eLife最新文献

{"title":"Bayesian meta-analysis reveals the mechanistic role of slow oscillation-spindle coupling in sleep-dependent memory consolidation.","authors":"Thea Ng, Eunsol Noh, Rebecca M C Spencer","doi":"10.7554/eLife.101992","DOIUrl":"10.7554/eLife.101992","url":null,"abstract":"<p><p>The active system consolidation theory suggests that information transfer between the hippocampus and cortex during sleep underlies memory consolidation in humans. Neural oscillations during sleep, including the temporal coupling between slow oscillations (SO) and sleep spindles (SP), may play a mechanistic role in memory consolidation. However, differences in analytical approaches and the presence of physiological and behavioral moderators have led to inconsistent conclusions. This meta-analysis, comprising 23 studies and 297 effect sizes, focused on four standard phase-amplitude coupling measures including coupling phase, strength, percentage, and SP amplitude, and their relationship with memory retention. We developed a standardized approach to incorporate non-normal circular-linear correlations. We found strong evidence supporting that precise and strong SO-fast SP coupling in the frontal lobe predicts memory consolidation. The strength of this association is mediated by memory type, aging, and spatiotemporal features, including SP frequency and cortical topography. In conclusion, SO-fast SP coupling should be considered as a general physiological mechanism for memory consolidation.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250480","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":"High-content high-resolution microscopy and deep learning-assisted analysis reveals host and bacterial heterogeneity during <i>Shigella</i> infection.","authors":"Ana Teresa López-Jiménez, Dominik Brokatzky, Kamla Pillay, Tyrese Williams, Gizem Özbaykal Güler, Serge Mostowy","doi":"10.7554/eLife.97495","DOIUrl":"10.7554/eLife.97495","url":null,"abstract":"<p><p><i>Shigella flexneri</i> is a Gram-negative bacterial pathogen and causative agent of bacillary dysentery. <i>S. flexneri</i> is closely related to <i>Escherichia coli</i> but harbours a virulence plasmid that encodes a type III secretion system (T3SS) required for host cell invasion. Widely recognised as a paradigm for research in cellular microbiology, <i>S. flexneri</i> has emerged as important to study mechanisms of cell-autonomous immunity, including septin cage entrapment. Here, we use high-content high-resolution microscopy to monitor the dynamic and heterogeneous <i>S. flexneri</i> infection process by assessing multiple host and bacterial parameters (DNA replication, protein translation, T3SS activity). In the case of infected host cells, we report a reduction in DNA and protein synthesis together with morphological changes that suggest <i>S. flexneri</i> can induce cell-cycle arrest. We developed an artificial intelligence image analysis approach using convolutional neural networks to reliably quantify, in an automated and unbiased manner, the recruitment of SEPT7 to intracellular bacteria. We discover that heterogeneous SEPT7 assemblies are recruited to bacteria with increased T3SS activation. Our automated microscopy workflow is useful to illuminate diverse host and bacterial interactions at the single-cell and population level, and to fully characterise the intracellular microenvironment controlling the <i>S. flexneri</i> infection process.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250496","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":"Megakaryocytes assemble a three-dimensional cage of extracellular matrix that controls their maturation and anchoring to the vascular niche.","authors":"Claire Masson, Cyril Scandola, Jean-Yves Rinckel, Fabienne Proamer, Emily Janus-Bell, Fareeha Batool, Naël Osmani, Jacky G Goetz, Léa Mallo, Nathalie Brouard, Catherine Leon, Alicia Bornert, Renaud Poincloux, Olivier Destaing, Alma Mansson, Hong Qian, Maxime Lehmann, Anita Eckly","doi":"10.7554/eLife.104963","DOIUrl":"10.7554/eLife.104963","url":null,"abstract":"<p><p>Megakaryocytes, the progenitor cells of blood platelets, play a crucial role in hemostasis by residing in the bone marrow and ensuring continuous platelet production. Unlike other hematopoietic cells, megakaryocytes do not enter the blood circulation intact. They remain anchored within the bone marrow while extending cytoplasmic protrusions called proplatelets through the sinusoidal endothelial barrier. These proplatelets subsequently fragment into functional platelets. This unique