Nature最新文献

{"title":"AI tool diagnoses diabetes, HIV and COVID from a blood sample","authors":"","doi":"10.1038/d41586-025-00528-y","DOIUrl":"https://doi.org/10.1038/d41586-025-00528-y","url":null,"abstract":"‘One-shot’ approach that uses machine learning to screen immune cells could help to detect conditions with overlapping symptoms.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"40 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462217","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":"Snapshots of acyl carrier protein shuttling in human fatty acid synthase","authors":"Kollin Schultz, Pedro Costa-Pinheiro, Lauren Gardner, Laura V. Pinheiro, Julio Ramirez-Solis, Sarah M. Gardner, Kathryn E. Wellen, Ronen Marmorstein","doi":"10.1038/s41586-025-08587-x","DOIUrl":"https://doi.org/10.1038/s41586-025-08587-x","url":null,"abstract":"<p>The mammalian fatty acid synthase (FASN) enzyme is a dynamic multienzyme that belongs to the megasynthase family. In mammals, a single gene encodes six catalytically active domains and a flexibly tethered acyl carrier protein (ACP) domain that shuttles intermediates between active sites for fatty acid biosynthesis¹. FASN is an essential enzyme in mammalian development through the role that fatty acids have in membrane formation, energy storage, cell signalling and protein modifications. Thus, FASN is a promising target for treatment of a large variety of diseases including cancer, metabolic dysfunction-associated fatty liver disease, and viral and parasite infections^2,3. The multi-faceted mechanism of FASN and the dynamic nature of the protein, in particular of the ACP, have made it challenging to understand at the molecular level. Here we report cryo-electron microscopy structures of human FASN in a multitude of conformational states with NADPH and NADP⁺ plus acetoacetyl-CoA present, including structures with the ACP stalled at the dehydratase (DH) and enoyl-reductase (ER) domains. We show that FASN activity in vitro and de novo lipogenesis in cells is inhibited by mutations at the ACP–DH and ACP–ER interfaces. Together, these studies provide new molecular insights into the dynamic nature of FASN and the ACP shuttling mechanism, with implications for developing improved FASN-targeted therapeutics.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"50 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462153","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":"How leading a postdoc network boosted my career prospects","authors":"","doi":"10.1038/d41586-025-00207-y","DOIUrl":"https://doi.org/10.1038/d41586-025-00207-y","url":null,"abstract":"Tracy Wietecha says the experience swallowed up evenings and weekends, but taught her budgeting, networking and conflict-management skills.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"35 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462211","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":"Author Correction: The genetic origin of the Indo-Europeans","authors":"Iosif Lazaridis, Nick Patterson, David Anthony, Leonid Vyazov, Romain Fournier, Harald Ringbauer, Iñigo Olalde, Alexander A. Khokhlov, Egor P. Kitov, Natalia I. Shishlina, Sorin C. Ailincăi, Danila S. Agapov, Sergey A. Agapov, Elena Batieva, Baitanayev Bauyrzhan, Zsolt Bereczki, Alexandra Buzhilova, Piya Changmai, Andrey A. Chizhevsky, Ion Ciobanu, Mihai Constantinescu, Marietta Csányi, János Dani, Peter K. Dashkovskiy, Sándor Évinger, Anatoly Faifert, Pavel Flegontov, Alin Frînculeasa, Mădălina N. Frînculeasa, Tamás Hajdu, Tom Higham, Paweł Jarosz, Pavol Jelínek, Valeri I. Khartanovich, Eduard N. Kirginekov, Viktória Kiss, Alexandera Kitova, Alexeiy V. Kiyashko, Jovan Koledin, Arkady Korolev, Pavel Kosintsev, Gabriella Kulcsár, Pavel Kuznetsov, Rabadan Magomedov, Aslan M. Mamedov, Eszter Melis, Vyacheslav Moiseyev, Erika Molnár, Janet Monge, Octav Negrea, Nadezhda A. Nikolaeva, Mario Novak, Maria Ochir-Goryaeva, György Pálfi, Sergiu Popovici, Marina P. Rykun, Tatyana M. Savenkova, Vladimir P. Semibratov, Nikolai N. Seregin, Alena Šefčáková, Raikhan S. Mussayeva, Irina Shingiray, Vladimir N. Shirokov, Angela Simalcsik, Kendra Sirak, Konstantin N. Solodovnikov, Judit Tárnoki, Alexey A. Tishkin, Viktor Trifonov, Sergey Vasilyev, Ali Akbari, Esther S. Brielle, Kim Callan, Francesca Candilio, Olivia Cheronet, Elizabeth Curtis, Olga Flegontova, Lora Iliev, Aisling Kearns, Denise Keating, Ann Marie Lawson, Matthew Mah, Adam Micco, Megan Michel, Jonas Oppenheimer, Lijun Qiu, J. Noah Workman, Fatma Zalzala, Anna Szécsényi-Nagy, Pier Francesco Palamara, Swapan Mallick, Nadin Rohland, Ron Pinhasi, David Reich","doi":"10.1038/s41586-025-08789-3","DOIUrl":"https://doi.org/10.1038/s41586-025-08789-3","url":null,"abstract":"<p>Correction to: <i>Nature</i> https://doi.org/10.1038/s41586-024-08531-5 Published online 5 February 2025</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"14 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462139","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":"Rare genetic disorder treated in womb for the first time","authors":"","doi":"10.1038/d41586-025-00534-0","DOIUrl":"https://doi.org/10.1038/d41586-025-00534-0","url":null,"abstract":"The child, who is now almost three years old, shows no signs of the often fatal motor neuron disease.