PLoS Biology最新文献

{"title":"Eye movements reflect capacity-dependent organization of working memory.","authors":"Qiaoli Huang, Christian F Doeller","doi":"10.1371/journal.pbio.3004047","DOIUrl":"10.1371/journal.pbio.3004047","url":null,"abstract":"<p><p>Human cognition is capacity-limited, requiring strategies to actively structure information. Eye movements offer a natural mechanism for sequential sampling, but whether such sequences reflect memory organization is unknown. We developed a working-memory task where color-frequency pairings created a latent ordinal structure to optimally reduce memory load. Across two experiments, gaze patterns spontaneously aligned with this structure. Participants sampled items following this sequence during encoding and revisited them during maintenance. Critically, the expression of this structure depended on cognitive demand. In a 3-item task, high performers showed robust sequential sampling during encoding, whereas lower performers compensated with replay-like revisitation during maintenance. Under higher demand (4 items), encoding-based organization was disrupted, and structured revisitation emerged primarily during maintenance. These findings suggest that eye movements provide an overt expression of an internally generated organizational process that flexibly adapts to cognitive demands, revealing a behavioral analogue to neural replay when encoding resources are strained.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004047"},"PeriodicalIF":7.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interindividual vocal tract diversity influences the phonetic diversification of spoken languages.","authors":"Steven Moran, Tiena Danner, Marcia S Ponce de León, Christoph P E Zollikofer","doi":"10.1371/journal.pbio.3004003","DOIUrl":"https://doi.org/10.1371/journal.pbio.3004003","url":null,"abstract":"<p><p>Human vocal tracts, like other physical traits, exhibit extensive interindividual variation. However, little is known about how this variation translates into phonetic diversity between speakers, and ultimately, across languages. Here we develop a biocultural model of phonetic evolution, analogous to Russell Lande's model of multivariate phenotypic evolution. We show that individual vocal tract morphologies and associated articulatory strategies leave consistent acoustic signatures, resulting in a characteristic pattern of phonetic variation within speaker groups that correlates with the pattern observed between groups. Recalling a central tenet of evolutionary biology-that within-group variation feeds between-group diversification-our findings suggest that phonologically similar vowel systems can attain phonetically diverse realizations according to a neutral-like evolutionary process. Our model serves as a null hypothesis for disentangling the biological versus cultural mechanisms underlying phonetic diversification, where deviations from the neutral expectation may indicate culturally mediated language change.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004003"},"PeriodicalIF":7.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An inositol receptor Itr4 coordinates carbon catabolite regulation and virulence in Cryptococcus neoformans.","authors":"Yina Wang, Robert Tancer, Maggie Wear, Katrina M Jackson, Yu Zhang, Kan Li, Jun Wang, Yong-Gui Gao, Kirsten Nielsen, Arturo Casadevall, Chaoyang Xue","doi":"10.1371/journal.pbio.3003709","DOIUrl":"10.1371/journal.pbio.3003709","url":null,"abstract":"<p><p>Nutrient sensing and utilization are critical for microbes to adapt to their environment and evade predators. The encapsuled yeast Cryptococcus neoformans has a unique ability to sense and utilize the sugar inositol as both a signaling molecule and as a carbon source. This trait is advantageous not only in the natural environment but also to promote its pathogenesis, including invasion of the central nervous system. In this study, we have identified a novel inositol transporter-like receptor (transceptor) Itr4 that coordinates inositol and glucose metabolism by regulating inositol transporters (ITRs) and glucose sensor Hxs1. Itr4 binds inositol and regulates the function of other ITRs and its loss leads to a significant decrease in inositol uptake activity, resulting in a lack of mating, reduced capsule size, reduced blood-brain barrier (BBB) penetration, and virulence attenuation. Mutagenesis analysis of Itr4 protein identified an essential N-terminal tail and two amino acids, Q388 and Q389, as sites of functional importance. The ITR4Q388A, Q389A allele showed a dominant phenotype with increased inositol uptake, enlarged capsule and significantly attenuated virulence. In summary, we identify a new C. neoformans inositol transceptor, Itr4, the first such example in eukaryotes, with novel regulatory roles in both inositol and glucose metabolism and fungal virulence.