Jingyi Wang,Arielle Tambini,Laura Pritschet,Caitlin M Taylor,Emily G Jacobs,Regina C Lapate
{"title":"The intrinsic time tracker: temporal context is embedded in entorhinal and hippocampal functional connectivity patterns.","authors":"Jingyi Wang,Arielle Tambini,Laura Pritschet,Caitlin M Taylor,Emily G Jacobs,Regina C Lapate","doi":"10.1038/s41467-025-63633-6","DOIUrl":"https://doi.org/10.1038/s41467-025-63633-6","url":null,"abstract":"Changes in task-evoked activity in the entorhinal cortex (EC) and hippocampus have been shown to track changes in temporal context at short and long timescales. However, whether spontaneous changes in EC and hippocampal neural signals-in the absence of task demands-likewise reflect the passage of time remains unknown. Here, we leveraged a dense-sampling study in which two individuals underwent daily resting-state fMRI for 30 days. Similarity in EC- and anterior hippocampal-whole-brain resting connectivity patterns was negatively correlated with the time interval between sessions, suggesting a spontaneous, slow-drifting neural signature of time. These changes could not be explained by other time-varying factors (including session-wise changes in mood, hormones, or motion). Hippocampal connectivity temporal drifts followed an anterior-to-posterior gradient, and anterolateral EC showed stronger temporal drift than posteromedial EC. Finally, posterior networks (including visual and default mode) primarily drove drifts in EC- and hippocampal-whole-brain connectivity over time. Collectively, these findings reveal a resting-state connectivity signature that reflects the passage of time in the absence of task demands and follows a functional gradient along the longitudinal axis of the hippocampus.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"53 1","pages":"8817"},"PeriodicalIF":16.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tanja Maehr,Javier Lopez,Gabby Drake,Frederico M Ferreira,Richard Fraser,Rebecca Mckown,Reshma Kailath,Susan Morris,Adam Chambers,Leo P Graves,Susan L Walker,Akbar Dastjerdi,Katie L Edwards,Helder I Nakaya,Falko Steinbach
{"title":"A safe, T cell-inducing heterologous vaccine against elephant endotheliotropic herpesvirus in a proof-of-concept study.","authors":"Tanja Maehr,Javier Lopez,Gabby Drake,Frederico M Ferreira,Richard Fraser,Rebecca Mckown,Reshma Kailath,Susan Morris,Adam Chambers,Leo P Graves,Susan L Walker,Akbar Dastjerdi,Katie L Edwards,Helder I Nakaya,Falko Steinbach","doi":"10.1038/s41467-025-64004-x","DOIUrl":"https://doi.org/10.1038/s41467-025-64004-x","url":null,"abstract":"We report the results of the world's first trial of a vaccine against elephant endotheliotropic herpesvirus (EEHV) in elephants. EEHV-induced haemorrhagic disease is a major threat to juvenile Asian elephants. A vaccine preventing severe disease and death would support conservation efforts for this endangered species. We developed a heterologous, recombinant modified vaccinia virus Ankara prime and adjuvanted protein boost vaccine, containing regulatory protein EE2 and major capsid protein. Vaccine design targeted Th1 and cytotoxic T cell responses, crucial for herpesvirus immunity. In a proof-of-concept trial, safety and immunogenicity were tested in adult elephants. A modified interferon-γ release (IFNG) point-of-care vaccine-specific whole blood assay was established to avoid sample transport-related loss of immune readouts and determine T cell responses by RT-qPCR first. Subsequently, RNA sequencing was utilised to investigate transcriptomic changes post-vaccination. No adverse reactions were observed following heterologous vaccination. IFNG responses to candidate antigens were detected against the pre-existing latent immunity in adult elephants. Over-representation analysis revealed induction of T cell-associated pathways. Thus, we show that the vaccine has a favourable safety profile and stimulates EEHV-specific T cell-biased immune responses, warranting further evaluation.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"11 1","pages":"8374"},"PeriodicalIF":16.