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This feed contains articles for bioRxiv Subject Collection "All"
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<rdf:li rdf:resource="https://www.biorxiv.org/content/10.64898/2026.07.01.735776v1?rss=1"/>
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<title>bioRxiv</title>
<url>https://www.biorxiv.org/sites/default/files/bioRxiv_article.jpg</url>
<link>https://www.biorxiv.org</link>
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<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.30.735556v1?rss=1">
<title>
<![CDATA[
Tracking claim changes from preprint to publication across 72,644 biomedical studies using large language models 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.30.735556v1?rss=1
</link>
<description><![CDATA[
Preprints now disseminate a large share of biomedical research before peer review. Because they have not yet passed peer review, some scientists regard preprint claims as unverified or potentially unreliable, yet how much those claims change before publication has so far been quantified only in smaller cohorts, with results that vary by field and topic. Here, we compiled every bioRxiv preprint posted between 2018 and 2025 that we could match by DOI to a peer-reviewed published version, yielding 72,644 preprint-publication pairs. Using a large language model (Claude Sonnet 4.6), we parsed every preprint-publication abstract pair into one primary and two secondary claims, and classified each pair for content change (unchanged, minor, major) and hedging shift (more cautious, more confident, unchanged). On a validation subsample, the model agreed with two independent domain experts about as well as the experts agreed with each other (Cohen's kappa 0.63 to 0.66). The primary claim was unchanged in 39.9% of abstracts, minorly revised in 50.0%, and substantially revised in only 10.2%. Hedging shifts were uncommon and asymmetric, with twice as many claims becoming more cautious as more confident (8.4% vs 4.2%). Major revisions were more frequent after long peer review (14.1% in the slowest versus 7.0% in the fastest tertile of review time) and declined over the study period (17.0% in 2019 to 5.7% in 2024). Over the same period, biomedical papers that were never posted as preprints were retracted at roughly twice the rate of those that were. Together, these data show that the move from preprint to peer-reviewed publication leaves the central claims of most biomedical abstracts intact, indicating that preprints are a reliable source of biomedical research.
]]></description>
<dc:creator><![CDATA[ Yin, H., Rust, R. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.30.735556</dc:identifier>
<dc:title><![CDATA[Tracking claim changes from preprint to publication across 72,644 biomedical studies using large language models]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734806v1?rss=1">
<title>
<![CDATA[
Dietary Sodium Deprivation Remodels the Serum Lipidome and Reveals Systemic Metabolic Adaptation in Rats 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734806v1?rss=1
</link>
<description><![CDATA[
Background: Dietary sodium restriction is a common nutritional and physiological challenge that activates electrolyte-conserving endocrine pathways, but its impact on systemic lipid metabolism remains incompletely defined. We examined whether short-term dietary sodium deprivation alters the circulating lipidome and identifies lipid signatures of metabolic adaptation. Methods: Male Sprague-Dawley rats were maintained on sodium-sufficient (NaS) or sodium-deprived (NaD) diets for 7 days (n=3 per group). Serum lipids were profiled by untargeted LC-MS/MS in positive and negative ion modes. Lipidomic differences were evaluated using class-level and species-level analyses, principal component analysis, volcano plots, heatmaps, and pathway-oriented interpretation. Results: NaD rats exhibited a distinct serum lipidomic profile compared with NaS controls, indicating global remodeling of circulating lipid composition. Sodium deprivation produced class-specific and species-resolved changes, including selective depletion of subsets of neutral lipid species, prominent wax ester remodeling, increased phosphatidylcholine and lysophosphatidylcholine abundance, and altered acylcarnitine profiles. These signatures are consistent with coordinated changes in lipid storage, membrane phospholipid turnover, and mitochondrial fatty-acid handling. Conclusions: Dietary sodium deprivation induces coordinated serum lipidome remodeling in rats, supporting the concept that nutritional electrolyte status can influence systemic lipid metabolism. These exploratory findings identify sodium deprivation as a metabolic stressor linked to neutral lipid mobilization, phospholipid remodeling, and altered mitochondrial substrate handling, and provide a foundation for future mechanistic studies.
]]></description>
<dc:creator><![CDATA[ Cornman-Homonoff, J., Kolandaivelu, S., Veverka, J., Kupec, J. T., Sandle, G. I., Rajendran, V. M. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734806</dc:identifier>
<dc:title><![CDATA[Dietary Sodium Deprivation Remodels the Serum Lipidome and Reveals Systemic Metabolic Adaptation in Rats]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.07.01.735776v1?rss=1">
<title>
<![CDATA[
DESI-MS-Based Analysis of Drug Distribution in Human Renal Cystic Tissue Using the Chorioallantoic Membrane (CAM) as a 3D In Vivo Model 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.07.01.735776v1?rss=1
</link>
<description><![CDATA[
The chorioallantoic membrane (CAM) model represents a promising three-dimensional in vivo platform for preclinical drug testing in human tissues. In this study, we investigated whether the tissue penetration and distribution of benzbromarone, a known inhibitor of the Ca2+ activated chloride channel TMEM16A and potential therapeutic agent for autosomal dominant polycystic kidney disease (ADPKD), can be successfully visualized in human renal cyst tissue cultured on the CAM. To this end, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) combined with an ultrahigh-resolution time-of-flight mass spectrometer was employed. We achieved spatially resolved molecular mapping of endogenous metabolites and lipids as well as the applied compound. MSI enabled clear differentiation between CAM and cystic tissue based on their distinct lipid profiles. Benzbromarone was reproducibly detected in the cyst specimens and exhibited selective accumulation along the cyst epithelium, which is considered the principal site of action. These observations were complemented by multivariate analyses including Uniform Manifold Approximation and Projection (UMAP), and sparse multinomial logistic zero-sum classification. The data-driven approach confirmed molecular differences between tissue types and allowed accurate classification of drug-treated and untreated regions. This study demonstrates that topically applied benzbromarone penetrates human renal cyst tissue in the CAM model and localizes to pharmacologically relevant tissue regions, notably the location of the Ca2+ activated chloride channel TMEM16A in the epithelial lining. The integration of high-resolution DESI-MSI with advanced statistical analysis provides a robust and label-free method to study drug distribution in human tissue grafts. Our findings contribute to the advancement of translational research in analytical chemistry and pharmacology.
]]></description>
<dc:creator><![CDATA[ Dettmer, K., Hehemann, A. M. E., Schueler, J., Heckscher, S., Gross, V., May, M., Nuebel, B., Wullich, B., Buchholz, B., Werner, J. M., Jantsch, J., Gronwald, W., Takats, Z., Oefner, P. J., Schmidt, K. M., Haerteis, S. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.07.01.735776</dc:identifier>
<dc:title><![CDATA[DESI-MS-Based Analysis of Drug Distribution in Human Renal Cystic Tissue Using the Chorioallantoic Membrane (CAM) as a 3D In Vivo Model]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.07.01.735766v1?rss=1">
<title>
<![CDATA[
Deciphering the nucleotide driven kinetic and oligomeric dynamics in IMPDH regulation 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.07.01.735766v1?rss=1
</link>
<description><![CDATA[
Inosine monophosphate dehydrogenase (IMPDH) controls guanine nucleotide biosynthesis. Here, using biochemical and integrative structural biology approaches, we characterize the class II bacterial IMPDH from Burkholderia thailandensis. We demonstrate that MgGTP acts as a direct allosteric inhibitor independently of MgATP, promoting tetramer-to-octamer assembly via the Bateman domain. When both nucleotides are present, the enzyme exhibits a biphasic response: low MgGTP concentrations enhance activity, whereas higher concentrations restore inhibition. Structural analyses reveal distinct octameric conformations and capture a pre-catalytic Michaelis complex with substrates and effectors bound. These findings uncover a regulatory mechanism where the Bateman domain integrates opposing nucleotide signals to dynamically control guanine nucleotide biosynthesis, highlighting IMPDH as a potential antimicrobial target in pathogenic Burkholderia species.
