bioRxiv : the preprint server for biology最新文献

{"title":"Pupil size and pupil change correlate with distinct cortical neurochemical systems across the adult lifespan.","authors":"Elizabeth Riley, Eve De Rosa, Adam Anderson","doi":"10.64898/2026.08.24.746786","DOIUrl":"10.64898/2026.08.24.746786","url":null,"abstract":"<p><p>Pupillometry is often used as a proxy for locus coeruleus (LC) activity but whether this relationship changes across the lifespan is unknown. We collected simultaneous pupillometry and multi-echo fMRI in 89 adults aged 19-78 during a visual oddball task. Oddball-evoked pupillary responses were present in all age groups and largest in middle age. Oddball-evoked LC BOLD responses were detected only in younger adults and did not predict individual pupillary responses. Pupil size and its first derivative (pupil change) correlated with whole-brain BOLD on distinct timescales and in distinct spatial patterns. Against 19 PET maps, pupil derivative coupling correlated uniquely with norepinephrine transporter (NET) density, and pupil size-unique coupling with μ-opioid, cannabinoid CB1, and glutamatergic mGluR5 density. Only the pupil derivative-NET relationship weakened with age, though it remained significant in every group. Pupil size and pupil change therefore carry different information, and only pupil change correlates with activity in NET-rich regions across the lifespan.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reciprocal control of the stomach and intestine by viscerosensory neurons in caudal brainstem.","authors":"Naz Dundar, Ilayda Alkislar, Brooke C Jarvie, Ho Namkung, Kathryn Xie, Mahekdeep Kaur, Queenie Li, Anagh S Ravi, Alejandro Lopez, Antionette Spina, Longhui Qui, Truong Ly, Jun Oh, Kevin Yackle, Zachary A Knight","doi":"10.64898/2026.09.21.753299","DOIUrl":"10.64898/2026.09.21.753299","url":null,"abstract":"<p><p>Digestion requires precisely timed transit of food through the gastrointestinal tract. Here we show that emptying of food from the stomach occurs in discrete pulses, separated by pauses that allow the proximal duodenum to clear before the next bolus arrives. By combining X-ray fluoroscopy of the gut with calcium imaging of the brainstem, we identify a population of neurons defined by expression of neuropeptide FF (NPFF) that tracks these duodenal dynamics. Stimulation of NPFF neurons induces a coordinated response that inhibits gastric emptying and accelerates intestinal transit, thereby clearing the proximal intestine for the next bolus of food. These neurons also bidirectionally control food intake through cholinergic signaling in the gut. These findings reveal a mechanism by which brainstem transforms the sensory detection of nutrients in the duodenum into the opposing control of the stomach and intestine. They also establish an experimental approach for dissecting gut-brain signaling in behaving animals.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of gp130 Cytokine Receptor Family by Herpes Simplex Virus 1 as a Strategy for Immune Evasion.","authors":"Kimberly Foster-Lemieur, Sreenath Muraleedharan Suma, Meenu Ajith, Maria Kalamvoki","doi":"10.64898/2026.10.06.757054","DOIUrl":"10.64898/2026.10.06.757054","url":null,"abstract":"&lt;p&gt;&lt;p&gt;HSV-1 is a neurotropic human pathogen that establishes lifelong latency in sensory neurons. Periodic reactivation causes mucocutaneous lesions and, in some cases, severe corneal and neurological disease. While HSV-1 utilizes numerous viral proteins to extensively reprogram host signaling pathways and evade antiviral responses, how it alters host cytokine receptor networks remains poorly understood. Here, we demonstrate that HSV-1 infection selectively downmodulates multiple members of the gp130 (glycoprotein 130) cytokine receptor family, including gp130, Oncostatin M receptor β (OSMR-β), and leukemia inhibitory factor receptor (LIFR), while sparing IL-6Ra and CNTFRa (Ciliary Neurotrophic Factor Receptor). Because gp130 is the central signaling component of the IL-6 cytokine family and mediates JAK/STAT3 activation, its elimination likely represents a viral strategy to suppress inflammatory and antiviral signaling. Consistent with this, HSV-1 does not induce IL-6 mRNA expression in productively infected cells, suggesting coordinated inhibition of both cytokine production and receptor availability. Mechanistically, we found that the viral RNase VHS is at least partially responsible for gp130 family receptor downmodulation, likely in