1?rss=1"
</link>
<description><![CDATA[
Parkinson's disease is associated with mitochondrial decline in dopaminergic neurons of the substantia nigra. One of the genes, DJ- 1/PARK7, linked with the onset of Parkinson's disease, belongs to a novel glyoxalase family and influences mitochondrial activity. It has been assumed that glyoxalases fulfill this task by detoxifying aggressive aldehyde by-products of metabolism. Here we show that supplying either D-lactate or glycolate, products of DJ-1, rescues the requirement for the enzyme in maintenance of mitochondrial potential. We further show that glycolic acid and D-lactic acid can elevate lowered mitochondrial membrane potential caused by silencing PINK-1, another Parkinson's related gene, as well as by paraquat, an environmental toxin known to be linked with Parkinson's disease. We propose that DJ-1 and consequently its products are components of a novel pathway that stabilizes mitochondria during cellular stress. We go on to show that survival of cultured mesencephalic dopaminergic neurons, defective in Parkinson's disease, is enhanced by glycolate and D-lactate. Because glycolic and D-lactic acids occur naturally, they are therefore a potential therapeutic route for treatment or prevention of Parkinson's disease.
]]></description>
<dc:creator>Yusuke Toyoda</dc:creator>
<dc:creator>Cihan Erkut</dc:creator>
<dc:creator>Francisco Pan-Montojo</dc:creator>
<dc:creator>Sebastian Boland</dc:creator>
<dc:creator>Martin P. Stewart</dc:creator>
<dc:creator>Daniel J. M?ller</dc:creator>
<dc:creator>Wolfgang Wurst</dc:creator>
<dc:creator>Anthony A. Hyman</dc:creator>
<dc:creator>Teymuras V. Kurzchalia</dc:creator>
<dc:creator></dc:creator>
<dc:date>2014-07-04</dc:date>
<dc:identifier>doi:10.1101/006916</dc:identifier>
<dc:title><![CDATA[Products of the Parkinson’s-disease related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2014-07-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/067223v1?rss=1">
<title>
<![CDATA[
Polo kinase phosphorylation determines C. elegans centrosome size and density by biasing SPD-5 toward an assembly-competent conformation 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/067223v1?rss=1"
</link>
<description><![CDATA[
Centrosomes are major microtubule-organizing centers composed of centrioles surrounded by an extensive proteinacious layer called the pericentriolar material (PCM). In C. elegans embryos, the mitotic PCM expands by Polo-kinase (PLK-1) phosphorylation-accelerated assembly of SPD-5 molecules into supramolecular scaffolds. However, how PLK-1 phosphorylation regulates SPD-5 assembly is not known. We found that a mutant version of SPD-5 that is insensitive to PLK-1 phosphorylation (SPD-54A) could localize to PCM but was unable to rescue the reduction in PCM size and density when wild-type SPD-5 levels were decreased. In vitro, purified SPD-54A self-assembled into functional supramolecular scaffolds over long time scales, suggesting that phosphorylation only controls the rate of SPD-5 scaffold assembly. Furthermore, the SPD-5 scaffold, once assembled, remained intact and supported microtubule nucleation in the absence of PLK-1 activity in vivo. We conclude that Polo Kinase is required for rapid assembly of the PCM scaffold but not for scaffold maintenance or function. Based on this idea, we developed a theoretical model that adequately predicted PCM growth rates in different mutant conditions in vivo. We propose that PLK-1 phosphorylation-dependent conversion of SPD-5 into an assembly-competent form underlies PCM formation in vivo and that the rate of this conversion determines final PCM size and density.
]]></description>
<dc:creator>Oliver Wueseke</dc:creator>
<dc:creator>David Zwicker</dc:creator>
<dc:creator>Anne Schwager</dc:creator>
<dc:creator>Yao Liang Wong</dc:creator>
<dc:creator>Karen Oegema</dc:creator>
<dc:creator>Frank Julicher</dc:creator>
<dc:creator>Anthony A Hyman</dc:creator>
<dc:creator>Jeffrey Woodruff</dc:creator>
<dc:creator></dc:creator>
<dc:date>2016-08-01</dc:date>
<dc:identifier>doi:10.1101/067223</dc:identifier>
<dc:title><![CDATA[Polo kinase phosphorylation determines C. elegans centrosome size and density by biasing SPD-5 toward an assembly-competent conformation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2016-08-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/093054v1?rss=1">
<title>
<![CDATA[
The centrosome is a selective phase that nucleates microtubules by concentrating tubulin 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/093054v1?rss=1"
</link>
<description><![CDATA[
Centrosomes are non-membrane-bound compartments that nucleate microtubule arrays. They consist of nanometer-scale centrioles surrounded by a micron-scale, dynamic assembly of protein called the pericentriolar material (PCM). To study how PCM forms a spherical compartment that nucleates microtubules, we reconstituted PCM-dependent microtubule nucleation in vitro using recombinant C.elegans proteins. We found that macromolecular crowding drives phase separation of the key PCM scaffold protein SPD-5 into spherical droplets that morphologically and dynamically resemble in vivo PCM. These SPD-5 droplets recruited the microtubule polymerase ZYG-9 (XMAP215 homologue) and the microtubule-stabilizing protein TPXL-1 (TPX2 homologue). Together, these three proteins concentrated tubulin ~4- fold over background, which was sufficient to reconstitute nucleation of microtubule asters in vitro. Our results suggest that in vivo PCM is a selective phase that organizes microtubule arrays through localized concentration of tubulin by microtubule effector proteins.nnOne Sentence SummaryPhase separation of C. elegans centrosome proteins drive the formation of micron-sized microtubule organizing centers.
]]></description>
<dc:creator>Woodruff, J. B.</dc:creator>
<dc:creator>Ferreira Gomes, B.</dc:creator>
<dc:creator>Widlund, P. O.</dc:creator>
<dc:creator>Mahamid, J.</dc:creator>
<dc:creator>Hyman, A. A.</dc:creator>
<dc:date>2016-12-10</dc:date>
<dc:identifier>doi:10.1101/093054</dc:identifier>
<dc:title><![CDATA[The centrosome is a selective phase that nucleates microtubules by concentrating tubulin]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2016-12-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/096727v1?rss=1">
<title>
<![CDATA[
Parallel adaptation to higher temperatures in divergent clades of the nematode Pristionchus pacificus 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/096727v1?rss=1"
</link>
<description><![CDATA[
Studying the effect of temperature on fertility is particularly important in the light of ongoing climate change. We need to know if organisms can adapt to higher temperatures and, if so, what are the evolutionary mechanisms behind such adaptation. Such studies have been hampered by the lack different populations of sufficient sizes with which to relate the phenotype of temperature tolerance to the underlying genotypes. Here, we examined temperature adaptation in populations of the nematode Pristionchus pacificus, in which individual strains are able to successfully reproduce at 30{degrees}C. Analysis of the frequency of heat tolerant strains in different temperature zones on La Reunion supports that this trait is subject to natural selection. Reconstruction of ancestral states along the phylogeny of highly differentiated P. pacificus clades suggests that heat tolerance evolved multiple times independently. This is further supported by genome wide association studies showing that heat tolerance is a polygenic trait and that different loci are used by individual P. pacificus clades to develop heat tolerance. More precisely, analysis of allele frequencies indicated that most genetic markers that are associated with heat tolerance are only polymorphic in individual clades. While in some P. pacificus clades, parallel evolution of heat tolerance can be explained by ancestral polymorphism or by gene flow across clades, we observe at least one clearly distinct and independent scenario where heat tolerance emerged by de novo mutation. Thus, temperature tolerance evolved at least two times independently in the evolutionary history of this species. Our data suggest that studies of wild populations of P. pacificus will reveal distinct cellular mechanisms driving temperature adaptation.