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"AI-embodied multi-modal flexible electronic robots with programmable sensing, actuating and self-learning.","authors":"Junfeng Li,Zhangyu Xu,Nanpei Li,Kaijun Zhang,Guangyong Xiong,Minjie Sun,Chao Hou,Jingjing Ji,Fan Zhang,Junwen Zhong,YongAn Huang","doi":"10.1038/s41467-025-63881-6","DOIUrl":"https://doi.org/10.1038/s41467-025-63881-6","url":null,"abstract":"Achieving robust environmental interaction in small-scale soft robotics remains challenging due to limitations in terrain adaptability, real-time perception, and autonomous decision-making. Here, we introduce Flexible Electronic Robots constructed from programmable flexible electronic components and setae modules. The integrated platform combines multimodal sensing/actuation with embedded computing, enabling adaptive operation in diverse environments. Applying modular design principles to configure structural topologies, actuation sequences, and circuit layouts, these robots achieve multimodal locomotion, including vertical surface traversal, directional control, and obstacle navigation. The system implements proprioception (shape and attitude) and exteroception (vision, temperature, humidity, proximity and pathway shape recognition) under dynamic conditions. Onboard computational units enable autonomous behaviors like hazard evasion and thermal gradient tracking through adaptive decision-making, supported by embodied artificial intelligence. In this work, we establish a framework for creating small-scale soft robots with enhanced environmental intelligence through tightly integrated sensing, actuation, and decision-making architectures.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"206 1","pages":"8818"},"PeriodicalIF":16.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multiscale-engineered ferroelectric ceramics exhibiting superior electrocaloric performance.","authors":"Xiaowei Wei,Kun Zeng,Xiaoming Shi,Gengguang Luo,Zhengqian Fu,Houbing Huang,Guangzu Zhang,Bing Li,Xiang Lv,Jiagang Wu","doi":"10.1038/s41467-025-63909-x","DOIUrl":"https://doi.org/10.1038/s41467-025-63909-x","url":null,"abstract":"Electrocaloric effect referring to reversible temperature change (ΔT) under electrical excitation provides a promising alternative for next-generation thermal management. The ΔT essentially derives from the polarization change of polar system. However, conventional engineering hardly synchronizes large and flexible polarization change, so that large ΔT and high electrocaloric strength cannot realize concurrently. Herein, we propose a novel design strategy of multiscale engineering to boost the polar entropy of system, by which the large and flexible polarization change can be offered synchronously, availing large ΔT under a low driving field. The envision is validated in a heterogeneous Ba(Ti1-xSnx)O3 system, where the different Ba(Ti1-xSnx)O3 granules are mixed to enhance polarization heterogeneity of system. A large ΔT of 1.5 K and a high electrocaloric strength of 0.375 K mm kV-1 are achieved under a low driving field of 40 kV cm-1. Meanwhile, the substantial ΔT of more than 1.2 K is maintained within 30-50 °C. Our strategy provides a new paradigm for engineering electrocaloric material properties and can be expected for the design of other high-performance ferroelectrics.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"8 1","pages":"8851"},"PeriodicalIF":16.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura S Pfeiffer,Tobias Merkle,Paul Vogel,Inga Jarmoskaite,Jonathan M Geisinger,Ngadhnjim Latifi,Marco Herrera-Barrera,Feijie Zhang,Lisa Groß,Carolin Schlitz,Daniel T Hofacker,Clemens Lochmann,Davide Fumagalli,Stefanie Gackstatter,Vanessa Deisling,Mark A Kay,Jin Billy Li,Thorsten Stafforst
{"title":"Stereo-random oligonucleotides enable efficient recruitment of ADAR in vitro and in vivo.","authors":"Laura S Pfeiffer,Tobias Merkle,Paul Vogel,Inga Jarmoskaite,Jonathan M Geisinger,Ngadhnjim Latifi,Marco Herrera-Barrera,Feijie Zhang,Lisa Groß,Carolin Schlitz,Daniel T Hofacker,Clemens Lochmann,Davide Fumagalli,Stefanie Gackstatter,Vanessa Deisling,Mark A Kay,Jin Billy Li,Thorsten Stafforst","doi":"10.1038/s41467-025-64434-7","DOIUrl":"https://doi.org/10.1038/s41467-025-64434-7","url":null,"abstract":"Site-directed RNA editing is a promising and potentially safer alternative to genome editing. Previous methods have been developed that recruit the endogenously and ubiquitously expressed ADAR enzymes to initiate site-specific A-to-I edits, but often suffer from low efficacy or dependency on viral delivery. Chemically modified oligonucleotides may be a promising alternative, but the approach still lacks systematic in-depth studies. Furthermore, the best characterized platform uses stereo-pure backbone chemistry, which is not widely used, commercially unavailable and challenging to manufacture. Here, we report on single-stranded oligonucleotides of 30-60 nt length, which are fully chemically stabilized by applying commercially available, classical RNA drug modifications, like 2´-O-methyl, 2´-fluoro, and DNA on a stereo-random phosphate/phosphorothioate backbone. We demonstrate our so-called RESTORE 2.0 oligonucleotides to induce the correction of pathogenic point mutations, efficacy after GalNAc-mediated uptake into human primary hepatocytes, and proof of in-vivo efficacy in mice upon lipid nanoparticle-mediated delivery. The discovered design principles may increase the accessibility of site-directed RNA base editing to expand and support further research in this field.