@article{21509, abstract = {Chromatin remodeling complexes mobilize nucleosomes and promote transcription factor (TF) binding. Using ensemble and single-molecule assays combined with cryo-electron microscopy (cryo-EM), we studied the interaction between pioneer TFs OCT4–SOX2 and the human BRG1/BRM-associated factor (BAF) complex on nucleosomes. BAF engages TF-bound substrates in two orientations, placing OCT4–SOX2 at either the remodeler ENTRY or EXIT site. At the ENTRY site, OCT4–SOX2 initially coexists with BAF without structural interference. However, continued DNA translocation is expected to cause collisions with bound TFs, which can trigger remodeling direction reversals or may induce TF dissociation. To accommodate TFs at the EXIT site, BAF undergoes structural rearrangements, and ensemble assays reveal a nucleosome subpopulation translocating away from TF-binding sites. Moreover, single-molecule experiments show that nucleosome-bound BAF frequently changes remodeling direction, and we identify an ADP-bound remodeler conformation as a potential intermediate. Together, these findings reveal key aspects of the conformational dynamics and remodeling outcomes underlying BAF processing of TF-bound nucleosomes.}, author = {Weiss, Joscha and Vecchia, Luca and Domjan, David and Cavadini, Simone and Sabantsev, Anton and Kempf, Georg and Pathare, Ganesh R. and Brackmann, Klaus and Michael, Alicia and Kater, Lukas and Hietter-Pfeiffer, Eric and Haddawi, Mina and Kuber, Urja P. and Mühlhäusser, Sandra and Grand, Ralph S. and Stadler, Michael B. and Deindl, Sebastian and Thomä, Nicolas H.}, issn = {1097-2765}, journal = {Molecular Cell}, number = {4}, pages = {625--639.e8}, publisher = {Cell Press}, title = {{The human BAF chromatin remodeler processes nucleosomes bound by pioneer transcription factors OCT4–SOX2}}, doi = {10.1016/j.molcel.2026.01.021}, volume = {86}, year = {2026}, } @article{21761, abstract = {Neural tube closure is a critical morphogenetic process in vertebrate development, and failure to close cranial regions such as the hindbrain neuropore (HNP) leads to severe congenital malformations. While mechanical forces such as actomyosin purse-string contraction and directional cell crawling have been implicated in driving HNP closure, how these forces organize local cell shape and motion to produce large-scale tissue remodeling remains poorly understood. Using live and fixed imaging of mouse embryos combined with cell-based biophysical modeling, we show that these force-generating mechanisms are insufficient to explain the reproducible patterns of cell elongation and nematic alignment observed at the HNP border. Instead, we show that local anisotropic stress and cytoskeletal organization are required to generate these patterns and promote midline cell motion. Our model captures key features of cell shape dynamics and emergent nematic order, which we confirm experimentally, including the alignment of actin fibers with cell shape and enhanced midline cell speed. Comparative analysis with chick embryos, which lack supracellular purse strings, supports a conserved link between tension generation and cellular patterning. These findings establish a physical framework connecting force generation, cell shape anisotropy, and tissue morphodynamics during epithelial gap closure.}, author = {Perez Verdugo, Fernanda L and Maniou, Eirini and Galea, Gabriel L. and Banerjee, Shiladitya}, issn = {1879-0445}, journal = {Current Biology}, number = {8}, pages = {1903--1917.e5}, publisher = {Cell Press}, title = {{Mechanosensitive feedback organizes cell shape and motion during hindbrain neuropore morphogenesis}}, doi = {10.1016/j.cub.2026.02.068}, volume = {36}, year = {2026}, } @article{21955, abstract = {AgRP neurons cause hunger, the drive to seek and consume food. Their activation by fasting is key for survival and is thought to be triggered by feedback when energy stores are low. However, we know that environmental cues can also regulate AgRP neurons since cues that predict future food intake rapidly inhibit AgRP neurons, but is the converse true: can the prediction of future fasting rapidly activate AgRP neurons? Here, we show in mice that such rapid fasting activation of AgRP neurons does occur. This rapid activation is driven by excitatory input from paraventricular hypothalamic (PVH) neurons expressing Sim2, which are bidirectionally sensitive to predictions of future energy state. Thus, cognitively processed contextual information conveyed by PVHSim2 neurons strongly activates AgRP neurons. Lastly, chronic silencing of PVHSim2 neurons causes persistent hypophagia. This PVHSim2-to-AgRP-neuron circuit, by anticipating and preventing negative energy balance, provides an important new dimension of hunger regulation.