combination with virus-induced endocytosis/degradation pathways. Functionally, activation of gp130 signaling significantly impairs HSV-1 infection, demonstrating that suppression of antiviral cytokine responses is critical for virus replication. Finally, we determined that CNTF causes reactivation of latent HSV-1 using the LUHMES &lt;i&gt;in vitro&lt;/i&gt; latency model, illustrating CNTFRa signaling contribution to latency and reactivation. A similar effect has been reported for IL-6. Together, these findings reveal a previously unrecognized immune evasion mechanism by which HSV-1 remodels gp130 cytokine signaling to promote infection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Successful infection requires HSV-1 to overcome innate immunity that would otherwise restrict viral replication and spread. However, how the virus alters cytokine receptor signaling at the cell surface remains poorly understood. The gp130 family of cytokine receptors represents an important signaling network that governs immunity. These receptors mediate responses to IL-6 family cytokines and regulate antiviral defense, inflammation, cell survival, and neuronal function. Because individual gp130 family receptors can initiate distinct responses, understanding how HSV-1 alters these receptors is important for defining how the virus reshapes host cytokine networks. Here, we report that HSV-1 downmodulates specific gp130 family members to evade host antiviral and inflammatory signaling. However, CNTFRa, a receptor vital to neuronal function is preserved. Characterizing this distinct layer of HSV-1 immune evasion broadens our understanding of virus-host interactions and highlights novel signaling pathways that can be targeted to maximize host antiviral defenses.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tunable population diversity through a noise-driven differentiation switch.","authors":"Jialong Jiang, Sisi Chen, Jong H Park, Tiffany Tsou, Vickie Yang, Paul Rivaud, Matt Thomson","doi":"10.1101/2025.09.20.677552","DOIUrl":"10.1101/2025.09.20.677552","url":null,"abstract":"<p><p>During development, combinatorial signals modulate progenitor differentiation to build populations of diverse cell types. Classical deterministic fate-control circuits focus on stable commitment but do not explain how a diverse cell population is generated and tuned by signals. Here, using single-cell RNA-seq profiling of neural progenitor cells (NPCs) upon combinatorial signal inputs, we identify a candidate circuit-level mechanism for controlling cell type compositions through an annealed noise-driven switch. With 40 signaling conditions, we show that combinatorial signal inputs modulate the neuronal-glial population proportions following a simple log-linear model. Regulatory network models built by D-SPIN quantitatively capture cell state distribution shifts induced by signal combinations, and indicate a circuit model for the probabilistic fate specification by a differentiation switch with controlled transcriptional heterogeneity. Noise levels drive the system from highly plastic to committed states, allowing the relative level of signal inputs to shift population structures. The model further predicts an early bipotent state expressing lineage-specifying factors of both fates, which we verify in our single-cell profiling experiment and a mouse embryonic visual cortex development dataset. Our work identifies a design principle of noise-driven additive regulation in the logarithmic cell-fate probability space, providing a new strategy for population-level stem cell control.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13622004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The <i>C. elegans</i> gustatory receptor homolog LITE-1 is a chemoreceptor required for diacetyl avoidance.","authors":"Alan Koh, Eduard Bokman, Alexey Gavrikov, Javier Rodriguez, Changchun Chen, Alon Zaslaver, André Ex Brown","doi":"10.1101/2025.04.20.649642","DOIUrl":"10.1101/2025.04.20.649642","url":null,"abstract":"<p><p>The nematode <i>C. elegans</i> does not have eyes but can respond to aversive UV and blue light stimulation and even distinguish colours. The gustatory receptor homolog LITE-1 was identified in forward genetic screens for worms that failed to respond to blue light stimulation. When LITE-1 is expressed in body-wall muscles, it causes contraction in response to blue light suggesting that LITE-1 is both necessary and sufficient for blue light response. Here we show that in addition to light avoidance, LITE-1 is also required for worms' avoidance of high concentrations of diacetyl, an odorant that is attractive at low concentrations. Like blue light, diacetyl causes muscle contraction in transgenic worms engineered to express LITE-1 in body-wall muscles. These data are consistent with a direct chemoreceptor function for LITE-1 which would make it a multimodal sensor of aversive stimuli.