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"26 1","pages":"8849"},"PeriodicalIF":16.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitotic DNA repair by TMEJ suppresses replication stress-induced nuclear envelope reassembly defect.","authors":"Guojun Ye,Yide He,Yihui Zhang,Dongchen Li,Fuhai Liu,Yi Li,Qinglian Ge,Qiong Guo,Shuya Han,Chunyu Song,Weiping Chang,Haoyue Zhang,Qin Peng,Kun Sun,Weike Ji,Lin Deng","doi":"10.1038/s41467-025-63942-w","DOIUrl":"https://doi.org/10.1038/s41467-025-63942-w","url":null,"abstract":"Replication stress (RS), if not effectively and timely addressed, could result in DNA damage in mitosis. However, the relationship between RS and other mitotic events, such as nuclear envelope (NE) breakdown and reassembly, remains poorly understood. Here we report that RS can lead to NE defect. Importantly, rather than de novo NE rupture, the defect per se is a result of nuclear envelope reassembly defect (NERD) during mitosis. Interestingly, NERD is associated with mitotic DNA damage, and repair of the damage by DNA polymerase theta (Polθ)-mediated end joining (TMEJ) ameliorates NERD. Genomic mapping of lamina associated domains (LADs) by cleavage under targets and tagmentation (CUT&Tag) identifies a population of replication stress-sensitive LADs (RESSLADs). Strikingly, a substantial portion of RESSLADs reside in the common fragile sites (CFSs). The loss of RESSLADs-NE interaction under RS might be attributed to the sustained phosphorylation of Lamin A/C at the sites of NERD. In addition, prominent NE defect is observed under multiple conditions of synthetic lethality. Altogether, these findings establish a link between genome instability and nuclear vulnerability under replication stress.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"12 1","pages":"8836"},"PeriodicalIF":16.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiahui Ding,Anna Hu,Annie Thy Nguyen,Grace M Swanson,Aditi Singh,Nicholas Adzibolosu,Diana Manchorova,Elizabeth Findeis,Anthony Maxwell,Yuan He,Marta Rodriguez Garcia,Gil Mor
{"title":"Prenatal exposure to Zika virus shapes offspring neutrophil function in a sex-specific manner.","authors":"Jiahui Ding,Anna Hu,Annie Thy Nguyen,Grace M Swanson,Aditi Singh,Nicholas Adzibolosu,Diana Manchorova,Elizabeth Findeis,Anthony Maxwell,Yuan He,Marta Rodriguez Garcia,Gil Mor","doi":"10.1038/s41467-025-63941-x","DOIUrl":"https://doi.org/10.1038/s41467-025-63941-x","url":null,"abstract":"Maternal viral infection during pregnancy can have lasting consequences on offspring immune development. Zika virus (ZIKV) is known to trigger maternal immune activation (MIA), yet its impact on fetal and postnatal innate immunity remains poorly understood. Here, we investigate how prenatal exposure to ZIKV influences offspring neutrophil function using a murine model of maternal infection. We identify a sex-dimorphic placental response to ZIKV and observed hyperinflammation in ZIKV-exposed male offspring following LPS challenge. Functional assays reveal impaired reactive oxygen species production and defective neutrophil extracellular trap formation in neutrophils from ZIKV-exposed offspring. Furthermore, we identify A20 as a key sex-dimorphic regulator of neutrophil activation and survival. Here, we show that maternal viral infection during pregnancy programs long-term offspring immunity in a sex-specific manner, providing insights into the developmental origins of differential susceptibility to infections and inflammatory diseases later in life.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"3 1","pages":"8839"},"PeriodicalIF":16.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brittney L Dickey,Racheal S Dube Mandishora,Bradley Sirak,Wenyi Fan,Kimberly Isaacs-Soriano,Richard R Reich,Michael J Schell,Eduardo Lazcano-Ponce,Luisa L Villa,Anna R Giuliano
