Nature Communications最新文献_第2页

Ultrafast fMRI reveals serial queuing of information processing during multitasking in the human brain

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-03-29 DOI: 10.1038/s41467-025-58228-0

Qiuhai Yue, Allen T. Newton, René Marois

引用次数: 0

β-Carotene alleviates substrate inhibition caused by asymmetric cooperativity

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-03-29 DOI: 10.1038/s41467-025-58259-7

Jieren Liao, Umar F. Shahul Hameed, Timothy D. Hoffmann, Elisabeth Kurze, Guangxin Sun, Wieland Steinchen, Alessandro Nicoli, Antonella Di Pizio, Christina Kuttler, Chuankui Song, Dragana A. M. Catici, Farhah Assaad-Gerbert, Thomas Hoffmann, Stefan T. Arold, Wilfried G. Schwab

{"title":"β-Carotene alleviates substrate inhibition caused by asymmetric cooperativity","authors":"Jieren Liao, Umar F. Shahul Hameed, Timothy D. Hoffmann, Elisabeth Kurze, Guangxin Sun, Wieland Steinchen, Alessandro Nicoli, Antonella Di Pizio, Christina Kuttler, Chuankui Song, Dragana A. M. Catici, Farhah Assaad-Gerbert, Thomas Hoffmann, Stefan T. Arold, Wilfried G. Schwab","doi":"10.1038/s41467-025-58259-7","DOIUrl":"https://doi.org/10.1038/s41467-025-58259-7","url":null,"abstract":"Enzymes are essential catalysts in biological systems. Substrate inhibition, once dismissed, is now observed in 20% of enzymes1 and is attributed to the formation of an unproductive enzyme-substrate complex, with no structural evidence of unproductivity provided to date1,2,3,4,5,6. This study uncovers the molecular mechanism of substrate inhibition in tobacco glucosyltransferase NbUGT72AY1, which transfers glucose to phenols for plant protection. The peculiarity that β-carotene strongly attenuates the substrate inhibition of NbUGT72AY1, despite being a competitive inhibitor, allows to determine the conformational changes that occur during substrate binding in both active and substrate-inhibited complexes. Crystallography reveals structurally different ternary enzyme-substrate complexes that do not conform to classical mechanisms. An alternative pathway suggests substrates bind randomly, but the reaction occurs only if a specific order is followed (asymmetric cooperativity). This unreported paradigm explains substrate inhibition and reactivation by competitive inhibitors, opening new research avenues in metabolic regulation and industrial applications.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"48 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733859","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

Mechanically deformable organic ferroelectric crystal with plasticity optimized by fluorination

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-03-29 DOI: 10.1038/s41467-025-58416-y

Pei-Zhi Huang, Zunqi Liu, Lou-Kai Ye, Hao-Fei Ni, Jia-Qi Luo, Gele Teri, Qiang-Qiang Jia, Bo Zhuang, Chang-Feng Wang, Zhi-Xu Zhang, Yi Zhang, Da-Wei Fu

{"title":"Mechanically deformable organic ferroelectric crystal with plasticity optimized by fluorination","authors":"Pei-Zhi Huang, Zunqi Liu, Lou-Kai Ye, Hao-Fei Ni, Jia-Qi Luo, Gele Teri, Qiang-Qiang Jia, Bo Zhuang, Chang-Feng Wang, Zhi-Xu Zhang, Yi Zhang, Da-Wei Fu","doi":"10.1038/s41467-025-58416-y","DOIUrl":"https://doi.org/10.1038/s41467-025-58416-y","url":null,"abstract":"The ability of plastic deformation exerts in bulk crystals would offer great promise for ferroelectrics to achieve emerging and exciting applications. However, conventional ferroelectric crystals generally suffer from inherent brittleness and are easy to fracture. Here, by implementing fluorination on anion, we successfully design a flexible organic ferroelectric phenylethylammonium trifluoromethanesulfonate (PEA-TFMS) with interesting plasticity in its bulk crystals. To our knowledge, it is the first observation since the discovery of organic ferroelectric crystal triglycine sulfate in 1956. Compared to parent PEA-MS (phenylethylammonium mesylate), fluorination subtly alters ionic orientation and interactions to reorganize dipole arrangement, which not only brings switchable spontaneous polarization but also endows PEA-TFMS crystal with macroscopical bending and spiral deformability, making it a competitive candidate for flexible and wearable devices. Our work will bring inspiration for obtaining mechanically deformable organic ferroelectric crystals toward flexible electronics.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"72 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736353","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

Efficient and accurate framework for genome-wide gene-environment interaction analysis in large-scale biobanks

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-03-29 DOI: 10.1038/s41467-025-57887-3

