bioRxiv : the preprint server for biology最新文献

{"title":"Individual variation in the accuracy of saccades to sounds is correlated with the properties of eye movement-related eardrum oscillations (EMREOs).","authors":"Jesse L Herche, Cynthia D King, Jennifer M Groh","doi":"10.64898/2026.05.13.724941","DOIUrl":"10.64898/2026.05.13.724941","url":null,"abstract":"<p><p>Calibration of sound localization behavior in species with mobile eyes requires not only accurate visual input but also accurate oculomotor signals across the lifespan. The recent discovery of eye movement-related eardrum oscillations suggest that oculomotor signals may be incorporated into auditory processing at the level of the ear. One inference of this discovery is that individual variation in such signals might be correlated with individual variation in sound localization accuracy. Here, we tested this hypothesis in humans with normal hearing. We discovered that there is considerable variation in the accuracy of saccades to sounds even in normal individuals: median horizontal errors ranged from 2-6 deg., and median vertical errors could be as large as 36 deg. We separated the subject pool into groups with 'good' performance (median vectorial error < 8 deg) vs 'poor' performance (median vectorial error > 10 deg) and evaluated their respective EMREOs. The EMREOs differed across the two groups in how horizontal saccade amplitude and vertical initial eye position were encoded, with considerable individual variation in the 'poor' group. These results are consistent with the interpretation that EMREOs are associated with underlying processes that ensure the accuracy of sound localization.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13192641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019986","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":"Unbiased, systematic surfaceome profiling of Acute Leukemia to identify novel immunotherapy targets.","authors":"Benson M George, Anna Rodriguez-Pöhnlein, Donavelle J DeCastro, Jennifer Porat, Benyu Zhou, Dinah M Abeja, Ryan J Lumpkin, Rebecca J Metivier, Anna Schmoker, Wencke Walter, Torsten Haferlach, Yana Pikman, Katherine A Donovan, Kimberly Stegmaier, Eric S Fischer, Franziska Wachter, Ryan A Flynn","doi":"10.64898/2026.09.16.752145","DOIUrl":"10.64898/2026.09.16.752145","url":null,"abstract":"<p><p>Cell surface proteomics provides a direct topological assessment of the outer membrane of cells and enables the capture of low abundance proteins that may be missed by whole cell proteomics. Here we present an unbiased atlas of the whole cell and surface proteomes of 25 commonly used leukemic cell lines, encompassing both lymphoid and myeloid lineages, and a variety of driver mutations. Paired-wise analysis highlights recurrent surface proteins that are not detected by whole cell proteomics. Coupling this dataset to RNA-sequencing, we also discovered genes where protein and RNA abundances are discordant. In KMT2A-rearranged AML, CD70 expression was increased across cell lines and validated in primary patient samples, supporting CD70 as a candidate therapeutic target in this disease. Several proteins are enriched in the surface proteomes but lack surface annotation, adding to the list of non-canonical cell surface proteins, including RNA-binding proteins, an emerging class of candidate immunotherapeutic targets.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032760","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":"Male and female mice achieve equivalent protection against heterologous SARS-CoV-2 infection through divergent immune mechanisms.","authors":"Devin Kenney, Mao Matsuo, Andrea Pantelias, Joseph Leger, Ava Kaplan, Faith Cerbo, Da-Yuan Chen, Scott Adams, Giulia Unali, Douglas Wallace, Mohsan Saeed, Anna Belkina, Christelle Harly, Florian Douam","doi":"10.64898/2026.09.28.755090","DOIUrl":"10.64898/2026.09.28.755090","url":null,"abstract":"<p><p>Biological sex is a major determinant of antiviral immunity, yet how it shapes lung-resident antiviral immunity remains poorly understood. We report that prior mild SARS-CoV-2 BA.1 infection protects mice from lethal heterologous Delta challenge through distinct sex-biased immune mechanisms. Although heterologous protection is clinically equivalent between sexes, T- and B-cell depletions before BA.1 exposure abrogate protection only in males. Depletion with anti-CD4, but not anti-CD8, abolishes protection in both sexes, but co-depletion with anti-CD4/anti-CD8 partially restores protection in females only. Further, females exhibit enhanced IFN-gamma-associated myeloid inflammation upon secondary Delta infection. Using lymphoid-deficient mice that display female-biased resistance to Delta infection, IFN-gamma treatment provides partial protection to naive males against Delta. Female resistance is lost after previous BA.1 exposure, highlighting the importance of lymphoid-mediated inflammatory regulation. Together, equivalent antiviral protection against heterologous respiratory viral infection is governed by sexually dimorphic mechanisms, with significant implications for designing mucosal vaccines and immunotherapies.