IF 6.4 1区生物学

eLife Pub Date : 2025-10-07 DOI: 10.7554/eLife.97270

Ayako Ouchi, Taro Toyoizumi, Nobuyoshi Matsumoto, Yuji Ikegaya

{"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":"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.","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}

引用次数: 0

Social experience shapes fighting strategies in Drosophila. 社会经验塑造了果蝇的战斗策略。

IF 6.4 1区生物学

eLife Pub Date : 2025-10-07 DOI: 10.7554/eLife.104212

Can Gao, Mingze Ma, Jie Chen, Xiaoxiao Ji, Qionglin Peng, Yufeng Pan

{"title":"Social experience shapes fighting strategies in Drosophila.","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":"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 Drosophila, 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.","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}

引用次数: 0

A unified rodent atlas reveals the cellular complexity and evolutionary divergence of the dorsal vagal complex. 统一的啮齿动物图谱揭示了背迷走神经复合体的细胞复杂性和进化分化。

IF 6.4 1区生物学

eLife Pub Date : 2025-10-07 DOI: 10.7554/eLife.106217

Cecilia Hes, Abigail J Tomlinson, Lieke Michielsen, Hunter J Murdoch, Fatemeh Soltani, Maia V Kokoeva, Paul V Sabatini

{"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":"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 Kcnj3 expression in Ca+-permeable astrocytes as well as new cell populations like neurons co-expressing Th and Cck, and a leptin receptor-expressing neuron population in the rat area postrema which is marked by expression of the progenitor marker, Pdgfra. 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.","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}

引用次数: 0

Distinct waves of ovarian follicles contribute to mouse oocyte production. 不同的卵泡波有助于小鼠卵母细胞的产生。

IF 6.4 1区生物学

eLife Pub Date : 2025-10-07 DOI: 10.7554/eLife.107352

Qi Yin, Allan C Spradling

{"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":"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 Foxl2 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 Foxl2 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 Wnt4 and Igfbp5.","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}

引用次数: 0

Structure-guided secretome analysis of gall-forming microbes offers insights into effector diversity and evolution. 结构导向的胆囊形成微生物分泌组分析提供了对效应多样性和进化的见解。

IF 6.4 1区生物学

eLife Pub Date : 2025-10-07 DOI: 10.7554/eLife.105185

Soham Mukhopadhyay, Muhammad Asim Javed, Jiaxu Wu, Edel Perez-Lopez

{"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":"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 Arabidopsis 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.","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}

引用次数: 0

DIRseq as a method for predicting drug-interacting residues of intrinsically disordered proteins from sequences. DIRseq作为一种从序列中预测内在无序蛋白的药物相互作用残基的方法。

IF 6.4 1区生物学

eLife Pub Date : 2025-10-07 DOI: 10.7554/eLife.107470

Matt MacAinsh, Sanbo Qin, Huan-Xiang Zhou

{"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":"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.","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}

引用次数: 0

Unlocking the longevity code with stress. 用压力破解长寿密码。

IF 6.4 1区生物学

eLife Pub Date : 2025-10-06 DOI: 10.7554/eLife.109050

Loren Cocciolone, Valeria Uvarova, Patricija van Oosten-Hawle

引用次数: 0

Pan-tissue transcriptome analysis reveals sex-dimorphic human aging. 泛组织转录组分析揭示性别二态人类衰老。

IF 6.4 1区生物学

eLife Pub Date : 2025-10-03 DOI: 10.7554/eLife.102449

Siqi Wang, Danyue Dong, Xin Li, Zefeng Wang

{"title":"Pan-tissue transcriptome analysis reveals sex-dimorphic human aging.","authors":"Siqi Wang, Danyue Dong, Xin Li, Zefeng Wang","doi":"10.7554/eLife.102449","DOIUrl":"10.7554/eLife.102449","url":null,"abstract":"Complex diseases often exhibit sex dimorphism in morbidity and prognosis, many of which are age-related. However, the underlying mechanisms of sex-dimorphic aging remain foggy, with limited studies across multiple tissues. We systematically analyzed ~17,000 transcriptomes from 35 human tissues to quantitatively evaluate the individual and combined contributions of sex and age to transcriptomic variations. We discovered extensive sex dimorphisms during aging with distinct patterns of change in gene expression and alternative splicing (AS). Intriguingly, the male-biased age-associated AS events have a stronger association with Alzheimer's disease, and the female-biased events are often regulated by several sex-biased splicing factors that may be controlled by estrogen receptors. Breakpoint analysis showed that sex-dimorphic aging rates are significantly associated with decline of sex hormones, with males having a larger and earlier transcriptome change. Collectively, this study uncovered an essential role of sex during aging at the molecular and multi-tissue levels, providing insight into sex-dimorphic regulatory patterns.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212060","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}

