IF 6.4 1区生物学

eLife Pub Date : 2026-05-06 DOI: 10.7554/eLife.108644

Turner P Brown, Matthieu Chavent, Wonpil Im

{"title":"Dynamic architecture of mycobacterial outer membranes revealed by all-atom simulations.","authors":"Turner P Brown, Matthieu Chavent, Wonpil Im","doi":"10.7554/eLife.108644","DOIUrl":"https://doi.org/10.7554/eLife.108644","url":null,"abstract":"Tuberculosis remains a global health crisis due to the resilience of Mycobacterium tuberculosis (Mtb), largely attributed to its unique cell envelope. The impermeability and structural complexity of the outer membrane of this envelope, driven by mycolic acids and glycolipids, pose significant challenges for therapeutic intervention. Here, we present the first all-atom models of an Mtb outer membrane using molecular dynamics simulations. We demonstrate that α-mycolic acids adopt extended conformations to stabilize bilayers, with a phase transition near 338 K that underscores their thermal resilience. Lipids in the outer leaflet, such as PDIM and PAT, induce membrane heterogeneity, migrating to the interleaflet space and reducing lipid order. The simulated mycobacterial outer membrane has ordered inner leaflets and disordered outer leaflets, which contrasts with the outer membrane of Gram-negative bacteria. These findings reveal that PDIM- and PAT-driven lipid redistribution, reduced lipid order, and asymmetric fluidity gradients enable Mtb's outer membrane to resist host-derived stresses and limit antibiotic penetration, thereby promoting bacterial survival. Our work provides a foundational framework for targeting the mycobacterial outer membrane in future drug development.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835077","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

Are kinocilia motile?

IF 6.4 1区生物学

eLife Pub Date : 2026-05-05 DOI: 10.7554/eLife.111609

Ruth Anne Eatock, Marina Kabirova

引用次数: 0

Investments in photoreceptors compete with investments in optics to determine eye design. 光感受器上的投资与光学上的投资相互竞争，决定了眼睛的设计。

IF 6.4 1区生物学

eLife Pub Date : 2026-05-05 DOI: 10.7554/eLife.96517

Francisco J H Heras, Simon B Laughlin

{"title":"Investments in photoreceptors compete with investments in optics to determine eye design.","authors":"Francisco J H Heras, Simon B Laughlin","doi":"10.7554/eLife.96517","DOIUrl":"https://doi.org/10.7554/eLife.96517","url":null,"abstract":"Eyes provide opportunities to understand the function, design, development, and evolution of elaborate sense organs. We take a new cost-benefit approach to understanding eye design by considering that optics and photoreceptors compete for the resources invested in an integrated system. We investigate this competition theoretically and empirically using a new measure of cost, specific volume. This common currency for optics and photoreceptors relates investments to image quality via geometrical, optical, and physiological constraints. By covering the morphospace of an eye of given type and cost, we model how trading optics against photoreceptors changes information capacity. In apposition compound eyes and simple eyes, an optimum configuration maximises efficiency. Efficiency requires heavy investment in photoreceptors and depends on photoreceptor energy consumption. Optimum information capacities and efficiencies scale non-linearly with total investment. Diurnal insects' apposition eyes follow trends that promote efficiency: photoreceptor arrays take 40-80% of total specific volume, photoreceptor length increases systematically with spatial resolution, and photoreceptors are exceptionally long. Thus, competition between optics and photoreceptors shapes eye design, and matching investments in optics and photoreceptors to improve efficiency is a design principle. Our new methodology can be developed to view the adaptive radiation of eyes through a cost-benefit lens.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835074","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

Human adherent cortical organoids in a multi-well format. 人类贴壁皮质类器官在多井格式。

IF 6.4 1区生物学

eLife Pub Date : 2026-05-05 DOI: 10.7554/eLife.98340

Mark van der Kroeg, Sakshi Bansal, Maurits A Unkel, Hilde Smeenk, Steven A Kushner, Femke M S de Vrij

