eLifePub Date : 2026-10-06DOI: 10.7554/eLife.110073
Linda Choubani, Hisashi Miura, Takako Ichinose, Asami Oji, Saori Takahashi, Rory T Cerbus, Ichiro Hiratani
{"title":"Cell-cycle-resolved Hi-C reveals unexpected plasticity of A/B compartments across interphase.","authors":"Linda Choubani, Hisashi Miura, Takako Ichinose, Asami Oji, Saori Takahashi, Rory T Cerbus, Ichiro Hiratani","doi":"10.7554/eLife.110073","DOIUrl":"10.7554/eLife.110073","url":null,"abstract":"<p><p>The spatial organization of chromatin into active (A) and inactive (B) nuclear compartments is fundamental to genome regulation, yet their cell-cycle dynamics remain largely unexplored. Most research on chromatin dynamics during the cell cycle has primarily focused on events surrounding mitosis, providing only limited insight into chromatin behavior during S-phase. To address this gap, we developed a simple, drug-free approach that combines the Fucci cell-cycle indicator with in situ Hi-C to comprehensively analyze A/B compartment dynamics throughout interphase in mouse embryonic stem cells (mESCs). Unexpectedly, and contrary to prevailing views, we found that A/B compartment strength increased abruptly upon S-phase entry, stabilized during S-phase, and subsequently declined in late S/G2. This abrupt strengthening, which we termed 'compartment maturation', required passage through the G1/S transition but was independent of active DNA synthesis. This maturation involved substantial architectural remodeling, particularly within the A compartment, which consolidated into a more organized structure as individual A domains rearranged to form long-range interactions. Moreover, compartment maturation was not limited to mESCs but was also evident across different developmental contexts in mice. Based on these observations, we propose a revised, stepwise model of nuclear compartmentalization during cell-cycle progression, consisting of four distinct stages: chromosome unfolding (G1), chromatin maturation (G1/S), stabilization (S phase), and refolding (G2). These findings reveal the unexpected plasticity of A/B compartments and underscore the G1/S transition as a critical period for their reorganization.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105855","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}
eLifePub Date : 2026-10-06DOI: 10.7554/eLife.110165
Cody A Freas, Antoine Wystrach
{"title":"Scanning and active sampling behaviours emerge from conserved insect neural circuits.","authors":"Cody A Freas, Antoine Wystrach","doi":"10.7554/eLife.110165","DOIUrl":"10.7554/eLife.110165","url":null,"abstract":"<p><p>Navigating insects often pause and rotate to sample their surroundings, behaviours termed scanning. These and other active sampling behaviours embody navigational uncertainty and are key for spatial learning, yet their neural basis remains unclear and existing models impose scanning behaviours rather than explaining its emergence. Here, we show that desert ants' scanning dynamics can emerge spontaneously from the same conserved neural circuits used for goal-directed navigation, without requiring a specialised scanning module. We built a biologically grounded model combining central complex steering and lateral accessory lobe oscillators and added a downstream stochastic inhibition of forward speed. This minimal system produced diverse, realistic scan dynamics; saccades, fixations, and reversals, whose features were qualitatively compared to high-speed video recordings of <i>Melophorus bagoti</i> scanning. Detailed analysis of these natural scans confirmed model predictions, including how scan structure depends on oscillator phase, goal-heading deviation, and navigational uncertainty. Furthermore, the model reveals that simple modulation of forward speed unifies a broad range of behaviours across ant species, from dashes to smooth oscillatory trajectories to pirouettes and voltes. Crucially, this model suggests a distributed control principle where forward speed acts as a single adjustable parameter, for both individuals and through evolution, to regulate the balance between goal-driven exploitation and information-seeking exploration.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105605","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}
eLifePub Date : 2026-10-05DOI: 10.7554/eLife.109903
Pedro A Perez, Chung-Chih Liu, Alessandra Ferrari, Nicole K Littlejohn, John Paul Kennelly, Emma Marie Robinson, Vân T B Nguyen-Tran, Jon Athanacio, Sean B Joesph, Zaid Amso, Peter Tontonoz, Supriya Srinivasan