]]></description>
<dc:creator>Leaver, M.</dc:creator>
<dc:creator>Kayhan, M.</dc:creator>
<dc:creator>McGaughran, A.</dc:creator>
<dc:creator>Roedelsperger, C.</dc:creator>
<dc:creator>Hyman, A. A.</dc:creator>
<dc:creator>Sommer, R.</dc:creator>
<dc:date>2016-12-29</dc:date>
<dc:identifier>doi:10.1101/096727</dc:identifier>
<dc:title><![CDATA[Parallel adaptation to higher temperatures in divergent clades of the nematode Pristionchus pacificus]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2016-12-29</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/119800v1?rss=1">
<title>
<![CDATA[
Local Nucleation Of Microtubule Bundles Through Tubulin Concentration Into A Condensed Tau Phase 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/119800v1?rss=1"
</link>
<description><![CDATA[
Non-centrosomal microtubule bundles play important roles in cellular organization and function. Although many diverse proteins are known that can bundle microtubules, biochemical mechanisms by which cells could locally control the nucleation and formation of microtubule bundles are understudied. Here, we demonstrate that concentration of tubulin into a condensed, liquid-like compartment composed of the unstructured neuronal protein tau is sufficient to nucleate microtubule bundles. We show that under conditions of macro-molecular crowding, tau forms liquid drops. Tubulin partitions into these drops, efficiently increasing tubulin concentration and driving the nucleation of microtubules. These growing microtubules form bundles enclosed in a liquid sheath of tau. Our data suggest that condensed compartments of microtubule bundling proteins could promote the local formation of microtubule bundles in neurons by acting as non-centrosomal microtubule nucleation centers, and that liquid-like tau encapsulation could provide both stability and plasticity to long axonal microtubule bundles.
]]></description>
<dc:creator>Hernandez-Vega, A.</dc:creator>
<dc:creator>Braun, M.</dc:creator>
<dc:creator>Scharrel, L.</dc:creator>
<dc:creator>Jahnel, M.</dc:creator>
<dc:creator>Wegmann, S.</dc:creator>
<dc:creator>Hyman, B. T.</dc:creator>
<dc:creator>Alberti, S.</dc:creator>
<dc:creator>Diez, S.</dc:creator>
<dc:creator>Hyman, A. A.</dc:creator>
<dc:date>2017-04-12</dc:date>
<dc:identifier>doi:10.1101/119800</dc:identifier>
<dc:title><![CDATA[Local Nucleation Of Microtubule Bundles Through Tubulin Concentration Into A Condensed Tau Phase]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-04-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/200428v1?rss=1">
<title>
<![CDATA[
Rab5 and Alsin regulate stress-activated cytoprotective signaling on mitochondria 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/200428v1?rss=1"
</link>
<description><![CDATA[
Mitochondrial stress response is essential for cell survival, and damaged mitochondria are a hallmark of neurodegenerative diseases. It is thus fundamental to understand how mitochondria relay information within the cell. Here, by investigating mitochondrial-endosome contact sites we made the surprising observation that the small GTPase Rab5 translocates from early endosomes to the outer mitochondrial membrane upon oxidative stress. This is accompanied by an increase in Rab5-positive endosomes in contact with mitochondria. Interestingly, activation of Rab5 on mitochondria depend on the Rab5-GEF ALS2/Alsin, which is encoded by a gene mutated in amyotrophic lateral sclerosis (ALS). Alsin-/- human induced pluripotent stem cell-derived spinal motor neurons cannot relocate Rab5 to mitochondria and display increased susceptibility to oxidative stress. These findings define a novel pathway whereby Alsin catalyzes assembly of the Rab5 endocytic machinery on mitochondria. Defects in stress-sensing by endosomes could be crucial for mitochondrial quality control during the onset of ALS.
]]></description>
<dc:creator>Hsu, F.</dc:creator>
<dc:creator>Spannl, S.</dc:creator>
<dc:creator>Ferguson, C.</dc:creator>
<dc:creator>Hyman, A. A.</dc:creator>
<dc:creator>Parton, R. G.</dc:creator>
<dc:creator>Zerial, M.</dc:creator>
<dc:date>2017-10-09</dc:date>
<dc:identifier>doi:10.1101/200428</dc:identifier>
<dc:title><![CDATA[Rab5 and Alsin regulate stress-activated cytoprotective signaling on mitochondria]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-10-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/147918v1?rss=1">
<title>
<![CDATA[
Mutations in the Drosophila splicing regulator Prp31 as a model for Retinitis pigmentosa 11 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/147918v1?rss=1"
</link>
<description><![CDATA[
Retinitis pigmentosa is a clinically heterogeneous disease affecting 1.6 million people worldwide. A growing number of identified disease-causing genes are associated with the spliceosome, but the molecular consequences that link defects in splicing factor genes to the aetiology of the disease remain to be elucidated. In this paper, we present a Drosophila model for Retinitis pigmentosa 11, a human disease caused by mutations in the splicing factor PRPF31. Here, we induced mutations in the Drosophila orthologue Prp31. Mutant flies are viable and show a normal eye phenotype when kept under regular light conditions. However, when exposed to constant light, photoreceptors of mutant flies degenerate, thus resembling the human disease phenotype. Degeneration could be shown to be associated with increased oxidative stress. This increase was in agreement with severe dysregulation of genes involved in oxidation/reduction processes, as revealed by high throughput transcriptome sequencing. In fact, light induced photoreceptor cell degeneration could be attenuated by experimentally reducing oxidative stress. A comparable decrease in retinal degeneration was achieved by raising mutant larvae on a vitamin A-depleted medium, thereby reducing rhodopsin levels. Finally, transcriptome data further uncovered an overall retention of introns in mRNAs. Among those, mRNAs of genes involved in synapse assembly, growth and stability were most prominent. These results point to a multifactorial genesis of light induced degeneration in retinae of Prp31 mutant flies, including transcriptional and splicing dysregulation, oxidative stress and defects in vitamin A metabolism.
]]></description>
<dc:creator>Lehmann, M.</dc:creator>
<dc:creator>Hebbar, S.</dc:creator>
<dc:creator>Brandl, H.</dc:creator>
<dc:creator>Leng, W.</dc:creator>
<dc:creator>Lakshmanaperumal, N.</dc:creator>
<dc:creator>Winkler, S.</dc:creator>
<dc:creator>Knust, E.</dc:creator>
<dc:date>2017-06-09</dc:date>
<dc:identifier>doi:10.1101/147918</dc:identifier>
<dc:title><![CDATA[Mutations in the Drosophila splicing regulator Prp31 as a model for Retinitis pigmentosa 11]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-06-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/125716v1?rss=1">
<title>
<![CDATA[
Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/125716v1?rss=1"
</link>
<description><![CDATA[
SUMMARYUpon fertilization, the genome of animal embryos remains transcriptionally inactive until the maternal-to-zygotic transition. At this time, the embryo takes control of its development and transcription begins. How the onset of zygotic transcription is regulated remains unclear. Here, we show that a dynamic competition for DNA binding between nucleosome-forming histones and transcription factors regulates zebrafish genome activation. Taking a quantitative approach, we found that the concentration of non-DNA bound core histones sets the time for the onset of transcription. The reduction in nuclear histone concentration that coincides with genome activation does not affect nucleosome density on DNA, but allows transcription factors to compete successfully for DNA binding. In agreement with this, transcription factor binding is sensitive to histone levels and the concentration of transcription factors also affects the time of transcription. Our results demonstrate that the relative levels of histones and transcription factors regulate the onset of transcription in the embryo.
]]></description>
<dc:creator>Joseph, S.</dc:creator>
<dc:creator>Palfy, M.</dc:creator>
<dc:creator>Hilbert, L.</dc:creator>
<dc:creator>Kumar, M.</dc:creator>
<dc:creator>Karschau, J.</dc:creator>
<dc:creator>Zaburdaev, V.</dc:creator>
<dc:creator>Shevchenko, A.</dc:creator>
<dc:creator>Vastenhouw, N.</dc:creator>
<dc:date>2017-04-13</dc:date>
<dc:identifier>doi:10.1101/125716</dc:identifier>
<dc:title><![CDATA[Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-04-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/234112v1?rss=1">
<title>
<![CDATA[
Transcription establishes microenvironments that organize euchromatin 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/234112v1?rss=1"
</link>
<description><![CDATA[
Chromatin is organized into heterochromatin, which is transcriptionally inactive, and euchromatin, which can switch between transcriptionally active and inactive states. This switch in euchromatin activity is accompanied by changes in its spatial distribution. How euchromatin rearrangements are established is unknown. Here we use super-resolution and live-cell microscopy to show that transcriptionally inactive euchromatin moves away from transcriptionally active euchromatin. This movement is driven by the formation of RNA-enriched microenvironments that exclude inactive euchromatin. Using theory, we show that the segregation into RNA-enriched microenvironments and euchromatin domains can be considered an active microemulsion. The tethering of transcripts to chromatin via RNA polymerase II forms effective amphiphiles that intersperse the two segregated phases. Taken together with previous experiments, our data suggest that chromatin is organized in the following way: heterochromatin segregates from euchromatin by phase separation, while transcription organizes euchromatin similar to an active microemulsion.
