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    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025.
  • GeoEvoBuilder: A deep learning framework for efficient functional and thermostable protein design
    by Jiale LiuHantian YouZheng GuoQin XuChangsheng ZhangLuhua LaiaCenter for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, ChinabSchool of Elite Biomedical Engineers, China Pharmaceutical University, Nanjing 211198, ChinacBeijing National Center for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, ChinadShanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201204, ChinaeCenter for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, ChinafPeking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies, Chengdu, Sichuan 610213, China
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceEnhancing enzyme catalytic efficiency and thermal stability is crucial for biocatalytic and industrial applications. While structure-based protein sequence design can improve thermal stability, its success in enzyme engineering is limited by …
  • Inter- and intrahemispheric sources of vestibular signals to V1
    by Guy BouvierAlessandro SanzeniElizabeth HamadaNicolas BrunelMassimo ScanzianiaDepartment of Physiology, University of California San Francisco, San Francisco, CA 94158bHHMI, University of California San Francisco, San Francisco, CA 94158cCNRS, Institut des Neurosciences Paris-Saclay, Université Paris-Saclay, Saclay 91400, FrancedDepartment of Computing Sciences, Bocconi University, Milan 20100, ItalyeCenter for Theoretical Neuroscience, Columbia University, New York, NY 10027fMortimer B Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027gDepartment of Neurobiology, Duke University, Durham, NC 27710hDepartment of Neurology, University of California San Francisco, San Francisco, CA 94158
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceInformation about head motion is fundamental to the visual interpretation of our environment. Indeed, head motion signals originating from the vestibular system robustly modulate activity in the visual cortex (VC). Despite this profound …
  • Natural history of liver fluke infection underpins epidemiological patterns of biliary cancer
    by Thomas CrellenFrancesca VitaChiara BraconiPaiboon SithithawornT. DĂ©irdre HollingsworthaSaw Swee Hock School of Public Health, National University of Singapore, Singapore 117549, SingaporebBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, United KingdomcNuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford OX3 7LF, United KingdomdSchool of Biodiversity One Health and Veterinary Medicine, University of Glasgow, Glasgow G12 8QQ, United KingdomeSchool of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow G61 1QH, United KingdomfDepartment of Oncology, University of Turin, Turin 10043, ItalygBeatson West of Scotland Cancer Centre, Glasgow G12 0YN, United KingdomhCancer Research UK Scotland Cancer Centre, Glasgow G61 1BD, United KingdomiDepartment of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandjCholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceInfestation with parasitic worms can cause cancer in humans, though this decades-long process is challenging to study. Here, we show how liver fluke ecology determines the epidemiology of cholangiocarcinoma (bile duct cancer) in Thailand. We …
  • Metabolic controls on the carbon isotope fractionations of bacterial fermentation
    by Elliott P. MuellerVerena B. HeuerJared R. LeadbetterKai-Uwe HinrichsAlex L. SessionsaDivision of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125bDepartment of Geological Sciences, University of Colorado Boulder, Boulder, CO 80309cCenter for Marine Environmental Sciences (MARUM), University of Bremen, Bremen 330 400, Germany
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceMicroorganisms drive the global cycling of elements like carbon and regulate the Earth’s climate on both human and geologic timescales. Of particular importance is the microbial breakdown of organic matter, which generates greenhouse gases …
  • Activity-dependent citrate dynamics in neurons
    by Paul C. RosenPanhui FuBeatriz FerránErica KimDaniel J. BrooksDaniel C. LimCarlos Manlio Díaz-GarcíaGary YellenaDepartment of Neurobiology, Harvard Medical School, Boston, MA 02115bDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139cDepartment of Biochemistry and Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104dCenter for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104eHarold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceDifficulty in quantifying the small-molecule modulators of glycolysis dynamically and in specific compartments of live cells limits our understanding of metabolic regulation. We engineered a quantitative fluorescent biosensor to study the …
  • Unexpected heterogeneity and tissue-specific properties of the thymic hematopoietic antigen–presenting cell network