}, author = {Walker, Samuel J. and Lowenstein, Elijah D. and Douglass, Amelia May Barnett and Thomas, Callum M.P. and Madara, Joseph C. and Kucukdereli, Hakan and Barbosa-Meillon, Eunice A. and Tao, Jenkang and Resch, Jon M. and Lowell, Bradford B.}, issn = { 1097-4199}, journal = {Neuron}, keywords = {hunger, hypothalamus, AGRP neurons, neuroscience, metabolism, homeostasis, feeding, food intake, energy balance, appetite}, publisher = {Cell Press}, title = {{A hypothalamic circuit for anticipating future changes in energy balance}}, doi = {10.1016/j.neuron.2026.05.010}, year = {2026}, } @article{22144, abstract = {Most cells polarize and migrate in response to electrical fields. In this issue of Cell, Belliveau et al. identify TMEM154/Galvanin, a receptor that serves as a cellular antenna to sense electrical gradients and guide migration toward the cathode.}, author = {Riedl, Michael and Sixt, Michael K}, issn = {1097-4172}, journal = {Cell}, number = {13}, pages = {3845--3846}, publisher = {Cell Press}, title = {{A new sense for electrical fields}}, doi = {10.1016/j.cell.2026.05.038}, volume = {189}, year = {2026}, } @article{20972, abstract = {Small amounts of stress are thought to have beneficial effects. A new study reports a mechanism by which the psychedelic drug, psilocybin, causes acute release of stress hormones, despite its known long-term anti-anxiety effects.}, author = {Kücükdereli, Hakan and Douglass, Amelia May Barnett}, issn = {1879-0445}, journal = {Current Biology}, number = {1}, pages = {R27--R29}, publisher = {Cell Press}, title = {{Neuroscience: What doesn’t kill you makes you stronger}}, doi = {10.1016/j.cub.2025.11.056}, volume = {36}, year = {2026}, } @article{20859, abstract = {Effective immune responses rely on the efficient migration of leukocytes. Yet, how temperature regulates migration dynamics at the single-cell level has remained poorly understood. Using zebrafish embryos and mouse tissue explants, we found that temperature positively regulates leukocyte migration speed, exploration, and arrival frequencies to wounds and lymph vessels. Complementary 2D and 3D cultures revealed that this thermokinetic control of cell migration is conserved across immune cell types, independently of the 3D tissue environment. By applying precise (sub-)cellular temperature modulation, we identified a rapid and reversible thermo-response that depends on myosin II activity. Small physiological increases in temperature (1°C –2°C), as present during fever-like conditions, profoundly increased immune responses by accelerating arrival times at lymphatic vessels and tissue wounds. These findings identify myosin-II-dependent actomyosin contractility as a critical mechanical structure regulating single-cell thermo-adaptability, with physiological implications for tuning the speed of immune responses in vivo.}, author = {Company-Garrido, Iván and Zurita Carpio, Alberto and Colomer-Rosell, Mariona and Ciraulo, Bernard and Molkenbur, Ronja and Lanzerstorfer, Peter and Pezzano, Fabio and Agazzi, Costanza and Hauschild, Robert and Jain, Saumey and Jacques, Jeroen M. and Venturini, Valeria and Knapp, Christian and Xie, Yufei and Merrin, Jack and Weghuber, Julian and Schaaf, Marcel and Quidant, Romain and Kiermaier, Eva and Ortega Arroyo, Jaime and Ruprecht, Verena and Wieser, Stefan}, issn = {1878-1551}, journal = {Developmental Cell}, keywords = {thermobiology, cell migration, thermo-adaptability of immune cells}, number = {2}, pages = {356--371.e12}, publisher = {Cell Press}, title = {{Myosin II regulates cellular thermo-adaptability and the efficiency of immune responses}}, doi = {10.1016/j.devcel.2025.10.006}, volume = {61}, year = {2026}, } @article{20935, abstract = {In situ cryo-electron tomography (cryo-ET) has emerged as the method of choice to investigate the structures of biomolecules in their native context. However, challenges remain for the efficient production and sharing of large-scale cryo-ET datasets. Here, we combined cryogenic plasma-based focused ion beam (cryo-PFIB) milling with