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166340","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":"Ringer Loss in <i>Drosophila</i> Uncovers Mitochondrial Complex I Deficits Relevant to Human Parkinson's Disease.","authors":"Haven G Tillmon, Savannah K Boyen, Raquel Velazquez, Michelle E Urbina-Berlanga, Marco Sciortino, Swati Banerjee","doi":"10.64898/2026.07.27.741040","DOIUrl":"10.64898/2026.07.27.741040","url":null,"abstract":"<p><p>Tubulin polymerization promoting proteins (TPPPs) are known for their cytoskeletal regulation across species; however, emerging evidence suggests broader cellular functions, including potential roles in mitochondrial biology. Here, we identify the <i>Drosophila</i> homolog of human TPPP, Ringer, as a previously unrecognized regulator of mitochondrial bioenergetics and electron transport chain Complex I (CI) function. Ringer is enriched in the mitochondrial matrix, and its loss results in reduced levels of multiple CI subunits and assembly factors and a significant decrease in CI enzymatic activity. Notably, in addition to TPPP dysfunction, similar deficits are observed in postmortem human Parkinson's disease (PD) brain tissues, underscoring the translational relevance of our <i>Drosophila</i> model. Pharmacological administration of resveratrol, a reactive oxygen species (ROS) scavenger, reduces mitochondrial superoxide levels and improves CI enzymatic activity and ATP production in <i>ringer</i> mutants, demonstrating that targeted antioxidant therapeutics can improve bioenergetic functions in <i>ringer</i> mutants. Together, these findings establish Ringer as a key regulator of mitochondrial bioenergetics and reveal Ringer-induced CI dysfunction as a phenotype relevant to mitochondrial abnormalities observed in PD, and provide a robust and translationally meaningful framework for investigating mitochondrial dysfunction in PD.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148804627","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":"Live-cell imaging and ultrastructure expansion microscopy reveal the dynamic intracellular life cycle of the microsporidian parasite <i>Encephalitozoon intestinalis</i>.","authors":"Kacie L McCarty, Sabrina Absalon, Gira Bhabha, Damian C Ekiert","doi":"10.64898/2026.09.25.754474","DOIUrl":"10.64898/2026.09.25.754474","url":null,"abstract":"<p><p>Microsporidia are divergent fungal pathogens that infect a wide range of hosts. Microsporidia have evolved highly reduced genomes, resulting in the loss of many metabolic pathways. <i>Encephalitozoon intestinalis</i> is a human-infecting microsporidian species with the smallest known eukaryotic genome (2.3 Mbp). As an obligate intracellular parasite, <i>E. intestinalis</i> is dependent on its host for replication. Our current understanding of <i>E. intestinalis</i> cell biology remains limited. This is largely due to genetic intractability, which has made live-cell imaging challenging, and its small size (~2 μm), which is within the diffraction limit of conventional microscopy. Here we develop a live-cell imaging technique, \"silhouette microscopy\", that does not rely on genetic manipulation of microsporidia, and enables us to study the live cell dynamics of <i>E. intestinalis</i> replication in host cells, from entry to exit. We report the timing of cell division, kinetics of the parasite life cycle, and dynamics of the parasitophorous vacuole within which <i>E. intestinalis</i> resides. The parasitophorous vacuole undergoes frequent fission and fusion, and ultimately ruptures to facilitate parasite release from the host cell. Silhouette microscopy provides an excellent platform to study the life cycle dynamics of other microsporidian species as well as other genetically intractable intracellular pathogens. To gain a higher resolution understanding into the cell biology of <i>E. intestinalis</i> development, we performed ultrastructure expansion microscopy (U-ExM) on infected cells. U-ExM reveals the organization of the <i>E. intestinalis</i> cytoskeleton and development of the specialized invasion organelle, the polar tube. The combination of live-cell imaging and U-ExM provide a platform to study the <i>E. intestinalis</i> life cycle, and sheds light on the dynamics and cell biology of <i>E. intestinalis</i> in host cells.