Science最新文献

{"title":"Quantum effects in circuits honored with Physics Nobel.","authors":"Adrian Cho","doi":"10.1126/science.aec9016","DOIUrl":"https://doi.org/10.1126/science.aec9016","url":null,"abstract":"Breakthrough paved the way to many of today's budding quantum computers.","PeriodicalId":21678,"journal":{"name":"Science","volume":"40 1","pages":"113"},"PeriodicalIF":56.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254500","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 genome-to-proteome map reveals how natural variants drive proteome diversity and shape fitness","authors":"Christopher M. Jakobson,&nbsp;Johannes Hartl,&nbsp;Pauline Trébulle,&nbsp;Michael Mülleder,&nbsp;Daniel F. Jarosz,&nbsp;Markus Ralser","doi":"10.1126/science.adu3198","DOIUrl":"10.1126/science.adu3198","url":null,"abstract":"<div >Understanding how genetic variation translates into complex phenotypes remains a fundamental challenge. In this work, we address this by mapping genome-to-proteome relationships in 800 progeny of a cross between two yeast strains adapted to distinct environments. Despite the modest genetic distance between the parents, we observed notable proteomic diversity and mapped more than 6400 genotype-protein associations, with more than 1600 linked to individual genetic variants. Proteomic adaptation emerged from a conserved network of cis- and trans-regulatory variants, often originating from proteins not traditionally linked to gene regulation. This atlas allowed us to forecast organismal fitness effects across diverse conditions. By connecting genomic and proteomic landscapes at unprecedented resolution, our study provides a framework for predicting the phenotypic outcomes of natural genetic variation.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"390 6769","pages":""},"PeriodicalIF":45.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145248832","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":"Total solar eclipse triggers dawn behavior in birds: Insights from acoustic recordings and community science","authors":"Liz A. Aguilar,&nbsp;Isaac Miller-Crews,&nbsp;Jeremy M. Dobris,&nbsp;Jo Anne Tracy,&nbsp;Paul Macklin,&nbsp;Shantanu Dixit,&nbsp;Ryan A. Jacobson,&nbsp;Rachel L. Evans,&nbsp;Evan L. McGuire,&nbsp;Daniel P. Beverly,&nbsp;Dustin G. Reichard,&nbsp;Kimberly A. Rosvall","doi":"10.1126/science.adx3025","DOIUrl":"10.1126/science.adx3025","url":null,"abstract":"<div >On 8 April 2024, a total solar eclipse disrupted light-dark cycles for North American birds during the lead-up to spring reproduction. Compiling more than 10,000 community observations and artificial intelligence analyses of nearly 100,000 vocalizations, we found that bird behavior was substantially affected by these few minutes of unexpected afternoon darkness. More than half of wild bird species changed their biological rhythms, with many producing a dawn chorus in the aftermath of the eclipse. This natural experiment underscores the power of light in structuring animal behavior: Even when “night” lasts for just 4 minutes, robust behavioral changes ensue.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"390 6769","pages":""},"PeriodicalIF":45.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/science.adx3025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145248872","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":"A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging","authors":"Yu Chen,&nbsp;Zhixi Chen,&nbsp;Hao Wang,&nbsp;Zhen Cui,&nbsp;Kai-Le Li,&nbsp;Zhiwei Song,&nbsp;Lingjiang Chen,&nbsp;Xiaoxiang Sun,&nbsp;Xiaoyu Xu,&nbsp;Yixue Zhang,&nbsp;Li Tan,&nbsp;Jian Yuan,&nbsp;Rong Tan,&nbsp;Min-Hua Luo,&nbsp;Fang-Lin Sun,&nbsp;Haipeng Liu,&nbsp;Ying Jiang,&nbsp;Zhiyong Mao","doi":"10.1126/science.adp5056","DOIUrl":"10.1126/science.adp5056","url":null,"abstract":"<div >Efficient DNA repair might make possible the longevity of naked mole-rats. However, whether they have distinctive mechanisms to optimize functions of DNA repair suppressors is unclear. We find that naked mole-rat cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS) lacks the suppressive function of human or mouse homologs in homologous recombination repair through the alteration of four amino acids during evolution. The changes enable cGAS to retain chromatin longer upon DNA damage by weakening TRIM41-mediated ubiquitination and interaction with the segregase P97. Prolonged chromatin binding of cGAS enhanced the interaction between repair factors FANCI and RAD50 to facilitate RAD50 recruitment to damage sites, thereby potentiating homologous recombination repair. Moreover, the four amino acids mediate the function of cGAS in antagonizing cellular and tissue aging and extending life span. Manipulating cGAS might therefore constitute a mechanism for life-span extension.