]]></description>
<dc:creator><![CDATA[ Ayoub, N., Raynal, B., Gelin, M., Labesse, G., Haouz, A., Munier-Lehmann, H. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.07.01.735766</dc:identifier>
<dc:title><![CDATA[Deciphering the nucleotide driven kinetic and oligomeric dynamics in IMPDH regulation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.733976v1?rss=1">
<title>
<![CDATA[
Nitrogen use efficiency in pigs is associated with transcriptomic signatures related to amino acid metabolism, immune activity, and nutrient partitioning 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.733976v1?rss=1
</link>
<description><![CDATA[
Dietary protein restriction challenges the allocation of amino acids to growth and other physiological functions and therefore requires coordinated metabolic adaptation. Domestic pigs provide an informative system in which to study such responses, because nitrogen retention directly affects lean growth and can be quantified accurately under controlled feeding and housing conditions. Under reduced-protein diets, pigs differ in how effectively they retain nitrogen, and this variation has a genetic basis, making them well suited to investigate the molecular regulation of nitrogen use efficiency (NUE). Here, we characterise differential gene expression and enriched pathways in liver and skeletal muscle of more than 80 pigs with two divergent NUE phenotypes (high and low) maintained under the same protein-reduced, ad libitum dietary conditions. The two NUE phenotypes were clearly distinct at the transcriptomic level, with 177 differentially expressed genes in the liver and 133 in the muscle. In the liver, differential expression and enrichment analyses indicate reduced amino acid catabolism, lower inflammatory and detoxification activity, and a metabolic state that favours lipid processing and insulin-related regulation over the use of amino acids as energy sources. In skeletal muscle, they point to reduced lipid uptake, lower reliance on amino acid oxidation, and a greater emphasis on protein synthesis, translational regulation, mitochondrial energy metabolism, and growth-related processes. These gene-level patterns were supported and extended by pathway and gene-set enrichment analyses. Together, the results suggest that high and low-NUE pigs differ through coordinated, tissue-specific molecular adaptations. Overall, variation in NUE appears to reflect coordinated, tissue-specific differences in how nutrients are allocated between energy use, storage, and lean tissue growth.
]]></description>
<dc:creator><![CDATA[ Monney, B., Ewaoluwagbemiga, E. O., Kasper, C. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.733976</dc:identifier>
<dc:title><![CDATA[Nitrogen use efficiency in pigs is associated with transcriptomic signatures related to amino acid metabolism, immune activity, and nutrient partitioning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734820v1?rss=1">
<title>
<![CDATA[
CD56dimCD16dim NK cells are the dominant effector cells against HIV-infected primary T-cells 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734820v1?rss=1
</link>
<description><![CDATA[
Despite being rare among circulating natural killer (NK) cells and expressing 10-fold less CD16 than the predominant CD56dimCD16bright population, CD56dimCD16dim NK cells are expanded in HIV long-term elite controllers, yet their capacity to kill HIV-infected cells remained untested. Here, we show that these rare cells are the dominant effectors against HIV-infected T-cells, mediating approximately 4-fold higher direct cytotoxicity and 3-4-fold higher antibody-dependent cellular cytotoxicity (ADCC) than CD56dimCD16bright cells, and serially engaging multiple targets. This advantage is intrinsic, unexplained by cytotoxic granule content or inhibitory receptors recognizing MHC class I. Direct killing depends on NKG2D recognition of Vpr-induced ligands, with NKG2D elevated on CD56dimCD16dim cells; ADCC requires both NKG2D and ADAM17-mediated CD16 turnover for serial engagement. These findings explain the elite-controller reorganization, reveal that NK effector dominance is target-tuned rather than fixed (CD56dimCD16negative cells dominate against K562 cells), and identify high-NKG2D CD56dimCD16dim cells as the effector population HIV therapies should reproduce.
]]></description>
<dc:creator><![CDATA[ Howell, W., Branch, C., Ward, J., Davis, Z., Geatches, E., Barker, E. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734820</dc:identifier>
<dc:title><![CDATA[CD56dimCD16dim NK cells are the dominant effector cells against HIV-infected primary T-cells]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734859v1?rss=1">
<title>
<![CDATA[
Viral capsid delivery of cGAMP enhances STING-dependent antitumor immune response 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734859v1?rss=1
</link>
<description><![CDATA[
Therapies to activate the STING immune response pathway represent promising potential anticancer treatments. However, the native STING activating molecule, 2',3'-cGAMP, is a poor drug candidate due to its susceptibility to nuclease degradation and its relatively poor cell uptake. In this study, we present a nanoscale delivery vehicle based on the bacteriophage MS2 virus-like particle that can both protect cGAMP and deliver it into cells to access and bind cytosolic STING. MS2-delivered cGAMP achieved greatly increased STING activation potency relative to both free cGAMP and a nuclease-resistant synthetic cGAMP analog. In an in vivo murine colon carcinoma model, MS2-cGAMP elicited significant and prolonged antitumor activity in a STING-dependent manner at 50-fold lower concentrations relative to free cGAMP and synthetic analogs. These results demonstrate that MS2 delivery of cGAMP can yield a highly potent STING agonist immunotherapy with in vivo anticancer activity.
