综合性期刊最新文献

{"title":"Procollagen IIA mediates positive feedback control of the mouse cardiogenic transcriptional network.","authors":"Alan W Leung,Sandra Y Wong,Janet C Zhang,Keith K H Leung,Nelson W F Dung,Catherine A Shang,Owen W Prall,Hieu T Nim,Michael See,Mirana Ramialison,Danny Chan,Timothy J Mohun,Richard P Harvey,Patrick P L Tam,Kathryn S E Cheah","doi":"10.1073/pnas.2422592122","DOIUrl":"https://doi.org/10.1073/pnas.2422592122","url":null,"abstract":"Cardiogenesis relies on the integrated interplay between cardiac transcription factors and signaling pathways. Here, we uncover a role for type IIA procollagen (IIA), an extracellular matrix (ECM) protein encoded by an alternatively spliced Col2a1 transcript, encoding a N-terminal cysteine-rich domain, as a critical regulator in a cardiac gene regulatory feedback loop. The cysteine-rich domain of IIA protein was previously reported to interact with bone morphogenetic proteins (BMPs) and transforming growth factors-beta (TGFβ) in in vitro binding assays and acts as a BMP antagonist in amphibian embryo assays. We show that the Col2a1 gene in mice is activated in the developing heart by core cardiogenic factors (NKX2-5, GATA4, MEF2, and SRF) via cis-regulatory enhancer elements. IIA loss (ΔIIA) in mice results in depletion of Isl1- and Nkx2-5-expressing progenitors, causing outflow tract defects resembling disrupted BMP/TGFβ-SMAD signaling, alongside reduced nuclear pSMAD1/5/8 in cardiac tissues. Compound +/ΔIIA; Smad4+/- mutants exhibit aggravated malformations. IIA enhances BMP-responsive reporter activity in cells in transactivation assays. We propose that IIA supports a positive functional role on SMAD4-dependent signaling, fine-tuning BMP/TGFβ signaling, thereby regulating GATA4 and NKX2-5 activity during second heart field progenitor specification. These findings position IIA procollagen as a key ECM component that integrates BMP/TGFβ signaling with cardiac transcription factors such as NKX2-5, revealing a feedback loop essential for cardiogenesis. Given its role in cardiac development, IIA emerges as a potential congenital heart disease risk factor.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"19 1","pages":"e2422592122"},"PeriodicalIF":11.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960188","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":"Inverse stable isotope probing-metabolomics (InverSIP) identifies an iron acquisition system in a methane-oxidizing bacterial community.","authors":"Jose Miguel D Robes,Tashi C E Liebergesell,Delaney G Beals,Xinhui Yu,William J Brazelton,Aaron W Puri","doi":"10.1073/pnas.2507323122","DOIUrl":"https://doi.org/10.1073/pnas.2507323122","url":null,"abstract":"Methane is a potent greenhouse gas and a target for near-term climate change mitigation. In many natural ecosystems, methane is sequestered by microbial communities, yet little is known about how constituents of methane-oxidizing communities interact with each other and their environment. This lack of mechanistic understanding is a common issue for many important microbial communities, but it is difficult to draw links between available sequencing information and the metabolites that govern community interactions. Here, we develop and apply a technique called inverse stable isotope probing-metabolomics (InverSIP) to bridge the gap between metagenomic and metabolomic information and functionally characterize interactions in a complex methane-oxidizing community. Using InverSIP, we link a highly transcribed biosynthetic gene cluster in the community with its secondary metabolite product: methylocystabactin, a triscatecholate siderophore not previously observed in nature. We find that production of methylocystabactin is widespread among methanotrophic alphaproteobacteria and that it can be used by another methanotroph in the community that does not produce this siderophore itself. Functional assays reveal that methylocystabactin supports methanotroph growth and the activity of the methane-oxidizing enzyme soluble methane monooxygenase under conditions where bioavailable iron is limited, establishing an important molecular link between methane-oxidation and the insoluble iron found in many natural environments. These findings contribute to a molecular-level understanding of these environmentally important bacterial communities and establish InverSIP as a broadly applicable genomics-guided strategy for characterizing metabolites in microbial ecosystems.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"36 1","pages":"e2507323122"},"PeriodicalIF":11.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960189","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":"Correction for Ninomiya and Isoda, Dynamic spatial representation of self and others' actions in the macaque frontal cortex.","authors":"","doi":"10.1073/pnas.2522320122","DOIUrl":"https://doi.org/10.1073/pnas.2522320122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 1","pages":"e2522320122"},"PeriodicalIF":11.