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"390 6769","pages":""},"PeriodicalIF":45.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145248890","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":"China’s emerging regulation toward an open future for AI","authors":"Yue Zhu,&nbsp;Bo He,&nbsp;Hongyu Fu,&nbsp;Naying Hu,&nbsp;Shaoqing Wu,&nbsp;Taolue Zhang,&nbsp;Xinyi Liu,&nbsp;Gang Xu,&nbsp;Linghan Zhang,&nbsp;Hui Zhou","doi":"10.1126/science.ady7922","DOIUrl":"10.1126/science.ady7922","url":null,"abstract":"<div >Open-source artificial intelligence (AI) systems from China are gaining momentum worldwide. In parallel to these technical advances, China’s AI regulation is also taking shape. But as this AI regulatory landscape is constantly evolving, already complicated, and awaiting more certainty, clarification, harmonization, and simplification are becoming more important than ever. An AI law that consolidates and improves existing laws, policies, and cases has the potential to be a solution. Although no official draft of such a law has been released in China yet, AI law experts in China have drafted two influential proposals, Model AI Law (v 3.0, with an article-by-article interpretation) and AI Law (Scholar’s Proposal), that have become important references for understanding and researching China’s AI regulation (<i>1</i>). We outline the current landscape, discuss both proposals, identify points for improvements of China’s AI regulation, and conclude with an outlook on the regulatory future and global implications.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"390 6769","pages":""},"PeriodicalIF":45.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145248893","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":"Mechanism of DNA targeting by human LINE-1","authors":"Wenxing Jin,&nbsp;Cong Yu,&nbsp;Yan Zhang,&nbsp;Changchang Cao,&nbsp;Tianfan Xia,&nbsp;Ge Song,&nbsp;Zhaokui Cai,&nbsp;Yuanchao Xue,&nbsp;Bing Zhu,&nbsp;Rui-Ming Xu","doi":"10.1126/science.adu3433","DOIUrl":"10.1126/science.adu3433","url":null,"abstract":"<div >Long interspersed nuclear element–1 (LINE-1 or L1), the only autonomously active retrotransposon in humans today, constitutes a large proportion of the genome and continues to evolve the genome and impact fundamental biological processes. L1 retrotransposition critically depends on its endonuclease and reverse transcriptase subunit open reading frame 2 protein (ORF2p), which targets genomic loci and nicks DNA using an evolutionarily distinct yet not fully understood mechanism. Our structural and biochemical analyses revealed that ORF2p is a structure-dependent endonuclease. It binds a double-stranded DNA region upstream of the nicking site and recognizes a downstream forked or flap structure for efficient DNA nicking. This discovery suggests that L1 mobilization piggybacks on chromosomal processes with noncanonical DNA structure intermediates.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"390 6769","pages":""},"PeriodicalIF":45.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145248831","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":"Constraining exoplanet interiors using observations of their atmospheres","authors":"Tim Lichtenberg,&nbsp;Oliver Shorttle,&nbsp;Johanna Teske,&nbsp;Eliza M.-R. Kempton","doi":"10.1126/science.ads3360","DOIUrl":"10.1126/science.ads3360","url":null,"abstract":"<div >Astronomical surveys have identified numerous exoplanets with bulk compositions that are unlike the planets of the Solar System, including rocky super-Earths and gas-enveloped sub-Neptunes. Observing the atmospheres of these objects provides information on the geological processes that influence their climates and surfaces. In this Review, we summarize the current understanding of these planets, including insights into the interaction between the atmosphere and interior based on observations made with the JWST. We describe the expected climatic and interior planetary regimes for planets with different density and stellar flux and how those regimes might be observationally distinguished. We also identify the observational, experimental, and theoretical innovations that will be required to characterize Earth-like exoplanets.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"390 6769","pages":""},"PeriodicalIF":45.