{"title":"Human adherent cortical organoids in a multi-well format.","authors":"Mark van der Kroeg, Sakshi Bansal, Maurits A Unkel, Hilde Smeenk, Steven A Kushner, Femke M S de Vrij","doi":"10.7554/eLife.98340","DOIUrl":"https://doi.org/10.7554/eLife.98340","url":null,"abstract":"In the growing diversity of human induced pluripotent stem cell (iPSC)-derived models of brain development, we present here a novel method that exhibits 3D cortical layer formation in a reproducible topography of minimal dimensions. The resulting adherent cortical organoids (ACOs) develop by self-organization after seeding frontal cortex-patterned iPSC-derived neural progenitor cells in 384-well plates during 8 weeks of differentiation. The organoids have stereotypical dimensions of 3 × 3 × 0.2 mm, contain multiple subtypes of neurons, astrocytes, and oligodendrocyte lineage cells, and are amenable to extended culture for at least 10 months. Longitudinal imaging revealed morphologically mature dendritic spines, axonal myelination, and robust neuronal activity. Moreover, ACOs compare favorably to existing free-floating brain organoid models on the basis of robust reproducibility in obtaining topographically standardized radial cortical structures and circumventing internal necrosis. Adherent human cortical organoids hold considerable potential for high-throughput drug discovery applications, neurotoxicological screening, and mechanistic pathophysiological studies of brain disorders.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835104","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

Hugin-AstA circuitry is a novel central energy sensor that directly regulates sweet sensation in Drosophila and mouse. Hugin-AstA电路是一种新型的中枢能量传感器，直接调节果蝇和小鼠的甜味感觉。

IF 6.4 1区生物学

eLife Pub Date : 2026-05-05 DOI: 10.7554/eLife.108551

Wusa Qin, Tingting Song, Zeliang Lai, Daihan Li, Liming Wang, Rui Huang

{"title":"Hugin-AstA circuitry is a novel central energy sensor that directly regulates sweet sensation in Drosophila and mouse.","authors":"Wusa Qin, Tingting Song, Zeliang Lai, Daihan Li, Liming Wang, Rui Huang","doi":"10.7554/eLife.108551","DOIUrl":"https://doi.org/10.7554/eLife.108551","url":null,"abstract":"Taste sensation plays a crucial role in shaping feeding behavior and is intricately influenced by internal states like hunger or satiety. Despite the identification of numerous neural substrates regulating feeding behavior, the central neural substrate that linked energy-sensing and taste sensation remained elusive. Here, we identified a novel neural circuitry that could directly sense internal energy state and modulate sweet sensation in the Drosophila brain. Specifically, a subset of neuropeptidergic neurons expressing hugin directly detected elevated levels of circulating glucose via glucose transporter Glut1 and ATP-sensitive potassium channels. Upon activation, these neurons released hugin peptide and activated downstream Allatostatin A (AstA)+ neurons via its cognate receptor PK2-R1. Subsequently, the activation of AstA+ neurons then directly inhibited sweet sensation via AstA peptide and its cognate receptor AstA-R1 expressed in sweet-sensing Gr5a+ neurons. We also showed that Neuromedin U (NMU), the mammalian homolog of fly hugin, served as an energy sensor to suppress sweet sensation. Therefore, these data identify hugin+ neuron as a glucose-responsive central energy-sensing module that modulates sweet sensation across species.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835053","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

Real-time transcriptomic profiling in distinct experimental conditions. 实时转录组分析在不同的实验条件。

IF 6.4 1区生物学

eLife Pub Date : 2026-05-05 DOI: 10.7554/eLife.98768

Tamer Butto, Stefan Pastore, Max Müller, Kaushik Viswanathan Iyer, Marko Jörg, Julia Brechtel, Stefan Mündnich, Anna Wierczeiko, Kristina Friedland, Mark Helm, Marie-Luise Winz, Susanne Gerber

{"title":"Real-time transcriptomic profiling in distinct experimental conditions.","authors":"Tamer Butto, Stefan Pastore, Max Müller, Kaushik Viswanathan Iyer, Marko Jörg, Julia Brechtel, Stefan Mündnich, Anna Wierczeiko, Kristina Friedland, Mark Helm, Marie-Luise Winz, Susanne Gerber","doi":"10.7554/eLife.98768","DOIUrl":"https://doi.org/10.7554/eLife.98768","url":null,"abstract":"Nanopore technology offers real-time sequencing opportunities, providing rapid access to sequenced data and allowing researchers to manage the sequencing process efficiently, resulting in cost-effective strategies. Here, we present focused case studies demonstrating the versatility of real-time transcriptomics analysis in rapid quality control for long-read RNA-seq. We illustrate its utility through four experimental setups: (1) transcriptome profiling of distinct human cellular populations, (2) identification of experimentally enriched transcripts, (3) transcriptional analysis of cells under heat shock conditions, and (4) identification of experimentally manipulated genes (knockout and overexpression) in several yeast strains. We show how to perform multiple layers of quality control as soon as sequencing has started, addressing both the quality of the experimental and sequencing traits. Real-time quality control measures assess sample/condition variability and determine the number of identified genes per sample/condition. Furthermore, real-time differential gene/transcript expression analysis can be conducted at various time points post-sequencing initiation (PSI), revealing dynamic changes in gene/transcript expression between two conditions. Using real-time analysis, which occurs in parallel to the sequencing run, we identified differentially expressed genes/transcripts as early as 1 hr PSI. These changes were consistently observed throughout the entire sequencing process. We discuss the new possibilities offered by real-time data analysis, which have the potential to serve as a valuable tool for rapid and cost-effective quality checks in specific experimental settings and can be potentially integrated into clinical applications in the future.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835113","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