process of intravasation facilitates efficient platelet production while maintaining the megakaryocyte cell body within the bone marrow niche, thus preventing potential thrombotic complications. How the extracellular matrix (ECM) influences the delicate balance between megakaryocyte retention and proplatelet extension remains largely unknown. Here, we investigate the spatial organization and functional role of ECM components in the megakaryocyte vascular niche of mice bone marrow. Our findings reveal that laminin and collagen IV form three-dimensional (3D) ECM cages encompassing megakaryocytes and anchor them to the sinusoidal basement membrane. Gene deletion shows the existence of laminin α4 in the ECM cage that is necessary to maintain megakaryocyte-sinusoid interactions. Notably, megakaryocytes actively contribute to the ECM cage assembly; β1/β3 integrin knockout weakens these structures, increasing intravasation and entire megakaryocyte entry into circulation. The retention of megakaryocytes by these 3D ECM cages depends on dynamic remodeling processes. Inhibition of ECM proteolysis results in denser cage formation, increasing the frequency of immature megakaryocytes with impaired demarcation membrane system (DMS) development. Thus, the ECM cage represents a novel concept of an active and dynamic 3D microenvironment that is continuously remodeled and essential for maintaining megakaryocyte perivascular positioning. This specific microarchitecture guides megakaryocyte maturation and intravasation, underscoring the critical role of ECM microarchitecture and dynamics in megakaryocyte function.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250438","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":"Balancing stability and flexibility when reshaping archaeal membranes.","authors":"Miguel Amaral, Felix Frey, Xiuyun Jiang, Buzz Baum, Anđela Šarić","doi":"10.7554/eLife.105432","DOIUrl":"10.7554/eLife.105432","url":null,"abstract":"<p><p>Cellular membranes differ across the tree of life. In most bacteria and eukaryotes, single-headed lipids self-assemble into flexible bilayer membranes. By contrast, thermophilic archaea tend to possess bilayer lipids together with double-headed, monolayer spanning bolalipids, which are thought to enable cells to survive in harsh environments. Here, using a minimal computational model for bolalipid membranes, we explore the trade-offs at play when forming membranes. We find that flexible bolalipids form membranes that resemble bilayer membranes because they are able to assume a U-shaped conformation. Conversely, rigid bolalipids, which resemble the bolalipids with cyclic groups found in thermophilic archaea, take on a straight conformation and form membranes that are stiff and prone to pore formation when they undergo changes in shape. Strikingly, however, the inclusion of small amounts of bilayer lipids in a bolalipid membrane is enough to achieve fluid bolalipid membranes that are both stable and flexible, resolving this trade-off. Our study suggests a mechanism by which archaea can tune the material properties of their membranes as and when required to enable them to survive in harsh environments and to undergo essential membrane remodelling events like cell division.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244223","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":"Distributed subthreshold representation of sharp wave-ripples by hilar mossy cells.","authors":"Ayako Ouchi, Taro Toyoizumi, Nobuyoshi Matsumoto, Yuji Ikegaya","doi":"10.7554/eLife.97270","DOIUrl":"10.7554/eLife.97270","url":null,"abstract":"<p><p>In neural information processing, the nervous system transmits neuronal activity between layers of neural circuits, occasionally passing through small layers composed only of sparse neurons. Hippocampal hilar mossy cells (MCs) constitute such a typical bottleneck layer. However, how efficient information encoding is achieved within such constrained layers remains poorly understood. To address this, we focused on sharp wave-ripples (SWRs) - synchronous neural events originating in the CA3 region - and investigated functional diversity within MC populations using in vivo/in vitro patch-clamp recordings in mice. By combining machine learning algorithms, we developed a model to predict CA3 SWR waveforms based on the synaptic response waveforms of MCs, suggesting that SWR-related information is indeed encoded in their subthreshold activity. While individual MCs were generally associated with specific SWR clusters, partial overlap across some MCs was also observed, indicating that CA3 activity is distributed across the MC population. Our findings suggest that CA3 SWR activity is represented in a pseudo-orthogonal manner across MC populations, allowing the small MC layer to effectively compress and relay hippocampal information.