Yuzhuo Ma, Yanlong Zhao, Ji-Feng Zhang, Wenjian Bi

{"title":"Efficient and accurate framework for genome-wide gene-environment interaction analysis in large-scale biobanks","authors":"Yuzhuo Ma, Yanlong Zhao, Ji-Feng Zhang, Wenjian Bi","doi":"10.1038/s41467-025-57887-3","DOIUrl":"https://doi.org/10.1038/s41467-025-57887-3","url":null,"abstract":"Gene-environment interaction (G×E) analysis elucidates the interplay between genetic and environmental factors. Genome-wide association studies (GWAS) have expanded to encompass complex traits like time-to-event and ordinal traits, which provide richer phenotypic information. However, most existing scalable approaches focus only on quantitative or binary traits. Here we propose SPAGxECCT, a scalable and accurate framework for diverse trait types. SPAGxECCT fits a genotype-independent model and employs a hybrid strategy including saddlepoint approximation (SPA) for accurate p value calculation, especially for low-frequency variants and unbalanced phenotypic distributions. We extend SPAGxECCT to SPAGxEmixCCT, which accounts for population stratification and is applicable to multi-ancestry or admixed populations. SPAGxEmixCCT can further be extended to SPAGxEmixCCT-local, which identifies ancestry-specific G×E effects using local ancestry. Through extensive simulations and real data analyses of UK Biobank data, we demonstrate that SPAGxECCT and SPAGxEmixCCT are scalable to analyze large-scale study cohort, control type I error rates effectively, and maintain power.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"72 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733925","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

Aberrant gene expression prediction across human tissues

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-03-29 DOI: 10.1038/s41467-025-58210-w

Florian R. Hölzlwimmer, Jonas Lindner, Georgios Tsitsiridis, Nils Wagner, Francesco Paolo Casale, Vicente A. Yépez, Julien Gagneur

{"title":"Aberrant gene expression prediction across human tissues","authors":"Florian R. Hölzlwimmer, Jonas Lindner, Georgios Tsitsiridis, Nils Wagner, Francesco Paolo Casale, Vicente A. Yépez, Julien Gagneur","doi":"10.1038/s41467-025-58210-w","DOIUrl":"https://doi.org/10.1038/s41467-025-58210-w","url":null,"abstract":"Despite the frequent implication of aberrant gene expression in diseases, algorithms predicting aberrantly expressed genes of an individual are lacking. To address this need, we compile an aberrant expression prediction benchmark covering 8.2 million rare variants from 633 individuals across 49 tissues. While not geared toward aberrant expression, the deleteriousness score CADD and the loss-of-function predictor LOFTEE show mild predictive ability (1–1.6% average precision). Leveraging these and further variant annotations, we next train AbExp, a model that yields 12% average precision by combining in a tissue-specific fashion expression variability with variant effects on isoforms and on aberrant splicing. Integrating expression measurements from clinically accessible tissues leads to another two-fold improvement. Furthermore, we show on UK Biobank blood traits that performing rare variant association testing using the continuous and tissue-specific AbExp variant scores instead of LOFTEE variant burden increases gene discovery sensitivity and enables improved phenotype predictions.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"993 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733919","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

Food and water intake are regulated by distinct central amygdala circuits revealed using intersectional genetics

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-03-29 DOI: 10.1038/s41467-025-58144-3

Federica Fermani, Simon Chang, Ylenia Mastrodicasa, Christian Peters, Louise Gaitanos, Pilar L. Alcala Morales, Charu Ramakrishnan, Karl Deisseroth, Rüdiger Klein

{"title":"Food and water intake are regulated by distinct central amygdala circuits revealed using intersectional genetics","authors":"Federica Fermani, Simon Chang, Ylenia Mastrodicasa, Christian Peters, Louise Gaitanos, Pilar L. Alcala Morales, Charu Ramakrishnan, Karl Deisseroth, Rüdiger Klein","doi":"10.1038/s41467-025-58144-3","DOIUrl":"https://doi.org/10.1038/s41467-025-58144-3","url":null,"abstract":"The central amygdala (CeA) plays a crucial role in defensive and appetitive behaviours. It contains genetically defined GABAergic neuron subpopulations distributed over three anatomical subregions, capsular (CeC), lateral (CeL), and medial (CeM). The roles that these molecularly- and anatomically-defined CeA neurons play in appetitive behavior remain unclear. Using intersectional genetics in mice, we found that neurons driving food or water consumption are confined to the CeM. Separate CeM subpopulations exist for water only versus water or food consumption. In vivo calcium imaging revealed that CeMHtr2a neurons promoting feeding are responsive towards appetitive cues with little regard for their physical attributes. CeMSst neurons involved in drinking are sensitive to the physical properties of salient stimuli. Both CeM subtypes receive inhibitory input from CeL and send projections to the parabrachial nucleus to promote appetitive behavior. These results suggest that distinct CeM microcircuits evaluate liquid and solid appetitive stimuli to drive the appropriate behavioral responses.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"70 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736352","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

A chemical-genetic system to rapidly inhibit the PP2A-B56 phosphatase reveals a role at metaphase kinetochores

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-03-29 DOI: 10.1038/s41467-025-58185-8

Lindsey A. Allan, Andrea Corno, Juan Manuel Valverde, Rachel Toth, Tony Ly, Adrian T. Saurin

