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作者：Lu, Yi; Yue, Chen-Xi; Zhang, Li; Yao, Deqiang; Xia, Ying; Zhang, Qing; Zhang, Xinchen; Li, Shaobai; Shen, Yafeng; Cao, Mi; Guo, Chang-Run; Qin, An; Zhao, Jie; Zhou, Lu; Yu, Ye; Cao, Yu
作者单位：Shanghai Jiao Tong University; Shanghai Jiao Tong University; China Pharmaceutical University; University of Texas System; University of Texas Southwestern Medical Center; Shanghai Jiao Tong University; Fudan University; Shanghai Jiao Tong University
摘要：Precise regulation of intracellular phosphate (Pi) is critical for cellular function, with xenotropic and polytropic retrovirus receptor 1 (XPR1) serving as the sole Pi exporter in humans. The mechanism of Pi efflux, activated by inositol pyrophosphates (PP-IPs), has remained unclear. This study presents cryo-electron microscopy structures of XPR1 in multiple conformations, revealing a transmembrane pathway for Pi export and a dual-binding activation pattern for PP-IPs. A canonical binding sit...
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作者：Nguyen, Eric; Poli, Michael; Durrant, Matthew G.; Kang, Brian; Katrekar, Dhruva; Li, David B.; Bartie, Liam J.; Thomas, Armin W.; King, Samuel H.; Brixi, Garyk; Sullivan, Jeremy; Ng, Madelena Y.; Lewis, Ashley; Lou, Aaron; Ermon, Stefano; Baccus, Stephen A.; Hernandez-Boussard, Tina; Re, Christopher; Hsu, Patrick D.; Hie, Brian L.
作者单位：Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Stanford University
摘要：The genome is a sequence that encodes the DNA, RNA, and proteins that orchestrate an organism's function. We present Evo, a long-context genomic foundation model with a frontier architecture trained on millions of prokaryotic and phage genomes, and report scaling laws on DNA to complement observations in language and vision. Evo generalizes across DNA, RNA, and proteins, enabling zero-shot function prediction competitive with domain-specific language models and the generation of functional CRI...
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作者：Shilts, Jarrod
作者单位：University of Cambridge
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作者：Gerden, Eugene
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作者：Brainard, Jeffrey
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作者：Kaiser, Jocelyn
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作者：Wenzel, Gabi; Cooke, Ilsa R.; Changala, P. Bryan; Bergin, Edwin A.; Zhang, Shuo; Burkhardt, Andrew M.; Byrne, Alex N.; Charnley, Steven B.; Cordiner, Martin A.; Duffy, Miya; Fried, Zachary T. P.; Gupta, Harshal; Holdren, Martin S.; Lipnicky, Andrew; Loomis, Ryan A.; Shay, Hannah Toru; Shingledecker, Christopher N.; Siebert, Mark A.; Stewart, D. Archie; Willis, Reace H. J.; Xue, Ci; Remijan, Anthony J.; Wendlandt, Alison E.; Mccarthy, Michael C.; Mcguire, Brett A.
作者单位：Massachusetts Institute of Technology (MIT); University of British Columbia; Smithsonian Institution; University of Michigan System; University of Michigan; Massachusetts System of Public Higher Education; Worcester State University; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; National Science Foundation (NSF); NSF - Directorate for Mathematical & Physical Sciences (MPS); NSF - Division of Astronomical Sciences (AST); National Radio Astronomy Observatory (NRAO); University of Virginia; Chalmers University of Technology
摘要：Polycyclic aromatic hydrocarbons (PAHs) are organic molecules containing adjacent aromatic rings. Infrared emission bands show that PAHs are abundant in space, but only a few specific PAHs have been detected in the interstellar medium. We detected 1-cyanopyrene, a cyano-substituted derivative of the related four-ring PAH pyrene, in radio observations of the dense cloud TMC-1, using the Green Bank Telescope. The measured column density of 1-cyanopyrene is similar to 1.52x1012 cm-2, from which w...
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作者：Boon, Sarah
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作者：Prieto-Garcia, Cristian; Matkovic, Vigor; Mosler, Thorsten; Li, Congxin; Liang, Jie; Oo, James A.; Haidle, Felix; Macinkovic, Igor; Cabrera-Orefice, Alfredo; Berkane, Rayene; Giuliani, Giulio; Xu, Fenfen; Jacomin, Anne-Claire; Tomaskovic, Ines; Basoglu, Marion; Hoffmann, Marina E.; Rathore, Rajeshwari; Cetin, Ronay; Boutguetait, Doha; Bozkurt, Sueleyman; Canas, Maria Clara Hernandez; Keller, Mario; Busam, Jonas; Shah, Varun Jayeshkumar; Wittig, Ilka; Kaulich, Manuel; Beli, Petra; Galej, Wojciech P.; Ebersberger, Ingo; Wang, Likun; Muench, Christian; Stolz, Alexandra; Brandes, Ralf P.; Tse, William Ka Fai; Eimer, Stefan; Stainier, Didier Y. R.; Legewie, Stefan; Zarnack, Kathi; Mueller-McNicoll, Michaela; Dikic, Ivan
作者单位：Goethe University Frankfurt; Goethe University Frankfurt; Institute of Molecular Biology (IMB); University of Stuttgart; University of Stuttgart; Max Planck Society; German Centre for Cardiovascular Research; Goethe University Frankfurt; German Centre for Cardiovascular Research; Goethe University Frankfurt; Goethe University Frankfurt; Goethe University Frankfurt; Goethe University Frankfurt; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; Institute of Biophysics, CAS; Goethe University Frankfurt; Goethe University Frankfurt; Johannes Gutenberg University of Mainz; European Molecular Biology Laboratory (EMBL); Goethe University Frankfurt; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Kyushu University; Max Planck Society
摘要：RNA splicing enables the functional adaptation of cells to changing contexts. Impaired splicing has been associated with diseases, including retinitis pigmentosa, but the underlying molecular mechanisms and cellular responses remain poorly understood. In this work, we report that deficiency of ubiquitin-specific protease 39 (USP39) in human cell lines, zebrafish larvae, and mice led to impaired spliceosome assembly and a cytotoxic splicing profile characterized by the use of cryptic 5 ' splice...
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作者：Lyu, Junhua; Gu, Zhimin; Zhang, Yuannyu; Vu, Hieu S.; Lechauve, Christophe; Cai, Feng; Cao, Hui; Keith, Julia; Brancaleoni, Valentina; Granata, Francesca; Motta, Irene; Cappellini, Maria Domenica; Huang, Lily Jun-Shen; Deberardinis, Ralph J.; Weiss, Mitchell J.; Ni, Min; Xu, Jian
作者单位：St Jude Children's Research Hospital; University of Texas System; University of Texas Southwestern Medical Center; St Jude Children's Research Hospital; IRCCS Ca Granda Ospedale Maggiore Policlinico; University of Milan; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; St Jude Children's Research Hospital
摘要：Metabolic requirements vary during development, and our understanding of how metabolic activity influences cell specialization is incomplete. Here, we describe a switch from glutamine catabolism to synthesis required for erythroid cell maturation. Glutamine synthetase (GS), one of the oldest functioning genes in evolution, is activated during erythroid maturation to detoxify ammonium generated from heme biosynthesis, which is up-regulated to support hemoglobin production. Loss of GS in mouse e...