]]></description>
<dc:creator><![CDATA[ Huang, P., Jo, Y., Martin, H. S., Luteijn, R. D., Raulet, D. H., Francis, M. B. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734859</dc:identifier>
<dc:title><![CDATA[Viral capsid delivery of cGAMP enhances STING-dependent antitumor immune response]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.733622v1?rss=1">
<title>
<![CDATA[
ARL15 promotes inflammatory fibroblast activation and disease severity in rheumatoid arthritis: integrated transcriptomic and collagen-induced arthritis model analyses 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.733622v1?rss=1
</link>
<description><![CDATA[
Background ADP-ribosylation factor-like protein 15 (ARL15) is a rheumatoid arthritis (RA) susceptibility gene identified through GWAS. Previous studies suggested a role for ARL15 in synovial fibroblast (SF) pathogenicity, but its contribution to inflammatory arthritis remains unclear. We investigated the inflammatory role of ARL15 and its therapeutic potential in RA. Methods ARL15 was overexpressed in MH7A cells followed by bulk RNA sequencing and pathway enrichment analyses. Therapeutic relevance was evaluated in collagen-induced arthritis (CIA) mouse model using anti-ARL15 monoclonal antibodies, ARL15 targeting siRNA, or isoquinoline. Arthritis scores, histopathology, microCT and serum cytokines were assessed. Publicly available single-cell RNA sequencing (scRNA-seq) datasets were analyzed to determine ARL15 expression in RASF subsets. Results ARL15 overexpression induced a pro-inflammatory transcriptional program characterized by upregulation of IL1A, IL1B, IL6, IL8, CXCL1, CXCL10, and CCL20. Gene set enrichment analysis revealed activation of IL6 JAK STAT, TNF, interferon-response, and KRAS signaling pathways, with suppression of oxidative phosphorylation, lipid metabolism, and mTORC1 signaling. In CIA mice, ARL15 inhibition significantly reduced arthritis severity, inflammatory infiltrates, and joint destruction while preserving cartilage and bone integrity. Serum TNF, IL6, and IL1{beta} levels were markedly decreased following ARL15 blockade. Combination monoclonal antibody treatment demonstrated the greatest therapeutic benefit. scRNAseq analysis showed broad ARL15 expression across RA fibroblast populations, with enrichment in inflammatory lining and SF subsets. Conclusions ARL15 is a pro-inflammatory regulator of SF activation and arthritis progression. Integrated transcriptomic, single-cell, and in vivo analyses identify ARL15 as a therapeutic target for RA and support further translational development of ARL15 based therapies.
]]></description>
<dc:creator><![CDATA[ Kashyap, S., Pandey, A. k., Saini, M., Vijaya, K., Kunnoth, S., Mahajan, P., Kundu, S., Kumar, U., Thelma, B. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.733622</dc:identifier>
<dc:title><![CDATA[ARL15 promotes inflammatory fibroblast activation and disease severity in rheumatoid arthritis: integrated transcriptomic and collagen-induced arthritis model analyses]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734809v1?rss=1">
<title>
<![CDATA[
Multi-compartment immune and tumor cell reprogramming by IFNa2 overcomes colon cancer immunotherapy resistance 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734809v1?rss=1
</link>
<description><![CDATA[
Tumor cell PD-L1 represses IFN signaling to limit anti-tumor immunity, despite an IFN-responsive immunophenotype predicting colorectal cancer response to immune checkpoint inhibitor therapy. Lipid nanoparticle (LNP)-encapsulated IFNa2-encoding nanoplasmid (LNP-mIFNa2) gene therapy suppresses tumor progression, however, the underlying mechanism and therapeutic trade-offs of the accompanying proinflammatory cytokine response triggered by nucleic acid delivery remain undefined. Here, we show that LNP-mIFNa2 selectively transfects tumor cells to restore local IFNa2 production in lung metastases, suppressing colon cancer lung metastasis in syngeneic and humanized mouse models and sensitizing tumors to ICI therapy. Efficacy required canonical IFNAR1 signaling, and was further enhanced by neutralizing co-induced IL6. Single-cell RNA sequencing revealed coordinated tumor microenvironment reprogramming with SPP1+ macrophages underwent apoptosis while incoming monocytes acquired an IFN-responsive identity, Tpex cells lost their quiescence program and expanded, and tumor cells lost their high-cycling phenotype while increasing antigen presentation and immune-cell-recruiting chemokines. Tumor cells also shifted away from a hypoxia/HIF1a-driven cuproptosis-resistance program, with increased Fdx1 and copper-importer expression and decreased metallothionein Mt1, suggesting sensitization to coproptosis pathway. The LNP-mIFN2-treated tumor microenvironment transcriptionally recapitulated T cell and myeloid signatures of pembrolizumab-responsive patients. Our findings establish LNP-delivered IFNa2 as a multi-compartment TME regulator that reprograms myeloid suppression, reinvigorates exhausted T cells, and restores tumor immunogenicity.
]]></description>
<dc:creator><![CDATA[ Tiamiyu, Z., Czabala, P., Worthy, J., Zarate, L. V., Zheng, M., Poschel, D. B., Fick, K., Yang, D., Monnig, H. R., Rashmi, R., Bombin, S., Redd, P. S., Liu, K. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734809</dc:identifier>
<dc:title><![CDATA[Multi-compartment immune and tumor cell reprogramming by IFNa2 overcomes colon cancer immunotherapy resistance]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734644v1?rss=1">
<title>
<![CDATA[
Structural determinants of dynamical state transitions in disorders of consciousness: a whole-brain modeling approach 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734644v1?rss=1
</link>
<description><![CDATA[
Disorders of consciousness (DoC) are associated with large scale alterations in brain dynamics, yet the structural factors that constrain these changes remain unclear. Here, we investigate how the topology of the structural connectome shapes the sensitivity of brain dynamics to perturbation using a whole brain computational model constrained by diffusion MRI derived connectivity. We systematically probed the effects of node removal and targeted modulation of local excitation/inhibition balance on dynamic functional connectivity, quantifying dynamical richness via transitions between recurrent connectivity states and jump length distributions in functional connectivity space. We show that a node's integration within the structural connectome, quantified using a spectral integration measure, strongly predicts its impact on global brain dynamics. Lesions to highly integrative hubs drive the system toward low complexity dynamical regimes resembling those observed in DoC, particularly posterior medial regions such as the precuneus and posterior cingulate cortex. Analogously, increasing excitability in these regions restores healthy like dynamics in silico. In contrast, perturbations to weakly integrated regions have limited global effects. These results demonstrate that generic features of structural connectivity constrain whole brain dynamical stability and help explain why damage to specific hubs disproportionately disrupts conscious brain activity.
]]></description>
<dc:creator><![CDATA[ Lehue, F., Mindlin, I., Coronel-Oliveros, C., Sitt, J., Orio, P. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734644</dc:identifier>
<dc:title><![CDATA[Structural determinants of dynamical state transitions in disorders of consciousness: a whole-brain modeling approach]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734703v1?rss=1">
<title>
<![CDATA[
Enhanced environmental complexity worsens experimental colitis and dysregulates microbiota-gut-brain axis signalling in female mice 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734703v1?rss=1
</link>
<description><![CDATA[
Ulcerative colitis (UC) is a chronic inflammatory disease characterized by colonic inflammation and bloody diarrhoea. Accumulating evidence suggests that UC not only affects the intestinal tract, but also distant organs including the brain. Environmental factors are key determinants of the disease course, yet the impact and potential disease modifying effects of living environment complexity on microbiota-gut-brain axis signalling during colitis remain unclear. To address this gap, we investigated how enhanced environmental complexity (EC) affects the disease course and gut-brain axis signalling during experimental colitis in mice. Our results show that EC exacerbates dextran sulphate sodium (DSS)-induced colitis in female mice, but not in male mice, as evidenced by greater weight loss and higher disease activity. Immune cell profiling across the gut-brain axis reveals strong effects of DSS treatment on colonic, circulating and brain immune cell populations and a restriction of central nervous system (CNS) T cell infiltration due to EC. In addition, female EC/DSS mice have higher circulating corticosterone levels than controls indicating chronic stress. Metabolomics across the gut-brain axis revealed that EC exacerbates colitis-induced metabolite perturbations in plasma, brain tissue, brain interstitial and cerebrospinal fluid. Notably, microbiota-derived metabolites, including deoxycholic acid and trimethylamine-N-oxide (TMAO), are increased in EC/DSS mice, concordant with EC-associated microbiome changes and anxiety-like behaviour. Overall, this study indicates that EC worsens experimental colitis in female mice and directs microbiota-gut-brain axis signalling during colitis towards a less favourable state. From a translational perspective, this study highlights the importance of environmental factors for a sex-specific disease course of UC and associated neurobehavioral comorbidities.