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"130 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452261","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: First in-womb treatment for motor-neuron condition is a success","authors":"","doi":"10.1038/d41586-025-00556-8","DOIUrl":"https://doi.org/10.1038/d41586-025-00556-8","url":null,"abstract":"A motor-neuron condition has been successfully treated in the womb. Plus, how has one month of Donald Trump’s second presidency affected science?","PeriodicalId":18787,"journal":{"name":"Nature","volume":"31 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462213","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":"Revealed: NIH research grants still frozen despite lawsuits challenging Trump order","authors":"","doi":"10.1038/d41586-025-00540-2","DOIUrl":"https://doi.org/10.1038/d41586-025-00540-2","url":null,"abstract":"The Trump administration is exploiting a loophole to keep a funding freeze in place, leaving researchers in limbo.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"25 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462215","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":"Microsoft claims quantum-computing breakthrough — but some physicists are sceptical","authors":"","doi":"10.1038/d41586-025-00527-z","DOIUrl":"https://doi.org/10.1038/d41586-025-00527-z","url":null,"abstract":"The tech giant aims to make ‘topological’ quantum computers that will reach useful scales faster than competing technologies.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"51 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452179","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":"How chronic stress warps decision-making","authors":"","doi":"10.1038/d41586-025-00502-8","DOIUrl":"https://doi.org/10.1038/d41586-025-00502-8","url":null,"abstract":"Nerve-cell ‘highways’ identified in mice suggest that stress pushes the brain towards rigid habit and away from thoughtful choices.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"2 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452180","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 neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer","authors":"Zachary Sethna, Pablo Guasp, Charlotte Reiche, Martina Milighetti, Nicholas Ceglia, Erin Patterson, Jayon Lihm, George Payne, Olga Lyudovyk, Luis A. Rojas, Nan Pang, Akihiro Ohmoto, Masataka Amisaki, Abderezak Zebboudj, Zagaa Odgerel, Emmanuel M. Bruno, Siqi Linsey Zhang, Charlotte Cheng, Yuval Elhanati, Evelyna Derhovanessian, Luisa Manning, Felicitas Müller, Ina Rhee, Mahesh Yadav, Taha Merghoub, Jedd D. Wolchok, Olca Basturk, Mithat Gönen, Andrew S. Epstein, Parisa Momtaz, Wungki Park, Ryan Sugarman, Anna M. Varghese, Elizabeth Won, Avni Desai, Alice C. Wei, Michael I. D’Angelica, T. Peter Kingham, Kevin C. Soares, William R. Jarnagin, Jeffrey Drebin, Eileen M. O’Reilly, Ira Mellman, Ugur Sahin, Özlem Türeci, Benjamin D. Greenbaum, Vinod P. Balachandran","doi":"10.1038/s41586-024-08508-4","DOIUrl":"https://doi.org/10.1038/s41586-024-08508-4","url":null,"abstract":"<p>A fundamental challenge for cancer vaccines is to generate long-lived functional T cells that are specific for tumour antigens. Here we find that mRNA–lipoplex vaccines against somatic mutation-derived neoantigens may solve this challenge in pancreatic ductal adenocarcinoma (PDAC), a lethal cancer with few mutations. At an extended 3.2-year median follow-up from a phase 1 trial of surgery, atezolizumab (PD-L1 inhibitory antibody), autogene cevumeran¹ (individualized neoantigen vaccine with backbone-optimized uridine mRNA–lipoplex nanoparticles) and modified (m) FOLFIRINOX (chemotherapy) in patients with PDAC, we find that responders with vaccine-induced T cells (<i>n</i> = 8) have prolonged recurrence-free survival (RFS; median not reached) compared with non-responders without vaccine-induced T cells (<i>n</i> = 8; median RFS 13.4 months; <i>P</i> = 0.007). In responders, autogene cevumeran induces CD8⁺ T cell clones with an average estimated lifespan of 7.7 years (range 1.5 to roughly 100 years), with approximately 20% of clones having latent multi-decade lifespans that may outlive hosts. Eighty-six percent of clones per patient persist at substantial frequencies approximately 3 years post-vaccination, including clones with high avidity to PDAC neoepitopes. Using PhenoTrack, a novel computational strategy to trace single T cell phenotypes, we uncover that vaccine-induced clones are undetectable in pre-vaccination tissues, and assume a cytotoxic, tissue-resident memory-like T cell state up to three years post-vaccination with preserved neoantigen-specific effector function. Two responders recurred and evidenced fewer vaccine-induced T cells. Furthermore, recurrent PDACs were pruned of vaccine-targeted cancer clones. Thus, in PDAC, autogene cevumeran induces de novo CD8⁺ T cells with multiyear longevity, substantial magnitude and durable effector functions that may delay PDAC recurrence. Adjuvant mRNA–lipoplex neoantigen vaccines may thus solve a pivotal obstacle for cancer vaccination.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"64 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452284","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}