recent advances in cryo-ET acquisition and processing to generate a dataset of 1,829 annotated tomograms of the green alga Chlamydomonas reinhardtii, which we provide as a community resource to drive method development and inspire biological discovery. To assay data quality, we performed subtomogram averaging of both soluble and membrane-bound complexes ranging in size from >3 MDa to ∼200 kDa, including 80S ribosomes, Rubisco, nucleosomes, microtubules, clathrin, photosystem II, and mitochondrial ATP synthase. The majority of these density maps reached sub-nanometer resolution, demonstrating the potential of this C. reinhardtii dataset as well as the promise of modern cryo-ET workflows and open data sharing to empower visual proteomics.}, author = {Kelley, Ron and Khavnekar, Sagar and Righetto, Ricardo D. and Heebner, Jessica and Obr, Martin and Zhang, Xianjun and Chakraborty, Saikat and Tagiltsev, Grigory and Michael, Alicia and Van Dorst, Sofie and Waltz, Florent and Mccafferty, Caitlyn L. and Lamm, Lorenz and Zufferey, Simon and Van Der Stappen, Philippe and Van Den Hoek, Hugo and Wietrzynski, Wojciech and Harar, Pavol and Wan, William and Briggs, John A.G. and Plitzko, Jürgen M. and Engel, Benjamin D. and Kotecha, Abhay}, issn = {1097-4164}, journal = {Molecular Cell}, number = {1}, pages = {213--230.e7}, publisher = {Cell Press}, title = {{Toward community-driven visual proteomics with large-scale cryo-electron tomography of Chlamydomonas reinhardtii}}, doi = {10.1016/j.molcel.2025.11.029}, volume = {86}, year = {2026}, } @article{20986, abstract = {During complex vocal interactions, different features of acoustic stimuli are integrated to produce appropriate vocal responses,1 such as copying sounds during vocal matching behavior in some animals.2,3,4,5,6,7,8,9,10,11,12 However, little is known about the interplay and possible trade-offs between the different temporal and spectral acoustic features during these vocal exchanges.2,13,14 Nightingales can flexibly match the pitch of their tonal “whistle songs” in real time during counter-singing duels.15,16 Here, we show that the syllable duration of whistle playbacks could alter the song responses of wild nightingales, causing their whistle duration distribution to shift toward the presented stimulus duration. When exposed to whistle playbacks featuring unnatural combinations of pitch and duration, nightingales demonstrate a flexible trade-off between pitch matching and temporal imitation, yet they are constrained by their vocal repertoire. They selectively adapted their vocal responses to approximate these novel stimuli, aligning them with their natural whistle repertoire. We developed a computational model of nightingale whistle-matching behavior that revealed a hierarchical organization of acoustic feature production. During whistle matching, the feature integration process is constrained by the duration of syllables, and pitch matching follows within this temporal framework, forcing a trade-off between the two features. Our findings reveal a complex interplay between the spectral and temporal domains that shapes song-matching behavior.}, author = {Calderon Garcia, Juan Sebastian and Costalunga, Giacomo and Vogels, Tim P and Vallentin, Daniela}, issn = {1879-0445}, journal = {Current Biology}, number = {3}, pages = {791--798.e6}, publisher = {Cell Press}, title = {{Interplay between syllable duration and pitch during whistle matching in wild nightingales}}, doi = {10.1016/j.cub.2025.12.025}, volume = {36}, year = {2026}, } @article{21502, abstract = {The mammalian brain stores glucose, the main circulating energy substrate, as glycogen. In rodents, the cerebellum contains relatively high glycogen levels, yet its cellular and subcellular distribution remains poorly defined. Using monoclonal antibodies against glycogen, we examined its distribution in the mouse cerebellar cortex. Glycogen was predominantly localized to Bergmann glia (BG) processes in the molecular layer and was also detected in Purkinje cells (PCs), the principal cerebellar neurons. To assess the functional significance of cerebellar glycogen, we analyzed behavior in mice lacking glycogen synthase 1 (Gys1) in BG or PCs using a floxed Gys1 line. Gys1 deficiency in either PCs or GFAP-positive cells reduced anxiety-like behavior, whereas combined deletion caused PC degeneration and ataxia. These findings reveal a critical role for glycogen metabolism in both astrocytes and neurons in cerebellar function.