]]></description>
<dc:creator>Hilbert, L.</dc:creator>
<dc:creator>Sato, Y.</dc:creator>
<dc:creator>Kimura, H.</dc:creator>
<dc:creator>Jülicher, F.</dc:creator>
<dc:creator>Honigmann, A.</dc:creator>
<dc:creator>Zaburdaev, V.</dc:creator>
<dc:creator>Vastenhouw, N.</dc:creator>
<dc:date>2017-12-15</dc:date>
<dc:identifier>doi:10.1101/234112</dc:identifier>
<dc:title><![CDATA[Transcription establishes microenvironments that organize euchromatin]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-12-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/174078v1?rss=1">
<title>
<![CDATA[
Autocatalytic microtubule nucleation determines the size and mass of spindles 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/174078v1?rss=1"
</link>
<description><![CDATA[
Regulation of size and growth is a fundamental problem in biology. A prominent example is the formation of the mitotic spindle, where protein concentration gradients around chromosomes are thought to regulate spindle growth by controlling microtubule nucleation (1, 2). Previous evidence suggests that microtubules nucleate throughout the spindle structure (3-5). However, the mechanisms underlying microtubule nucleation and its spatial regulation are still unclear. Here, we developed an assay based on laser ablation to directly probe microtubule nucleation events in Xenopus laevis egg extracts. Combining this method with theory and quantitative microscopy, we show that the size of a spindle is controlled by autocatalytic growth of microtubules, driven by microtubule-stimulated microtubule nucleation. The autocatalytic activity of this nucleation system is spatially regulated by the limiting amounts of active microtubule nucleators, which decrease with distance from the chromosomes. Thus, the size of spindles is determined by the distance where one microtubule nucleates on average less than one new microtubule. This mechanism provides an upper limit to spindle size even when resources are not limiting and may have implications for spindle scaling during development (6, 7).
]]></description>
<dc:creator>Decker, F.</dc:creator>
<dc:creator>Oriola, D.</dc:creator>
<dc:creator>Dalton, B.</dc:creator>
<dc:creator>Brugues, J.</dc:creator>
<dc:date>2017-08-09</dc:date>
<dc:identifier>doi:10.1101/174078</dc:identifier>
<dc:title><![CDATA[Autocatalytic microtubule nucleation determines the size and mass of spindles]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-08-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/177733v1?rss=1">
<title>
<![CDATA[
Dynamic, non-contact 3D sample rotation for microscopy 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/177733v1?rss=1"
</link>
<description><![CDATA[
In vivo imaging of growing and developing samples requires a dynamic adaptation of the sample orientation to continuously achieve optimal performance. Here, we present how, after the injection of magnetic beads, a sample can be freely positioned by applying a magnetic field. We demonstrate its performance for zebrafish on an epi-fluorescence microscope and on a light sheet system for superior multi-view acquisition.
]]></description>
<dc:creator>Berndt, F.</dc:creator>
<dc:creator>Shah, G.</dc:creator>
<dc:creator>Brugues, J.</dc:creator>
<dc:creator>Huisken, J.</dc:creator>
<dc:date>2017-08-17</dc:date>
<dc:identifier>doi:10.1101/177733</dc:identifier>
<dc:title><![CDATA[Dynamic, non-contact 3D sample rotation for microscopy]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-08-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/003277v1?rss=1">
<title>
<![CDATA[
Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/003277v1?rss=1"
</link>
<description><![CDATA[
One of the key questions in biology is how the metabolism of a cell responds to changes in the environment. In budding yeast, starvation causes a drop in intracellular pH, but the functional role of this pH change is not well understood. Here, we show that the enzyme glutamine synthetase (Gln1) forms filaments at low pH and that filament formation leads to enzyme inactivation. Filament formation by Gln1 is a highly cooperative process, strongly dependent on macromolecular crowding, and involves back-to-back stacking of cylindrical homo-decamers into filaments that associate laterally to form higher order fibrils. Other metabolic enzymes also assemble into filaments at low pH. Hence, we propose that filament formation is a general mechanism to inactivate and store key metabolic enzymes during a state of advanced cellular starvation. These findings have broad implications for understanding the interplay between nutritional stress, the metabolism and the physical organization of a cell.
]]></description>
<dc:creator>Ivana Petrovska</dc:creator>
<dc:creator>Elisabeth Nüske</dc:creator>
<dc:creator>Matthias C Munder</dc:creator>
<dc:creator>Gayathrie Kulasegaran</dc:creator>
<dc:creator>Liliana Malinovska</dc:creator>
<dc:creator>Sonja Kroschwald</dc:creator>
<dc:creator>Doris Richter</dc:creator>
<dc:creator>Karim Fahmy</dc:creator>
<dc:creator>Kimberley Gibson</dc:creator>
<dc:creator>Jean-Marc Verbavatz</dc:creator>
<dc:creator>Simon Alberti</dc:creator>
<dc:creator></dc:creator>
<dc:date>2014-03-07</dc:date>
<dc:identifier>doi:10.1101/003277</dc:identifier>
<dc:title><![CDATA[Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2014-03-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/076224v1?rss=1">
<title>
<![CDATA[
Tracking single-cell gene regulation in dynamically controlled environments using an integrated microfluidic and computational setup 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/076224v1?rss=1"
</link>
<description><![CDATA[
Bacteria adapt to changes in their environment by regulating gene expression, often at the level of transcription. However, since the molecular processes underlying gene regulation are subject to thermodynamic and other stochastic fluctuations, gene expression is inherently noisy, and identical cells in a homogeneous environment can display highly heterogeneous expression levels. To study how stochasticity affects gene regulation at the single-cell level, it is crucial to be able to directly follow gene expression dynamics in single cells under changing environmental conditions. Recently developed microfluidic devices, used in combination with quantitative fluorescence time-lapse microscopy, represent a highly promising experimental approach, allowing tracking of lineages of single cells over long time-scales while simultaneously measuring their growth and gene expression. However, current devices do not allow controlled dynamical changes to the environmental conditions which are needed to study gene regulation. In addition, automated analysis of the imaging data from such devices is still highly challenging and no standard software is currently available. To address these challenges, we here present an integrated experimental and computational setup featuring, on the one hand, a new dual-input microfluidic chip which allows mixing and switching between two growth media and, on the other hand, a novel image analysis software which jointly optimizes segmentation and tracking of the cells and allows interactive user-guided fine-tuning of its results. To demonstrate the power of our approach, we study the lac operon regulation in E. coli cells grown in an environment that switches between glucose and lactose, and quantify stochastic lag times and memory at the single cell level.
]]></description>
<dc:creator>Matthias Kaiser</dc:creator>
<dc:creator>Florian Jug</dc:creator>
<dc:creator>Olin Silander</dc:creator>
<dc:creator>Siddharth Deshpande</dc:creator>
<dc:creator>Thomas Pfohl</dc:creator>
<dc:creator>Thomas Julou</dc:creator>
<dc:creator>Gene Myers</dc:creator>
<dc:creator>Erik van Nimwegen</dc:creator>
<dc:creator></dc:creator>
<dc:date>2016-09-20</dc:date>
<dc:identifier>doi:10.1101/076224</dc:identifier>
<dc:title><![CDATA[Tracking single-cell gene regulation in dynamically controlled environments using an integrated microfluidic and computational setup]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2016-09-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/066761v1?rss=1">
<title>
<![CDATA[
Independent modes of ganglion cell translocation ensure correct lamination of the zebrafish retina 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/066761v1?rss=1"
</link>
<description><![CDATA[
The arrangement of neurons into distinct layers is critical for neuronal connectivity and function of the nervous system. During development, most neurons move from their birthplace to the appropriate layer, where they polarize. However, kinetics and modes of many neuronal translocation events still await exploration. Here, we investigate ganglion cell (RGC) translocation across the embryonic zebrafish retina. After completing their translocation, RGCs establish the most basal retinal layer where they form the optic nerve. Using in toto light sheet microscopy, we show that somal translocation of RGCs is a fast and directed event. It depends on basal process attachment and stabilized microtubules. Interestingly, interference with somal translocation induces a switch to multipolar migration. This multipolar mode is less efficient but still leads to successful RGC layer formation. When both modes are inhibited, RGCs that fail to translocate induce lamination defects, indicating that correct RGC translocation is crucial for subsequent retinal lamination.