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238274","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":"Social experience shapes fighting strategies in <i>Drosophila</i>.","authors":"Can Gao, Mingze Ma, Jie Chen, Xiaoxiao Ji, Qionglin Peng, Yufeng Pan","doi":"10.7554/eLife.104212","DOIUrl":"10.7554/eLife.104212","url":null,"abstract":"<p><p>Social isolation generally increases aggression but decreases mating competition, resulting in an intricate and ambiguous relationship between social experience, aggression, and reproductive success. In male <i>Drosophila</i>, aggression is often characterized by lunging, a frequent and comparatively low-intensity combat behavior. Here, we provide a behavioral paradigm for studying a less frequent but more vigorous fighting form known as tussling. While social enrichment decreases lunging, aligning with past observations, it heightens the more forceful tussling behavior. These two forms of aggression rely on different olfactory receptor neurons, specifically Or67d for lunging and Or47b for tussling. We further identify three pairs of central pC1 neurons that specifically promote tussling. Moreover, shifting from lunging to tussling in socially enriched males is accompanied by better territory control and mating success. Our findings identify distinct sensory and central neurons for two fighting forms and suggest that social experience may shape fighting strategies to optimize reproductive success.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238228","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 unified rodent atlas reveals the cellular complexity and evolutionary divergence of the dorsal vagal complex.","authors":"Cecilia Hes, Abigail J Tomlinson, Lieke Michielsen, Hunter J Murdoch, Fatemeh Soltani, Maia V Kokoeva, Paul V Sabatini","doi":"10.7554/eLife.106217","DOIUrl":"10.7554/eLife.106217","url":null,"abstract":"<p><p>The dorsal vagal complex (DVC) is a region in the brainstem comprised of an intricate network of specialized cells responsible for sensing and propagating many appetite-related cues. Understanding the dynamics controlling appetite requires deeply exploring the cell types and transitory states harbored in this brain site. We generated a multi-species DVC cell atlas using single-nuclei RNA-sequencing, by curating and harmonizing mouse and rat data, which includes >180,000 cells and 123 cell identities at 5 granularities of cellular resolution. We report unique DVC features such as <i>Kcnj3</i> expression in Ca⁺-permeable astrocytes as well as new cell populations like neurons co-expressing <i>Th</i> and <i>Cck</i>, and a leptin receptor-expressing neuron population in the rat area postrema which is marked by expression of the progenitor marker, <i>Pdgfra</i>. In summary, our findings demonstrate a high degree of complexity within the DVC and provide a valuable tool for the study of this metabolic center.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238257","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":"Distinct waves of ovarian follicles contribute to mouse oocyte production.","authors":"Qi Yin, Allan C Spradling","doi":"10.7554/eLife.107352","DOIUrl":"10.7554/eLife.107352","url":null,"abstract":"<p><p>The earliest growing mouse follicles, wave 1, rapidly develop in the ovarian medulla, while the great majority, wave 2, are stored for later use as resting primordial follicles in the cortex. Wave 1 follicles are known to mostly undergo atresia, a fate sometimes associated with the persistence of steroidogenic theca cells, but this connection is poorly understood. We characterized wave 1 follicle biology using tissue clearing, lineage tracing, and scRNA-seq to clarify their contributions to offspring and steroidogenesis. Wave 1 follicles, lineage-marked by E16.5 <i>Foxl2</i> expression in granulosa cells, reach preantral stages containing theca cell layers by 2 weeks. Atresia begins about a week later, during which 80-100% of wave 1 follicles degrade their oocytes, turn over most granulosa cells, but retain theca cells which expand in number together with interstitial gland cells in the medulla. During puberty (5 weeks), these cells ultrastructurally resemble steroidogenic cells and highly express androgen biosynthetic genes. Unexpectedly, the <i>Foxl2</i> lineage tag also marked about 400 primordial follicles, located near the medullary-cortical boundary, that become the earliest activated wave 2 follicles. These 'boundary' or 'wave 1.5' follicles generate 70-100% of the earliest mature oocytes, while fewer than 26 wave 1 follicles with oocytes survive. Consistent with their largely distinct fates in steroid or oocyte production, granulosa cells of antral wave 1 and 2 follicles differentially express multiple genes, including <i>Wnt4</i> and <i>Igfbp5</i>.