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960190","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":"Analog optical computer for AI inference and combinatorial optimization","authors":"Kirill P. Kalinin, Jannes Gladrow, Jiaqi Chu, James H. Clegg, Daniel Cletheroe, Douglas J. Kelly, Babak Rahmani, Grace Brennan, Burcu Canakci, Fabian Falck, Michael Hansen, Jim Kleewein, Heiner Kremer, Greg O’Shea, Lucinda Pickup, Saravan Rajmohan, Ant Rowstron, Victor Ruhle, Lee Braine, Shrirang Khedekar, Natalia G. Berloff, Christos Gkantsidis, Francesca Parmigiani, Hitesh Ballani","doi":"10.1038/s41586-025-09430-z","DOIUrl":"https://doi.org/10.1038/s41586-025-09430-z","url":null,"abstract":"<p>Artificial intelligence (AI) and combinatorial optimization drive applications across science and industry, but their increasing energy demands challenge the sustainability of digital computing. Most unconventional computing systems^{1,2,3,4,5,6,7} target either AI or optimization workloads and rely on frequent, energy-intensive digital conversions, limiting efficiency. These systems also face application-hardware mismatches, whether handling memory-bottlenecked neural models, mapping real-world optimization problems or contending with inherent analog noise. Here we introduce an analog optical computer (AOC) that combines analog electronics and three-dimensional optics to accelerate AI inference and combinatorial optimization in a single platform. This dual-domain capability is enabled by a rapid fixed-point search, which avoids digital conversions and enhances noise robustness. With this fixed-point abstraction, the AOC implements emerging compute-bound neural models with recursive reasoning potential and realizes an advanced gradient-descent approach for expressive optimization. We demonstrate the benefits of co-designing the hardware and abstraction, echoing the co-evolution of digital accelerators and deep learning models, through four case studies: image classification, nonlinear regression, medical image reconstruction and financial transaction settlement. Built with scalable, consumer-grade technologies, the AOC paves a promising path for faster and sustainable computing. Its native support for iterative, compute-intensive models offers a scalable analog platform for fostering future innovation in AI and optimization.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"52 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930446","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":"Single-cell transcriptomic and genomic changes in the ageing human brain","authors":"Ailsa M. Jeffries, Tianxiong Yu, Jennifer S. Ziegenfuss, Allie K. Tolles, Christina E. Baer, Cesar Bautista Sotelo, Yerin Kim, Zhiping Weng, Michael A. Lodato","doi":"10.1038/s41586-025-09435-8","DOIUrl":"https://doi.org/10.1038/s41586-025-09435-8","url":null,"abstract":"<p>Over time, cells in the brain and in the body accumulate damage, which contributes to the ageing process¹. In the human brain, the prefrontal cortex undergoes age-related changes that can affect cognitive functioning later in life². Here, using single-nucleus RNA sequencing (snRNA-seq), single-cell whole-genome sequencing (scWGS) and spatial transcriptomics, we identify gene-expression and genomic changes in the human prefrontal cortex across lifespan, from infancy to centenarian. snRNA-seq identified infant-specific cell clusters enriched for the expression of neurodevelopmental genes, as well as an age-associated common downregulation of cell-essential homeostatic genes that function in ribosomes, transport and metabolism across cell types. Conversely, the expression of neuron-specific genes generally remains stable throughout life. These findings were validated with spatial transcriptomics. scWGS identified two age-associated mutational signatures that correlate with gene transcription and gene repression, respectively, and revealed gene length- and expression-level-dependent rates of somatic mutation in neurons that correlate with the transcriptomic landscape of the aged human brain. Our results provide insight into crucial aspects of human brain development and ageing, and shed light on transcriptomic and genomic dynamics.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"27 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930448","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":"Infrastructure deficits and informal settlements in sub-Saharan Africa.","authors":"Luís M A Bettencourt,Nicholas Marchio","doi":"10.1038/s41586-025-09465-2","DOIUrl":"https://doi.org/10.1038/s41586-025-09465-2","url":null,"abstract":"Sustainable development is an imperative worldwide1-3 but metrics and data on poverty and quality of life have remained too coarse and abstract to characterize challenges adequately and guide practical progress4,5. Nowhere is this challenge greater than in Africa4-6, where we still know little about the spatial details of development3,7-9. Here we leverage a comprehensive, high-precision dataset of building footprints to identify infrastructure deficits and infer informal settlements down to the street block level10-12 everywhere in sub-Saharan Africa. We identify a general pattern of informality with cities showing, on average, greater access to infrastructure and services than rural and peri-urban areas. We show that such patterns of informality are characterized by consistent statistical distributions reflecting uneven local development2,13,14. We also show that these physical measures of informality are systematically associated with many indicators of human deprivation, which form a single principal component co-varying predictably with specific changes in street access to buildings. These results demonstrate that the localization of sustainable development is possible down to the street level at a continental scale and provide a general distributed strategy for accelerating progress in infrastructure and service expansion that taps local innovations in systematic, equitable and context-appropriate ways7,11,12,15.