]]></description>
<dc:creator><![CDATA[ Petracco, G., Faimann, I., Gruden, E., Kienzl, M., Zuegner, E., Monedeiro, F., Kumpitsch, C., Tatzl, E., Rauter, G., Obermueller, S., Altendorfer-Kroath, T., Moissl-Eichinger, C., Schicho, R., Magnes, C., Reichmann, F. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734703</dc:identifier>
<dc:title><![CDATA[Enhanced environmental complexity worsens experimental colitis and dysregulates microbiota-gut-brain axis signalling in female mice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734424v1?rss=1">
<title>
<![CDATA[
Machine learning on magnetoencephalography data yields generalizable low-dimensional neural fingerprints that distinguish individuals across task conditions 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734424v1?rss=1
</link>
<description><![CDATA[
Individual brains are unique in structure and function. Functional differences are captured by neural fingerprints, which reflect individual differences in behavior and cognition as well as group-level changes related to neurodegenerative diseases. Most research efforts so far have focused on fingerprints comprising full functional connectomes. However, the high dimensionality of the connectomes can increase computational load and impede performance of machine learning methods in potential applications. A low-dimensional alternative that retains individual features of the full connectomes would thus be beneficial. The present study employed latent-noise Bayesian Reduced Rank Regression (lnBRRR) to learn low-dimensional latent spaces that capture individual features in functional connectivity and power spectral density data derived from MEG recordings. LnBRRR performance was assessed with low training set sizes (N=20-44), and against principal component analysis and linear discriminant analysis. Model performance was also assessed with task data, and the solutions were compared across task conditions with cosine similarity to establish whether individual features are altered by different cognitive processes. LnBRRR captured generalizable individual patterns already at N=20 but N=30-35 was needed to reach optimal test accuracies and to prevent potential overfitting. The model also achieved comparable performance to the alternative models. Latent fingerprints derived from task data attained comparable performance to resting-state latent fingerprints, and lnBRRR solutions were shown to generalize across conditions. Additionally, the model solutions for power spectral density data were discovered to be notably similar, yet differently rotated, over task conditions, suggesting that similar patterns of individual features were captured by the model regardless of the task condition. Altogether, the present results highlight lnBRRR as a potential tool for neuroimaging data analysis and demonstrate that individual differences in power spectral density are largely intrinsic and unaffected by varying cognitive processes.
]]></description>
<dc:creator><![CDATA[ Karhula, J., Ojanperä, A., Yılmaz, E., Merz, S., Kaski, S., Salmelin, R. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734424</dc:identifier>
<dc:title><![CDATA[Machine learning on magnetoencephalography data yields generalizable low-dimensional neural fingerprints that distinguish individuals across task conditions]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734784v1?rss=1">
<title>
<![CDATA[
A CSF Proteomic Clock Reveals Opposing Brain-Aging Programs and Predicts Neurological Disease Progression 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734784v1?rss=1
</link>
<description><![CDATA[
Aging is a major risk factor for neurological disease, yet the molecular architecture of human brain aging remains poorly defined. Here, we analyzed more than 10,000 cerebrospinal fluid (CSF) proteomes across multiple cohorts and proteomic platforms to develop a 249-protein CSF aging clock that accurately predicted chronological age and generalized across independent datasets. CSF brain-age acceleration was increased across diverse neurological diseases, associated with blood-brain barrier (BBB) dysfunction, and predictive of longitudinal cognitive decline, neuroimaging progression and dementia conversion. A simplified 30-protein panel retained similar prognostic performance. Biologically, the clock resolved two opposing programs: pro-aging activation of immune, vascular/BBB, extracellular matrix and coagulation pathways, marked by CHI3L1, CD14, VWF, LRG1 and LTBP2, and collapse of anti-aging neuronal-maintenance programs, marked by NPTX2, COL1A2, NID1, CDH8 and PENK. Brain-wide single-cell and regional mapping linked these programs to disease-vulnerable compartments. These findings establish a CSF-based molecular framework for quantifying biological brain aging and predicting neurological disease progression.
]]></description>
<dc:creator><![CDATA[ Xu, S., Guo, Y., Fang, K., Li, S., Wang, T., li, Y., Zhang, M., Li, H., Miao, Z., Yang, Y., Li, Z. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734784</dc:identifier>
<dc:title><![CDATA[A CSF Proteomic Clock Reveals Opposing Brain-Aging Programs and Predicts Neurological Disease Progression]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.732000v1?rss=1">
<title>
<![CDATA[
Molecular Basis of Core Fucosylation-Dependent Modulation of IgG1-FcCD16a Binding 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.732000v1?rss=1
</link>
<description><![CDATA[
Core fucosylation of the IgG1 Fc N297 glycan is known to reduce binding affinity to the FcYRIIIa (CD16a) receptor and attenuate antibody-dependent cellular cytotoxicity (ADCC), yet the structural mechanisms underlying this effect remain incompletely understood. Here, we use extensive all-atom molecular dynamics simulations to systematically investigate how Fc glycosylation modulates the structural, energetic, and dynamical landscape of the IgG1 Fc-CD16a complex across multiple systems with fucosylation and galactosylation. Relative binding free energy calculations reproduce experimentally established trends, showing that afucosylation consistently strengthens Fc-CD16a interactions. Mechanistically, dual fucosylation (on both Fc arms) increases inter-glycan packing between the Fc N297 glycans, restricts Fc glycan conformational sampling, and destabilizes the conformational organization of the CD16a N162 glycan. These glycan-mediated perturbations propagate to the protein interface. The result is reduced Fc-CD16a contact persistence, redistribution of energetically important residues away from the canonical binding interface, and broader, less stable receptor-bound conformational states. Dynamic cross-correlation analysis further reveals that afucosylated systems maintain substantially stronger coordinated motions across the Fc-CD16a assembly, whereas fucosylation disrupts long-range dynamic coupling between the receptor and antibody domains. Across these different energetic, structural, conformational, and dynamical readouts, fucosylation systematically shifts the Fc-CD16a assembly from a compact, interface-stabilized binding mode toward a more heterogeneous and weakly coupled receptor-bound ensemble. Together, our findings set forth a mechanistic basis for Fc glycosylation regulating receptor engagement through ensemble-level conformational and dynamical reorganization rather than simple local steric effects. These results provide mechanistic design principles for rational Fc glycoengineering and the development of therapeutic antibodies with enhanced effector functions. More broadly, this work highlights how glycan composition can be leveraged as a tunable molecular design parameter for engineering protein recognition, conformational stability, and immune effector function in therapeutic glycoproteins.