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3003709"},"PeriodicalIF":7.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does perturbed adaptive myelination contribute to cognitive dysfunction in Alzheimer's disease?","authors":"Charles Ffrench-Constant","doi":"10.1371/journal.pbio.3004033","DOIUrl":"10.1371/journal.pbio.3004033","url":null,"abstract":"<p><p>The consequences of oligodendrocyte involvement in Alzheimer's disease are poorly understood. Could a key role of gray-matter oligodendrocytes-activity-dependent adaptive myelination to sustain changes in activity-be perturbed, leading to cognitive loss?</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004033"},"PeriodicalIF":7.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Cryptococcus neoformans titanide is a pathogenic cell type that arises from typical yeast cells in response to host conditions.","authors":"Abigail M Potton, Iana Kalinina, Gordon D Brown, Maria Makarova, Sandra Catania, Dora E Corzo-Leon, Elizabeth R Ballou","doi":"10.1371/journal.pbio.3004031","DOIUrl":"10.1371/journal.pbio.3004031","url":null,"abstract":"<p><p>Fungal morphogenesis is a major driver of disease outcome. For the opportunistic fungal pathogen Cryptococcus neoformans, extreme morphological heterogeneity within the lung environment drives dissemination, immune evasion, and drug resistance. One such cell type is the small, oval, titanide (2-4 µm). This poorly understood cell type is prevalent in lung histology as well as host-relevant in vitro conditions. In conditions that generate cellular heterogeneity, titanides comprise 4%-10% of cells 24 hours post-induction and by 72 hours are the dominant cell type. Despite their prevalence and the significance of cryptococcal morphogenesis for virulence, key questions pertaining to their origin, fate, and underlying biology remain unstudied. Using TEM, SEM, and fluorescence microscopy we demonstrate that titanides display distinct morphological features; they possess thin cell walls, single birth scars, and capsules, with reduced Pathogen-Associated Molecular Pattern exposure and altered distribution. These features distinguish titanides from previously described C. neoformans 'small cells' such as in vivo seed cells (6 µm, high cell-wall mannan content) and micro cells (round, <1 μm, with thick cell walls) among others. Using microfluidics, we reveal that titanides arise from yeast-like 'typical' mothers, highlighting the morphological plasticity of typical cells in host-relevant conditions. Upon birth, titanides have compact nuclei and do not immediately proliferate, but transfer to fresh media results in rapid swelling and cell division. Consistent with this, titanides are more resistant to some cell wall/membrane stressors and are an effective infectious propagule in a murine model. Together, these findings establish a definition and essential characterisation of the titanide cell type and provide new insight into a key player in C. neoformans cell biology and pathogenesis.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004031"},"PeriodicalIF":7.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombination shapes the dynamics of selective constraint in global populations of human gut bacteria.","authors":"Zhiru Liu, Benjamin H Good","doi":"10.1371/journal.pbio.3004052","DOIUrl":"https://doi.org/10.1371/journal.pbio.3004052","url":null,"abstract":"<p><p>The ratio of nonsynonymous to synonymous substitutions (dN/dS) encodes important information about the selection pressures acting on protein-coding genes. In bacterial populations, dN/dS often declines with the sequence divergence between strains, but the mechanisms responsible for this broad empirical trend are still debated. Existing models have primarily focused on de novo mutations, overlooking the older genetic variants that are continually introduced through horizontal gene transfer and recombination. Here we introduce a phenomenological model of dN/dS in recombining populations of bacteria, which allows us to disentangle the effects of recombination among pairs of closely related strains. We find that clonally inherited regions of the genome exhibit consistently higher dN/dS ratios, and that the accumulation of recombined segments can quantitatively explain the majority of the decline in dN/dS. We use these observations to re-examine models of purifying selection and adaptive reversion in human gut bacteria, and uncover evidence for widespread weak selection at a large fraction of protein-coding sites. Our findings show that horizontal gene transfer can be an important factor in shaping genome-wide patterns of selective constraint, and raise new questions about the effectiveness of natural selection in complex bacterial populations.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004052"},"PeriodicalIF":7.