引用次数: 0

Pleomorphic effects of three small-molecule inhibitors on transcription elongation by Mycobacterium tuberculosis RNA polymerase. 三种小分子抑制剂对结核分枝杆菌RNA聚合酶转录延伸的多形性影响。

IF 6.4 1区生物学

eLife Pub Date : 2025-10-03 DOI: 10.7554/eLife.105545

Omar Herrera-Asmat, Alexander B Tong, Wenxia Lin, Tiantian Kong, Juan R Del Valle, Daniel G Guerra, Yon W Ebright, Richard H Ebright, Carlos Bustamante

{"title":"Pleomorphic effects of three small-molecule inhibitors on transcription elongation by Mycobacterium tuberculosis RNA polymerase.","authors":"Omar Herrera-Asmat, Alexander B Tong, Wenxia Lin, Tiantian Kong, Juan R Del Valle, Daniel G Guerra, Yon W Ebright, Richard H Ebright, Carlos Bustamante","doi":"10.7554/eLife.105545","DOIUrl":"10.7554/eLife.105545","url":null,"abstract":"The Mycobacterium tuberculosis RNA polymerase (MtbRNAP) is the target of the first-line anti-tuberculosis inhibitor rifampin, however, the emergence of rifampin resistance necessitates the development of new antibiotics. Here, we communicate the first single-molecule characterization of MtbRNAP elongation and its inhibition by three diverse small-molecule inhibitors: N(α)-aroyl-N-aryl-phenylalaninamide (D-IX216), streptolydigin (Stl), and pseudouridimycin (PUM) using high-resolution optical tweezers. Compared to Escherichia coli RNA polymerase (EcoRNAP), MtbRNAP transcribes more slowly, has similar mechanical robustness, and only weakly recognizes E. coli pause sequences. The three small-molecule inhibitors of MtbRNAP exhibit strikingly different effects on transcription elongation. In the presence of D-IX216, which inhibits RNAP active-center bridge-helix motions required for nucleotide addition, the enzyme exhibits transitions between slowly and super-slowly elongating inhibited states. Stl, which inhibits the RNAP trigger-loop motions also required for nucleotide addition, inhibits RNAP primarily by inducing pausing and backtracking. PUM, a nucleoside analog of UTP, in addition to acting as a competitive inhibitor, induces the formation of slowly elongating RNAP inhibited states. Our results indicate that the three classes of small-molecule inhibitors affect the enzyme in distinct ways and show that the combination of Stl and D-IX216, which both target the RNAP bridge helix, has a strong synergistic effect on the enzyme.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212037","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}

引用次数: 0

Dual transcranial electromagnetic stimulation of the precuneus boosts human long-term memory. 双经颅电磁刺激楔前叶增强人的长期记忆。

IF 6.4 1区生物学

eLife Pub Date : 2025-10-03 DOI: 10.7554/eLife.104220

Ilaria Borghi, Lucia Mencarelli, Michele Maiella, Elias Paolo Casula, Matteo Ferraresi, Francesca Candeo, Elena Savastano, Martina Assogna, Sonia Bonnì, Giacomo Koch

{"title":"Dual transcranial electromagnetic stimulation of the precuneus boosts human long-term memory.","authors":"Ilaria Borghi, Lucia Mencarelli, Michele Maiella, Elias Paolo Casula, Matteo Ferraresi, Francesca Candeo, Elena Savastano, Martina Assogna, Sonia Bonnì, Giacomo Koch","doi":"10.7554/eLife.104220","DOIUrl":"10.7554/eLife.104220","url":null,"abstract":"Non-invasive brain stimulation techniques have the potential to improve memory functions. However, the results so far have been relatively modest and time-consuming. Here, we implemented a novel 3-min combination of personalized repetitive transcranial magnetic stimulation (intermittent theta burst, iTBS) coupled with simultaneous application of gamma transcranial alternating current stimulation (γtACS) over the precuneus, a brain area connected with the hippocampus, to modulate long-term memory in healthy subjects. Only dual electromagnetic stimulation of the precuneus produced an increase in long-term associative memory as compared to iTBS alone and sham conditions in a sample of healthy volunteers. The effects were replicated in another independent sample, in which the increased associative memory was retained for up to 1 week. Moreover, dual stimulation increased gamma oscillations and precuneus-hippocampus functional connectivity through the white matter tracts linking the precuneus with the temporal lobe. These findings show that dual stimulation may lead neuronal assemblies in a state favorable to enhance long-term plasticity. Personalized dual electromagnetic stimulation of the precuneus may represent a new powerful approach for enhancing memory functions in several healthy and clinical conditions.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211975","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}

引用次数: 0

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