]]></description>
<dc:creator><![CDATA[ Mani, N., Polozova, A., Chakraborty, S. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.732000</dc:identifier>
<dc:title><![CDATA[Molecular Basis of Core Fucosylation-Dependent Modulation of IgG1-FcCD16a Binding]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734647v1?rss=1">
<title>
<![CDATA[
CryoGO enables high-resolution structural profiling of endogenous cellular macromolecules 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734647v1?rss=1
</link>
<description><![CDATA[
Resolving macromolecular structures within their native cellular environment is essential for connecting molecular architecture to physiological function, yet the field lacks accessible, high-throughput methods for generating suitable specimens from cells. Here, we introduce cryoGO (on-Grid Opening cryo-electron microscopy), a simple, rapid, and scalable strategy that mechanically opens cells directly on EM grids to produce cell-derived specimens for high-resolution single-particle cryo-EM. This approach enables near-atomic structure determination of diverse endogenous macromolecular assemblies spanning a broad molecular-weight range. We show that cryoGO captures the rich ribosomal conformational and compositional landscape while preserving physiological state distributions and aspects of spatial heterogeneity originating from cells. Furthermore, this rapid workflow enables time-resolved structural profiling, capturing both long-term cellular adaptation and acute remodeling on timescales of seconds. Compatible with standard cryo-EM infrastructure and diverse biological samples, while requiring only small numbers of cells, cryoGO lowers the technical barrier to high-resolution native structural biology.
]]></description>
<dc:creator><![CDATA[ Li, Y., Zhang, Y., Wu, C., Zhu, C., Xiong, Y. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734647</dc:identifier>
<dc:title><![CDATA[CryoGO enables high-resolution structural profiling of endogenous cellular macromolecules]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.732348v1?rss=1">
<title>
<![CDATA[
MCD Stitcher: An open-source tool for whole-slide stitching and conversion of Imaging Mass Cytometry data 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.732348v1?rss=1
</link>
<description><![CDATA[
Imaging Mass Cytometry (IMC) combines metal-tagged antibody labelling with laser ablation mass spectrometry to generate highly multiplexed spatial images of tissue sections. However, the area that can be acquired within a single region of interest (ROI) is limited by hardware and software constraints, requiring large tissues to be imaged as multiple tiled ROIs. Reconstructing these ROIs into whole-slide images requires additional processing, while the proprietary .mcd file format can hinder integration with standard bioimage analysis workflows. Here, we present MCD Stitcher, an open-source Python package for converting .mcd files into OME-TIFF images with automated whole-slide stitching. The tool supports rectangular and polygonal ROIs, accommodates variable pixel sizes between ROIs, and uses memory-aware chunked reading during data ingestion to process large datasets on standard workstations. The generated OME-TIFF outputs preserve spatial, channel, and acquisition metadata for downstream analysis in tools such as QuPath, napari, and ImageJ/Fiji. MCD Stitcher provides a reproducible workflow for converting raw IMC data into interoperable image formats, enabling whole-slide spatial analysis without reliance on vendor-specific software.
]]></description>
<dc:creator><![CDATA[ Chaurasia, P. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.732348</dc:identifier>
<dc:title><![CDATA[MCD Stitcher: An open-source tool for whole-slide stitching and conversion of Imaging Mass Cytometry data]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734767v1?rss=1">
<title>
<![CDATA[
Direct probabilistic quantification of mosaic loss of chromosome Y from sequencing data 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734767v1?rss=1
</link>
<description><![CDATA[
Loss of chromosome Y (LOY) is the most common aneuploidy in aging men and is increasingly recognized as a marker of aging and genomic instability. Because LOY occurs in mosaic form, its degree reflects the fraction of cells lacking the Y chromosome. Existing SNP-array- and sequencing-based methods rely largely on single genomic features and indirect transformations to estimate this fraction. We developed BaySeq-Y, a Bayesian method that directly estimates LOY mosaicism from sequencing data using VCF files with read depth (DP) and allelic depth (AD). Within a rigorous Bayesian framework, BaySeq-Y integrates complementary LOY-associated genomic features, including decreased read depth and allelic imbalance, and can additionally leverage haplotype phasing to improve precision. In simulations and fluorescence in situ hybridization validation (FISH), BaySeq-Y provided accurate estimates and outperformed existing methods. Applications to ROSMAP and GTEx supported its biological relevance through transcriptomic validation, demonstrating its utility for quantifying LOY across diverse sequencing datasets.
]]></description>
<dc:creator><![CDATA[ Lin, J.-R., Chang, Y.-C., Maslov, A. Y., Song, Y., Gao, T., Shan, J., Bennett, D. A., Milman, S., Barzilai, N., Vijg, J., Montagna, C., Zhang, Z. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734767</dc:identifier>
<dc:title><![CDATA[Direct probabilistic quantification of mosaic loss of chromosome Y from sequencing data]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734379v1?rss=1">
<title>
<![CDATA[
Pericystic brain transcriptomics reveals molecular signatures of immune activation and neurovascular remodelling in viable and post-treatment porcine neurocysticercosis 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734379v1?rss=1
</link>
<description><![CDATA[
Neurocysticercosis (NCC), the infection of the central nervous system by Taenia solium larvae, is a leading cause of acquired epilepsy in endemic regions. While viable cysticerci can persist asymptomatically for extended periods, their spontaneous or drug-induced degradation triggers marked perilesional inflammation and severe neurological symptoms. Despite well-documented histopathological characterisation of these lesion states, the host transcriptional programmes associated with viable parasite persistence and early post-treatment lesion disruption remain poorly understood. To address this gap, we performed the first bulk RNA sequencing of pericystic brain tissue using a physiologically relevant porcine model of NCC. Comparing uninfected controls (n = 3), infected untreated pigs with intact viable cysts (n = 6), and antiparasitic-treated pigs with disrupted cysts (n = 3), we identified distinct transcriptional signatures associated with each disease state. Viable infection was associated with broad transcriptional changes (461 upregulated and 175 downregulated genes), characterised by local immune activation alongside suppression of blood-brain barrier (BBB) remodelling, vascular, and neuronal signalling molecular signatures. The post-treatment state with confirmed BBB disruption was associated with a smaller but directionally distinct response (160 upregulated and 57 downregulated genes), marked by inflammatory signalling and increased expression of genes associated with endothelial activation, vascular regulation, and BBB-associated remodelling. Together, these findings suggest that, while immune engagement is a feature shared across both lesion states, the BBB-associated transcriptional axis shifts substantially following treatment. These results provide an exploratory transcriptomic framework for understanding parasite persistence, treatment-induced neuroinflammation, and neurovascular remodelling in NCC, and highlight candidate pathways and genes for future mechanistic investigation.
