综合性期刊最新文献

{"title":"Meeting metformin again for the first time.","authors":"Douglas R Green","doi":"10.1126/sciadv.adu7436","DOIUrl":"https://doi.org/10.1126/sciadv.adu7436","url":null,"abstract":"<p><p>New evidence convincingly shows that metformin, a drug that reduces circulating glucose, acts by inhibiting mitochondrial complex I.</p>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 51","pages":"eadu7436"},"PeriodicalIF":11.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855529","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":"Daily briefing: Explore 2024 with Leif Penguinson","authors":"","doi":"10.1038/d41586-024-04208-1","DOIUrl":"https://doi.org/10.1038/d41586-024-04208-1","url":null,"abstract":"Can you spot the penguin in every game this year?","PeriodicalId":18787,"journal":{"name":"Nature","volume":"265 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866985","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":"Approaching the standard quantum limit of a Rydberg-atom microwave electrometer","authors":"Hai-Tao Tu, Kai-Yu Liao, Hong-Lei Wang, Yi-Fei Zhu, Si-Yuan Qiu, Hao Jiang, Wei Huang, Wu Bian, Hui Yan, Shi-Liang Zhu","doi":"10.1126/sciadv.ads0683","DOIUrl":"https://doi.org/10.1126/sciadv.ads0683","url":null,"abstract":"The development of a microwave electrometer with inherent uncertainty approaching its ultimate limit carries both fundamental and technological significance. However, because of the thermal motion of atoms, the state-of-art Rydberg electrometer falls considerably short of the standard quantum limit by about three orders of magnitude. Here, we use an optically thin medium with approximately 5.2 × 10 <jats:sup>5</jats:sup> laser-cooled atoms to implement the microwave heterodyne detection. By mitigating various noises and strategically optimizing the electrometer parameters, our study reduces the equivalent noise temperature by a factor of 20 and achieves an electric field sensitivity of 10.0 nV cm <jats:sup>−1</jats:sup> Hz <jats:sup>−1/2</jats:sup> , lastly reaching a factor of 2.6 above the standard quantum limit. Our work also provides valuable insights into the inherent capabilities and limitations of Rydberg electrometers, offering superior sensitivity in detecting weak microwave signals for numerous applications.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"83 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867143","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":"RNA-dependent RNA polymerase of predominant human norovirus forms liquid-liquid phase condensates as viral replication factories","authors":"Soni Kaundal, Ramakrishnan Anish, B. Vijayalakshmi Ayyar, Sreejesh Shanker, Gundeep Kaur, Sue E. Crawford, Jeroen Pollet, Fabio Stossi, Mary K. Estes, B. V. Venkataram Prasad","doi":"10.1126/sciadv.adp9333","DOIUrl":"https://doi.org/10.1126/sciadv.adp9333","url":null,"abstract":"Many viral proteins form biomolecular condensates via liquid-liquid phase separation (LLPS) to support viral replication and evade host antiviral responses, and thus, they are potential targets for designing antivirals. In the case of nonenveloped positive-sense RNA viruses, forming such condensates for viral replication is unclear and less understood. Human noroviruses (HuNoVs) are positive-sense RNA viruses that cause epidemic and sporadic gastroenteritis worldwide. Here, we show that the RNA-dependent RNA polymerase (RdRp) of pandemic GII.4 HuNoV forms distinct condensates that exhibit all the signature properties of LLPS with sustained polymerase activity and the capability of recruiting components essential for viral replication. We show that such condensates are formed in HuNoV-infected human intestinal enteroid cultures and are the sites for genome replication. Our studies demonstrate the formation of phase-separated condensates as replication factories in a positive-sense RNA virus, which plausibly is an effective mechanism to dynamically isolate RdRp replicating the genomic RNA from interfering with the ribosomal translation of the same RNA.