}, author = {Akther, Sonam and Lee, Ashley Bomin and Konno, Ayumu and Asiminas, Antonis and Vittani, Marta and Mishima, Tsuneko and Hirai, Hirokazu and Meehan, Claire Francesca and Duran, Jordi and Guinovart, Joan and Ashida, Hitoshi and Morita, Tsuyoshi and Baba, Otto and Shigemoto, Ryuichi and Nedergaard, Maiken and Hirase, Hajime}, issn = {2589-0042}, journal = {iScience}, number = {4}, publisher = {Cell Press}, title = {{Distribution and functional significance of rodent cerebellar glycogen}}, doi = {10.1016/j.isci.2026.115192}, volume = {29}, year = {2026}, } @article{20924, abstract = {Pioneer transcription factors (TFs) possess the ability to read out DNA motifs embedded within nucleosomes, driving changes in gene expression during cellular differentiation and reprogramming. Here, we present selected engagement on nucleosome sequencing (SeEN-seq), a protocol designed to systematically identify potential TF-binding sites on the nucleosome. We describe steps for nucleosome library assembly, SeEN-seq assay, and cryoelectron microscopy (cryo-EM) sample preparation. This protocol facilitates the preparation of homogeneous pioneer TF-nucleosome complexes for cryo-EM structure determination using single-particle analysis. For complete details on the use and execution of this protocol, please refer to Michael et al.1}, author = {Kobayashi, Wataru and Michael, Alicia and Ruangroengkulrith, Siwat and Kümmecke, Maximilian and Tachibana, Kikuë}, issn = {2666-1667}, journal = {STAR Protocols}, number = {1}, publisher = {Cell Press}, title = {{Protocol for integrative analysis of transcription factor-nucleosome interactions using SeEN-seq and cryo-EM structure determination}}, doi = {10.1016/j.xpro.2025.104295}, volume = {7}, year = {2026}, } @article{20725, abstract = {The canonical mechanism by which the phytohormone auxin regulates transcription has been one of the cornerstones of plant signaling. The recent unexpected discovery of cyclic AMP (cAMP) as a second messenger in this pathway has revised its foundations while leaving many open questions and gaps in our understanding; these will be discussed in this forum article.}, author = {Friml, Jiří}, issn = {1878-4372}, journal = {Trends in Plant Science}, number = {2}, pages = {136--138}, publisher = {Cell Press}, title = {{Role of cAMP in TIR1/AFB auxin signaling: Open issues}}, doi = {10.1016/j.tplants.2025.10.018}, volume = {31}, year = {2026}, } @article{20636, abstract = {The versatile and pivotal roles of the phytohormone auxin in regulating plant growth and development are typically linked to its directional transport, relying on the polarized PIN-FORMED (PIN) auxin exporters at the plasma membrane (PM). For decades, auxin has been proposed to promote PIN polarization, generating self-regulatory feedback mediating much of plant development, but mechanistic insight into this regulation is lacking. Here, we uncover an auxin-induced protein complex at the PM, containing auxin co-receptors transmembrane kinases (TMKs) and PIN1 auxin exporter, as the core machinery that underlies this feedback regulation. Auxin promotes PIN1 phosphorylation by TMKs, modulating PIN1 polarization and transport activity. We also provide evidence that PIN1-exported extracellular auxin is crucial for TMK activation and cell elongation, thus forming the simplest two-element self-regulatory feedback circuit. Thus, these findings offer direct mechanistic insights into a potential self-organizing circuit for auxin signaling and transport to ensure proper plant development in Arabidopsis.}, author = {Huang, R and Wang, J and Chang, M and Tang, W and Yu, Y and Zhang, Y and Peng, Y and Wang, Y and Guo, Y and Lu, T and Cao, Y and Zhou, Y and Zhang, Q and Huang, Y and Wu, A and Ren, L and Gallei, Michelle C and Dong, J and Chen, H and He, J and Wen, M and Friml, Jiří and Sun, L and Xiong, Y and Yang, Z and Xu, T}, issn = {1878-1551}, journal = {Developmental Cell}, number = {1}, pages = {73--84}, publisher = {Cell Press}, title = {{TMK-PIN1 drives a short self-organizing circuit for auxin export and signaling in Arabidopsis}}, doi = {10.1016/j.devcel.2025.09.009}, volume = {61}, year = {2026}, } @article{22286, abstract = {Plants are remarkable organisms. Unlike animals, they cannot flee and, rooted in one place, they must cope with whatever challenges arise — nutrient