Nature Communications最新文献_第10页

Disentangling associations between complex traits and cell types with seismic. 用地震解开复杂性状和细胞类型之间的联系。

IF 15.7 1区综合性期刊

Nature Communications Pub Date : 2025-10-01 DOI: 10.1038/s41467-025-63753-z

Qiliang Lai, Ruth Dannenfelser, Jean-Pierre Roussarie, Vicky Yao

{"title":"Disentangling associations between complex traits and cell types with seismic.","authors":"Qiliang Lai, Ruth Dannenfelser, Jean-Pierre Roussarie, Vicky Yao","doi":"10.1038/s41467-025-63753-z","DOIUrl":"https://doi.org/10.1038/s41467-025-63753-z","url":null,"abstract":"Integrating single-cell RNA sequencing with Genome-Wide Association Studies (GWAS) can uncover cell types involved in complex traits and disease. However, current methods often lack scalability, interpretability, and robustness. We present seismic, a framework that computes a novel specificity score capturing both expression magnitude and consistency across cell types and introduces influential gene analysis, an approach to identify genes driving each cell type-trait association. Across over 1000 cell-type characterizations at different granularities and 28 polygenic traits, seismic corroborates known associations and uncovers trait-relevant cell groups not apparent through other methodologies. In Parkinson's and Alzheimer's, seismic unveils both cell- and brain-region-specific differences in pathology. Analyzing a pathology-based Alzheimer's GWAS with seismic enables the identification of vulnerable neuron populations and molecular pathways implicated in their neurodegeneration. In general, seismic is a computationally efficient, powerful, and interpretable approach for mapping the relationships between polygenic traits and cell-type-specific expression, offering new insights into disease mechanisms.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"8744"},"PeriodicalIF":15.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206973","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}

引用次数: 0

Hypertrophic cardiomyopathy mutations Y115H and E497D disrupt the folded-back state of human β-cardiac myosin allosterically. 肥厚性心肌病突变Y115H和E497D变弹性地破坏人β-心肌蛋白的折叠状态。

IF 15.7 1区综合性期刊

Nature Communications Pub Date : 2025-10-01 DOI: 10.1038/s41467-025-63816-1

Neha Nandwani, Debanjan Bhowmik, Camille Glaser, Matthew Carter Childers, Rama Reddy Goluguri, Aminah Dawood, Michael Regnier, Anne Houdusse, James A Spudich, Kathleen M Ruppel

{"title":"Hypertrophic cardiomyopathy mutations Y115H and E497D disrupt the folded-back state of human β-cardiac myosin allosterically.","authors":"Neha Nandwani, Debanjan Bhowmik, Camille Glaser, Matthew Carter Childers, Rama Reddy Goluguri, Aminah Dawood, Michael Regnier, Anne Houdusse, James A Spudich, Kathleen M Ruppel","doi":"10.1038/s41467-025-63816-1","DOIUrl":"https://doi.org/10.1038/s41467-025-63816-1","url":null,"abstract":"At the molecular level, clinical hypercontractility associated with many hypertrophic cardiomyopathy (HCM)-causing mutations in β-cardiac myosin appears to be driven by their disruptive effect on the energy-conserving, folded-back 'OFF'-state of myosin, which results in increased number of heads free to interact with actin and produce force. While many characterized mutations likely act by directly perturbing intramolecular interfaces stabilizing the OFF-state, others may function allosterically by altering conformational states of the myosin motor. We investigate two such allosteric HCM mutations, Y115H (Transducer) and E497D (Relay helix), which do not directly contact OFF-state interfaces. Biochemical analyses and high-resolution crystallography reveal that both mutations increase active myosin head availability likely by destabilizing the pre-powerstroke conformation required for OFF-state formation. We propose that destabilization of the folded-back state of myosin, either directly or allosterically, represents a common molecular mechanism underlying hypercontractility in HCM across a broader spectrum of pathogenic mutations than previously recognized.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"8751"},"PeriodicalIF":15.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206979","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}

引用次数: 0

Structural insights into Wnt/β-catenin signaling regulation by LGR4, R-spondin, and ZNRF3. LGR4、R-spondin和ZNRF3调控Wnt/β-catenin信号的结构研究

IF 15.7 1区综合性期刊

Nature Communications Pub Date : 2025-10-01 DOI: 10.1038/s41467-025-64129-z

Yuxuan Peng, Akiko Fujimura, Jinta Asami, Zhikuan Zhang, Toshiyuki Shimizu, Umeharu Ohto