]]></description>
<dc:creator><![CDATA[ Apaza-Quiroz, C. A., Rojas-Portocarrero, C. C., Gutierrez Guarnizo, S. A., Ponce-Nakatahara, E. K., Bustos, J. A., Arroyo, G., Gilman, R. H., Garcia, H. H., Zimic, M. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734379</dc:identifier>
<dc:title><![CDATA[Pericystic brain transcriptomics reveals molecular signatures of immune activation and neurovascular remodelling in viable and post-treatment porcine neurocysticercosis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734751v1?rss=1">
<title>
<![CDATA[
Comparison of directional random walk and weighted least squares modeling of sparse fossil data 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734751v1?rss=1
</link>
<description><![CDATA[
The general random walk model (GRW) of Hunt (2006) is used to infer directional evolution in mean trait values from sparse fossil data by modeling phenotypic change as the accumulated result of small steps with mean step sizes and step variances. Using simulations and real data cases, Ergon (2026) showed that the step variances can be estimated reasonably well only when the mean trait values have small measurement errors, while for fossil data with realistic measurement errors they appear to be extremely difficult to find, and they are often found to be negative. In the simulations Ergon (2026) assumed that the true phenotypic mean values were known. Here, I essentially repeat these simulations under the assumption that only mean trait values with large measurement errors are known, and based on weighted mean squared error (WMSE) comparisons the conclusion is that weighted least squares (WLS) is a better method than GRW. A second conclusion is that WLS is a better method also in the possibly rare cases with large measurement errors where the GRW parameters are estimated well. The GRW method is simply not flexible enough to handle such cases. A third conclusion is that Akaike Information Criterion (AIC) results for GRW models with large measurement errors relative to the step variance may be overly optimistic.
]]></description>
<dc:creator><![CDATA[ Ergon, R. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734751</dc:identifier>
<dc:title><![CDATA[Comparison of directional random walk and weighted least squares modeling of sparse fossil data]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734870v1?rss=1">
<title>
<![CDATA[
From migrants to residents: Genomic insights into adaptive strategies in European robins (Erithacus rubecula) 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734870v1?rss=1
</link>
<description><![CDATA[
Bird migration evolved as an adaptation to seasonally changing habitats. Migratory behaviour can vary within the same species in case of partial migratory behaviour, i.e. one population (or individual) is migratory and another one is resident. Species that exhibit a wide variety of migratory phenotypes provide valuable systems to understand the evolutionary drivers behind different phenotypes and how populations adapt to habitats with distinct seasonality. The European robin (Erithacus rubecula) expresses migratory behaviour in central and northern areas of the species distribution range, whereas populations in the South and on the Macaronesian islands are predominantly resident, providing a suitable system to investigate these questions. We use high coverage whole genome re-sequencing data of 125 European robins to investigate how migration behaviour affects population structure and demography, and how it affects the selection landscape in the genome. Genetic structure in European robins coincides with migratory phenotype and geography and populations are characterised by distinct demographic histories. Our results suggest that both the continental resident population as well as the Macaronesian island populations have derived independently from an ancestral migratory population. Unexpectedly, tests for differential selection revealed extensive positive selection pressure acting across all chromosomes in the resident populations, while selective sweeps are largely absent from migrants. We speculate that this might be an analytical artifact due to mismatching timescales between what population genomics methods can detect and the scale on which migration behaviour likely evolved in the robin. We suggest that future studies on the genomics of migration should more focally account for different time scales on which these processes happen, such as including the wider phylogenomic background of the target species, to capture the full evolutionary history of migratory traits.
]]></description>
<dc:creator><![CDATA[ Langebrake, C., Langebrake, G., Perez-Tris, J., Illera, J. C., Liedvogel, M. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734870</dc:identifier>
<dc:title><![CDATA[From migrants to residents: Genomic insights into adaptive strategies in European robins (Erithacus rubecula)]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.28.735056v1?rss=1">
<title>
<![CDATA[
Novel human monoclonal antibodies with enhanced sensitivity for lipoarabinomannan antigens present in urines of TB patients 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.28.735056v1?rss=1
</link>
<description><![CDATA[
Lipoarabinomannan (LAM) is a useful biomarker for detection of M. tuberculosis infection and disease. Related antigens can be detected in urine samples of TB patients by combinations of monoclonal anti-bodies (mAbs) directed against specific epitopes expressed in LAM. While sensitive for samples from patients with active TB disease who have HIV-1 co-infections, these assays are less effective for other populations, and there is therefore a need for more sensitive antibodies that can improve the sensitivity of these assays. Here we characterize the antigen and epitope specificities, sequence diversity and isotype dependencies of eight LAM-specific human mAbs that target five distinct arabinose- and man-nose-dependent epitopes present in LAM and lipoarabinomannan (LM). Whereas all of the mAbs rec-ognized ManLAM, only a few, including A194-01, consistently detected antigens in TB+ urine samples. Converting A194-01 from the IgG1 to the IgM isotype resulted in broader recognition of poly-Ara glycan epitopes, and increased sensitivity for clinical antigens when combined with several capture reagents, including RU95-C1, a novel antibody targeting the mannan domain of LAM. These results define novel epitopes that are differentially expressed in bacterial and urinary forms of LAM, and identify novel anti-body combinations which possess enhanced diagnostic utility for clinical forms of LAM.
]]></description>
<dc:creator><![CDATA[ Choudhary, A. K., Patel, D., Honnen, W., Kolloli, A., Reichman, C., Kaur, K., Zheng, R. B., Nakabugo, E., Nasinghe, E., Nakiyingi, L., Lowary, T., Pinter, A. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.28.735056</dc:identifier>
<dc:title><![CDATA[Novel human monoclonal antibodies with enhanced sensitivity for lipoarabinomannan antigens present in urines of TB patients]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734783v1?rss=1">
<title>
<![CDATA[
Early retinal microglial activation and ganglion cell dysfunction following severe traumatic brain injury in mice 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734783v1?rss=1
</link>
<description><![CDATA[
Traumatic brain injury (TBI) induces rapid neuroinflammatory responses not only in the brain but also in anatomically and immunologically connected central nervous system (CNS) compartments, including the retina. In our study, we investigated retinal microglial activation, retinal ganglion cell (RGC) calcium dynamics, and caspase3 activation in adult mice subjected to severe traumatic brain injury using the Marmarou impact acceleration model at 24 and 48 h post-injury. Carrying out Ca2+ imaging, immunohistochemistry, and ex vivo lapse microscopy, we found robust microglial activation in both the superficial and deep retinal layers following TBI, accompanied by increased microglial motility. RGCs exhibited a transient surge in degeneration-induced spontaneous activity at 24 h, followed by a marked reduction below control levels at 48 h, consistent with early degenerative changes. Activated caspase3 levels were significantly elevated in both microglia and other retinal cell types at both time points, indicating ongoing apoptotic effects. Together, these findings demonstrate that TBI rapidly triggers inflammatory and apoptotic mechanisms in the retina, which are detectable within the first 48 hours. Our results highlight the retina as a sensitive indicator of early CNS pathology after traumatic injury and underscore the potential of retinal analysis for monitoring TBI-induced neurodegeneration for future clinical implementation.