]]></description>
<dc:creator>Jaroslav Icha</dc:creator>
<dc:creator>Christiane Grunert</dc:creator>
<dc:creator>Mauricio Rocha-Martins</dc:creator>
<dc:creator>Caren Norden</dc:creator>
<dc:creator></dc:creator>
<dc:date>2016-07-29</dc:date>
<dc:identifier>doi:10.1101/066761</dc:identifier>
<dc:title><![CDATA[Independent modes of ganglion cell translocation ensure correct lamination of the zebrafish retina]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2016-07-29</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/156943v1?rss=1">
<title>
<![CDATA[
MS Western, a method of multiplexed absolute protein quantification is a practical alternative to western blotting 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/156943v1?rss=1"
</link>
<description><![CDATA[
Absolute quantification of proteins elucidates the molecular composition, regulation and dynamics of multiprotein assemblies and networks. Here we report on a method termed MS Western that accurately determines the molar abundance of dozens of user-selected proteins at the sub-femtomole level in whole cell or tissue lysates without metabolic or chemical labelling and without using specific antibodies. MS Western relies upon GeLC-MS/MS and quantifies proteins by in-gel co-digestion with an isotopically labelled QconCAT protein chimera composed of concatenated proteotypic peptides. It requires no purification of the chimera and relates the molar abundance of all proteotypic peptides to a single reference protein. In comparative experiments, MS Western outperformed immunofluorescence Western blotting by the protein detection specificity, linear dynamic range and sensitivity of protein quantification. To validate MS Western in an in vivo experiment, we quantified the molar content of zebrafish core histones H2A, H2B, H3 and H4 during ten stages of early embryogenesis. Accurate quantification (CV<10%) corroborated the anticipated histones equimolar stoichiometry and revealed an unexpected trend in their total abundance.
]]></description>
<dc:creator>Kumar, M.</dc:creator>
<dc:creator>Joseph, S. R.</dc:creator>
<dc:creator>Augsburg, M.</dc:creator>
<dc:creator>Bogdanova, A.</dc:creator>
<dc:creator>Drechsel, D.</dc:creator>
<dc:creator>Vastenhouw, N. L.</dc:creator>
<dc:creator>Buchholz, F.</dc:creator>
<dc:creator>Gentzel, M.</dc:creator>
<dc:creator>Shevchenko, A.</dc:creator>
<dc:date>2017-07-03</dc:date>
<dc:identifier>doi:10.1101/156943</dc:identifier>
<dc:title><![CDATA[MS Western, a method of multiplexed absolute protein quantification is a practical alternative to western blotting]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-07-03</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/143057v1?rss=1">
<title>
<![CDATA[
Cell-Accurate Optical Mapping Across The Entire Developing Heart 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/143057v1?rss=1"
</link>
<description><![CDATA[
Organogenesis depends on orchestrated interactions between individual cells and morphogenically relevant cues at the tissue level. This is true for the heart, whose function critically relies on well-ordered communication between neighbouring cells, which is established and fine-tuned during development. For an integrated understanding of the development of structure and function, we need to move from isolated snap-shot observations of either microscopic or macroscopic parameters to simultaneous and, ideally continuous, cell-to-organ scale imaging. We introduce cell-accurate three-dimensional Ca2+-mapping of all cells in the entire heart during the looping stage in live embryonic zebrafish, using high-speed light sheet microscopy and tailored image processing and analysis. We show how myocardial region-specific heterogeneity in cell function emerges during early development and how structural patterning goes hand-in-hand with functional maturation of the entire heart. Our method opens the way to systematic, scale-bridging, in vivo studies of vertebrate organogenesis by cell-accurate structure-function mapping across entire organs.
]]></description>
<dc:creator>Weber, M.</dc:creator>
<dc:creator>Scherf, N.</dc:creator>
<dc:creator>Kohl, P.</dc:creator>
<dc:creator>Huisken, J.</dc:creator>
<dc:date>2017-05-27</dc:date>
<dc:identifier>doi:10.1101/143057</dc:identifier>
<dc:title><![CDATA[Cell-Accurate Optical Mapping Across The Entire Developing Heart]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-05-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/173583v1?rss=1">
<title>
<![CDATA[
Pan-embryo cell dynamics of germlayer formation in zebrafish 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/173583v1?rss=1"
</link>
<description><![CDATA[
Cell movements are coordinated across spatio-temporal scales to achieve precise positioning of organs during vertebrate gastrulation. In zebrafish, mechanisms governing such morphogenetic movements have so far only been studied within a local region or a single germlayer. Here, we present pan-embryo analyses of fate specification and dynamics of all three germlayers simultaneously within a gastrulating embryo, showing that cell movement characteristics are predominantly determined by its position within the embryo, independent of its germlayer identity. The spatially confined fate specification establishes a distinct distribution of cells in each germlayer during early gastrulation. The differences in the initial distribution are subsequently amplified by a unique global movement, which organizes the organ precursors along the embryonic body axis, giving rise to the blueprint of organ formation.
]]></description>
<dc:creator>Shah, G.</dc:creator>
<dc:creator>Thierbach, K.</dc:creator>
<dc:creator>Schmid, B.</dc:creator>
<dc:creator>Reade, A.</dc:creator>
<dc:creator>Roeder, I.</dc:creator>
<dc:creator>Scherf, N.</dc:creator>
<dc:creator>Huisken, J.</dc:creator>
<dc:date>2017-08-08</dc:date>
<dc:identifier>doi:10.1101/173583</dc:identifier>
<dc:title><![CDATA[Pan-embryo cell dynamics of germlayer formation in zebrafish]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-08-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/082958v1?rss=1">
<title>
<![CDATA[
Collective epithelial migration drives timely morphogenesis of the retinal neuroepithelium 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/082958v1?rss=1"
</link>
<description><![CDATA[
Organ formation is a multi-scale event that involves changes at the intracellular, cellular and tissue level. Organogenesis often starts with the formation of characteristically shaped organ precursors. However, the cellular mechanisms driving organ precursor formation are often not clear. Here, using zebrafish, we investigate the epithelial rearrangements responsible for the development of the hemispherical retinal neuroepithelium (RNE), a part of the optic cup. We show that in addition to basal shrinkage of RNE cells, active migration of connected epithelial cells into the RNE is a crucial player in its formation. This cellular movement is driven by progressive cell-matrix contacts and actively translocates prospective RNE cells to their correct location before they adopt neuroepithelial fate. Failure of this migration during neuroepithelium formation leads to ectopic determination of RNE cells and consequently impairs optic cup formation. Overall, this study illustrates how spatiotemporal coordination between morphogenic movements and fate determination critically influences organogenesis.
]]></description>
<dc:creator>Norden, C.</dc:creator>
<dc:creator>Sidhaye, J.</dc:creator>
<dc:creator>Ifflaender, N.</dc:creator>
<dc:date>2016-10-24</dc:date>
<dc:identifier>doi:10.1101/082958</dc:identifier>
<dc:title><![CDATA[Collective epithelial migration drives timely morphogenesis of the retinal neuroepithelium]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2016-10-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/236463v1?rss=1">
<title>
<![CDATA[
Content-Aware Image Restoration: Pushing the Limits of Fluorescence Microscopy 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/236463v1?rss=1"
</link>
<description><![CDATA[
Fluorescence microscopy is a key driver of discoveries in the life-sciences, with observable phenomena being limited by the optics of the microscope, the chemistry of the fluorophores, and the maximum photon exposure tolerated by the sample. These limits necessitate trade-offs between imaging speed, spatial resolution, light exposure, and imaging depth. In this work we show how image restoration based on deep learning extends the range of biological phenomena observable by microscopy. On seven concrete examples we demonstrate how microscopy images can be restored even if 60-fold fewer photons are used during acquisition, how near isotropic resolution can be achieved with up to 10-fold under-sampling along the axial direction, and how tubular and granular structures smaller than the diffraction limit can be resolved at 20-times higher frame-rates compared to state-of-the-art methods. All developed image restoration methods are freely available as open source software in Python, FO_SCPLOWIJIC_SCPLOW, and KO_SCPLOWNIMEC_SCPLOW.