{"title":"A chemical-genetic system to rapidly inhibit the PP2A-B56 phosphatase reveals a role at metaphase kinetochores","authors":"Lindsey A. Allan, Andrea Corno, Juan Manuel Valverde, Rachel Toth, Tony Ly, Adrian T. Saurin","doi":"10.1038/s41467-025-58185-8","DOIUrl":"https://doi.org/10.1038/s41467-025-58185-8","url":null,"abstract":"Serine-threonine phosphatases have been challenging to study because of the lack of specific inhibitors. Their catalytic domains are druggable, but these are shared or very similar between individual phosphatase complexes, precluding their specific inhibition. Instead, phosphatase complexes often achieve specificity by interacting with short linear motifs (SLiMs) in substrates or their binding partners. We develop here a chemical-genetic system to rapidly inhibit these interactions within the PP2A-B56 family. Drug-inducible recruitment of ectopic SLiMs (“directSLiMs”) is used to rapidly block the SLiM-binding pocket on the B56 regulatory subunit, thereby displacing endogenous interactors and inhibiting PP2A-B56 activity within seconds. We use this system to characterise PP2A-B56 substrates during mitosis and to identify a role for PP2A-B56 in allowing metaphase kinetochores to properly sense tension and maintain microtubule attachments. The directSLiMs approach can be used to inhibit any other phosphatase, enzyme or protein that uses a critical SLiM-binding interface, providing a powerful strategy to inhibit and characterise proteins once considered “undruggable”.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"49 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736387","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

Genome-scale CRISPRi screen identifies pcnB repression conferring improved physiology for overproduction of free fatty acids in Escherichia coli

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-03-29 DOI: 10.1038/s41467-025-58368-3

Lixia Fang, Xueyan Hao, Jie Fan, Xiaolei Liu, Yaru Chen, Lian Wang, Xiaoying Huang, Hao Song, Yingxiu Cao

{"title":"Genome-scale CRISPRi screen identifies pcnB repression conferring improved physiology for overproduction of free fatty acids in Escherichia coli","authors":"Lixia Fang, Xueyan Hao, Jie Fan, Xiaolei Liu, Yaru Chen, Lian Wang, Xiaoying Huang, Hao Song, Yingxiu Cao","doi":"10.1038/s41467-025-58368-3","DOIUrl":"https://doi.org/10.1038/s41467-025-58368-3","url":null,"abstract":"Microbial physiology plays a pivotal role in construction of superior microbial cell factories for efficient biosynthesis of desired products. Here we identify that pcnB repression confers improved physiology for overproduction of free fatty acids (FFAs) in Escherichia coli through genome-scale CRISPRi modulation combining fluorescence-activated cell sorting (FACS) and next-generation sequencing (NGS). The repression of pcnB can enhance the stability and abundance of the transcripts of genes involved in the proton-consuming system, thereby supporting global improvements in membrane properties, redox state, and energy level. Based on pcnB repression, further repression of acrD increases FFAs biosynthesis by enhancing FFAs efflux. The engineered strain pcnBi-acrDi-fadR+ achieves 35.1 g L−1 FFAs production in fed-batch fermentation, which is the maximum titer reported to date in E. coli. This study highlights the significance of uncovering hidden genetic determinants that confer improved microbial physiology for enhancing the biosynthesis of desired products.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"30 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733911","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

Dopamine prediction error signaling in a unique nigrostriatal circuit is critical for associative fear learning

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-03-29 DOI: 10.1038/s41467-025-58382-5

Daphne Zafiri, Ximena I. Salinas-Hernández, Eloah S. De Biasi, Leonor Rebelo, Sevil Duvarci

引用次数: 0

Non-reciprocal Coulomb drag between Chern insulators

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-03-29 DOI: 10.1038/s41467-025-58401-5

Yu Fu, Yu Huang, Qing Lin He

{"title":"Non-reciprocal Coulomb drag between Chern insulators","authors":"Yu Fu, Yu Huang, Qing Lin He","doi":"10.1038/s41467-025-58401-5","DOIUrl":"https://doi.org/10.1038/s41467-025-58401-5","url":null,"abstract":"Coulomb interaction between two closely spaced but electrically isolated conductors can induce a voltage in one of them upon feeding a current into the other. This effect has been widely studied in nonmagnetic strongly interacting systems and historically interpreted in terms of momentum and energy exchanges, which thus complies with Onsager’s reciprocity. Here we report the non-reciprocal Coulomb drag observed between two ferromagnetic Chern insulators that host quantum anomalous Hall effects. By measurements with current and circuit reversals, we discovered strong drag signals in both the longitudinal and transverse directions which violate Onsager’s reciprocity. These drag signals only emerge when the Chern insulator is in a multidomain state. Combined with the nonlinear (I-V) characteristics and power-law temperature dependence, this drag is attributed to the rectifications of mesoscopic fluctuations and quantum shot noise as well as the current cumulant. The drag signals are accompanied by strong magnetic fluctuations, highlighting the role played by magnetic dynamics. The present study expands the Coulomb drag to the realm of magnetic topological systems.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"59 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733912","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