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FuChi is a cell cycle biosensor for tracking cell cycle dynamics during avian development.","authors":"Zoe R Sudderick, Tiernan Briggs, Shirooza Mubarak, Melinda Van Kerckvoorde, Ana R Hernandez Rodriguez, Sudeepta K Panda, Jon Riddell, Cameron Batho-Samblas, Lorna Taylor, Lynn McTeir, Dominique Meunier, Amy Findlay, Flossie S Roberts, Anna Raper, Asako Sakaue-Sawano, Atsushi Miyawaki, Joe Rainger, Jeffrey J Schoenebeck, Cornelis J Weijer, Mike J McGrew, Denis J Headon, Megan G Davey, Richard L Mort, James D Glover","doi":"10.1371/journal.pbio.3004036","DOIUrl":"https://doi.org/10.1371/journal.pbio.3004036","url":null,"abstract":"<p><p>The ability to monitor the proliferative status of live cells both in vitro and in vivo over time has revolutionised our understanding of development, growth and disease. This was first made possible by fluorescent ubiquitination-based cell cycle indicator (Fucci) technology, which distinguishes specific cell cycle phases through the reciprocal degradation of fluorescently tagged, truncated forms of human CDT1 and GMNN proteins. Fucci genetic systems have been successfully implemented in transgenic mice, zebrafish, and axolotls. To date, no viable, stably expressing Fucci line has been developed in an avian species. Although a range of continuously improving Fucci constructs have been developed in recent years, existing in vivo Fucci models remain limited because they rely on older reporter technology that fails to distinguish cells in S, G2, and M phases or to label cells in early G1. As a result, these models can be challenging to interpret and their utility for continuous cell tracking and precise analysis of cell-cycle dynamics is limited. Here, we introduce FuChi, a multicistronic Fucci-expressing chicken line incorporating a newly optimised reporter construct composed of an mCerulean-tagged histone H1.0 linker protein fused via a self-cleaving 2A peptide to the tandem Fucci(CA)2 cell cycle biosensor, with additional epitope tags included for detection in fixed tissues. We show that this system accurately discriminates and permits tracking of cells in G1, S, G2, and M phases both in vitro and in vivo, enabling faithful visualisation of cell cycle status in intact tissues and organs. Using FuChi embryos, we mapped proliferation dynamics across developing tissues, analysed cell cycle states of migrating cells, and performed live imaging of early embryos. These latter experiments revealed that transition from S phase may be a key morphogenetic event during gastrulation as mesendoderm cells egress from the primitive streak to form embryonic structures including the prechordal plate. Pairing this advanced reporter with the intrinsic experimental advantages of the chicken embryo positions FuChi as a premier in vivo system for studying cell-cycle kinetics in development, delivering clear technological improvements over current Fucci models. FuChi chickens provide a powerful new resource for studying embryonic development, organ growth, tissue homeostasis, disease processes, and infection responses.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004036"},"PeriodicalIF":7.2,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implicit sensorimotor adaptation comprises distinct mechanisms for action selection and execution.","authors":"Tianhe Wang, Tony Lam, Jordan A Taylor, Richard B Ivry","doi":"10.1371/journal.pbio.3004057","DOIUrl":"10.1371/journal.pbio.3004057","url":null,"abstract":"<p><p>The sensorimotor system is continuously adjusted to minimize error. Current theories assume that this adaptation process entails the operation of multiple learning systems, with a key division between implicit and explicit components. Recent studies have revealed several inconsistencies regarding the characteristics and constraints of the implicit system, suggesting that the current framework is incomplete. Here, we propose that these conflicting findings can be understood by recognizing that there are multiple implicit subcomponents, each with distinct computational goals. One well-studied component is implicit recalibration, a process critical for action execution which uses sensory-prediction errors to automatically refine the sensorimotor map. In the current study, we describe a second, novel component, implicit aiming, a process which contributes to action selection to achieve specific goals. Through a series of studies using human participants, we find compelling evidence that those two implicit processes show a clear separation in their temporal stabilities and contextual modulations. These distinct properties correspond to different computational frameworks attributing learning dynamics to either contextual inference or cancellation of competing neural populations, respectively. Together, these findings suggest an alternative framework for sensorimotor adaptation based on the computational goals of the system rather than phenomenology.