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"32 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867289","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":"Molecular basis for plasma membrane recruitment of PI4KA by EFR3","authors":"Sushant Suresh, Alexandria L. Shaw, Joshua G. Pemberton, Mackenzie K. Scott, Noah J. Harris, Matthew A. H. Parson, Meredith L. Jenkins, Pooja Rohilla, Alejandro Alvarez-Prats, Tamas Balla, Calvin K. Yip, John E. Burke","doi":"10.1126/sciadv.adp6660","DOIUrl":"https://doi.org/10.1126/sciadv.adp6660","url":null,"abstract":"The lipid kinase phosphatidylinositol 4 kinase III α (PI4KIIIα/PI4KA) is a master regulator of the lipid composition and asymmetry of the plasma membrane. PI4KA exists primarily in a heterotrimeric complex with its regulatory proteins TTC7 and FAM126. Fundamental to PI4KA activity is its targeted recruitment to the plasma membrane by the lipidated proteins EFR3A and EFR3B. Here, we report a cryogenic electron microscopy structure of the C terminus of EFR3A bound to the PI4KA-TTC7B-FAM126A complex, with extensive validation using both hydrogen deuterium exchange mass spectrometry, and mutational analysis. The EFR3A C terminus undergoes a disorder-order transition upon binding to the PI4KA complex, with an unexpected direct interaction with both TTC7B and FAM126A. Complex disrupting mutations in TTC7B, FAM126A, and EFR3 decrease PI4KA recruitment to the plasma membrane. Multiple posttranslational modifications and disease linked mutations map to this site, providing insight into how PI4KA membrane recruitment can be regulated and disrupted in human disease.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"15 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867295","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":"I create routes through trees to help stop howler monkeys being electrocuted by power lines","authors":"","doi":"10.1038/d41586-024-04170-y","DOIUrl":"https://doi.org/10.1038/d41586-024-04170-y","url":null,"abstract":"Inés Azofeifa Rojas monitors troop behaviour to maintain canopy connectivity.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"90 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857873","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 common immune response node in diverse plants.","authors":"Jeffery L Dangl, Jonathan D G Jones","doi":"10.1126/science.adu4930","DOIUrl":"https://doi.org/10.1126/science.adu4930","url":null,"abstract":"<p><p>Small molecules activate a defense mechanism shared by all flowering plants.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6728","pages":"1344-1346"},"PeriodicalIF":44.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865450","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 psychedelics improve well-being in autism?","authors":"Rachel Nuwer","doi":"10.1126/science.adv4102","DOIUrl":"https://doi.org/10.1126/science.adv4102","url":null,"abstract":"<p><p>A brace of new studies probes benefits and risks for an understudied group.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6728","pages":"1333"},"PeriodicalIF":44.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865484","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":"News at a glance.","authors":"","doi":"10.1126/science.adv4099","DOIUrl":"https://doi.org/10.1126/science.adv4099","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6728","pages":"1328-1329"},"PeriodicalIF":44.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865498","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":"Noncanonical role of ALAS1 as a heme-independent inhibitor of small RNA-mediated silencing.","authors":"Seungjae Lee, Sangmi Lee, Robert Desnick, Makiko Yasuda, Eric C Lai","doi":"10.1126/science.adp9388","DOIUrl":"https://doi.org/10.1126/science.adp9388","url":null,"abstract":"<p><p>microRNAs (miRNAs) and small interfering RNAs (siRNAs) are 21- to 22-nucleotide RNAs that guide Argonaute-class effectors to targets for repression. In this work, we uncover 5-aminolevulinic acid synthase 1 (ALAS1), the initiating enzyme for heme biosynthesis, as a general repressor of miRNA accumulation. Although heme is known to be a positive cofactor for the nuclear miRNA processing machinery, ALAS1-but not other heme biosynthesis enzymes-limits the assembly and activity of Argonaute complexes under heme-replete conditions. This involves a cytoplasmic role for ALAS1, previously considered inactive outside of mitochondria. Moreover, conditional depletion of ALAS activity from mouse hepatocytes increases miRNAs and enhances siRNA-mediated knockdown. Notably, because <i>ALAS1</i> is the target of a Food and Drug Administration-approved siRNA drug, agents that suppress ALAS may serve as adjuvants for siRNA therapies.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6728","pages":"1427-1434"},"PeriodicalIF":44.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865538","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}