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13419714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative profiling of basal and stress-induced ribosome collisions.","authors":"James Marks, Pedro H Ayres-Galhardo, Bavavarshini Tamilselvam, Alexis B Roberson, Ruby Pitts, Nicholas R Guydosh, Sezen Meydan","doi":"10.64898/2026.07.21.739814","DOIUrl":"10.64898/2026.07.21.739814","url":null,"abstract":"<p><strong>Background: </strong>Ribosomes stall when they encounter problematic codons or cellular stress that perturbs translation. Stalled ribosomes can lead to the formation of ribosome collisions, also known as disomes, that engage cellular surveillance and stress signaling pathways. How many disomes form during basal conditions and how disome levels change under stress remain poorly understood.</p><p><strong>Results: </strong>We used spike-in normalized Ribo-seq and Disome-seq to quantify transcriptome-wide disome levels. Applying this approach in yeast and human cells, we found that disomes generate approximately 2-10% of all footprints under basal conditions. A high-resolution Disome-seq experiment in human cells identified reproducible disome-forming sites that contribute to the basal level of disome formation in the cell. Exposure of yeast cells to methyl methanesulfonate and human cells to anisomycin increased disome abundance up to four-fold and redistributed collisions in a stress-specific and context-dependent manner.</p><p><strong>Conclusions: </strong>These data provide a quantitative, transcriptome-wide framework for measuring disome levels and reveal how translational stress reshapes the landscape of ribosome collisions in cells.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13419767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatially Constrained Monte Carlo Permutation Test Reveals Diffusion Changes Near Stress Granules.","authors":"Elizaveta Korunova, Vitali Sikirzhytski, Jeffery L Twiss, Michael Shtutman, Paula Vasquez","doi":"10.64898/2026.09.17.752460","DOIUrl":"10.64898/2026.09.17.752460","url":null,"abstract":"<p><p>Intracellular diffusion is inherently heterogeneous, yet single-particle tracking (SPT) analyses are often summarized using cell-wide average parameters that can obscure localized effects. Here, we tracked 40-nm genetically encoded multimeric (GEM) nanoparticles during stress granule (SG) formation and developed SPaCe-MC (Spatially Constrained Monte Carlo permutation test), a statistical framework that generates cytoplasm-specific null models to test whether diffusion associated with a specific cellular structure differs from that expected in the surrounding heterogeneous cytoplasm. Across three SG-inducing conditions, including oxidative stress, DDX3 inhibition, and combined treatment, bulk cytoplasmic analyses revealed distinct responses ranging from increased nanoparticle mobility to increased subdiffusive behavior. In contrast, SPaCe-MC consistently detected a local diffusion constraint in SG-associated regions relative to their treatment-matched cytoplasmic background, revealing a conserved local diffusion effect despite divergent global cytoplasmic responses. Together, our findings establish SPaCe-MC as a framework for identifying compartment-specific diffusion changes in heterogeneous cellular environments.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-redundant cardiolipin synthase family proteins shape lipid composition and stress resilience in <i>Bacteroides fragilis</i>.","authors":"Matthew K Schnizlein, Bongjin Hong, Jennifer N T Nguyen, Katarina Jones, Alyssa I Rodriguez, Aretha Fiebig, Shawn R Campagna, Marcy J Balunas, Thomas V O'Halloran, Sean Crosson","doi":"10.1101/2025.05.12.653583","DOIUrl":"10.1101/2025.05.12.653583","url":null,"abstract":"<p><p>Gut-resident bacteria must withstand membrane-disrupting stresses, such as bile acids, to persist in the intestinal environment. The Bacteroidota are a dominant phylum of the human gut microbiota. However, the genes responsible for the synthesis of membrane lipids in this phylum remain relatively