{"title":"Structural insights into Wnt/β-catenin signaling regulation by LGR4, R-spondin, and ZNRF3.","authors":"Yuxuan Peng, Akiko Fujimura, Jinta Asami, Zhikuan Zhang, Toshiyuki Shimizu, Umeharu Ohto","doi":"10.1038/s41467-025-64129-z","DOIUrl":"https://doi.org/10.1038/s41467-025-64129-z","url":null,"abstract":"Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) plays a critical role in regulating the wingless-related integration site (Wnt) signaling pathway and is essential for organ development and carcinogenesis. LGR4, along with its ligand R-spondin (RSPO), potentiates Wnt/β-catenin signaling by recruiting its signaling suppressor, E3 ligase Zinc and Ring Finger 3 (ZNRF3), and inducing its membrane clearance. However, detailed mechanisms underlying this process remain unknown. In this study, we present the cryo-electron microscopy structures of human LGR4, the LGR4-RSPO2 and LGR4-RSPO2-ZNRF3 complexes. Upon RSPO2 binding, LGR4 undergoes no significant conformational changes in its transmembrane and extracellular domain structures or their relative orientations. LGR4, RSPO2, and ZNRF3 assemble into a 2:2:2 complex with the ZNRF3 dimer enclosed at the center. This ternary arrangement and forced dimerization of ZNRF3 likely underpin how LGR4 and RSPO2 potentiate Wnt/β-catenin signaling by sequestering ZNRF3 from Wnt receptors and facilitating its auto-inactivation. This study provides a structural basis for understanding the regulatory mechanism of Wnt/β-catenin signaling through the LGR4-RSPO2-ZNRF3 pathway and may offer opportunities for future drug development targeting this axis.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"8337"},"PeriodicalIF":15.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207037","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}

引用次数: 0

Processive ring-opening metathesis polymerization of low ring strain cycloalkenes via molecularly confined catalyst. 低环应变环烯烃分子受限催化剂的开环复分解过程聚合。

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-10-01 DOI: 10.1038/s41467-025-62412-7

Zefeng Zhou,Yang Wang,Wei-Shang Lo,Gavin J Giardino,Kanika Lalit,Michael Goldstein,Wenqi Wang,Chloe Fields,Alfred Barney,Chia-Kuang Tsung,Udayan Mohanty,Wenyu Huang,Jia Niu

{"title":"Processive ring-opening metathesis polymerization of low ring strain cycloalkenes via molecularly confined catalyst.","authors":"Zefeng Zhou,Yang Wang,Wei-Shang Lo,Gavin J Giardino,Kanika Lalit,Michael Goldstein,Wenqi Wang,Chloe Fields,Alfred Barney,Chia-Kuang Tsung,Udayan Mohanty,Wenyu Huang,Jia Niu","doi":"10.1038/s41467-025-62412-7","DOIUrl":"https://doi.org/10.1038/s41467-025-62412-7","url":null,"abstract":"Controlling the reactivity of the propagating chain end in polymerization reactions is crucial for achieving well-defined polymers in both synthetic polymer chemistry and biology. Processive enzymes in nature have evolved substrate-enclosing structures, safeguarding the catalytic center against reentry by the nascent polymer. Here, we present a strategy for processive catalytic polymerization by encapsulating catalysts for ring-opening metathesis polymerization (ROMP) into the sub-surface cages of a metal-organic framework. The sub-surface encapsulation of the catalysts within the framework allowed the nascent polymer to grow out of the framework with minimal impedance and achieve continuous chain growth, while protecting the propagating polymer chain end from the secondary metathesis reaction with the alkenes in the backbone of the nascent polymer. As a result, ultra-high-molecular-weight polymers with low dispersity were generated from the ROMP of low ring strain cycloalkenes such as cis-cyclooctene and cyclopentene. We demonstrate that ultra-high-molecular-weight polymers with degradable backbones and enhanced mechanical and adhesive properties could be readily generated from this approach.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"1 1","pages":"8738"},"PeriodicalIF":16.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203840","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}

引用次数: 0

Functional ultrasound neuroimaging reveals mesoscopic organization of saccades in the lateral intraparietal area. 功能超声神经显像显示外侧顶叶内区跳眼的介观组织。

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-10-01 DOI: 10.1038/s41467-025-63826-z

Whitney S Griggs,Sumner L Norman,Mickael Tanter,Charles Liu,Vasileios Christopoulos,Mikhail G Shapiro,Richard A Andersen