    by Yi WangXin LiuAmelie C. BondSeungyoul OhSotaro OchiaiAbbie R. LarsonAnita E. QuallsIm Hong SunMichaël ChopinJames M. GardnerStephen L. NuttFranca RoncheseDaniel G. PellicciMark M. W. ChongaSt. Vincent’s Institute of Medical Research, Fitzroy, VIC 3065, AustraliabDepartment of Medicine (St. Vincent’s), University of Melbourne, Fitzroy, VIC 3065, AustraliacMalaghan Institute of Medical Research, Wellington 6012, New ZealanddDepartment of Surgery, University of California San Francisco, San Francisco, CA 94143eWalter and Eliza Hall Institute of Medical Research, Parkville, VIC 3010, AustraliafDepartment of Medical Biology, University of Melbourne, Parkville, VIC 3010, AustraliagDepartment of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, AustraliahDiabetes Center, University of California San Francisco, San Francisco, CA 94143iParker Institute for Cancer Immunotherapy, University of California San Francisco, San Francisco, CA 94143jDepartment of Microbiology and Immunology, University of Melbourne, Parkville, VIC 3010, AustraliakMurdoch Children’s Research Institute, Parkville, VIC 3010, Australia
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceThymic antigen–presenting cells (APCs) play critical roles in regulating T cell development. Yet, apart from the medullary thymic epithelial cells, the functions of the vast array of other hematopoietic APCs remains poorly understood. Here, we …
  • A midbrain-to-ventral-striatum dopaminergic pathway orchestrates odor-guided insect predation in mice
    by Wenqiang WangYanbiao ZhongRuiyi TanMaoyuan WangJia LiuDing WangHaiping WangYue LiGuanqing LiJian YangPeng WangJialiang WuJianxu ZhangChen-Zhu WangHaishui ShiMinghong MaYiqun YuYun-Feng ZhangaState Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, ChinabState Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, ChinacSchool of Life Sciences, Hebei University, Baoding 071002, ChinadDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, ChinaeGanzhou Intelligent Rehabilitation Technology Innovation Center, Ganzhou 341000, ChinafDepartment of Nuclear Medicine, Peking University People’s Hospital, Beijing 100044, ChinagDepartment of Otorhinolaryngology Head and Neck Surgery, Children’s Hospital, Capital Institute of Pediatrics, Beijing 100020, ChinahUniversity of Chinese Academy of Sciences, Beijing 100101, ChinaiSchool of Rehabilitation Medicine, Gannan Medical University, GanZhou 341000, ChinajNational Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital affiliated to Capital Medical University, Beijing 100088, ChinakThe Hebei Key Laboratory of Early Life Health Promotion, Nursing School, Hebei Medical University, Shijiazhuang 050031, ChinalDepartment of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104mEar, Nose, and Throat Institute and Department of Otorhinolaryngology, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai 200031, ChinanOlfactory Disorder Diagnosis and Treatment Center, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai 200031, China
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceUnderstanding how predators identify and select nutritious prey is fundamental to deciphering interspecies interactions and energy flow within ecosystems. This study reveals that both laboratory and wild rodents preferentially feed on …
  • BTK autoinhibition analyzed by high-throughput swaps of SH2 domains
    by Timothy J. EisenSam Ghaffari-KashaniChien-Lun HungJay T. GrovesJohn KuriyanaDepartment of Chemistry, University of California, Berkeley, CA 94720bCalifornia Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720cDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37240dDepartment of Chemistry, Vanderbilt University, Nashville, TN 37240
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceBruton’s Tyrosine Kinase (BTK) is an important target in cancer treatment, motivating studies into its mechanism. Like many other tyrosine kinases, BTK contains an SH2 domain that binds to phosphotyrosine residues. However, unlike kinases in …
  • Chimeric RNA isoforms generated by diverse mechanisms from two C-type lectins modulate innate immunity in arthropods
    by Ying HuangXin HuangLi-Hua ZhangQian RenaState Key Laboratory of Climate System Prediction and Risk Management, School of Marine Sciences, Nanjing University of Information Science and Technology, Nanjing 210044, ChinabJiangsu Province Engineering Research Center for Marine Bio-resources Sustainable Utilization, College of Oceanography, Hohai University, Nanjing 210024, ChinacJiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, College of Marine Science and Engineering, Nanjing Normal University, Nanjing 210023, China
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. Chimeric RNA formation represents a critical mechanism for expanding protein functional diversity, yet its role in invertebrate immune adaptation remains poorly characterized. Here, we report that two C-typelectingenes (MnLec2andMnLec3) from distinct …