{"title":"NK2R signaling governs intestinal lipid mobilization and mucosal inflammation.","authors":"Pedro A Perez, Chung-Chih Liu, Alessandra Ferrari, Nicole K Littlejohn, John Paul Kennelly, Emma Marie Robinson, Vân T B Nguyen-Tran, Jon Athanacio, Sean B Joesph, Zaid Amso, Peter Tontonoz, Supriya Srinivasan","doi":"10.7554/eLife.109903","DOIUrl":"https://doi.org/10.7554/eLife.109903","url":null,"abstract":"<p><p>Neuropeptidergic control of lipid metabolism is conserved and increasingly implicated in metabolic diseases, but receptor-level mechanisms remain unclear. Here, we identify the neurokinin-2 receptor (NK2R) as a central node linking tachykinin signals to intestinal lipid mobilization, epithelial composition, and mucosal inflammation. Across complementary genetic and pharmacological perturbations, modulation of NK2R drives bidirectional effects. Loss or blockade of NK2R increases postprandial triglyceridemia and expands intestinal lipid stores, whereas agonism suppresses chylomicron output, reduces adiposity, and improves glycemia in diet-induced obesity. Transcriptomic and cellular analyses indicate coordinated upregulation of lipid-metabolic programs with a concomitant dampening of immune pathways in the absence of NK2R, accompanied by sex-specific remodeling of secretory lineages and male-biased protection from colitis. NK2R signaling also shaped the fecal microbiota in a genotype- and diet-dependent manner, highlighting crosstalk among neuropeptide signaling, epithelial physiology, and host-microbe interactions. These findings position NK2R as a molecular switch for intestinal lipid handling and mucosal inflammation and suggest that NK2R-targeted agonists or antagonists could be deployed as context- and sex-dependent therapeutic strategies for metabolic disease and inflammatory bowel disease.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105270","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}
eLifePub Date : 2026-10-05DOI: 10.7554/eLife.110428
Stijn Robben, Patricia Davidson, Rita S Rodrigues Ribeiro, Thomas Voets
{"title":"A high-throughput assay for the measurement of Ca<sup>2+</sup> oscillations and insulin release from uniformly sized <i>mouse β-cell (MIN6</i>) spheroids.","authors":"Stijn Robben, Patricia Davidson, Rita S Rodrigues Ribeiro, Thomas Voets","doi":"10.7554/eLife.110428","DOIUrl":"https://doi.org/10.7554/eLife.110428","url":null,"abstract":"<p><p>Diabetes mellitus is a rapidly growing global health challenge, necessitating the development of more effective anti-diabetic therapies, including drugs that improve insulin release from pancreatic β-cells. Traditional high-throughput screening methods typically rely on 2D β-cell cultures, but such cultures do not mimic the 3D organization and cell-to-cell communication of β-cells in pancreatic islets of Langerhans. Existing 3D β-cell culture models are hindered by high costs, technical complexity, and limited compatibility with high-throughput screening platforms. In this work, we developed an approach for generating 19 homogeneously shaped pancreatic β-cell spheroids in each well of a 96-well plate, using micropatterned polyethylene glycol (PEG)-based hydrogels and murine mouse insulinoma 6 (MIN6) insulinoma cells. The uniform shape and positioning of the individual spheroids enabled the simultaneous, real-time imaging of Ca<sup>2+</sup> signals in up to 1824 independent spheroids in response to glucose and various test compounds. Using this approach, we show that increasing glucose causes concentration-dependent Ca<sup>2+</sup> oscillations in individual spheroids, that these Ca<sup>2+</sup> oscillations are sensitive to modulators of ATP-sensitive K<sup>+</sup> channels, and that the frequency of Ca<sup>2+</sup> oscillations correlates with insulin secretion. Finally, we demonstrate that the neurosteroid pregnenolone sulfate, an agonist of the cation channel TRPM3, increases the frequency of glucose-induced Ca<sup>2+</sup> oscillations and enhances insulin release; the TRPM3 antagonist isosakuranetin inhibited these responses. In conclusion, we established a cost-effective and scalable 3D β-cell platform for high-throughput screening of insulin release-modifying compounds, with potential applications in drug development and personalized medicine for the management of diabetes mellitus.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105850","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}
eLifePub Date : 2026-10-05DOI: 10.7554/eLife.110341
Matthew Milton, Sahar H Farag, Diana Garay-Baquero, Jennie Gullick, Kinga Niedobecka, Daniel Burns, Rita Szoke-Kovacs, Patrick Trimby-Smith, Alex Look, Richard Stopforth, Marco Lepore, David K Cole, Laura Denney, Andrew White, Sally Sharpe, Alasdair Leslie, Andres Vallejo, Liku Tezera, Paul Elkington, Salah Mansour