]]></description>
<dc:creator>Weigert, M.</dc:creator>
<dc:creator>Schmidt, U.</dc:creator>
<dc:creator>Boothe, T.</dc:creator>
<dc:creator>Muuml</dc:creator>
<dc:creator>ller, A.</dc:creator>
<dc:creator>Dibrov, A.</dc:creator>
<dc:creator>Jain, A.</dc:creator>
<dc:creator>Wilhelm, B.</dc:creator>
<dc:creator>Schmidt, D.</dc:creator>
<dc:creator>Broaddus, C.</dc:creator>
<dc:creator>Culley, S.</dc:creator>
<dc:creator>Rocha-Martins, M.</dc:creator>
<dc:creator>Segovia-Miranda, F.</dc:creator>
<dc:creator>Norden, C.</dc:creator>
<dc:creator>Henriques, R.</dc:creator>
<dc:creator>Zerial, M.</dc:creator>
<dc:creator>Solimena, M.</dc:creator>
<dc:creator>Rink, J.</dc:creator>
<dc:creator>Tomancak, P.</dc:creator>
<dc:creator>Royer, L.</dc:creator>
<dc:creator>Jug, F.</dc:creator>
<dc:creator>Myers, E. W.</dc:creator>
<dc:date>2017-12-19</dc:date>
<dc:identifier>doi:10.1101/236463</dc:identifier>
<dc:title><![CDATA[Content-Aware Image Restoration: Pushing the Limits of Fluorescence Microscopy]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-12-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/106252v1?rss=1">
<title>
<![CDATA[
Non Hybrid Long Read Consensus Using Local De Bruijn Graph Assembly 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/106252v1?rss=1"
</link>
<description><![CDATA[
While second generation sequencing led to a vast increase in sequenced data, the shorter reads which came with it made assembly a much harder task and for some regions impossible with only short read data. This changed again with the advent of third generation long read sequencers. The length of the long reads allows a much better resolution of repetitive regions, their high error rate however is a major challenge. Using the data successfully requires to remove most of the sequencing errors. The first hybrid correction methods used low noise second generation data to correct third generation data, but this approach has issues when it is unclear where to place the short reads due to repeats and also because second generation sequencers fail to sequence some regions which third generation sequencers work on. Later non hybrid methods appeared. We present a new method for non hybrid long read error correction based on De Bruijn graph assembly of short windows of long reads with subsequent combination of these correct windows to corrected long reads. Our experiments show that this method yields a better correction than other state of the art non hybrid correction approaches.
]]></description>
<dc:creator>Tischler, G.</dc:creator>
<dc:creator>Myers, E. W.</dc:creator>
<dc:date>2017-02-06</dc:date>
<dc:identifier>doi:10.1101/106252</dc:identifier>
<dc:title><![CDATA[Non Hybrid Long Read Consensus Using Local De Bruijn Graph Assembly]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-02-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/145474v1?rss=1">
<title>
<![CDATA[
Haplotype And Repeat Separation In Long Reads 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/145474v1?rss=1"
</link>
<description><![CDATA[
Resolving the correct structure and succession of highly similar sequence stretches is one of the main open problems in genome assembly. For non haploid genomes this includes determining the sequences of the different haplotypes. For all but the smallest genomes it also involves separating different repeat instances. In this paper we discuss methods for resolving such problems in third generation long reads by classifying alignments between long reads according to whether they represent true or false read overlaps. The main problem in this context is the high error rate found in such reads, which greatly exceeds the amount of difference between the similar regions we want to separate. Our methods can separate read classes stemming from regions with as little as 1% difference.
]]></description>
<dc:creator>Tischler, G.</dc:creator>
<dc:date>2017-06-02</dc:date>
<dc:identifier>doi:10.1101/145474</dc:identifier>
<dc:title><![CDATA[Haplotype And Repeat Separation In Long Reads]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2017-06-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/263061v1?rss=1">
<title>
<![CDATA[
Forget Pixels: Adaptive Particle Representation of Fluorescence Microscopy Images 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/263061v1?rss=1"
</link>
<description><![CDATA[
Modern microscopy modalities create a data deluge with gigabytes of data generated each second, and terabytes per day. Storing and processing these data is a severe bottleneck, not fully alleviated by data compression. We argue that this is because images are processed as regular grids of pixels. To address the root of the problem, we here propose a content-adaptive representation of fluorescence microscopy images called the Adaptive Particle Representation (APR). The APR replaces the regular grid of pixels with particles positioned according to image content. This overcomes storage bottlenecks, as data compression does, but additionally overcomes memory and processing bottlenecks, since the APR can directly be used in processing without going back to pixels. We present the ideas, concepts, and algorithms of the APR and validate them using noisy 3D image data. We show that the APR represents the content of an image while maintaining image quality. We then show that the adaptivity of the APR provides orders of magnitude benefits across a range of image processing tasks. Therefore, the APR provides a simple, extendable, and efficient content-aware representation of images that relaxes current data and processing bottlenecks.
]]></description>
<dc:creator>Cheeseman, B. L.</dc:creator>
<dc:creator>Günther, U.</dc:creator>
<dc:creator>Susik, M.</dc:creator>
<dc:creator>Gonciarz, K.</dc:creator>
<dc:creator>Sbalzarini, I. F.</dc:creator>
<dc:date>2018-02-09</dc:date>
<dc:identifier>doi:10.1101/263061</dc:identifier>
<dc:title><![CDATA[Forget Pixels: Adaptive Particle Representation of Fluorescence Microscopy Images]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-02-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/278937v1?rss=1">
<title>
<![CDATA[
Expansion stimulated emission depletion microscopy (ExSTED) 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/278937v1?rss=1"
</link>
<description><![CDATA[
Stimulated emission depletion (STED) microscopy is routinely used to resolve the ultra-structure of cells with a [~]10-fold higher resolution compared to diffraction limited imaging. While STED microscopy is based on preparing the excited state of fluorescent probes with light, the recently developed expansion microscopy (ExM) provides sub-diffraction resolution by physically enlarging the sample before microscopy. Expansion of fixed cells by crosslinking and swelling of hydrogels easily enlarges the sample [~]4-fold and hence increases the effective optical resolution by this factor. To overcome the current limits of these complimentary approaches, we here combined ExM with STED (ExSTED) and demonstrate an increase in resolution of up to 30-fold compared to conventional microscopy (<10 nm lateral and [~]50 nm isotropic). While the increase in resolution is straight forward, we found that high fidelity labelling via multi-epitopes is required to obtain emitter densities that allow to resolve ultra-structural details with ExSTED. Our work provides a robust template for super resolution microscopy of entire cells in the ten nanometer range.
]]></description>
<dc:creator>Gao, M.</dc:creator>
<dc:creator>Maraspini, R.</dc:creator>
<dc:creator>Beutel, O.</dc:creator>
<dc:creator>Zehtabian, A.</dc:creator>
<dc:creator>Eickholt, B.</dc:creator>
<dc:creator>Honigmann, A.</dc:creator>
<dc:creator>Ewers, H.</dc:creator>
<dc:date>2018-03-08</dc:date>
<dc:identifier>doi:10.1101/278937</dc:identifier>
<dc:title><![CDATA[Expansion stimulated emission depletion microscopy (ExSTED)]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-03-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/296566v1?rss=1">
<title>
<![CDATA[
Active gelation breaks time-reversal-symmetry of mitotic chromosome mechanics 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/296566v1?rss=1"
</link>
<description><![CDATA[
In cell division, mitosis is the phase in which duplicated sets of chromosomes are mechanically aligned to form the metaphase plate before being segregated in two daughter cells. Irreversibility is a hallmark of this process, despite the fundamental laws of Newtonian mechanics being time symmetric.nnHere we show experimentally that mitotic chromosomes receive the arrow of time by time-reversal-symmetry breaking of the underlying mechanics in prometaphase. By optically inducing hydrodynamic flows within prophase nuclei, we find that duplicated chromatid pairs initially form a fluid suspension in the nucleoplasm: although showing little motion on their own, condensed chromosomes are free to move through the nucleus in a time-reversible manner. Actively probing chromosome mobility further in time, we find that this viscous suspension of chromatin transitions into a gel after nuclear breakdown. This gel state, in which chromosomes cannot be moved by flows, persists even when chromosomes start moving to form the metaphase plate. Complemented by minimal reconstitution experiments, our active intra-nuclear micro-rheology reveals time-reversal-symmetry breaking of chromosome mechanics to be caused by the transition from a purely fluid suspension into an active gel.nnGraphical abstractnnO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/296566_ufig1.gif" ALT="Figure 1">nView larger version (36K):norg.highwire.dtl.DTLVardef@15b00edorg.highwire.dtl.DTLVardef@199eb2dorg.highwire.dtl.DTLVardef@1f0550org.highwire.dtl.DTLVardef@95cb5a_HPS_FORMAT_FIGEXP  M_FIG C_FIG One sentence summaryFlows induced in living cell nuclei reveal the rheological changes that bring chromosomes under mechanical control during mitosis.