]]></description>
<dc:creator><![CDATA[ Pentek, L., Czeiter, E., Amrein, K., Szentivanyi, A., Kovacs, B., Balogh, B., Szarka, G., Volgyi, B., Kovacs-Oller, T. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734783</dc:identifier>
<dc:title><![CDATA[Early retinal microglial activation and ganglion cell dysfunction following severe traumatic brain injury in mice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734768v1?rss=1">
<title>
<![CDATA[
Conserved and diverged patterns of senescence in Pristionchus nematodes 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734768v1?rss=1
</link>
<description><![CDATA[
Healthspan, the period of life where organisms are without frailty and/or disease, is a major focus of biogerontological research. To understand late-life decline and increased mortality risk, short-lived organisms such as nematode worms are commonly used. Pristionchus nematodes are established models for evolutionary developmental genetics research and show promise as systems for comparative and experimental study of ageing. To support this, we developed phenotypic ageing profiles for the evo-devo model Pristionchus pacificus and its little-studied congener Pristionchus fissidentatus. We find that various life history traits differ between P. pacificus and P. fissidentatus (lifespan, brood size, and reproductive period), demonstrating their utility for studying divergent ageing trajectories. Further, several traits are consistently impacted by age, including intestinal barrier function, body size, and locomotory ability. Additionally, in P. pacificus, rupture avoidance, cuticle integrity, and feeding rate decline with age, indicating dysregulation across many tissue types. Several age-linked patterns resemble those documented for Caenorhabditis elegans despite considerable evolutionary distance, suggesting conserved senescent processes across the Rhabditida family of nematodes. This work highlights similarities and differences in the impact of ageing in two Pristionchus nematodes and supports their development as models for evolutionary genetic study of senescence.
]]></description>
<dc:creator><![CDATA[ White, R. J., Weadick, C. J. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734768</dc:identifier>
<dc:title><![CDATA[Conserved and diverged patterns of senescence in Pristionchus nematodes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734718v1?rss=1">
<title>
<![CDATA[
Development of a multiplex immunofluorescence panel to study heterogenous cancer-associated fibroblast subtypes with spatial resolution 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734718v1?rss=1
</link>
<description><![CDATA[
Background: Single cell RNA sequencing provides a wealth of information to explore the complexities of the tumour microenvironment, but crucially the spatial topology of the tumour is lost and studying cellular interactions is limited. Spatial transcriptomics aims to address this however the technique remains cost prohibitive for the generation of data from meaningfully-sized clinical cohorts. In contrast, spatial proteomic profiling with multiplex immunofluorescence, preserves spatial interactions, is relatively cost accessible, and is scalable for large clinical cohorts to address powerful translational questions. Whilst multiplex approaches have advanced in recent years, we note that cancer-associated fibroblasts (CAFs) have been explored in less detail, potentially due to difficulties associated with CAF heterogeneity and the diversity of markers used to define them. Methods: We designed, optimised, and validated a multiplex immunofluorescence panel that combines four frequently used CAF markers; alpha smooth muscle actin (aSMA), fibroblast activation protein (FAP), podoplanin (PDPN) and platelet-derived growth factor receptor alpha (PDGFRa) with CD8 and pan-cytokeratin. Here we share our methodology and the practical considerations taken to inform the final panel design. We also highlight the benefits of robust optimisation experiments.
]]></description>
<dc:creator><![CDATA[ Burley, A., Silveira, T., James, N., Salto-Tellez, M., Wilkins, A. C. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734718</dc:identifier>
<dc:title><![CDATA[Development of a multiplex immunofluorescence panel to study heterogenous cancer-associated fibroblast subtypes with spatial resolution]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734744v1?rss=1">
<title>
<![CDATA[
FPGA-based scanner and SerialEM server for 4D-STEM Electron Tomography 
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</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734744v1?rss=1
</link>
<description><![CDATA[
Four-dimensional scanning transmission electron microscopy (4D-STEM) enables the acquisition of diffraction patterns at every probe position in a dense array. For imaging applications this approach offers significant benefits in terms of spatial resolution and contrast enhancement. In this work, we present the development of a synchronous scan generator integrated with SerialEM software to enable automation of complex experimental protocols such as tomography. The proposed hardware functions as an interface between SerialEM, the scan controls of the microscope, a fast annular dark-field detector, and a synchronized trigger for a pixelated detector. Our previous implementation, named SavvyScan, relied on a dedicated computer equipped with a multichannel acquisition and signal-generation cards, as well as a separate microcontroller for synchronization. Here, we report a low-cost implementation based on a Red Pitaya board, utilizing direct programming of its embedded FPGA and Linux server components. We provide detailed instructions for system installation and operation, along with practical guidance for modifying the source code. System performance is validated through oscilloscope measurements and imaging of a replica grating sample. The utility of the approach is further demonstrated by generating a 3D electron tomogram of a cryogenic sample of mitochondria from a tilt series of shadow montage projections.
]]></description>
<dc:creator><![CDATA[ Seifer, S., Elbaum, M. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734744</dc:identifier>
<dc:title><![CDATA[FPGA-based scanner and SerialEM server for 4D-STEM Electron Tomography]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734786v1?rss=1">
<title>
<![CDATA[
Tyrosine kinases sample unique activation ensembles 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734786v1?rss=1
</link>
<description><![CDATA[
Protein kinase activation is driven by conformational changes across multiple structural components, including the conserved Asp--Phe--Gly (DFG) motif, but whether these transitions follow a universal mechanism remains unclear. Here we combine over 8.3 milliseconds of distributed unbiased molecular dynamics simulations with Markov state models (MSMs) to compare the conformational landscapes of the ABL1, EGFR and MET kinase domains. To maximize unbiased sampling of functionally relevant conformational space, we use a transfer seeding strategy that steers AlphaFold2 models derived from homologous templates to sample MET conformational states absent from available experimental databases. We find that related DFG-motif geometries separate into distinct kinetic networks. These shared structural states are connected by kinase-specific activation pathways with different regulatory elements controlling the slowest step of activation. Our findings reveal that the shared nomenclature masks distinct transition mechanisms between kinase domains, revealing new regions critical for activity and targetable conformations for inhibitor design.
]]></description>
<dc:creator><![CDATA[ Zhu, Y., Degiacomi, M. T., Mey, A. S. J. S., Singh, S. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734786</dc:identifier>
<dc:title><![CDATA[Tyrosine kinases sample unique activation ensembles]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734559v1?rss=1">
<title>
<![CDATA[
MintCNA: A Unified Framework for Integrative Copy Number Profiling with Single-Cell Multi-Omics Data 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734559v1?rss=1
</link>
<description><![CDATA[
Chromosomal copy number alterations (CNAs) are key drivers of tumor evolution, disease progression and therapeutic resistance, and the identification of them is an important step to delineate tumor clonal structure. However, accurately resolving CNA landscapes from single-cell data remains challenging. Most existing tools analyze one omics layer at a time and are susceptible to assay-specific noises, limiting their ability to recover shared or modality-specific CNAs. Recent single-cell multi-omics techniques enable joint sequencing of multiple molecular layers in the same cells, yet in silico methods that fully exploit such complementary multi-modal data for CNA analysis are still missing. Here we present a single-cell multi-omics integration framework, MintCNA, a unified framework for CNA detection from paired multi-omics data. MintCNA integrates traditional statistical modeling with embedded deep learning structure to enhance CNA profiling across multi-omics. We use an attention-guided convolutional autoencoder for data denoising and perform multivariate change-point detection utilizing a sliding-window screening and ranking procedure. Missingness-adjusted CUSUM statistics are constructed which jointly aggregate omics features by a data-adaptive projection to detect genome-wide chromosomal breakpoints. Across various simulations and applications to a colorectal cancer multi-omics dataset, MintCNA consistently outperforms existing single-omics CNA callers in detection accuracy. MintCNA provides a single-cell CNA tool that integrates paired scDNA-seq and scRNA-seq, supporting the study of intra-tumor heterogeneity and tumor evolution.