scarcity, drought, shade, wind or obstacles in the soil. Their extraordinary ability to survive in such unstable environmental conditions lies in their capacity to adapt. In response to environmental signals, plants can rapidly adjust the rate of organ growth, change the direction of growth, bend toward resources, or remodel their body architecture by promoting or suppressing the formation of new organs such as lateral roots, branches, leaves, or flowers. This unique developmental plasticity depends on chemical signals, plant hormones that serve as regulators and coordinators of endogenous molecular and cellular processes. Chief among these signals is auxin, a plant hormone central to nearly every aspect of plant life.}, author = {Leitner, Valentin and Benková, Eva}, issn = {0960-9822}, journal = {Current Biology}, number = {13}, pages = {R739--R744}, publisher = {Cell Press}, title = {{Auxin and the control of plant growth and development}}, doi = {10.1016/j.cub.2026.04.047}, volume = {36}, year = {2026}, } @article{22305, abstract = {Active dendrites enrich the repertoire of single-neuron computations. Whereas a lot is known about the function of dendrites in vitro, information about their in vivo properties is limited. A new study1 uses advanced imaging to study hippocampal CA1 pyramidal neuron dendrites in head-fixed, awake animals.}, author = {Bhattacharya, Subhodeep and Jonas, Peter M}, issn = {0896-6273}, journal = {Neuron}, number = {10}, pages = {1706--1708}, publisher = {Cell Press}, title = {{Mission impossible? Quantitative analysis of dendritic computations in vivo}}, doi = {10.1016/j.neuron.2026.04.002}, volume = {114}, year = {2026}, } @article{21746, abstract = {As vertebrates transitioned from water to land, locomotion shifted from undulatory swimming to limb-based movement. How spinal circuits and their cell types evolved to support this transition remains unclear. We leverage frog metamorphosis, which recapitulates this transition within a single organism, to define how spinal circuits generate aquatic versus terrestrial motor patterns. At swim stages, spinal architecture is uniform, with a transcriptionally and anatomically homogeneous motor and interneurons. As limbs develop and their movement complexifies, spinal circuits expand in neuron number and subtype diversity. This expansion is most pronounced for V1 inhibitory neurons, which increase ∼70-fold and diversify into transcriptionally distinct subtypes. Disrupting transcription factors defining emerging motor and V1 populations reveals molecular segregation between swim and limb circuits, highlighting the role of subtype diversity in motor coordination. A multifold increase in inhibitory neuron diversity thus underlies the tail-to-limb locomotor transition, providing a framework for spinal circuit adaptation during vertebrate evolution.}, author = {Vijatovic, David and Toma, Florina Alexandra and Ignatyev, Y and Harrington, Zoe P and Sommer, Christoph M and Hauschild, Robert and Smits, Matthijs Geert and Dalla Vecchia, Marco and Trevisan, Alexandra J. and Chapman, Phillip and Julseth, Mara and Brenner-Morton, Susan and Gabitto, Mariano I. and Dasen, Jeremy S. and Bikoff, Jay B. and Sweeney, Lora Beatrice Jaeger}, issn = {2211-1247}, journal = {Cell Reports}, number = {4}, publisher = {Cell Press}, title = {{Multifold increase in spinal inhibitory cell types with emergence of limb movement}}, doi = {10.1016/j.celrep.2026.117227}, volume = {45}, year = {2026}, } @article{21987, abstract = {We introduce JODIE, a genetic joint modeling approach that estimates how DNA loci influence human traits by partitioning genetic effects into four components: direct effects (from a child’s alleles), indirect maternal and paternal effects (from parents’ alleles), and parent-of-origin (PofO) effects (dependent on parental transmission of alleles), while uniquely accounting for assortative mating. We analyze 30,000 child-mother-father trios from the Estonian Biobank and the Norwegian Mother, Father, and Child Cohort, focusing on height, body mass index, and childhood educational test scores. We find direct effects to be the largest contributor to trait variation, but combined, indirect parental and PofO effects are similarly substantial. We support our results by within-family genome-wide association testing and identify 276 independently associated DNA regions with a complex interplay between direct, indirect, and PofO effects. By joint modeling, we show that direct, indirect, and PofO effects collectively shape human phenotypic variation across loci genome-wide.