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Noncanonical role of ALAS1 as a heme-independent inhibitor of small RNA-mediated silencing.
IF 44.7 1区 综合性期刊
Science Pub Date : 2024-12-20 Epub Date: 2024-12-19 DOI: 10.1126/science.adp9388
Seungjae Lee, Sangmi Lee, Robert Desnick, Makiko Yasuda, Eric C Lai
{"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}
引用次数: 0
Aged neurons don't register energy need.
IF 44.7 1区 综合性期刊
Science Pub Date : 2024-12-20 Epub Date: 2024-12-19 DOI: 10.1126/science.adu4935
Deniz Bingul, Scott F Owen
{"title":"Aged neurons don't register energy need.","authors":"Deniz Bingul, Scott F Owen","doi":"10.1126/science.adu4935","DOIUrl":"https://doi.org/10.1126/science.adu4935","url":null,"abstract":"<p><p>Neuronal activity and mitochondrial gene expression become decoupled in aged mice.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6728","pages":"1349-1350"},"PeriodicalIF":44.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865471","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
FDA should consider drug-therapy regimens.
IF 44.7 1区 综合性期刊
Science Pub Date : 2024-12-20 Epub Date: 2024-12-19 DOI: 10.1126/science.adt1480
Eero Castrén, Claus Normann
{"title":"FDA should consider drug-therapy regimens.","authors":"Eero Castrén, Claus Normann","doi":"10.1126/science.adt1480","DOIUrl":"https://doi.org/10.1126/science.adt1480","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6728","pages":"1356-1357"},"PeriodicalIF":44.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865447","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
Biocatalytic C-H oxidation meets radical cross-coupling: Simplifying complex piperidine synthesis.
IF 44.7 1区 综合性期刊
Science Pub Date : 2024-12-20 Epub Date: 2024-12-19 DOI: 10.1126/science.adr9368
Jiayan He, Kenta Yokoi, Breanna Wixted, Benxiang Zhang, Yu Kawamata, Hans Renata, Phil S Baran
{"title":"Biocatalytic C-H oxidation meets radical cross-coupling: Simplifying complex piperidine synthesis.","authors":"Jiayan He, Kenta Yokoi, Breanna Wixted, Benxiang Zhang, Yu Kawamata, Hans Renata, Phil S Baran","doi":"10.1126/science.adr9368","DOIUrl":"https://doi.org/10.1126/science.adr9368","url":null,"abstract":"<p><p>Modern medicinal chemists are targeting more complex molecules to address challenging biological targets, which leads to synthesizing structures with higher sp<sup>3</sup> character (Fsp<sup>3</sup>) to enhance specificity as well as physiochemical properties. Although traditional flat, high-fraction sp<sup>2</sup> molecules, such as pyridine, can be decorated through electrophilic aromatic substitution and palladium (Pd)-based cross-couplings, general strategies to derivatize three-dimensional (3D) saturated molecules are far less developed. In this work, we present an approach for the rapid, modular, enantiospecific, and diastereoselective functionalization of piperidine (saturated analog of pyridine), combining robust biocatalytic carbon-hydrogen oxidation with radical cross-coupling. This combination is directly analogous to electrophilic aromatic substitution followed by Pd-couplings for flat molecules, streamlining synthesis of 3D molecules. This study offers a generalizable strategy for accessing complex architectures, appealing to both medicinal and process chemists.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6728","pages":"1421-1427"},"PeriodicalIF":44.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865477","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
Hydrogenotrophic methanogens overwrite isotope signals of subsurface methane.
IF 44.7 1区 综合性期刊
Science Pub Date : 2024-12-20 Epub Date: 2024-12-19 DOI: 10.1126/science.ado0126
Daisuke Mayumi, Hideyuki Tamaki, Souichiro Kato, Kensuke Igarashi, Ellen Lalk, Yasunori Nishikawa, Hideki Minagawa, Tomoyuki Sato, Shuhei Ono, Yoichi Kamagata, Susumu Sakata
{"title":"Hydrogenotrophic methanogens overwrite isotope signals of subsurface methane.","authors":"Daisuke Mayumi, Hideyuki Tamaki, Souichiro Kato, Kensuke Igarashi, Ellen Lalk, Yasunori Nishikawa, Hideki Minagawa, Tomoyuki Sato, Shuhei Ono, Yoichi Kamagata, Susumu Sakata","doi":"10.1126/science.ado0126","DOIUrl":"https://doi.org/10.1126/science.ado0126","url":null,"abstract":"<p><p>Methane, a greenhouse gas and energy source, is commonly studied using stable isotope signals as proxies for its formation processes. In subsurface environments, methane often exhibits equilibrium isotopic signals, but the equilibration process has never been demonstrated in the laboratory. We cocultured a hydrogenotrophic methanogen with an H<sub>2</sub>-producing bacterium under conditions (55°C, 10 megapascals) simulating a methane-bearing subsurface. This resulted in near-complete reversibility of methanogenesis, leading to equilibria for both hydrogen and carbon isotopes. The methanogen not only equilibrated kinetic isotope signals of initially produced methane but also modified the isotope signals of amended thermogenic methane. These findings suggest that hydrogenotrophic methanogenesis can overwrite the isotope signals of subsurface methane, distorting proxies for its origin and formation temperature-insights crucial for natural gas exploration.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6728","pages":"1372-1376"},"PeriodicalIF":44.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865488","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
Tolerance on trial.