  • Electing amateur politicians reduces cross-party collaboration
    by Rachel PorterJeffrey J. HardenMackenzie R. DobsonaDepartment of Political Science, University of Notre Dame, Notre Dame, IN 46556bDepartment of Politics, University of Virginia, Charlottesville, VA 22904
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. Public trust in democratic institutions has dropped to historic lows, prompting electorates in major democracies to turn to “amateur” politicians with the expectation that these political outsiders will cut through stalemates to deliver policy results. …
  • Soil microbial life history strategies covary with ecosystem multifunctionality across aridity gradients
    by Tao ZhouManuel Delgado-BaquerizoChengjie RenNianpeng HeZhenghu ZhouYanghui HeaInstitute of Carbon Neutrality, Key Laboratory of Sustainable Forest Ecosystem Management-Ministry of Education, School of Ecology, Northeast Forestry University, Harbin 150040, ChinabNortheast Asia Biodiversity Research Center, Northeast Forestry University, Harbin 150040, ChinacHeilongJiang Maoershan Forest Ecosystem National Observation and Research Station, Northeast Forestry University, Harbin 150040, ChinadLaboratorio de Biodiversidad y Funcionamiento Ecosistémico, Instituto de Recursos Naturales y Agrobiología de Sevilla, Consejo Superiorde Investigaciones Científicas, Sevilla E-41012, SpaineCollege of Agronomy, Northwest A&F University, Yangling, Shaanxi 712100, China
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceAs global climate change escalates aridity, ecosystem functions face increasing risk of collapse. Understanding functional persistence under aridity, particularly the contribution of soil microbiomes, is crucial for effective conservation …
  • Turning the FeFe hydrogenase from Clostridium beijerinckii into an efficient H2 oxidation catalyst using a redox-active matrix
    by Dawit T. FilmonJan JaeneckeMartin WinklerVincent FourmondChristophe LégerNicolas PlumeréaTechnical University of Munich (TUM), Campus Straubing for Biotechnology and Sustainability, Uferstraße 53, Straubing 94315, GermanybCNRS, Aix-Marseille Universite, Laboratoire de Bioénergétique et Ingénierie des Protéines, Marseille 13009, France
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceHydrogenases are large and efficient metalloenzymes that catalyze the conversion between protons and hydrogen, with an inorganic active site that coordinates cheap transition metals. They have long been considered to replace precious metals as …
  • Short-term experimental flooding impacts soil biogeochemistry but not aboveground vegetation in a coastal forest
    by Peter RegierBen Bond-LambertyNicholas WardVanessa BaileyRoberta Bittencourt PeixotoFausto Machado-SilvaNate McDowellKendalynn A. MorrisAllison Myers-PiggStephanie C. PenningtonMizanur RahmanRoy RichRichard W. SmithStephanie J. WilsonStella C. WoodardAlice StearnsDonnie DayKennedy DoroEfemena EmmanuelCharlotte GrossiordAnya HoppleOlawale OgunsolaKaizad PatelEvan PhillipsJ. Patrick MegonigalaMarine and Coastal Research Laboratory, Pacific Northwest National Laboratory, Sequim, WA 98382bPacific Northwest National Laboratory, Richland, WA 99354cUniversity of Toledo, Toledo, OH 43606dSmithsonian Environmental Research Center, Edgewater, MD 21037eGlobal Aquatic Research LLC, Sodus, NY 14551
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceChanging sea levels and storms are causing more flooding in coastal forests. This flooding kills trees, changing how coastal ecosystems function, but we do not fully understand what factors determine whether forests survive flooding. We …
  • Augmenting rice ANNEXIN expression to counter planthopper NlAnnexin-like5 as an antivirulence strategy against a major crop pest
    by Xiao-Ya ZhangShaoqin LiComzit OpachaloemphanChuan-Xi ZhangSheng Yang HeYanjuan JiangaInstitute of Insect Science, Zhejiang University, Hangzhou 310058, ChinabDepartment of Energy Plant Research Laboratory, Michigan State University, East Lansing, MI 48824cState Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, ChinadChinese Academy of Sciences Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming, Yunnan 650223, ChinaeDepartment of Biology, Duke University, Durham, NC 27708fState Key Laboratory for Quality and Safety of Agro-Products, Institute of Plant Virology, Ningbo University, Ningbo 315211, ChinagHHMI, Duke University, Durham, NC 27708
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceInsect pests represent a major threat to agriculture worldwide. Elucidating the molecular mechanisms by which insect pests attack plants could lead to new pest control strategies, thereby enhancing global food security. The brown planthopper (…
  • Disorder-driven non-Anderson transition in a Weyl semimetal