}, author = {Krätschmer, Ilse and Hegemann, Laura and Hofmeister, Robin J. and Corfield, Elizabeth C. and Mahmoudi, Mahdi and Delaneau, Olivier and Andreassen, Ole A. and Campbell, Archie and Hayward, Caroline and Marioni, Riccardo E. and Ystrom, Eivind and Havdahl, Alexandra and Robinson, Matthew Richard}, issn = {2666-979X}, journal = {Cell Genomics}, keywords = {direct genetic effects, DGE, indirect genetic effects, IGE, parent-of-origin effects, phenotypic variation, assortative mating, within-family GWAS, MoBa, EstBB}, number = {7}, publisher = {Cell Press}, title = {{Separating direct, indirect, and parent-of-origin genetic effects in the human population}}, doi = {10.1016/j.xgen.2026.101277}, volume = {6}, year = {2026}, } @phdthesis{22258, abstract = {Uncovering the genetic architecture of complex traits and pinpointing causal molecular drivers require the ability to distinguish true signals from noise within massive, high-dimensional omics datasets. To extract meaningful biological insights from these datasets, such as identifying causal genetic variants and proteins, scalable and accurate inference methods are essential. To this end, this thesis develops novel Bayesian inference frameworks based on Vector Approximate Message Passing and demonstrates their effectiveness in the modeling of disease onset times and quantitative physical and clinical measures. First, we introduce gVAMP, a Bayesian framework tailored for Genome-Wide Association Studies that enables the joint modeling of quantitative complex traits across millions of genetic variants. gVAMP demonstrates superior accuracy in variable selection and out-of-sample polygenic risk prediction compared to state-of-the-art approaches. We model human height using 17 million whole-genome sequence variants from the UK Biobank, incorporating a vast number of rare variants and revealing novel associations. gVAMP achieves a prediction accuracy of approximately 46% for human height, representing the highest reported performance for this trait to date. Second, we present vampW, a Bayesian framework for survival analysis applied to proteomic data. By effectively handling right-censoring and complex protein dependencies within the UK Biobank Pharma Proteomics Project dataset, vampW identifies 219 protein associations across 24 disease outcomes, the majority of which are not among the top marginal discoveries. We further adjust protein levels for exponential age effects, yielding 1,308 associations and highlighting the sensitivity of the analysis to the chosen age-correction methodology. Finally, vampW improves upon the variable selection capabilities of the commonly used (penalized) variants of the Cox proportional hazards model and delivers state-of-the-art out-of-sample prediction of disease onset times. Collectively, these methods provide powerful tools for dissecting the genetic architecture of complex traits and the proteomic drivers of disease onset. Furthermore, by delivering accurate polygenic risk scores and precise predictions of onset times, this work advances the capabilities of personalized medicine and clinical risk stratification.}, author = {Depope, Al}, issn = {2663-337X}, keywords = {Approximate Message Passing, GWAS, Genomics, Proteomics, Survival modeling}, pages = {169}, publisher = {Institute of Science and Technology Austria}, title = {{From sparse selection to risk prediction: Approximate message passing for proteomic survival models and large-scale genomics}}, doi = {10.15479/AT-ISTA-22258}, year = {2026}, } @article{21488, abstract = {Human height is a model for the genetic analysis of complex traits, and recent studies suggest the presence of thousands of common genetic variant associations and hundreds of low-frequency/rare variants. Here, we develop a new algorithmic paradigm based on approximate message passing (genomic vector approximate message passing [gVAMP]) for identifying DNA sequence variants associated with complex traits and common diseases in large-scale whole-genome sequencing (WGS) data. We show that gVAMP accurately localizes associations to variants with the correct frequency and position in the DNA, outperforming existing fine-mapping methods in selecting the appropriate genetic variants within