uncharacterized. <i>Bacteroides fragilis</i> is a prevalent member of this phylum and encodes two predicted cardiolipin synthase family proteins, ClsA and ClsB. We previously identified both <i>cls</i> genes as bile-acid fitness factors in <i>B. fragilis</i> P207, but the contributions of <i>clsA</i> and <i>clsB</i> to cell physiology remained unclear. Here, we combine targeted gene deletion with high-resolution lipidomics, metabolomics, and elemental mass spectrometry to show that ClsA and ClsB have distinct and non-redundant functions in the cell. Each <i>cls</i> gene differs in its growth-phase expression pattern, and deletion of each gene produces distinct effects on cell morphology, fitness under membrane-perturbing stress, and the broader metabolome. <i>clsA</i> and <i>clsB</i> strongly influence the levels of different glycyl-seryl peptidolipids, a <i>Bacteroides</i> lipid family that includes immune-active lipids, and whose loss impairs bile acid resistance and gut colonization. In contrast to the acute ion-gradient disruption caused by the secondary bile acid deoxycholate, deletion of <i>clsA</i> and <i>clsB</i> did not measurably alter steady-state intracellular ion levels under standard growth conditions. Together, these results define related but non-redundant roles for two cardiolipin synthase family proteins in a common member of the human gut microbiota.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of compound eye cell types shapes visual behaviors across <i>Heliconius</i> butterflies.","authors":"Wei Lu, Nicholas W VanKuren, Christopher Catalano, Michael S Levine, Charlotte Wallsten, Marcus R Kronforst","doi":"10.64898/2026.07.22.740151","DOIUrl":"10.64898/2026.07.22.740151","url":null,"abstract":"<p><p>The evolution of visual systems is tightly linked to the diversification of visually guided behaviors. Using <i>Heliconius</i> butterflies, renowned for their rapid diversification of wing color patterns and corresponding visual mate preferences, we investigate the evolution of compound eye cell types across a complete speciation continuum. By integrating population genomics, chromatin conformation capture, and single-nucleus multi-omics, we uncover multi-modal mechanisms driving visual system evolution. Within a population polymorphic for mate preference, we identify <i>senseless-2</i> as a glia-expressing candidate visual preference gene. Across species, we reveal that photoreceptors, particularly the color-sensing R7s, are the fastest-evolving cell types. Furthermore, we molecularly characterize novel R2/5 and R7 photoreceptor subtypes, showing that cellular subfunctionalization arises through the co-option of existing gene regulatory networks. Together, this comparative single-cell analysis of compound eyes bridges microevolutionary transcriptomic divergence with macroevolutionary cellular innovations.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13419707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agentic campaign control for high-throughput de novo binder design.","authors":"Minkyu Jeon, Jinyeop Song, Jina Kim, Ellen D Zhong","doi":"10.64898/2026.09.22.753604","DOIUrl":"10.64898/2026.09.22.753604","url":null,"abstract":"<p><p>Progress in artificial intelligence has produced a rapidly growing ecosystem of methods for <i>de novo</i> protein design. With access to many specialized and often complementary tools, how does one use them effectively, especially with a finite compute budget? Here, we introduce <b>Target-adaptive Rescue-Explore-eXploit (T-REX)</b>, an agentic protein binder design framework that orchestrates multiple state-of-the-art protein generative models and structure evaluators. Over the course of a design campaign, T-REX leverages large language model (LLM) agents to reason over accumulating outcomes and decide whether to rescue promising candidates, explore alternative settings, or exploit productive routes, while a deterministic controller validates and schedules proposed actions. Across seven targets, we find that T-REX adaptively allocates its compute across methods in a target-dependent manner and achieves the highest throughput of structurally distinct hits compared to all baselines. These results suggest that adaptive orchestration can complement increasingly powerful protein design models, and we openly release T-REX to support compute-efficient binder design workflows.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13622205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}