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13622293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122183","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":"Shear Strain Stiffening in Cartilage is Governed by a Mechanical Phase Transition.","authors":"Japheth Omonira, Joshua D Clugston, Anna R Barth, Stephen J Thornton, James P Sethna, Moumita Das, Lawrence J Bonassar, Itai Cohen","doi":"10.64898/2026.09.28.751808","DOIUrl":"10.64898/2026.09.28.751808","url":null,"abstract":"<p><p>Large shear deformation in cartilage can lead to tissue failure and injury, which are often precursors to diseases such as post-traumatic osteoarthritis. Under shear, cartilage strain-stiffens prior to failure, which makes stiffening an important indicator of changes to the loading of the extracellular matrix that gives rise to this tissue's properties. While a variety of stiffening mechanisms ranging from uncrimping to fiber-alignment have been explored, whether such mechanisms apply to the depth dependent shear strain stiffening in articular cartilage remains poorly understood. Here, we present experiments and theory that support the idea that the strain-stiffening behavior is caused by a mechanical phase transition from a random isotropic network whose mechanics arise primarily from bending-dominated modes to one where the mechanics arise from stretching-dominated modes. Indeed, consistent with network model predictions, we find that stress-strain data for all depths can be collapsed onto a single universal curve that diverges at a depth-dependent critical strain. These results show that increasing the local concentration of collagen, which constitutes the primary load-bearing network in cartilage, decreases the critical strain at which the strain-stiffening transition occurs, while increasing the low-strain elastic modulus. Furthermore, we demonstrate that bulk compression leads to a higher critical strain and decreased low-strain elastic modulus. Network simulations capture this rich behavior, and indicate that under compression the network collapses, which allows for larger strains before the transition from bending-dominated to stretching-dominated mechanics occurs. Collectively, these findings shed light on the roles that tissue composition and axial strain play in the mechanisms that organize how articular cartilage stiffens during the lead-up to injury.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169027","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":"Survey of nucleotide-specific Rab GTPase interactions reveals multiple Rab effectors.","authors":"Tabitha A Peterson, Christopher P Ptak, Mark A Stamnes, Robert C Piper","doi":"10.64898/2026.09.15.751902","DOIUrl":"10.64898/2026.09.15.751902","url":null,"abstract":"<p><p>Rab GTPases control myriad molecular functions by acting as a nucleotide-dependent switch for protein-protein interactions localized in discrete subcellular regions (Zerial and McBride, 2001). Finding additional molecular roles for Rab GTPases depends on expanding the identification of their nucleotide-dependent interactions. Here we compare the interactome of Rab GTPases using a comprehensive large-scale yeast 2-hybrid approach powered by quantitative high-throughput sequencing, which was used to find interactions of the major mammalian Rab isoforms locked in a GDP or GTP conformation. These data revealed an expanded set of interactions specific for GTP-bound Rab proteins, with many known Rab effectors capable of binding a wider repertoire of Rab partners than previously appreciated. We also identified the RGS domain of SNX13 and SNX14 as a new Rab GTPase-binding domain that may bridge these ER-localized proteins with Rab5 and Rab11 endosomal compartments, respectively.