{"title":"Human CD1c-autoreactive T-cells recognise <i>Mycobacterium tuberculosis</i>-infected antigen-presenting cells and display cytotoxic effector programmes.","authors":"Matthew Milton, Sahar H Farag, Diana Garay-Baquero, Jennie Gullick, Kinga Niedobecka, Daniel Burns, Rita Szoke-Kovacs, Patrick Trimby-Smith, Alex Look, Richard Stopforth, Marco Lepore, David K Cole, Laura Denney, Andrew White, Sally Sharpe, Alasdair Leslie, Andres Vallejo, Liku Tezera, Paul Elkington, Salah Mansour","doi":"10.7554/eLife.110341","DOIUrl":"https://doi.org/10.7554/eLife.110341","url":null,"abstract":"<p><p>Tuberculosis (TB), caused by <i>Mycobacterium tuberculosis</i> (Mtb), remains the leading cause of death from infection globally yet the contribution of non-classical T-cell pathways to human immunity remains poorly defined. CD1c-autoreactive T-cells, which recognise self-lipids presented by the antigen-presenting molecule CD1c, are frequent in human blood but their role during infection remains unclear. Here, we investigate how CD1c-expressing antigen-presenting cells (APCs) and Mtb infection shape CD1c-autoreactive T-cell responses using engineered human APC systems, complemented by single-cell transcriptomic profiling to define the ex vivo phenotypic landscape of these T-cells. CD1c is present within human TB granulomas, whereas Mtb down-modulates CD1c expression on infected APCs, consistent with an immune evasion strategy. CD1c-autoreactive T-cells respond more strongly to Mtb-infected CD1c<sup>+</sup> APCs than to uninfected cells, exhibiting enhanced activation, cytotoxicity, and diverse cytokine secretion via CD1c-dependent recognition. Under in vitro conditions, these T-cells reduce relative Mtb burden in infected phagocytes. Single-cell RNA sequencing reveals cytotoxic effector-memory programmes and expression of antimicrobial molecules, providing a mechanistic basis for these responses. Together, these findings define a human CD1c-restricted T-cell response to Mtb-infected APCs and identify autoreactive CD1c-restricted T-cells as a candidate cellular axis for lipid-directed immunity in TB.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105853","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}
eLifePub Date : 2026-10-02DOI: 10.7554/eLife.110200
Beth A Shen, Kyle L Asfahl, Bentley Lim, Savannah K Bertolli, Samuel S Minot, Matthew C Radey, Kelsi M Penewit, Billy Ngo, Stephen J Salipante, Christopher D Johnston, S Brook Peterson, Andrew L Goodman, Joseph D Mougous
{"title":"The type VI secretion system governs strain maintenance in a wild mammalian gut microbiome.","authors":"Beth A Shen, Kyle L Asfahl, Bentley Lim, Savannah K Bertolli, Samuel S Minot, Matthew C Radey, Kelsi M Penewit, Billy Ngo, Stephen J Salipante, Christopher D Johnston, S Brook Peterson, Andrew L Goodman, Joseph D Mougous","doi":"10.7554/eLife.110200","DOIUrl":"https://doi.org/10.7554/eLife.110200","url":null,"abstract":"<p><p>Bacteria inhabiting the mammalian gut coexist in dense communities where contact-dependent antagonism mechanisms are widespread. The type VI secretion system (T6SS) is an interbacterial toxin delivery pathway prevalent among gut Bacteroidales, yet its function in naturally evolved microbiomes remains poorly defined. Here, we examine the role of the T6SS in <i>Bacteroides</i> within a physiologically relevant gut community derived from wild mice (the WildR microbiome). Using newly developed genetic tools and a strategy for functional replacement of strains within the WildR community, we demonstrate that the WildR isolate <i>B. acidifaciens</i> employs a T6SS to antagonize co-resident Bacteroidales. We also show that loss of T6SS function compromises the long-term maintenance of <i>B. acidifaciens</i> in the community but not its initial colonization, establishing the system as a determinant of strain persistence. The T6SS we identified resides on an integrative and conjugative element (ICE). ICE-seq, a targeted sequencing approach, reveals that the T6SS-ICE is distributed among select <i>Bacteroidales</i> and <i>Muribaculaceae</i> species in the WildR microbiome, between which it appears to be recently exchanged. We also show that transfer of the T6SS-ICE to WildR isolate <i>Phocaeicola vulgatus</i> confers transient colonization benefits in mice, but is linked to eventual population decline. Our findings demonstrate that the T6SS can stabilize the presence of specific strains within a complex, co-evolved gut microbiome, yet its value is context dependent and constrained by the ecological and physiological landscape of the host community.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105592","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}