    by Cong LiYang WangJianfeng ZhangHongxiong LiuWanyu ChenGuowei LiuHanbin DengTimur K. KimCraig PolleyBalasubramanian ThiagarajanJiaxin YinYouguo ShiTao XiangOscar TjernbergaDepartment of Applied Physics, Kungliga Tekniska högskolan Royal Institute of Technology, Stockholm 11419, SwedenbBeijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, ChinacDepartment of Physics, Southern University of Science and Technology, Shenzhen, Guangdong 518055, ChinadDiamond Light Source, Harwell Campus, Didcot OX11 0DE, United KingdomeMAX IV Laboratory, Lund University, Lund 22100, Sweden
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceMetal–insulator transitions are traditionally attributed to Anderson localization, where disorder traps electrons. However, recent theories predict a new type of transition–non-Anderson disorder-driven transitions–that occur without …
  • Microtubule remodeling by the innate immune factor Trim69 compromises dynein-dependent migration of HIV virion cores toward the nucleus
    by Charlotte VadonXuan-Nhi NguyenValerie SiahaanYuxin SongArya KrishnanVeronique HenriotAmandine ChantharathJulien Burlaud-GaillardPhilippe RoingeardCarsten JankeLucie EtienneFrancesca FioriniMaria M. MagieraAndrea CimarelliaCentre International de Recherche en Infectiologie, Université de Lyon, INSERM, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Nationale Supérieure de Lyon, Lyon 69007, FrancebInstitut Curie, Université Paris Sciences et lettres, CNRS UMR3348, Orsay 91405, FrancecUniversité Paris-Saclay, CNRS UMR3348, Orsay 91405, FrancedPlateforme Infrastructures en Biologie Sante et Agronomie de Microscopie Electronique, Université de Tours et Centre Hospitalier Universitaire de Tours, Tours 37032, FranceeINSERM U1259, Université de Tours et CHU de Tours, Tours 37032, FrancefMolecular Microbiology and Structural Biochemistry, Microbiologie Moléculaire et Biochimie Structurale-Institut de Biologie et de Chimie des Protéines, UMR 5086 CNRS University of Lyon, Lyon 69367, France
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceMicrotubules (MTs) are highways for the transport of voluminous cargo. While numerous examples in the literature have illustrated how viruses use MTs, we had previously identified Tripartite motif protein 69 (Trim69) as the first innate immune …
  • Apparent learning biases emerge from optimal inference: Insights from master equation analysis
    by Prakhar GodaraaDepartment of Psychology, New York University, New York, NY 10003
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceUnderstanding human decision-making in uncertain environments is crucial for fields ranging from cognitive science to artificial intelligence. Recent studies suggest that human behavior in two-armed bandit tasks is shaped by positivity and …
  • Freezing enhances CO2 mineralization in Ca2+-containing solutions
    by Minghao SunDong GaoBowen LiJoseph S. FranciscoGuoying BaiXinxing Zhanga“The Belt and Road Initiative” Advanced Materials International Joint Research Center of Hebei Province, School of Materials Science and Engineering, Hebei University of Technology, Tianjin 300401, People’s Republic of ChinabKey Laboratory of Hebei Province for Molecular Biophysics, Institute of Biophysics, School of Health Science and Bio-medical Engineering, Hebei University of Technology, Tianjin 300401, People’s Republic of ChinacCollege of Chemistry, Frontiers Science Centre for New Organic Matter, State Key Laboratory of Advanced Chemical Power Sources, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Nankai University, Tianjin 300071, People’s Republic of ChinadDepartment of Earth and Environmental Science, University of Pennsylvania, Philadelphia, PA 19104-6316eDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6316
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceThis study demonstrates that frozen solution acts as a self-amplifying carbon sink. We reveal a cryogenic acceleration mechanism on atmospheric CO2mineralization where freezing greatly accelerates CaCO3crystal formation. In artificial …
  • Platelets engage mast cells in a bilateral IL-33-driven feed-forward loop
    by Airi NishidaJun NagaiMadeline HastingsKendall ZaleskiMarie SasakiOmar SamirJuying LaiSofia A. MarshallHiroaki HayashiSreyashi MajumdarKinan AlhallakChunli FengTao LiuJoshua A. BoyceaDivision of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Boston, MA 02115bJeff and Penny Vinik Center for Translational Immunology Research, Harvard Medical School, Boston, MA 02115cDepartments of Medicine, Harvard Medical School, Boston, MA 02115dDepartments of Pediatrics, Harvard Medical School, Boston, MA 02115
    Proceedings of the National Academy of Sciences, Volume 122, Issue 41, October 2025. SignificanceBoth mast cells and platelets accumulate at sites of allergic inflammation and are key contributors to severe asthma and aspirin-exacerbated respiratory disease (AERD), yet their functional interactions remain poorly defined. We demonstrate …

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