{"title":"Functional ultrasound neuroimaging reveals mesoscopic organization of saccades in the lateral intraparietal area.","authors":"Whitney S Griggs,Sumner L Norman,Mickael Tanter,Charles Liu,Vasileios Christopoulos,Mikhail G Shapiro,Richard A Andersen","doi":"10.1038/s41467-025-63826-z","DOIUrl":"https://doi.org/10.1038/s41467-025-63826-z","url":null,"abstract":"The lateral intraparietal cortex (LIP), contained within the posterior parietal cortex (PPC), is crucial for transforming spatial information into saccadic eye movements, yet its functional organization for movement direction remains unclear. Here, we used functional ultrasound imaging (fUSI), a technique with high sensitivity, large spatial coverage, and good spatial resolution, to map movement direction encoding across the PPC by recording local changes in cerebral blood volume within PPC as two male monkeys performed memory-guided saccades. Our analysis revealed a heterogeneous organization where small patches of neighboring LIP cortex encoded different directions. These subregions demonstrated consistent tuning across several months to years. A rough topography emerged where anterior LIP represented more contralateral downward movements and posterior LIP represented more contralateral upward movements. These results address two fundamental gaps in our understanding of LIP's functional organization: the neighborhood organization of patches and the stability of these populations across long periods of time. By tracking LIP populations over extended periods, we developed mesoscopic maps of direction specificity previously unattainable with fMRI or electrophysiology methods.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"124 1","pages":"8752"},"PeriodicalIF":16.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203842","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}

引用次数: 0

Intrinsic metal-support interactions break the activity-stability dilemma in electrocatalysis. 固有的金属-载体相互作用打破了电催化中活性-稳定性的困境。

IF 15.7 1区综合性期刊

Nature Communications Pub Date : 2025-10-01 DOI: 10.1038/s41467-025-63397-z

Lingxi Zhou, Menghao Yang, Yihong Liu, Feiyu Kang, Ruitao Lv

{"title":"Intrinsic metal-support interactions break the activity-stability dilemma in electrocatalysis.","authors":"Lingxi Zhou, Menghao Yang, Yihong Liu, Feiyu Kang, Ruitao Lv","doi":"10.1038/s41467-025-63397-z","DOIUrl":"https://doi.org/10.1038/s41467-025-63397-z","url":null,"abstract":"Electrocatalysis plays a central role in clean energy conversion and sustainable technologies. However, the trade-off between activity and stability of electrocatalysts largely hinders their practical applications, notably in the oxygen evolution reaction for producing hydrogen and solar fuels. Here we report a steam-assisted synthesis armed with machine learning screening of an integrated Ru/TiMnOx electrode, featuring intrinsic metal-support interactions. These atomic-scale interactions with self-healing capabilities radically address the activity-stability dilemma across all pH levels. Consequently, the Ru/TiMnOx electrode demonstrate enhanced mass activities-48.5×, 112.8×, and 74.6× higher than benchmark RuO2 under acidic, neutral, and alkaline conditions, respectively. Notably, it achieves stable operation for up to 3,000 h, representing a multi-fold stability improvement comparable to other state-of-the-art catalysts. The breakthrough in activity-stability limitations highlights the potential of intrinsic metal-support interactions for enhancing electrocatalysis and heterogeneous catalysis in diverse applications.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"8739"},"PeriodicalIF":15.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206982","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}

引用次数: 0

Wafer-scale fabrication of memristive passive crossbar circuits for brain-scale neuromorphic computing. 用于脑级神经形态计算的记忆无源交叉电路的晶圆级制造。

IF 15.7 1区综合性期刊

Nature Communications Pub Date : 2025-10-01 DOI: 10.1038/s41467-025-63831-2

Sanghyeon Choi, Sai Sukruth Bezugam, Tinish Bhattacharya, Dongseok Kwon, Dmitri B Strukov

{"title":"Wafer-scale fabrication of memristive passive crossbar circuits for brain-scale neuromorphic computing.","authors":"Sanghyeon Choi, Sai Sukruth Bezugam, Tinish Bhattacharya, Dongseok Kwon, Dmitri B Strukov","doi":"10.1038/s41467-025-63831-2","DOIUrl":"https://doi.org/10.1038/s41467-025-63831-2","url":null,"abstract":"Memristive passive crossbar circuits hold great promise for neuromorphic computing, offering high integration density combined with massively parallel operation. However, scaling up the integration complexity of such circuits remains challenging due to low device yield, stemming from the intrinsic properties of filamentary switching and limitations in current crossbar fabrication technologies. Here, we report a scalable passive crossbar device technology achieved through a co-design approach for memristors and crossbar structures. The proposed hardware platform is fabricated using CMOS-compatible processes without complex and high-temperature steps, enabling high device yield along with reliable and multibit operation. Importantly, the fabrication process is successfully scaled to a 4-inch wafer, maintaining an average device yield (>~95%) and preserving key switching characteristics. The potential of this platform is showcased by implementing image classification of the fashion MNIST benchmark with an ex-situ trained spiking neural network. We believe that our work represents a significant step toward brain-scale neuromorphic computing systems.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"8757"},"PeriodicalIF":15.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207045","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}