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145248871","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":"MTAP deficiency confers resistance to cytosolic nucleic acid sensing and STING agonists","authors":"Jung-Mao Hsu,&nbsp;Chunxiao Liu,&nbsp;Weiya Xia,&nbsp;Chung-Yu Chen,&nbsp;Wei-Chung Cheng,&nbsp;Junwei Hou,&nbsp;Mien-Chie Hung","doi":"10.1126/science.adl4089","DOIUrl":"10.1126/science.adl4089","url":null,"abstract":"<div >Cytosolic nucleic acid–sensing pathways are potential targets for cancer immunotherapy. Although stimulator of interferon genes (STING) agonists have shown substantial antitumor effects in animal models, their clinical efficacy in human tumors remains unclear. Deletion of methylthioadenosine phosphorylase (MTAP) is a common genomic alteration in human tumors but is rare in preclinical syngeneic mouse models. We found that homozygous <i>MTAP</i> deletion in human tumors creates a tumor microenvironment that obstructs cytosolic nucleic acid–sensing pathways by down-regulating interferon regulatory factor 3 (IRF3), leading to resistance to STING agonists. Targeting polyamine biosynthesis reverses IRF3 down-regulation, restoring sensitivity to STING agonists in MTAP-deficient tumors. Our findings suggest that MTAP genetic status may inform patient responses to STING agonist therapy and offer an alternative strategy for boosting antitumor immune responses using STING agonists in <i>MTAP</i>-deleted tumors.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"390 6769","pages":""},"PeriodicalIF":45.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145248874","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":"Can COP30 put investment in research at the heart of adaptation?","authors":"Ismahane Elouafi","doi":"10.1126/science.aeb7893","DOIUrl":"10.1126/science.aeb7893","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"390 6769","pages":""},"PeriodicalIF":45.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145248881","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":"Covalent inhibitors of the PI3Kα RAS binding domain impair tumor growth driven by RAS and HER2","authors":"Joseph E. Klebba, Nilotpal Roy, Steffen M. Bernard, Stephanie Grabow, Melissa A. Hoffman, Hui Miao, Junko Tamiya, Jinwei Wang, Cynthia Berry, Antonio Esparza-Oros, Richard Lin, Yongsheng Liu, Marie Pariollaud, Holly Parker, Igor Mochalkin, Sareena Rana, Aaron N. Snead, Eric J. Walton, Taylor E. Wyrick, Erick Aitchison, Karl Bedke, Jacyln C. Brannon, Joel M. Chick, Kenneth Hee, Benjamin D. Horning, Mohamed Ismail, Kelsey N. Lamb, Wei Lin, Justine Metzger, Martha K. Pastuszka, Jonathan Pollock, John J. Sigler, Mona Tomaschko, Eileen Tran, Chanyu Yue, Todd M. Kinsella, Miriam Molina-Arcas, Brian N. Cook, Gabriel M. Simon, David S. Weinstein, Julian Downward, Matthew P. Patricelli","doi":"10.1126/science.adv2684","DOIUrl":"https://doi.org/10.1126/science.adv2684","url":null,"abstract":"Genetic disruption of the RAS binding domain (RBD) of Phosphoinositide 3-kinase alpha(PI3Kα) impairs the growth of tumors driven by the small guanosine triphosphatase RAS in mice and does not impact PI3Kα’s role in insulin mediated control of glucose homeostasis. Selectively blocking the RAS-PI3Kα interaction may represent a strategy for treating RAS-dependent cancers as it would avoid the toxicity associated with inhibitors of PI3Kα lipid kinase activity. We developed compounds that bind covalently to cysteine 242 in the RBD of PI3K p110α and block RAS activation of PI3Kα activity. In mice, inhibitors slow the growth of RAS mutant tumors and Human Epidermal Growth Factor Receptor 2 (HER2) overexpressing tumors, particularly when combined with other inhibitors of the RAS/Mitogen-activated protein kinase pathway, without causing hyperglycemia. Oncogenic mutations in the small guanosine triphosphatase RAS occur in 20% of human cancers, with RAS proteins activating both the mitogen-activated protein kinase (MAPK) and Phosphoinositide 3-kinase (PI3K) pathways ( <jats:xref ref-type=\"bibr\"> <jats:italic toggle=\"yes\">1</jats:italic> </jats:xref> – <jats:xref ref-type=\"bibr\"> <jats:italic toggle=\"yes\">3</jats:italic> </jats:xref> ). As each of these pathways has oncogenic potential, simultaneous activation, as occurs in mutant RAS driven cancers, generates aggressive disease. In RAS-driven cell and animal models, inhibition of both the MAPK and PI3K pathways is more efficacious than targeting the individual pathways ( <jats:xref ref-type=\"bibr\"> <jats:italic toggle=\"yes\">4</jats:italic> </jats:xref> ); however, dose-limiting toxicities in humans prevent clinical success of this strategy. Although physiological activation of the MAPK pathway is RAS-dependent, the interaction between RAS and the catalytic subunit of PI3Kα, p110α, serves as an amplifier but not a primary activator of this pathway, and is less important in normal cellular regulation than it is in cancer ( <jats:xref ref-type=\"bibr\"> <jats:italic toggle=\"yes\">5</jats:italic> </jats:xref> ).","PeriodicalId":21678,"journal":{"name":"Science","volume":"32 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255561","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}