Collective epithelial migration mediated by the unbinding of hexatic defects. 六边形缺陷解结合介导的集体上皮迁移。

IF 6.4 1区生物学

eLife Pub Date : 2026-05-05 DOI: 10.7554/eLife.105397

Dimitrios Krommydas, Livio N Carenza, Luca Giomi

{"title":"Collective epithelial migration mediated by the unbinding of hexatic defects.","authors":"Dimitrios Krommydas, Livio N Carenza, Luca Giomi","doi":"10.7554/eLife.105397","DOIUrl":"https://doi.org/10.7554/eLife.105397","url":null,"abstract":"Collective cell migration in epithelia relies on cell intercalation: a local remodeling of the cellular network that allows neighboring cells to swap their positions. Unlike foams and passive cellular fluid, in epithelial intercalation, these rearrangements crucially depend on activity. During these processes, the local geometry of the network and the contractile forces generated therein conspire to produce a burst of remodeling events, which collectively give rise to a vortical flow at the mesoscopic length scale. In this article, we formulate a continuum theory of the mechanism driving this process, built upon recent advances toward understanding the hexatic (i.e., sixfold ordered) structure of epithelial layers. Using a combination of active hydrodynamics and cell-resolved numerical simulations, we demonstrate that cell intercalation takes place via the unbinding of topological defects, naturally initiated by fluctuations and whose late-times dynamics is governed by the interplay between passive attractive forces and active self-propulsion. Our approach sheds light on the structure of the cellular forces driving collective migration in epithelia and provides an explanation of the observed extensile activity of in vitro epithelial layers.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835058","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

Mitochondrial ETF insufficiency drives neoplastic growth by selectively optimizing cancer bioenergetics. 线粒体ETF不足通过选择性地优化肿瘤生物能量来驱动肿瘤生长。

IF 6.4 1区生物学

eLife Pub Date : 2026-05-05 DOI: 10.7554/eLife.106587

David Papadopoli, Ranveer Palia, Predrag Jovanovic, Sébastien Tabariès, Emma Ciccolini, Valerie Sabourin, Sebastian Igelmann, Shannon McLaughlan, Lesley Zhan, HaEun Kim, Nabila Chekkal, Krzysztof J Szkop, Thierry Bertomeu, Jibin Zeng, Julia Vassalakis, Farzaneh Afzali, Slim Mzoughi, Ernesto Guccione, Mike Tyers, Daina Avizonis, Ola Larsson, Lynne-Marie Postovit, Sergej Djuranovic, Josie Ursini-Siegel, Peter M Siegel, Michael Pollak, Ivan Topisirovic

{"title":"Mitochondrial ETF insufficiency drives neoplastic growth by selectively optimizing cancer bioenergetics.","authors":"David Papadopoli, Ranveer Palia, Predrag Jovanovic, Sébastien Tabariès, Emma Ciccolini, Valerie Sabourin, Sebastian Igelmann, Shannon McLaughlan, Lesley Zhan, HaEun Kim, Nabila Chekkal, Krzysztof J Szkop, Thierry Bertomeu, Jibin Zeng, Julia Vassalakis, Farzaneh Afzali, Slim Mzoughi, Ernesto Guccione, Mike Tyers, Daina Avizonis, Ola Larsson, Lynne-Marie Postovit, Sergej Djuranovic, Josie Ursini-Siegel, Peter M Siegel, Michael Pollak, Ivan Topisirovic","doi":"10.7554/eLife.106587","DOIUrl":"https://doi.org/10.7554/eLife.106587","url":null,"abstract":"Mitochondrial electron transport flavoprotein (ETF) insufficiency causes metabolic diseases known as a multiple acyl-CoA dehydrogenase deficiency (MADD). In contrast to muscle, ETFDH is a non-essential gene in acute lymphoblastic leukemia NALM6 cells, and its expression is reduced across human cancers. In various human cancer cell lines and mouse models, ETF insufficiency caused by decreased ETFDH expression limits flexibility of OXPHOS fuel utilisation but paradoxically increases bioenergetics and accelerates neoplastic growth via activation of the mTORC1/BCL-6/4E-BP1 axis. Collectively, these findings reveal that while ETF insufficiency is rare and has detrimental effects in non-malignant tissues, it is common in neoplasia, where ETFDH downregulation leads to bioenergetic and signaling reprogramming that accelerates neoplastic growth.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835246","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