IF 44.7 1区 综合性期刊
Science Pub Date : 2024-12-20 Epub Date: 2024-12-19 DOI: 10.1126/science.adv2874
H Holden Thorp
{"title":"Tolerance on trial.","authors":"H Holden Thorp","doi":"10.1126/science.adv2874","DOIUrl":"https://doi.org/10.1126/science.adv2874","url":null,"abstract":"<p><p>Next year will mark the 100th anniversary of the Scopes trial, a 1925 court case in the US state of Tennessee on the teaching of evolution in public schools. John Scopes was tried for violating the Butler Act, a state rule that declared unlawful any teaching that denied the creation of man according to the Bible. The highly publicized event put an intense spotlight on William Jennings Bryan, a populist presidential candidate and religious fundamentalist who was counsel for the government, and on Clarence Darrow, a liberal agnostic and social justice advocate who defended Scopes. Scopes was found guilty, a verdict that was later overturned on a technicality. The trial was one of the first to be dubbed the \"trial of the century\" and has since been discussed, taught, and reflected on in books, plays, and movies (most notably, it was fictionalized in <i>Inherit the Wind</i>). A century later, the politics and sociology of that moment are still relevant, with implications for tolerance in today's world.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6728","pages":"1325"},"PeriodicalIF":44.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865507","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
Platform influencers-host RNA control of antiviral immunity.
IF 44.7 1区 综合性期刊
Science Pub Date : 2024-12-20 Epub Date: 2024-12-19 DOI: 10.1126/science.adu4928
Sonja M Best, Adam Hage
{"title":"Platform influencers-host RNA control of antiviral immunity.","authors":"Sonja M Best, Adam Hage","doi":"10.1126/science.adu4928","DOIUrl":"https://doi.org/10.1126/science.adu4928","url":null,"abstract":"<p><p>Cellular RNAs directly regulate the activity of an antiviral immune signaling complex.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6728","pages":"1346-1347"},"PeriodicalIF":44.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865542","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
Quantum collective motion of macroscopic mechanical oscillators.
IF 44.7 1区 综合性期刊
Science Pub Date : 2024-12-20 Epub Date: 2024-12-19 DOI: 10.1126/science.adr8187
Mahdi Chegnizadeh, Marco Scigliuzzo, Amir Youssefi, Shingo Kono, Evgenii Guzovskii, Tobias J Kippenberg
{"title":"Quantum collective motion of macroscopic mechanical oscillators.","authors":"Mahdi Chegnizadeh, Marco Scigliuzzo, Amir Youssefi, Shingo Kono, Evgenii Guzovskii, Tobias J Kippenberg","doi":"10.1126/science.adr8187","DOIUrl":"https://doi.org/10.1126/science.adr8187","url":null,"abstract":"<p><p>Collective phenomena arise from interactions within complex systems, leading to behaviors absent in individual components. Observing quantum collective phenomena with macroscopic mechanical oscillators has been impeded by the stringent requirement that oscillators be identical. We demonstrate the quantum regime for collective motion of <i>N</i> = 6 mechanical oscillators, a hexamer, in a superconducting circuit optomechanical platform. By increasing the optomechanical couplings, the system transitions from individual to collective motion, characterized by a [Formula: see text] enhancement of cavity-collective mode coupling, akin to superradiance of atomic ensembles. Using sideband cooling, we prepare the collective mode in the quantum ground state and measure its quantum sideband asymmetry, with zero-point motion distributed across distant oscillators. This regime of optomechanics opens avenues for studying multipartite entanglement, with potential advances in quantum metrology.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6728","pages":"1383-1388"},"PeriodicalIF":44.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865563","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
Red tape strangles viral surveillance programs.
IF 44.7 1区 综合性期刊
Science Pub Date : 2024-12-20 Epub Date: 2024-12-19 DOI: 10.1126/science.ads3461
Al Ozonoff, Annie Elong Ngono, Robert Frederick
{"title":"Red tape strangles viral surveillance programs.","authors":"Al Ozonoff, Annie Elong Ngono, Robert Frederick","doi":"10.1126/science.ads3461","DOIUrl":"https://doi.org/10.1126/science.ads3461","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6728","pages":"1357"},"PeriodicalIF":44.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865576","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
Climate scientists gird for Trump administration.
IF 44.7 1区 综合性期刊
Science Pub Date : 2024-12-20 Epub Date: 2024-12-19 DOI: 10.1126/science.adv4100
Paul Voosen
{"title":"Climate scientists gird for Trump administration.","authors":"Paul Voosen","doi":"10.1126/science.adv4100","DOIUrl":"https://doi.org/10.1126/science.adv4100","url":null,"abstract":"<p><p>Trump agents have vowed to squash research and fire adversaries.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6728","pages":"1330-1331"},"PeriodicalIF":44.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865397","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
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