]]></description>
<dc:creator><![CDATA[ Bao, W., Qin, F., Xiao, F. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734559</dc:identifier>
<dc:title><![CDATA[MintCNA: A Unified Framework for Integrative Copy Number Profiling with Single-Cell Multi-Omics Data]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.26.734637v1?rss=1">
<title>
<![CDATA[
Evidence that Dogs Can Use Temporal Difference in Odorant Arrival to Discriminate Odorant Mixtures 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.26.734637v1?rss=1
</link>
<description><![CDATA[
In turbulent environments, odorants from different sources arrive at different times, potentially providing cues for odor source segregation. In several invertebrate species, short differences in odorant onset enable freely moving animals to discriminate odorant mixtures. In vertebrates, however, studies of sensitivity to odorant onset asynchrony have been conducted under highly constrained sampling conditions, such as with odor delivery tightly coupled to respiration. In this study, we investigated whether domestic dogs could detect odorant onset asynchrony in odorant mixtures under conditions that preserve key features of natural odor sampling. Dogs performed a discrimination task in which odor stimuli were presented as ongoing pulse trains that began independently of animal behavior, avoiding artificial synchronization of odor delivery with sniff cycles. Dogs were trained to discriminate between mixtures of two odorants with synchronous onsets and mixtures with asynchronous onsets. Of the dogs trained, one was able to discriminate odorant onset asynchronies as short as 633 ms. Dogs also displayed sensitivity to auditory stimulus onset asynchrony, discriminating auditory asynchronies as short as 30 ms. These results provide the first demonstration of temporal sensitivity in canine olfaction and the first evidence that vertebrates can use odorant onset asynchrony under conditions that permit free odor sampling.
]]></description>
<dc:creator><![CDATA[ Downie, I., Szyszka, P., Hall, N. J., Edwards, T. L. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.26.734637</dc:identifier>
<dc:title><![CDATA[Evidence that Dogs Can Use Temporal Difference in Odorant Arrival to Discriminate Odorant Mixtures]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.29.734522v1?rss=1">
<title>
<![CDATA[
Cardiovascular Benefits of Menopause Hormone Treatment is Age-Dependent 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.29.734522v1?rss=1
</link>
<description><![CDATA[
Background: Hormone therapy (HT) has not consistently reduced atherosclerotic cardiovascular disease (ASCVD) events in post-menopausal women, yet the underlying mechanisms remain poorly understood. Methods: Female Ldlr-/- mice with established atherosclerosis were subjected to surgical menopause and treated with 17{beta}-estradiol (E2) following lipid normalization. Studies were performed in aging and young mice. To determine whether inflammation mediates the age-dependent response to HT, a cohort of aging mice underwent transplantation with Ifn{gamma}-/-bone marrow (BM) before hormone treatments. Metabolic parameters, HDL function, systemic inflammation, atherosclerotic burden, liver metabolic and oxidative stress signaling, and hepatic estrogen receptor signaling were evaluated. Results: In aging mice, menopause E2 treatment failed to reduce established atherosclerosis as shown in sham operated mice during lipid normalization. Instead, E2 treatment increased circulating IFN{gamma} and IL-6, impaired HDL antioxidant and cholesterol efflux functions, and promoted inflammatory and vulnerable plaque phenotypes. Suppression of inflammation through Ifn{gamma}-/-BM transplantation restored HDL function and significantly reduced atherosclerosis in E2-treated aging mice. In contrast to aging mice, young mice exhibited reduced systemic and plaque inflammation, improved HDL functions, and regression of atherosclerosis following E2 treatment. Liver RNA sequencing and qPCR validation identified activation of inflammatory, oxidative stress, and lipid metabolic pathways in aging E2-treated mice, which were largely attenuated following Ifn{gamma}-/- bone marrow transplantation as well as in young mice. Compared to young mice, aging mice presented hepatic estrogen receptor remodeling characterized by reduced estrogen receptor  (ER) expression and increased G-protein coupled estrogen receptor (GPER) expression. Constitutive GPER activation was accompanied by induction of NOX1-dependent oxidative stress, which was further exacerbated by E2 treatment, leading to persistent inflammation. Conclusions: The cardiovascular effects of estrogen therapy are fundamentally age dependent. Aging shifts estrogen signaling toward hepatic oxidative stress and inflammation through increased GPER. While E2 treatment preserves both metabolic and cardiovascular protection in young mice, aging exacerbates GPER-NOX1-mediated oxidative stress, resulting in impaired HDL function and persistent residual ASCVD risk. These findings identify inflammation-driven, non-lipid mechanisms as potential therapeutic targets to improve cardiovascular outcomes during hormone therapy in postmenopausal women.
]]></description>
<dc:creator><![CDATA[ Lalisan, C. D., Gavin, C., Litts, B., Rein, J. A., An, J., Zhong, M., Boobalan, R., Wang, Y., Van Aelst, A., Chinnarasu, S., Xu, Y., Linton, M., Stafford, J. M., Zhu, L. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.29.734522</dc:identifier>
<dc:title><![CDATA[Cardiovascular Benefits of Menopause Hormone Treatment is Age-Dependent]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.30.735663v1?rss=1">
<title>
<![CDATA[
Assessing the Relative Impact of Grasp and Object on Inferior Frontal Gyrus Activity during a Grasping Task 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.30.735663v1?rss=1
</link>
<description><![CDATA[
The lateral grasp network, responsible for translating visual properties of an object to execution of a motor act, is comprised of the anterior intraparietal area (AIP), area F5, and the primary motor cortex (M1). Non-human primate studies of F5 have shown that it encodes a wide range of hand positions and object properties. Human studies in F5 human homologue, the inferior frontal gyrus (IFG), have leveraged the ability of this area to encode grasp-object pairs for the purposes of Brain Machine Interface (BMI) control. However, whether modulation is driven by grasp, object, or the interaction between grasp and object is unclear. In the present study, sixty-four features were recorded from IFG during a motor visualization task where grasp and object were varied. Grasp was found to be the predominant factor driving modulation of IFG signals. Object was found to only be weakly represented in neural data. However, object contribution peaked earlier than grasp contribution, indicating early integration of object information. Grasp-object interactions were also found to have a significant impact. Cortical separation between grasping conditions varied based on the object presented. In addition, subspace analysis showed that the underlying neural population structure associated with each object type was significantly different from one another. Despite the impact of object type, the present study suggests that due to the significantly larger impact of grasp, BMI decoders can be used to decode grasp with above chance accuracy across a variety of grasp-object pairs.
]]></description>
<dc:creator><![CDATA[ Conlan, E. C., Foli, C., Memberg, W., Herring, E. Z., Sweet, J. A., Ajiboye, A. B. ]]></dc:creator>
<dc:date>2026-07-01</dc:date>
<dc:identifier>doi:10.64898/2026.06.30.735663</dc:identifier>
<dc:title><![CDATA[Assessing the Relative Impact of Grasp and Object on Inferior Frontal Gyrus Activity during a Grasping Task]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-07-01</prism:publicationDate>
<prism:section></prism:section>
</item>
</rdf:RDF>