Auditory perception and neural representation of temporal features are altered by age but not by cochlear synaptopathy. 听觉感知和时间特征的神经表征随年龄而改变，但不受耳蜗突触病的影响。

IF 6.4 1区生物学

eLife Pub Date : 2026-05-05 DOI: 10.7554/eLife.102890

Friederike Steenken, Rainer Beutelmann, Henning Oetjen, Christine Köppl, Georg M Klump

{"title":"Auditory perception and neural representation of temporal features are altered by age but not by cochlear synaptopathy.","authors":"Friederike Steenken, Rainer Beutelmann, Henning Oetjen, Christine Köppl, Georg M Klump","doi":"10.7554/eLife.102890","DOIUrl":"https://doi.org/10.7554/eLife.102890","url":null,"abstract":"Age-related hearing loss is a complex phenomenon. The earliest-onset degenerative event is the gradual loss of neural connections between the cochlea and auditory brainstem. To probe for perceptual deficits that might arise from this loss, cochlear synaptopathy was induced pharmacologically in young-adult gerbils, which were then tested in a challenging listening task for the perception of temporal fine structure. Treated gerbils behaved no differently than normal-hearing, young-adult animals. In contrast, old gerbils, which typically express many cochlear and central-neural pathologies, showed impaired perception. To probe for the underlying mechanisms, single-unit responses were obtained from the auditory nerve to the same test stimuli. Responses from old gerbils showed no impairment in temporal locking to the stimulus fine structure. However, responses were significantly more driven by slower temporal fluctuations of the stimulus envelope, suggesting that the central auditory system may be unable to extract the relevant information for discrimination from such altered inputs.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835146","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

Herbivorous insects independently evolved salivary effectors to regulate plant immunity by destabilizing the malectin-LRR RLP NtRLP4. 食草昆虫独立进化出唾液效应物，通过破坏雄性内分泌素- lrr RLP NtRLP4来调节植物免疫。

IF 6.4 1区生物学

eLife Pub Date : 2026-05-05 DOI: 10.7554/eLife.108737

Xin Wang, Jia-Bao Lu, Yi-Zhe Wang, Xu-Hong Zhou, Jian-Ping Chen, Chuan-Xi Zhang, Jun-Min Li, Hai-Jian Huang

{"title":"Herbivorous insects independently evolved salivary effectors to regulate plant immunity by destabilizing the malectin-LRR RLP NtRLP4.","authors":"Xin Wang, Jia-Bao Lu, Yi-Zhe Wang, Xu-Hong Zhou, Jian-Ping Chen, Chuan-Xi Zhang, Jun-Min Li, Hai-Jian Huang","doi":"10.7554/eLife.108737","DOIUrl":"https://doi.org/10.7554/eLife.108737","url":null,"abstract":"Plants utilize receptor-like proteins and receptor-like kinases (RLPs/RLKs) to perceive and respond to a wide variety of invading pathogens and insect herbivores. While the strategies employed by microbial pathogens to suppress plant immunity have been well characterized, it remains unclear how herbivorous insects counteract receptor-mediated defenses. Here, we show that salivary effectors evolve independently in whiteflies and planthoppers to dampen RLP4-mediated plant immunity. RLP4, as a leucine-rich repeat RLP (LRR-RLP), confers plant resistance against herbivorous insects by forming the RLP4/SOBIR1 complexes. In the whitefly Bemisia tabaci, BtRDP, the Aleyrodidae-specific salivary sheath protein, interacts with RLP4 from multiple plant species and promotes its ubiquitin-dependent degradation. Overexpression of NtRLP4 in transgenic plants exerts a detrimental effect on B. tabaci by exploiting the crosstalk between the salicylic acid and jasmonic acid pathways. Conversely, overexpression of BtRDP or silencing of NtRLP4 effectively alleviates such negative effects. In planthopper Nilaparvata lugens, the Delphacidae-restricted salivary protein NlSP104 also targets and promotes the degradation of OsRLP4 from rice plants. These findings reveal convergent evolution of salivary proteins in insects and underscore the complex interactions between plants and herbivorous insects.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835119","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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