eLifePub Date : 2026-10-02DOI: 10.7554/eLife.110887
Wang Xu, Narendra Kumar Gonepudi, Junyu Liu, Yufan He, Revansiddha Katte, Ran Wang, Harry Baffour Awuah, Yang Han, Baoshan Zhang, Jian Yu, Bo Hu, David D Ho, Priyamvada Acharya, Peter D Kwong, Maolin Lu
{"title":"Distinct allosteric remodeling of HIV-1 Env dynamics on virions by gp41-directed antibodies reveals two modes of neutralization.","authors":"Wang Xu, Narendra Kumar Gonepudi, Junyu Liu, Yufan He, Revansiddha Katte, Ran Wang, Harry Baffour Awuah, Yang Han, Baoshan Zhang, Jian Yu, Bo Hu, David D Ho, Priyamvada Acharya, Peter D Kwong, Maolin Lu","doi":"10.7554/eLife.110887","DOIUrl":"https://doi.org/10.7554/eLife.110887","url":null,"abstract":"<p><p>HIV-1 envelope glycoprotein (Env), a gp120-gp41 trimer, undergoes coordinated conformational changes that drive membrane fusion and allow immune evasion by transiently concealing neutralization-sensitive epitopes. Most broadly neutralizing antibodies (bNAbs) target gp120, whereas a distinct subset recognizes conserved gp41 regions, such as the fusion peptide and the membrane-proximal external region; however, their impact on Env dynamics and associated neutralization mechanisms remains unclear. By using bioorthogonal tagging for single-molecule FRET, we monitored real-time bNAb-induced conformational sampling of Env on intact virions. Most gp41-directed bNAbs allosterically stabilized the prefusion-closed (PC) state, whereas the bivalent 10E8.4/iMab favored both PC and CD4-bound open (predominant) states. Antibodies redistributed the conformational populations of Env with modest kinetic effects, preserving a sequential transition pathway. These findings reveal two modes of neutralization for gp41-directed antibodies, fixing the PC conformation and opening it up - in both cases, with neutralization occurring via long-range allosteric control of Env dynamics.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105872","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}
eLifePub Date : 2026-10-02DOI: 10.7554/eLife.105930
Hugo T Chow-Wing-Bom, Matteo Lisi, Noah C Benson, Freya Lygo-Frett, Patrick Yu-Wai-Man, Frederic Dick, Roni O Maimon-Mor, Tessa M Dekker
{"title":"Mapping human visual contrast sensitivity and vision loss across the visual field with model-based fMRI.","authors":"Hugo T Chow-Wing-Bom, Matteo Lisi, Noah C Benson, Freya Lygo-Frett, Patrick Yu-Wai-Man, Frederic Dick, Roni O Maimon-Mor, Tessa M Dekker","doi":"10.7554/eLife.105930","DOIUrl":"https://doi.org/10.7554/eLife.105930","url":null,"abstract":"<p><p>Peripheral vision is crucial for daily activities and quality of life, yet traditional measures of visual function like visual acuity primarily assess central vision. Visual field tests can evaluate peripheral vision but require extended focus and precise fixation, often challenging for patients with severe sight loss. Functional MRI (fMRI) with population receptive field (pRF) mapping offers a non-invasive way to map scotomas but relies on single contrast levels and accurate fixation. We developed an fMRI-based approach to measure contrast sensitivity across the visual field without requiring precise fixation. Combining large-field stimulation with varying spatial frequencies and contrast levels, and either pRF mapping or a structure-based retinotopic atlas, we modeled contrast sensitivity in the primary visual cortex (V1) over a large (40 deg) expanse of the visual field. In seven normally sighted participants, we characterized differences in V1 sensitivity across eccentricities and visual quadrants, finding reliable and reproducible patterns at individual and session levels. To test robustness to fixation variability, we investigated how varying levels of eye movement affected V1 sensitivity patterns in two participants: cortical sensitivity patterns were largely preserved despite eye movements, particularly at low spatial frequencies. This suggests our approach can accommodate several degrees of fixation instability, making it suitable for populations with unstable or biased fixation for whom visual field maps are harder to acquire behaviorally (e.g., patients with dense central scotoma or strabismus). Additionally, our method effectively visualized simulated and disease-linked sensitivity loss at the cortical level. Crucially, these results could be largely recovered using the structure-based retinotopic atlas, eliminating the need for pRF mapping and precise fixation, although with reduced sensitivity. This approach, integrating large-field stimulation with a retinotopic atlas, offers a promising tool for monitoring vision loss and recovery across a range of visual impairments, addressing a significant challenge in current clinical assessments.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105912","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}