WGS data. We then apply gVAMP to jointly model the relationship of tens of millions of WGS variants with human height in hundreds of thousands of UK Biobank individuals. We identify 59 rare variants and gene burden scores alongside many hundreds of DNA regions containing common variant associations and show that understanding the genetic basis of complex traits will require the joint analysis of hundreds of millions of variables measured on millions of people. The polygenic risk scores obtained from gVAMP have high accuracy (including a prediction accuracy of ∼46% for human height) and outperform current methods for downstream tasks such as mixed linear model association testing across 13 UK Biobank traits. In conclusion, gVAMP offers a scalable foundation for a wider range of analyses in WGS data.}, author = {Depope, Al and Bajzik, Jakub and Mondelli, Marco and Robinson, Matthew Richard}, issn = {2666-979X}, journal = {Cell Genomics}, number = {5}, publisher = {Cell Press}, title = {{Joint modeling of whole-genome sequencing data for human height via approximate message passing}}, doi = {10.1016/j.xgen.2026.101162}, volume = {6}, year = {2026}, } @article{22267, abstract = {Thermal pollution, whether local or driven by global warming, threatens biodiversity in part through its detrimental effects on reproduction. Non-coding small RNAs (sRNAs) are crucial for maintaining germline developmental robustness under heat stress. Remarkably, we uncovered that neuronal sRNAs regulate germ cells’ thermotolerance, affecting both spermatogenic and oogenic germlines in a cell-non-autonomous manner. Furthermore, we demonstrate that, in RNAi mutants, an oxygen-sensing neural circuit, modulated by neuropeptide signaling, antagonizes germline maintenance, likely reflecting the nematode’s innate association of reduced oxygen levels with food availability and reproductive permissive environments. Finally, we provide evidence that laboratory-domesticated alleles of oxygen-response genes encoding neuropeptide receptor NPR-1 and hexacoordinated globin GLB-5 compromise germline thermotolerance. Hence, our findings raise the possibility that sensory perception, independent of direct environmental change, modulates germline integrity, highlighting a novel mechanism by which neural circuits integrate environmental information to safeguard reproductive fitness in fluctuating environments.}, author = {Ewe, Chee Kiang and Achache, Hanna and Schön, Hanna and Kontorovich, Leonid and Teichman, Guy and Weiss, Shir and Mogilevskaya, Anna and Valenski, Myriam and Anava, Sarit and Bardapurkar, Rutwik and Gingold, Hila and Posner, Rachel and Antonova, Olga and De Bono, Mario and Tzur, Yonatan B. and Rechavi, Oded}, issn = {1879-0445}, journal = {Current Biology}, number = {14}, pages = {3566--3579.e5}, publisher = {Cell Press}, title = {{Neuronal RNAi and oxygen-sensing circuit shape germline resilience to heat stress}}, doi = {10.1016/j.cub.2026.06.016}, volume = {36}, year = {2026}, } @article{22148, abstract = {How the twin-arginine translocase (Tat) system transports fully folded substrate proteins across cellular membranes without disrupting membrane integrity has been a fundamental question in cell biology for decades. The Tat system, found in prokaryotes and plant organelles, recognizes a cargo signal peptide via a conserved twin-arginine motif. The multi-subunit Tat complex facilitates the proton-motive-force-dependent translocation process, yet its overall architecture has remained unknown. Here, we present the cryo-electron microscopy (cryo-EM) structure of the Escherichia coli (E. coli) trimeric TatB₃C₃ complex with bound substrate SufI, assembled in vivo. The complex adopts an unusual, wide-open, bowl-shaped architecture with a polar inner cavity. Unexpectedly, the cargo is engaged in a dual-contact mode: while the signal peptide binds inside one TatBC unit, the folded domain docks tightly onto an adjacent unit, possibly performing a proofreading function. This structure provides a mechanistic framework for substrate engagement and suggests the direct involvement of the entire Tat complex in substrate translocation.}, author = {Zhao, Ziyu and Sazanov, Leonid A}, issn = {1097-4164}, journal = {Molecular Cell}, publisher = {Cell Press}, title = {{Structure of E. Coli twin-arginine translocase (Tat) complex with bound cargo}}, doi = {10.1016/j.molcel.2026.05.026}, year = {2026}, }