]]></description>
<dc:creator>Mittasch, M.</dc:creator>
<dc:creator>Fritsch, A. W.</dc:creator>
<dc:creator>Nestler, M.</dc:creator>
<dc:creator>Iglesias-Artola, J. M.</dc:creator>
<dc:creator>Subramanian, K.</dc:creator>
<dc:creator>Petzold, H.</dc:creator>
<dc:creator>Kar, M.</dc:creator>
<dc:creator>Voigt, A.</dc:creator>
<dc:creator>Kreysing, M.</dc:creator>
<dc:date>2018-04-07</dc:date>
<dc:identifier>doi:10.1101/296566</dc:identifier>
<dc:title><![CDATA[Active gelation breaks time-reversal-symmetry of mitotic chromosome mechanics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-04-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/324822v1?rss=1">
<title>
<![CDATA[
Multi-scale coordination of planar cell polarity in planarians 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/324822v1?rss=1"
</link>
<description><![CDATA[
Polarity is a universal design principle of biological systems that manifests at all organizational scales. Although well understood at the cellular level, the mechanisms that coordinate polarity at the tissue or organismal scale remain poorly understood. Here, we make use of the extreme body plan plasticity of planarian flatworms to probe the multi-scale coordination of polarity. Quantitative analysis of ciliary rootlet orientation in the epidermis reveals a global polarization field with head and tail as independent mediators of anteroposterior (A/P) polarization and the body margin influencing mediolateral (M/L) polarization. Mathematical modeling demonstrates that superposition of separate A/P- and M/L-fields can explain the global polarity field and we identify the core planar cell polarity (PCP) and Ft/Ds pathways as their specific mediators. Overall, our study establishes a mechanistic framework for the multi-scale coordination of planar polarity in planarians and establishes the core PCP and Ft/Ds pathways as evolutionarily conserved 2D-polarization module.
]]></description>
<dc:creator>Vu, H. T.-K.</dc:creator>
<dc:creator>Mansour, S.</dc:creator>
<dc:creator>Kuecken, M.</dc:creator>
<dc:creator>Blasse, C.</dc:creator>
<dc:creator>Basquin, C.</dc:creator>
<dc:creator>Azimzadeh, J.</dc:creator>
<dc:creator>Myers, E. W.</dc:creator>
<dc:creator>Brusch, L.</dc:creator>
<dc:creator>Rink, J. C.</dc:creator>
<dc:date>2018-05-17</dc:date>
<dc:identifier>doi:10.1101/324822</dc:identifier>
<dc:title><![CDATA[Multi-scale coordination of planar cell polarity in planarians]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-05-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/332916v1?rss=1">
<title>
<![CDATA[
Body size-dependent energy storage causes Kleibers law scaling of the metabolic rate in planarians 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/332916v1?rss=1"
</link>
<description><![CDATA[
Kleibers law, or the [3/4]-power law scaling of the metabolic rate with body mass, is considered one of the few quantitative laws in biology, yet its physiological basis remains unknown. Here, we report Kleibers law scaling in the planarian Schmidtea mediterranea. Its reversible and life history-independent changes in adult body size over 2 orders of magnitude reveal that Kleibers law does not emerge from the size-dependent decrease in cellular metabolic rate, but from a size-dependent increase in mass per cell. Through a combination of experiment and theoretical analysis of the organismal energy balance, we further show that the mass allometry is caused by body size dependent energy storage. Our results reveal the physiological origins of Kleibers law in planarians and thus have general implications for understanding a fundamental scaling law in biology.
]]></description>
<dc:creator>Rink, J. C.</dc:creator>
<dc:creator>Thommen, A.</dc:creator>
<dc:creator>Werner, S.</dc:creator>
<dc:creator>Frank, O.</dc:creator>
<dc:creator>Philipp, J.</dc:creator>
<dc:creator>Knittelfelder, O.</dc:creator>
<dc:creator>Quek, Y.</dc:creator>
<dc:creator>Fahmy, K.</dc:creator>
<dc:creator>Shevchenko, A.</dc:creator>
<dc:creator>Friedrich, B. M.</dc:creator>
<dc:creator>Jülicher, F.</dc:creator>
<dc:date>2018-05-29</dc:date>
<dc:identifier>doi:10.1101/332916</dc:identifier>
<dc:title><![CDATA[Body size-dependent energy storage causes Kleibers law scaling of the metabolic rate in planarians]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-05-29</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/395830v1?rss=1">
<title>
<![CDATA[
Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/395830v1?rss=1"
</link>
<description><![CDATA[
The evolutionary increase in size and complexity of the primate neocortex is thought to underlie the higher cognitive abilities of humans. ARHGAP11B is a human-specific gene that, based on its expression pattern in fetal human neocortex and progenitor effects in embryonic mouse neocortex, has been proposed to have a key function in the evolutionary expansion of the neocortex. Here, we study the effects of ARHGAP11B expression in the developing neocortex of the gyrencephalic ferret. In contrast to its effects in mouse, ARHGAP11B markedly increases proliferative basal radial glia, a progenitor cell type thought to be instrumental for neocortical expansion, and results in extension of the neurogenic period and an increase in upper-layer neurons. As a consequence, the postnatal ferret neocortex exhibits an increased neuron density in the upper cortical layers and expands in the radial dimension. Thus, human-specific ARHGAP11B can elicit hallmarks of neocortical expansion in developing ferret neocortex.
]]></description>
<dc:creator>Kalebic, N.</dc:creator>
<dc:creator>Gilardi, C.</dc:creator>
<dc:creator>Albert, M.</dc:creator>
<dc:creator>Namba, T.</dc:creator>
<dc:creator>Long, K. R.</dc:creator>
<dc:creator>Kostic, M.</dc:creator>
<dc:creator>Langen, B.</dc:creator>
<dc:creator>Huttner, W. B.</dc:creator>
<dc:date>2018-08-20</dc:date>
<dc:identifier>doi:10.1101/395830</dc:identifier>
<dc:title><![CDATA[Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-08-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/495952v1?rss=1">
<title>
<![CDATA[
Liquid-crystal organization of liver tissue 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/495952v1?rss=1"
</link>
<description><![CDATA[
Functional tissue architecture originates by self-assembly of distinct cell types, following tissue-specific rules of cell-cell interactions. In the liver, a structural model of the lobule was pioneered by Elias in 1949. This model, however, is in contrast with the apparent random 3D arrangement of hepatocytes. Since then, no significant progress has been made to derive the organizing principles of liver tissue. To solve this outstanding problem, we computationally reconstructed 3D tissue geometry from microscopy images and analyzed it applying soft-condensed-matter-physics concepts. Surprisingly, analysis of the spatial organization of cell polarity revealed that hepatocytes are not randomly oriented but follow a long-range liquid-crystal order. This does not depend exclusively on hepatocytes receiving instructive signals by endothelial cells as generally assumed, since silencing Integrin-{beta}1 disrupted both liquid-crystal order and organization of the sinusoidal network. Our results suggest that bi-directional communication between hepatocytes and sinusoids underlies the self-organization of liver tissue.
]]></description>
<dc:creator>Morales-Navarrete, H.</dc:creator>
<dc:creator>Nonaka, H.</dc:creator>
<dc:creator>Scholich, A.</dc:creator>
<dc:creator>Segovia-Miranda, F.</dc:creator>
<dc:creator>de Back, W.</dc:creator>
<dc:creator>Meyer, K.</dc:creator>
<dc:creator>Bogorad, R. L.</dc:creator>
<dc:creator>Koteliansky, V.</dc:creator>
<dc:creator>Brusch, L.</dc:creator>
<dc:creator>Kalaidzidis, Y.</dc:creator>
<dc:creator>Julicher, F.</dc:creator>
<dc:creator>Friedrich, B. M.</dc:creator>
<dc:creator>Zerial, M.</dc:creator>
<dc:date>2018-12-13</dc:date>
<dc:identifier>doi:10.1101/495952</dc:identifier>
<dc:title><![CDATA[Liquid-crystal organization of liver tissue]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-12-13</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/421701v1?rss=1">
<title>
<![CDATA[
Integrin-mediated attachment of the blastoderm to the vitelline envelope impacts gastrulation of insects 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/421701v1?rss=1"
</link>
<description><![CDATA[
During gastrulation, physical forces reshape the simple embryonic tissue to form a complex body plan of multicellular organisms1. These forces often cause large-scale asymmetric movements of the embryonic tissue2,3. In many embryos, the tissue undergoing gastrulation movements is surrounded by a rigid protective shell4,5. While it is well recognized that gastrulation movements depend on forces generated by tissue-intrinsic contractility6,7, it is not known if interactions between the tissue and the protective shell provide additional forces that impact gastrulation. Here we show that a particular part of the blastoderm tissue of the red flour beetle Tribolium castaneum tightly adheres in a temporally coordinated manner to the vitelline envelope surrounding the embryo. This attachment generates an additional force that counteracts the tissue-intrinsic contractile forces to create asymmetric tissue movements. Furthermore, this localized attachment is mediated by a specific integrin, and its knock-down leads to a gastrulation phenotype consistent with complete loss of attachment. Moreover, analysis of another integrin in the fruit fly Drosophila melanogaster suggests that gastrulation in this organism also relies on adhesion between the blastoderm and the vitelline. Together, our findings reveal a conserved mechanism whereby the spatiotemporal pattern of tissue adhesion to the vitelline envelope provides controllable counter-forces that shape gastrulation movements in insects.