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"20 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960136","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":"Ancient DNA clarifies the early history of the Slavs.","authors":"Steffen Patzold","doi":"10.1038/d41586-025-02525-7","DOIUrl":"https://doi.org/10.1038/d41586-025-02525-7","url":null,"abstract":"","PeriodicalId":18787,"journal":{"name":"Nature","volume":"61 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960184","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":"Marsquakes indicate that the inner core of the red planet is solid, not liquid","authors":"Nicholas C. Schmerr","doi":"10.1038/d41586-025-02530-w","DOIUrl":"10.1038/d41586-025-02530-w","url":null,"abstract":"An analysis of seismic waves propagating through Mars finds evidence that the planet has a small, solid inner core, which challenges existing planetary models. An analysis of seismic waves propagating through Mars finds evidence that the planet has a small, solid inner core, which challenges existing planetary models.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"645 8079","pages":"50-52"},"PeriodicalIF":48.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935513","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":"An ancient and essential miRNA family controls cellular interaction pathways in C. elegans","authors":"Emilio M. Santillan,&nbsp;Eric D. Cormack,&nbsp;Jingkui Wang,&nbsp;Micaela Rodriguez-Steube,&nbsp;Luisa Cochella","doi":"10.1126/sciadv.adz1934","DOIUrl":"10.1126/sciadv.adz1934","url":null,"abstract":"<div >The transition from unicellular to multicellular life required the acquisition of coordinated and regulated cellular behaviors, including adhesion and migration. In metazoans, this involves adhesion proteins, signaling systems, and an elaborate extracellular matrix (ECM) that contributes to adhesion and signaling interactions. Innovations that enabled complex multicellularity occurred through new genes in these pathways, novel functions for existing genes, and regulatory changes. Gene regulation by microRNAs (miRNAs) expanded with multicellularity. A single miRNA, miR-100, arose in the last common eumetazoan ancestor and is widely conserved across animals. We reveal the molecular function of its <i>C. elegans</i> homolog, the miR-51 family. This family acts in a dose-dependent manner to control morphogenesis by regulating several genes involved in cell signaling, adhesion, and migration, including ECM modifiers—specifically heparan sulfate sulfotransferases (HSTs). Some of these targets are also predicted to be conserved targets across vertebrates. Our work suggests that this miRNA provided an innovation in the regulation of cellular interactions early in metazoan evolution.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 36","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adz1934","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COSINE-100 full dataset challenges the annual modulation signal of DAMA/LIBRA","authors":"Nelson Carlin,&nbsp;Jae Young Cho,&nbsp;Jae Jin Choi,&nbsp;Seonho Choi,&nbsp;Anthony C. Ezeribe,&nbsp;Luis Eduardo França,&nbsp;Chang Hyon Ha,&nbsp;In Sik Hahn,&nbsp;Sophia J. Hollick,&nbsp;Eunju Jeon,&nbsp;Han Wool Joo,&nbsp;Woon Gu Kang,&nbsp;Matthew Kauer,&nbsp;Bongho Kim,&nbsp;Hongjoo Kim,&nbsp;Jinyoung Kim,&nbsp;Kyungwon Kim,&nbsp;SungHyun Kim,&nbsp;Sun Kee Kim,&nbsp;Won Kyung Kim,&nbsp;Yeongduk Kim,&nbsp;Yong-Hamb Kim,&nbsp;Young Ju Ko,&nbsp;Doohyeok Lee,&nbsp;Eun Kyung Lee,&nbsp;Hyunseok Lee,&nbsp;Hyun Su Lee,&nbsp;Hye Young Lee,&nbsp;In Soo Lee,&nbsp;Jaison Lee,&nbsp;Jooyoung Lee,&nbsp;Moo Hyun Lee,&nbsp;Seo Hyun Lee,&nbsp;Seung Mok Lee,&nbsp;Yujin Lee,&nbsp;Douglas S. Leonard,&nbsp;Nguyen Thanh Luan,&nbsp;Vitor Hugo de Almeida Machado,&nbsp;Bruno B. Manzato,&nbsp;Reina H. Maruyama,&nbsp;Robert J. Neal,&nbsp;Stephen L. Olsen,&nbsp;Byung Ju Park,&nbsp;Hyang Kyu Park,&nbsp;Hyeonseo Park,&nbsp;Jong-Chul Park,&nbsp;Kangsoon Park,&nbsp;Se Dong Park,&nbsp;Ricardo L. C. Pitta,&nbsp;Hafizh Prihtiadi,&nbsp;Sejin Ra,&nbsp;Carsten Rott,&nbsp;Keon Ah Shin,&nbsp;David F. F. S. Cavalcante,&nbsp;Min Ki Son,&nbsp;Neil J. C. Spooner,&nbsp;Lam Tan Truc,&nbsp;Liang Yang,&nbsp;Gyun Ho Yu","doi":"10.1126/sciadv.adv6503","DOIUrl":"10.1126/sciadv.adv6503","url":null,"abstract":"<div >For over 25 years, the DAMA/LIBRA collaboration has claimed to observe an annual modulation signal, suggesting the existence of dark matter interactions. However, no experiment using different target materials has observed a dark matter signal consistent with their result. To address this puzzle, the COSINE-100 collaboration conducted a model-independent test using sodium iodide crystal detectors, the same target material as DAMA/LIBRA. Analyzing data collected over 6.4 years by the effective mass of 61.3 kilograms, with improved energy calibration and time-dependent background modeling, we found no evidence of an annual modulation signal, challenging the DAMA/LIBRA result with a confidence level greater than 3σ. This finding represents a substantial step toward resolving the long-standing debate surrounding DAMA/LIBRA’s dark matter claim, indicating that the observed modulation is unlikely to be caused by dark matter interactions.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 36","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adv6503","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}