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238283","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":"Structure-guided secretome analysis of gall-forming microbes offers insights into effector diversity and evolution.","authors":"Soham Mukhopadhyay, Muhammad Asim Javed, Jiaxu Wu, Edel Perez-Lopez","doi":"10.7554/eLife.105185","DOIUrl":"10.7554/eLife.105185","url":null,"abstract":"<p><p>Phytopathogens secrete effector molecules to manipulate host immunity and metabolism. Recent advances in structural genomics have identified fungal effector families whose members adopt similar folds despite sequence divergence, highlighting their importance in virulence and immune evasion. To extend the scope of comparative structure-guided analysis to more evolutionarily distant phytopathogens with similar lifestyles, we used AlphaFold2 to predict the 3D structures of the secretome from selected plasmodiophorid, oomycete, and fungal gall-forming pathogens. Clustering protein folds based on structural homology revealed species-specific expansions and a low abundance of known orphan effector families. We identified novel sequence-unrelated but structurally similar (SUSS) effector clusters, rich in conserved motifs such as 'CCG' and 'RAYH'. We demonstrate that these motifs likely play a central role in maintaining the overall fold. We also identified a SUSS cluster adopting a nucleoside hydrolase-like fold conserved among various gall-forming microbes. Notably, ankyrin proteins (ANK) were significantly expanded in gall-forming plasmodiophorids, with most being highly expressed during clubroot disease, suggesting a role in pathogenicity. Subsequently, we screened ANK proteins against <i>Arabidopsis</i> immunity hubs using AlphaFold-Multimer and verified one of the positive results by Y2H and BiFC assays to show that the ankyrin effector PbANK1 targets host MPK3 and a zinc-binding dehydrogenase. These findings suggest a potential new mechanism in which ANK effectors target multiple host proteins involved in stress sensing, opening a novel avenue to study the role of ANK in host-pathogen interactions. Altogether, this study advances our understanding of secretome landscapes in gall-forming microbes and provides a valuable resource for broadening structural phylogenomic studies across diverse phytopathogens.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238271","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":"DIRseq as a method for predicting drug-interacting residues of intrinsically disordered proteins from sequences.","authors":"Matt MacAinsh, Sanbo Qin, Huan-Xiang Zhou","doi":"10.7554/eLife.107470","DOIUrl":"10.7554/eLife.107470","url":null,"abstract":"<p><p>Intrinsically disordered proteins (IDPs) are now well-recognized as drug targets. Identifying drug-interacting residues is valuable for both optimizing compounds and elucidating the mechanism of action. Currently, NMR chemical shift perturbation and all-atom molecular dynamics (MD) simulations are the primary tools for this purpose. Here, we present DIRseq, a fast method for predicting drug-interacting residues from the amino-acid sequence. All residues contribute to the propensity of a particular residue to be drug-interacting; the contributing factor of each residue has an amplitude that is determined by its amino-acid type and attenuates with increasing sequence distance from the particular residue. DIRseq predictions match well with drug-interacting residues identified by NMR chemical shift perturbation and other methods, including residues L₂₂WK₂₄ and Q₅₂WFT₅₅ in the tumor suppressor protein p53. These successes augur well for deciphering the sequence code for IDP-drug binding. DIRseq is available as a web server at https://zhougroup-uic.github.io/DIRseq/ and has many applications, such as virtual screening against IDPs and designing IDP fragments for in-depth NMR and MD studies.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238276","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}