{"title":"Persistence and clearance of oral human papillomavirus among a multi-national cohort of men.","authors":"Brittney L Dickey,Racheal S Dube Mandishora,Bradley Sirak,Wenyi Fan,Kimberly Isaacs-Soriano,Richard R Reich,Michael J Schell,Eduardo Lazcano-Ponce,Luisa L Villa,Anna R Giuliano","doi":"10.1038/s41467-025-62963-9","DOIUrl":"https://doi.org/10.1038/s41467-025-62963-9","url":null,"abstract":"In response to the growing burden of HPV-associated oropharyngeal cancer, this study investigated clearance of oral HPV, the obligate precursor, in a longitudinal cohort of men from the US, Brazil, and Mexico. Oral gargles collected every 6 months from the HPV Infection in Men Study were HPV genotyped using SPF10 PCR-DEIA-LiPA25. Oral HPV infection clearance and associated factors were assessed using Kaplan-Meier curves and Cox proportional hazards models, respectively. Median follow-up was 44.8 months with 403 and 186 men with an incident and prevalent oral HPV infection, respectively; and lower probability of clearance observed in prevalent infections. Infections were less likely to clear in the presence of increased sexual behaviors; and among prevalent infections, older men were less likely to clear their infection. Here, we report differences in prevalently and incidently detected infections with sexual behavior as a key factor and older age as a potential factor associated with clearance.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"7 1","pages":"8816"},"PeriodicalIF":16.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A physiologically-relevant intermediate state structure of a voltage-gated potassium channel.","authors":"Efthimios Kyriakis,Daniel Sastre,Jodene Eldstrom,Agnese Roscioni,Sophia Russo,Fariba Ataei,Ying Dou,Magnus Chan,Steven Molinarolo,Luca Maragliano,Filip Van Petegem,David Fedida","doi":"10.1038/s41467-025-64060-3","DOIUrl":"https://doi.org/10.1038/s41467-025-64060-3","url":null,"abstract":"Voltage-gated potassium ion (K+) channels perform critical roles in many physiological processes, while gain- or loss-of-function mutations lead to life-threatening pathologies. Here, we establish the high-resolution structure of a pivotal intermediate state of the Kv7.1 (KCNQ1) channel using cryogenic electron microscopy. The 3.53 Å resolution structure reveals straightened upper S1 and S2 voltage sensor helices, distancing them from the pore filter helix compared to fully activated channels. The outward translation of the S4 voltage sensor is essentially complete in this intermediate state, and the S4-S6 helices and the S4-S5 linker do not change position significantly between intermediate and activated states. The PIP2 ligand can bind in both states. Movement of S1 and S2 helices towards the filter helix from intermediate to activated states may explain smaller components of KCNQ1 voltage sensor fluorescence, differential Rb+/K+ selectivity, and pharmacological responses to activators and inhibitors. Single channel recordings and the location of long QT mutations suggest the potential physiological and disease importance of the intermediate state.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"9 1","pages":"8814"},"PeriodicalIF":16.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The mechanism of thioamide formation by the YcfA-YcfC system in 6-thioguanine biosynthesis.","authors":"Li Zhang,Chao Dou,Weizhu Yan,Pengpeng Chen,Xinyu Jia,Na Zhang,Dan Zhou,Zhaolin Long,Lu Zhang,Xiaofeng Zhu,Wei Cheng","doi":"10.1038/s41467-025-63937-7","DOIUrl":"https://doi.org/10.1038/s41467-025-63937-7","url":null,"abstract":"6-thioguanine (6-TG) is a therapeutic medication for childhood acute lymphoblastic leukemia (ALL) and a potent antimicrobial agent. Its biosynthesis relies on the YcfA-YcfC system, yet the formation of its critical thioamide moiety remains incompletely understood. Here, we provide a detailed biochemical and structural characterization of YcfA, including apo and substrate-bound crystal structures, which reveal that substrate adenylation and L-cysteine addition are key initial steps in the reaction cascade. Cryo-electron microscopy (cryo-EM) and functional analyses highlight YcfA's assembly into a two-layered heptameric structure, essential for the enzymatic function. GTP serves a dual role as a substrate and oligomerization enhancer. Additionally, pyridoxal 5'-phosphate (PLP), a cofactor for YcfC, the partner enzyme in this system, promotes YcfA oligomerization but inhibits its activity by obstructing GTP binding. Biochemical and structural evidence confirms that YcfC acts as a C‒S lyase, which is essential for thioamide formation in the presence of PLP. Exploiting substrate flexibility, we synthesized a seleno analog with antimicrobial properties. Multi-omics analyses of the biosynthetic precursor underscore its potential as an antibiotic. Collectively, our findings unravel the distinct architecture and functionality of the YcfA-YcfC system, offering an evolutionary perspective on noncanonical thioamide biosynthesis and a foundation for synthetic biology applications in drug development.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"17 1","pages":"8840"},"PeriodicalIF":16.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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