]]></description>
<dc:creator>Munster, S.</dc:creator>
<dc:creator>Jain, A.</dc:creator>
<dc:creator>Mietke, A.</dc:creator>
<dc:creator>Pavlopoulos, A.</dc:creator>
<dc:creator>Grill, S. W.</dc:creator>
<dc:creator>Tomancak, P.</dc:creator>
<dc:date>2018-09-19</dc:date>
<dc:identifier>doi:10.1101/421701</dc:identifier>
<dc:title><![CDATA[Integrin-mediated attachment of the blastoderm to the vitelline envelope impacts gastrulation of insects]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-09-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/532325v1?rss=1">
<title>
<![CDATA[
Yorkie controls tube length and apical barrier integrity in the developing Drosophila airways 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/532325v1?rss=1"
</link>
<description><![CDATA[
Epithelial organ size and shape depend on cell shape changes, cell-matrix communication and apical membrane growth. The Drosophila embryonic tracheal network is an excellent model to study these processes. Here, we show that the transcriptional co-activator of the Hippo pathway, Yorkie (YAP in vertebrates), plays distinct roles in the developing Drosophila airways. Yorkie exerts a cytoplasmic function by binding Drosophila Twinstar, the orthologue of the vertebrate actin-severing protein Cofilin, to regulate F-actin levels and apical cell membrane size, which are required for proper tracheal tube elongation. Second, Yorkie controls water-tightness of tracheal tubes by transcriptional regulation of the enzyme{delta} -aminolevulinate synthase (Alas). We conclude that Yorkie has a dual role in tracheal development to ensure proper tracheal growth and functionality.

Short SummaryThis work identified an alternative role of the transcriptional co-activator Yorkie (Yki) in controlling water impermeability and tube size of the developing Drosophila airways. Tracheal impermeability is triggered by Yki-mediated transcriptional regulation of{delta} -aminolevulinate synthase, Alas, whereas tube elongation is controlled by binding of Yki to the actin severing factor Twinstar.
]]></description>
<dc:creator>Papadopoulos, D. K.</dc:creator>
<dc:creator>Tomancak, P.</dc:creator>
<dc:creator>Tsarouhas, V.</dc:creator>
<dc:creator>Samakovlis, C.</dc:creator>
<dc:creator>Knust, E.</dc:creator>
<dc:creator>Skouloudaki, K.</dc:creator>
<dc:date>2019-01-28</dc:date>
<dc:identifier>doi:10.1101/532325</dc:identifier>
<dc:title><![CDATA[Yorkie controls tube length and apical barrier integrity in the developing Drosophila airways]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-01-28</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/524231v1?rss=1">
<title>
<![CDATA[
Phase separation provides a mechanism to reduce noise in cells 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/524231v1?rss=1"
</link>
<description><![CDATA[
A central problem in cellular control is how cells cope with the inherent noise in gene expression. Although transcriptional and posttranscriptional feedback mechanisms can suppress noise, they are often slow, and cannot explain how cells buffer acute fluctuations. Here, by using a physical model that links fluctuations in protein concentration to the theory of phase separation, we show that liquid droplets can act as fast and effective buffers for gene expression noise. We confirm our theory experimentally using an engineered phase separating protein that forms liquid-like compartments in mammalian cells. These data suggest a novel role of phase separation in biological information processing.
]]></description>
<dc:creator>Oltsch, F.</dc:creator>
<dc:creator>Klosin, A.</dc:creator>
<dc:creator>Julicher, F.</dc:creator>
<dc:creator>Hyman, A. A.</dc:creator>
<dc:creator>Zechner, C.</dc:creator>
<dc:date>2019-01-22</dc:date>
<dc:identifier>doi:10.1101/524231</dc:identifier>
<dc:title><![CDATA[Phase separation provides a mechanism to reduce noise in cells]]></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/cgi/content/short/357186v1?rss=1">
<title>
<![CDATA[
Mechanosensitive binding of p120-Catenin at cell junctions regulates E-Cadherin turnover and epithelial viscoelasticity 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/357186v1?rss=1"
</link>
<description><![CDATA[
Studying how epithelia respond to mechanical stresses is key to understanding tissue shape changes during morphogenesis. Here, we study the viscoelastic deformation of the Drosophila pupal wing epithelium in response to mechanical stress that evolves during morphogenesis. We show that wing epithelial tissue viscoelasticity depends on endocytic turnover of E-Cadherin. The fraction of ECadherin undergoing turnover depends on mechanical stress in the epithelium. We identified mechanosensitive binding of the endocytic regulator p120-Catenin (p120) as a mechanism to regulate E-Cadherin turnover. Under high stress, p120 is released into the cytoplasm, destabilizing E-Cadherin complexes and increasing its turnover. In p120 mutants, E-Cadherin turnover is insensitive to mechanical stress. Furthermore, we show that p120 is crucial for the viscoelastic deformation of the wing epithelium. Taken together, our findings reveal that mechanosensitive binding of p120-Catenin tunes epithelial tissue viscoelasticity during morphogenesis.
]]></description>
<dc:creator>Iyer, K. V.</dc:creator>
<dc:creator>Piscitello-Gomez, R.</dc:creator>
<dc:creator>Jülicher, F.</dc:creator>
<dc:creator>Eaton, S.</dc:creator>
<dc:date>2018-06-27</dc:date>
<dc:identifier>doi:10.1101/357186</dc:identifier>
<dc:title><![CDATA[Mechanosensitive binding of p120-Catenin at cell junctions regulates E-Cadherin turnover and epithelial viscoelasticity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-06-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/543066v1?rss=1">
<title>
<![CDATA[
Soluble tubulin is locally enriched at mitotic centrosomes in C. elegans 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/543066v1?rss=1"
</link>
<description><![CDATA[
During mitosis, the centrosome expands its capacity to nucleate microtubules. Understanding the mechanisms of centrosomal microtubule nucleation is, however, constrained by a lack of knowledge of the amount of soluble and polymer tubulin at mitotic centrosomes. Here we combined light microscopy and serial-section electron tomography to measure the amount of dimer and polymer at mitotic centrosomes in early C. elegans embryos. We show that a C. elegans one-cell stage centrosome at metaphase contains more than ten thousand microtubules with a total polymer concentration of 230 M. Centrosomes concentrate soluble /{beta} tubulin by about tenfold over the cytoplasm, reaching peak values of 470 M, giving a combined total monomer and polymer tubulin concentration at centrosomes of up to 660 M. These findings support in vitro data suggesting that microtubule nucleation in C. elegans centrosomes is driven in part by concentrating soluble tubulin.