引用次数: 0

Polarons shape the interlayer exciton emission of MoSe₂/WSe₂ heterobilayers. 极化子影响MoSe2/WSe2异质层的层间激子发射。

IF 15.7 1区综合性期刊

Nature Communications Pub Date : 2025-10-01 DOI: 10.1038/s41467-025-64176-6

Pedro Soubelet, Alex Delhomme, Elena Blundo, Andreas V Stier, Jonathan J Finley

引用次数: 0

Synthetic chaperone based on Hsp90-Tau interaction inhibits Tau aggregation and rescues physiological Tau-Microtubule interaction. 基于Hsp90-Tau相互作用的合成伴侣蛋白抑制Tau聚集，挽救生理性Tau-微管相互作用。

IF 15.7 1区综合性期刊

Nature Communications Pub Date : 2025-10-01 DOI: 10.1038/s41467-025-63824-1

Davide Di Lorenzo, Nicolo Bisi, Julia Kaffy, Lisa Marie Ramirez, Markus Zweckstetter, Olivier Lequin, Irene Garfagnini, Jinghui Luo, Yvonne Hannappel, Inga Ennen, Veronica Dodero, Norbert Sewald, Maria Luisa Gelmi, Nicolo Tonali, Roland Brandt, Sandrine Ongeri

{"title":"Synthetic chaperone based on Hsp90-Tau interaction inhibits Tau aggregation and rescues physiological Tau-Microtubule interaction.","authors":"Davide Di Lorenzo, Nicolo Bisi, Julia Kaffy, Lisa Marie Ramirez, Markus Zweckstetter, Olivier Lequin, Irene Garfagnini, Jinghui Luo, Yvonne Hannappel, Inga Ennen, Veronica Dodero, Norbert Sewald, Maria Luisa Gelmi, Nicolo Tonali, Roland Brandt, Sandrine Ongeri","doi":"10.1038/s41467-025-63824-1","DOIUrl":"https://doi.org/10.1038/s41467-025-63824-1","url":null,"abstract":"The accumulation of intracellular aggregates of Tau protein is one main hallmark of Alzheimer's disease (AD) and is the consequence of Tau conformational changes, increased phosphorylation, and self-association to form fibrillar aggregates. This pathological process prevents the physiological interaction of Tau with microtubules to the detriment of the structural integrity of neurons. In healthy cells, aberrant protein misfolding and aggregation are counteracted by chaperone proteins whose protective capacity decreases with age. The role of the chaperone Hsp90 and the mechanism by which it can prevent Tau aggregation are controversial. In this work, the strategy of mimicking Hsp90 through the design of the β-hairpin like peptidomimetic β-Hsp90, inspired by two Hsp90/Tau interaction sequences, is presented. β-Hsp90 inhibits Tau aggregation both in vitro and in cells, restoring Tau's physiological interaction with microtubules. β-Hsp90, which interacts with the P1 region of Tau, is more effective than individual peptide sequences from the chaperone HSP90 and another β-hairpin mimic based on Tau sequences. Moreover, β-Hsp90 reduces AD-associated Aβ1-42 aggregation, offering the development of a dual inhibitor. This work paves the way for the design of new drugs targeting devastating untreated amyloid diseases, by mimicking physiological chaperones with small synthetic peptide drugs.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"8756"},"PeriodicalIF":15.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207052","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}

引用次数: 0

Bacterial RNA promotes proteostasis through inter-tissue communication in C. elegans. 在秀丽隐杆线虫中，细菌RNA通过组织间通讯促进蛋白质静止。

IF 15.7 1区综合性期刊

Nature Communications Pub Date : 2025-10-01 DOI: 10.1038/s41467-025-63987-x

Emmanouil Kyriakakis, Chiara Medde, Danilo Ritz, Geoffrey Fucile, Alexander Schmidt, Anne Spang

引用次数: 0