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004057"},"PeriodicalIF":7.2,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13667926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A histidine-mediated supramolecular mechanism links temperature and pH activation of the sperm channel CatSper.","authors":"Billy Zhao, Shweta Bhagwat, Juan Ferreira, Kiersten M Ruff, Dilip K Swain, Rohit V Pappu, Celia M Santi, Ziao Fu, Polina V Lishko","doi":"10.1371/journal.pbio.3003776","DOIUrl":"10.1371/journal.pbio.3003776","url":null,"abstract":"<p><p>The cation channel of sperm, CatSper, is a sperm-specific calcium channel essential for male fertility across metazoans. CatSper is activated by intracellular alkalinization, membrane depolarization, and elevated temperature, which together ensure maximal current generation. However, the structural mechanisms by which these physiological stimuli jointly regulate channel activation remain poorly understood, in part because CatSper is an unusually complex ~15-subunit assembly organized in zigzag supramolecular arrays along the sperm flagellum. Here, we combine comparative genomics across 47 species with AlphaFold3-based modeling and evolutionary sequence-structure analyses to investigate a mechanism underlying temperature and pH sensitivity of CatSper. Phylogenetic analysis shows that N-terminal length and histidine enrichment of the pore-forming subunit CatSper1 strongly correlate with species-specific fertilization temperatures, suggesting evolutionary adaptation of temperature and pH sensitivity. Structural modeling further revealed conserved surface-exposed histidine clusters that form predicted contact interfaces between adjacent CatSper assemblies, with this contact interface positioned near the dominant voltage-sensing module. Functional validation using electrophysiology and calcium imaging in mouse sperm shows that capacitation-associated partial removal of the CatSper1 N-terminus selectively impairs temperature-dependent activation. Together, these findings support a model in which temperature-dependent histidine deprotonation functionally couples neighboring CatSper complexes within the supramolecular assembly, thereby promoting synchronized channel activation.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3003776"},"PeriodicalIF":7.2,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The histone methyltransferase complex subunit RBBP5 serves as a central epigenetic regulator of proteostasis dynamics.","authors":"Syeda Kubra, Michelle Sun, William Dion, Yu Bian, Ahmet Catak, Hannah Luong, Haokun Wang, Yinghong Pan, Jia-Jun Liu, Aishwarya Ponna, Lijun Liu, Ian Sipula, Jian-Hua Luo, Michael J Jurczak, Silvia Liu, Bokai Zhu","doi":"10.1371/journal.pbio.3004048","DOIUrl":"10.1371/journal.pbio.3004048","url":null,"abstract":"<p><p>Proteostasis is essential for cellular health, with its disruption contributing to aging, neurodegeneration, and metabolic disorders. While the upstream proteotoxic stress-sensing and protein-folding mechanisms in the ER and cytosol are well studied, the transcriptional regulation of proteostasis remains incompletely understood, particularly concerning the temporal epigenome dynamics, chromatin landscapes, and co-regulatory networks underlying dynamic proteostasis control. Traditionally, proteotoxic stress responses were viewed as acute reactions to noxious stimuli, but recent evidence shows that many proteostasis genes exhibit ~12-hour ultradian rhythms under physiological conditions, driven by an XBP1s-dependent oscillator independent of the canonical circadian clock and cell cycle. By mapping the chromatin landscape of the murine 12-hour oscillator, we identified RBBP5-an essential subunit of the COMPASS complex responsible for H3K4 trimethylation-as a pivotal epigenetic regulator of proteostasis dynamics. In contrast, histone acetyltransferases and H3K9 acetylation were dispensable for dynamic proteostasis gene expression. RBBP5 is not only indispensable for the 12-hour oscillator but also essential for the transcriptional regulation of diverse proteotoxic stresses response, by coactivating XBP1s and promoting H3K4me3 deposition at the promoters of proteostasis genes. As a result, loss of RBBP5 sensitizes cells to proteotoxic stress in part due to impaired autophagy. Proximity labeling of H3K4me3 further uncovered a dynamic chromatin-associated proteomic architecture, including components of COMPASS, the Integrator complex and SWI/SNF remodelers, that constitutes the transcriptional response to proteotoxic stress. Together, these findings establish RBBP5 as a central regulator of proteostasis dynamics, essential for maintaining cellular resilience.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004048"},"PeriodicalIF":7.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13667922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}