]]></description>
<dc:creator>Baumgart, J.</dc:creator>
<dc:creator>Kirchner, M.</dc:creator>
<dc:creator>Redemann, S.</dc:creator>
<dc:creator>Woodruff, J.</dc:creator>
<dc:creator>Verbavatz, J.-M.</dc:creator>
<dc:creator>Julicher, F.</dc:creator>
<dc:creator>Hyman, A.</dc:creator>
<dc:creator>Mueller-Reichert, T.</dc:creator>
<dc:creator>Brugues, J.</dc:creator>
<dc:date>2019-02-06</dc:date>
<dc:identifier>doi:10.1101/543066</dc:identifier>
<dc:title><![CDATA[Soluble tubulin is locally enriched at mitotic centrosomes in C. elegans]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-02-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/499004v1?rss=1">
<title>
<![CDATA[
Retrograde transport of Akt by a neuronal Rab5-APPL1 endosome 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/499004v1?rss=1"
</link>
<description><![CDATA[
Long-distance axonal trafficking plays a critical role in neuronal function, and transport defects have been linked to neurodegenerative disorders. Various lines of evidence suggest that the small GTPase Rab5 plays a role in neuronal signaling via early endosomal transport. Here, we characterized the motility of Rab5 endosomes in primary cultures of mouse hippocampal pyramidal cells by live-cell imaging and showed that they exhibit bi-directional long-range motility in axons, with a strong bias toward retrograde transport. Characterization of key Rab5 effectors revealed that endogenous Rabankyrin-5, Rabenosyn-5 and APPL1 are all present in axons. Further analysis of APPL1-positive endosomes showed that, similar to Rab5-endosomes, they display more frequent long-range retrograde than anterograde movement, with the endosomal levels of APPL1 correlated with faster retrograde movement. Interestingly, APPL1-endosomes transport the neurotrophin receptor TrkB and mediate retrograde axonal transport of the kinase Akt1. FRET analysis revealed that APPL1 and Akt1 interact in an endocytosis-dependent manner. We conclude that Rab5-APPL1 endosomes exhibit the hallmarks of axonal signaling endosomes to transport Akt1 in hippocampal pyramidal cells.
]]></description>
<dc:creator>Goto-Silva, L.</dc:creator>
<dc:creator>McShane, M. P.</dc:creator>
<dc:creator>Salinas, S.</dc:creator>
<dc:creator>Kalaidzidis, Y.</dc:creator>
<dc:creator>Schiavo, G.</dc:creator>
<dc:creator>Zerial, M.</dc:creator>
<dc:date>2018-12-17</dc:date>
<dc:identifier>doi:10.1101/499004</dc:identifier>
<dc:title><![CDATA[Retrograde transport of Akt by a neuronal Rab5-APPL1 endosome]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-12-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/650762v1?rss=1">
<title>
<![CDATA[
Promoters adopt distinct dynamic manifestations depending on transcription factor context 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/650762v1?rss=1"
</link>
<description><![CDATA[
Cells respond to external signals and stresses by activating transcription factors (TF), which induce gene expression changes. Previous work suggests that signal-specific gene expression changes are partly achieved because different gene promoters exhibit varying induction dynamics in response to the same TF input signal. Here, using high-throughput quantitative single-cell measurements and a novel statistical method, we systematically analyzed transcription in individual cells to a large number of dynamic TF inputs. In particular, we quantified the scaling behavior among different transcriptional features extracted from the measured trajectories such as the gene activation delay or duration of promoter activity. Surprisingly, we found that even the same gene promoter can exhibit qualitatively distinct induction and scaling behaviors when exposed to different dynamic TF contexts. That is, promoters can adopt context-dependent "manifestations". Our analysis suggests that the full complexity of signal processing by genetic circuits may be significantly underestimated when studied in specific contexts only.
]]></description>
<dc:creator>Hansen, A. S.</dc:creator>
<dc:creator>Zechner, C. S.</dc:creator>
<dc:date>2019-05-26</dc:date>
<dc:identifier>doi:10.1101/650762</dc:identifier>
<dc:title><![CDATA[Promoters adopt distinct dynamic manifestations depending on transcription factor context]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-05-26</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/711291v1?rss=1">
<title>
<![CDATA[
Addressing lipid structural diversity in signalling: Photochemical probes for live-cell lipid biochemistry 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/711291v1?rss=1"
</link>
<description><![CDATA[
Every cell produces thousands of distinct lipid species, but methodology for studying the biological roles of individual lipids is insufficient. Using the example of diacylglycerols, prominent second messengers, we here investigate whether lipid chemical diversity can provide a basis for cellular signal specification. We developed novel photo-caged lipid probes, which allow acute manipulation of distinct diacylglycerol species in the plasma membrane. Combining uncaging experiments with mathematical modelling enabled the determination of binding constants for diacylglycerol-protein interactions and kinetic parameters for diacylglycerol transbilayer movement and turnover in quantitative live-cell experiments. Strikingly, we find that affinities and kinetics vary by orders of magnitude due to diacylglycerol structural diversity. These differences are sufficient to explain differential recruitment of diacylglycerol binding proteins and thus differing downstream phosphorylation patterns. Our approach represents a generally applicable method for elucidating the biological function of single lipid species on subcellular scales.
]]></description>
<dc:creator>Schuhmacher, M.</dc:creator>
<dc:creator>Grasskamp, A. T.</dc:creator>
<dc:creator>Wagner, N.</dc:creator>
<dc:creator>Lombardot, B.</dc:creator>
<dc:creator>Schuhmacher, J. S.</dc:creator>
<dc:creator>Sala, P.</dc:creator>
<dc:creator>Lohmann, A.</dc:creator>
<dc:creator>Henry, I.</dc:creator>
<dc:creator>Shevchenko, A.</dc:creator>
<dc:creator>Coskun, U.</dc:creator>
<dc:creator>Walter, A. M.</dc:creator>
<dc:creator>Nadler, A.</dc:creator>
<dc:date>2019-07-22</dc:date>
<dc:identifier>doi:10.1101/711291</dc:identifier>
<dc:title><![CDATA[Addressing lipid structural diversity in signalling: Photochemical probes for live-cell lipid biochemistry]]></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/cgi/content/short/721001v1?rss=1">
<title>
<![CDATA[
Small molecules for modulating protein driven liquid-liquid phase separation in treating neurodegenerative disease 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/721001v1?rss=1"
</link>
<description><![CDATA[
Neurodegenerave diseases such as amyotrophic lateral sclerosis (ALS) are oten associated with mutaons in proteins that are associated with stress granules. Stress granules are condensates formed by liquid-liquid phase separaon which, when aberrant, can lead to altered condensaon behaviours and disease phenotypes. Here, we identified lipoamide, a small molecule which specifically prevents cytoplasmic condensaon of stress granule proteins. Thermal proteome profiling showed that lipoamide preferentially stabilises intrinsically disordered domain-containing proteins. These include SRSF1 and SFPQ, stress granule proteins necessary for lipoamide activity. The redox state of SFPQ correlates with its condensate-dissolving behaviour, in concordance with the importance of the dithiolane ring for lipoamide activity. In animals, lipoamide ameliorates aging-associated aggregaon of a stress granule reporter, improves neuronal morphology, and recovers motor defects caused by expression of ALS-associated FUS and TDP-43 mutants. In conclusion, lipoamide is a well-tolerated small molecule modulator of stress granule condensaon and dissection of its molecular mechanism identified a cellular pathway for redox regulaon of stress granule formaon.
]]></description>
<dc:creator>Wheeler, R. J.</dc:creator>
<dc:creator>Lee, H. O.</dc:creator>
<dc:creator>Poser, I.</dc:creator>
<dc:creator>Pal, A.</dc:creator>
<dc:creator>Doeleman, T.</dc:creator>
<dc:creator>Kishigami, S.</dc:creator>
<dc:creator>Kour, S.</dc:creator>
<dc:creator>Anderson, E. N.</dc:creator>
<dc:creator>Marrone, L.</dc:creator>
<dc:creator>Murthy, A. C.</dc:creator>
<dc:creator>Jahnel, M.</dc:creator>
<dc:creator>Zhang, X.</dc:creator>
<dc:creator>Boczek, E.</dc:creator>
<dc:creator>Fritsch, A.</dc:creator>
<dc:creator>Fawzi, N. L.</dc:creator>
<dc:creator>Sterneckert, J.</dc:creator>
<dc:creator>Pandey, U.</dc:creator>
<dc:creator>David, D. C.</dc:creator>
<dc:creator>Davis, B. G.</dc:creator>
<dc:creator>Baldwin, A. J.</dc:creator>
<dc:creator>Hermann, A.</dc:creator>
<dc:creator>Bickle, M.</dc:creator>
<dc:creator>Alberti, S.</dc:creator>
<dc:creator>Hyman, A. A.</dc:creator>
<dc:date>2019-08-05</dc:date>
<dc:identifier>doi:10.1101/721001</dc:identifier>
<dc:title><![CDATA[Small molecules for modulating protein driven liquid-liquid phase separation in treating neurodegenerative disease]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-08-05</prism:publicationDate>
<prism:section></prism:section>
</item>
</rdf:RDF>