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032771","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":"Reversing aging-like 3D genome disorganization in a <i>Drosophila</i> interphase model.","authors":"Alexey V Onufriev, Junkai Zhang, Igor V Sharakhov, Igor S Tolokh","doi":"10.64898/2026.07.16.739007","DOIUrl":"10.64898/2026.07.16.739007","url":null,"abstract":"<p><p>Recent experimental evidence suggests that aging may arise from the progressive deterioration of the epigenetic landscape, while reversing the trend can result in cell and tissue rejuvenation. A mechanistic understanding of how restoration of a key component of this landscape - the 3D structure of the genome - can be accomplished is lacking. Here we investigate the lamina-dependent disruption and recovery of the 3D architecture of the <i>Drosophila melanogaster</i> genome at topologically associating domains (TADs) resolution (~ 100 kb), using a model of the entire nucleus; weakening of chromatin-lamina interactions mimics a loss of chromatin organization associated with aging. We characterize this loss using the Shannon entropy of the appropriately normalized Hi-C contact and by deterioration of the chromosome territories. Our main finding is that increase in Hi-C map disorder and deterioration of chromosome territories induced by lamina depletion are largely reversible when the wild-type (WT)-like Lamina-associated domain (LAD)-nuclear-envelope interactions are restored; the original and recovered conformational states of chromatin are essentially indistinguishable by the bulk Hi-C contact matrix, and the recovered WT state of chromatin remains stable. The recovery is robust: we find that the WT-like 3D architecture can also be recovered from a more severely perturbed lamina-depleted and compartment-disrupted state, in which all attractive interactions have been switched off. The direct experimentally testable prediction is that the restoration of functional LAD-lamina interactions will promote recovery of the WT-like 3D chromatin architecture after lamina-dependent architectural disruption. We further hypothesize that lamin restoration may increase lifespan of the fruit fly and improve other aging-associated phenotypes through the recovery of young-like LAD-lamina attachments.</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/PMC13419808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650352","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":"Thermal pre-treatment of algal symbiont species differentially affects coral development.","authors":"Maria Ruggeri, Samuel A Bedgood, Jun B Cai, Jennifer Qian, Federica Montesanto, Mark McCauley, Grayce E Dyer, Ayobami Oluokun, Mojibola Fowowe, Odunayo Oluokun, Yehia Mechref, Saki Harii, Sandra Loesgen, Virginia M Weis","doi":"10.64898/2026.07.24.739192","DOIUrl":"10.64898/2026.07.24.739192","url":null,"abstract":"<p><p>The foundation of coral reef ecosystems centered around the nutritional relationship between corals and intracellular algal symbionts. Although these symbioses are highly obligate for coral hosts, many partnerships are re-established anew with each coral generation. Furthermore, climate change destabilizes the symbiosis, and the cellular mechanisms underlying successful symbiont colonization of hosts and host development, and how they are affected by thermal stress are poorly understood. Here, we explored the effect of algal species and thermal treatments on symbiont and host cell proliferation by offering Acropora tenuis larvae one of four algal species pre-exposed to elevated or ambient temperature. In addition, we characterized the cell-surface glycome of each species-temperature combination to understand its role in symbiont recognition and proliferation. We found that thermal pre-treatment negatively affected algal photosynthetic efficiency and initial symbiont density in hosts, but did not affect symbiont colonization rate or cell proliferation. In contrast, host cell proliferation was affected in a species-specific manner. Thermal pre-treatment of B. minutum and D. trenchii negatively affected host cell proliferation compared to control symbionts, whereas thermal treatment of S. microadriaticum did not affect developmental outcomes. Further, uptake of thermally pre-treated D. trenchii decreased host cell proliferation below that of larvae not offered any symbionts, indicating that this relationship is costly to host development despite the high thermal tolerance of this species. Algal surface glycan composition varied across species but not by thermal pre-treatment, suggesting reductions in density of thermally pre-treated algae may be due to changes in physiology rather than altered surface chemistry. Further, variation in glycan abundance across species did not track differences in colonization rate or symbiont density, hinting towards a smaller role of glycans in host-symbiont specificity.</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/PMC13483763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148804544","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":"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}