eLifePub Date : 2026-10-01DOI: 10.7554/eLife.108588
Jinghan Qiao, Pengyu Yu, Hongzhe Peng, Wenjie Shi, Bo Li, Bo Dong
{"title":"Bidirectional redistribution of actomyosin drives epithelial invagination in ascidian siphon tube morphogenesis.","authors":"Jinghan Qiao, Pengyu Yu, Hongzhe Peng, Wenjie Shi, Bo Li, Bo Dong","doi":"10.7554/eLife.108588","DOIUrl":"https://doi.org/10.7554/eLife.108588","url":null,"abstract":"<p><p>How epithelia perform a spatiotemporal heterogeneous force-generating program to drive a sequential tissue morphogenesis remains unclear, particularly the underlying precise mechanical mechanisms. This study investigated dynamic actomyosin reorganization between apical and lateral membrane cortex regions during two sequentially invaginated stages of atrial siphon tube morphogenesis in the ascidian <i>Ciona</i>. At the initial invagination stage, the originally lateral-located actomyosin redistributed to the apical domains, while that actomyosin redistributed back to lateral domains at the accelerated invagination stage. Using genetic mutants to modulate myosin activities, the initial invagination was strengthened or abolished, indicating invagination is apical constriction-dependent. Optogenetic inhibition of myosin activities in lateral domains after initial invagination stage blocked the further processes, suggesting lateral constriction of actomyosin is required for the accelerated invagination. Vertex model simulations uncovered a coupled mechanism underlying epithelial invagination driven by apicobasal tension imbalance and lateral contraction. We thus propose an actomyosin redistribution mechanical model: lateral actomyosin first redistributes apically to drive apical constriction and shape the initial invagination, then apical actomyosin redistributes laterally to promote lateral contractility and accelerate invagination. Our findings reveal a bidirectional reorganization of the actomyosin network as a central mechanism driving epithelial invagination, providing insights on epithelial invagination and organ morphogenesis during development.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105888","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}
eLifePub Date : 2026-10-01DOI: 10.7554/eLife.105146
Blair R K Shevlin, Loren Gianini, Joanna Steinglass, Karin Foerde, E Caitlin Lloyd, Kelsey Hagan, Laura A Berner
{"title":"Negative affect influences the computations underlying food choice in bulimia nervosa.","authors":"Blair R K Shevlin, Loren Gianini, Joanna Steinglass, Karin Foerde, E Caitlin Lloyd, Kelsey Hagan, Laura A Berner","doi":"10.7554/eLife.105146","DOIUrl":"https://doi.org/10.7554/eLife.105146","url":null,"abstract":"<p><p>Individuals often consume tasty, calorically dense foods in response to negative emotions, a phenomenon exemplified by notions of 'stress eating' and 'comfort food'. While this link between food and mood can become pathological in binge eating, the decision-making processes underlying this link are poorly understood. Here, we investigated the impact of acute increases in negative affect on when and how strongly the perceived tastiness and healthiness of foods influence food choices in healthy adults and individuals with bulimia nervosa (BN), an eating disorder characterized by cycles of over- and under-consumption of food. In a randomized crossover design, 25 women with BN and 21 healthy controls completed two sessions where they received either a neutral or negative affect induction and then completed a food choice task. Using a time-varying diffusion decision model, we assessed how negative affect influences food choice dynamics for high- and low-fat foods. In the neutral affect condition, individuals with BN considered tastiness relative to healthiness of high-fat foods sooner than healthy controls but maintained a restrictive food choice policy by reducing the weight on tastiness. After a negative affect induction, both groups showed a stronger bias toward considering tastiness before healthiness, but this bias was exaggerated in individuals with BN. This affect-induced bias for high-fat foods predicted more frequent subjective binge episodes over 3 months. These results provide insights into how negative emotion influences food choices and may explain why binge eating in BN is more likely during high negative affect, while dietary restriction is more likely during low negative affect.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105822","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}