Proceedings of the National Academy of Sciences of the United States of America

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• Cocrystal structure reveals the mechanism of FSP1 inhibition by FSEN1 AI翻译
  作者：Zhang, Sitao; Megarioti, Amalia H.; Hendricks, Joseph M.; Zhou, Junshu; Sun, Qingxiang; Jia, Da; Olzmann, James A.
  作者单位：Sichuan University; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of Electronic Science & Technology of China; Sichuan Provincial People's Hospital
  摘要：FSP1 is an FAD-dependent oxidoreductase that uses NAD(P)H to regenerate the reduced forms of lipophilic quinone antioxidants, such as coenzyme Q10 and vitamin K. These quinone antioxidants function as radical scavenging agents that prevent the propagation of lipid peroxidation and the induction of ferroptosis. Although several small-molecule inhibitors of FSP1 have been developed and found to sensitize cancer cells to ferroptosis, our understanding of their molecular mechanisms remains limited...
• Ethanol induction of FGF21 in the liver is dependent on histone acetylation and ligand activation of ChREBP by glycerol-3-phosphate AI翻译
  作者：Cheong, Mi Cheong; Mackowiak, Bryan; Kim, Hyung Bum; Hernandez, Genaro; Nandu, Tulip; Vale, Kevin; Zhang, Yuan; Zacharias, Lauren G.; Mathews, Thomas P.; Gao, Bin; Kraus, W. Lee; Kliewer, Steven A.; Mangelsdorf, David J.
  作者单位：University of Texas System; University of Texas Southwestern Medical Center; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA); University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute
  摘要：Ethanol rapidly stimulates the liver to synthesize the hormone fibroblast growth factor 21 (FGF21), which then acts on the brain to elicit a multifaceted protective response. We show that in mice, this induction of FGF21 occurs at the level of gene transcription and is regulated by two byproducts of ethanol metabolism, glycerol-3-phosphate (G3P) and acetyl-CoA. Using cell-based reporter and thermal shift binding assays, we show that G3P binds to a conserved domain and activates the transcripti...
• Resonant valence bond Coulomb phase: From spins to phonons AI翻译
  作者：Castelnovo, Claudio
  作者单位：University of Cambridge
• Phase separation in mitochondrial fate and mitochondrial diseases AI翻译
  作者：Chen, Qingyi; An, Sanqi; Wang, Chuanlong; Zhou, Yanshuang; Liu, Xingguo; Ren, Wenkai
  作者单位：Guangxi Medical University; South China Agricultural University; Guangxi Medical University; Chinese Academy of Sciences; Guangzhou Institute of Biomedicine & Health, CAS; Guangzhou Medical University; Chinese Academy of Sciences; Guangzhou Institute of Biomedicine & Health, CAS; Guangzhou Medical University
  摘要：Mitochondria are central metabolic organelles that control cell fate and the development of mitochondrial diseases. Traditionally, phase separation directly regulates cell functions by driving RNA, proteins, or other molecules to concentrate into lipid droplets. Recent studies show that phase separation regulates cell functions and diseases through the regulation of subcellular organelles, particularly mitochondria. In fact, phase separation is involved in various mitochondrial activities incl...
• A viral necrosome mediates direct RIPK3 activation to promote inflammatory necroptosis AI翻译
  作者：Li, Shufen; Li, Hao; Zhou, Zhenxing; Ye, Meidi; Wang, Yifei; Li, Wenqin; Guan, Zhenqiong; Guan, Zihan; Zhang, Chongtao; Zhang, Yulan; Liu, Wei; Peng, Ke
  作者单位：Chinese Academy of Sciences; Wuhan Institute of Virology, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Academy of Military Medical Sciences - China
  摘要：Necroptosis is an inflammatory programmed cell death pathway triggered by RIPK3 activation through one of the upstream RHIM-domain-containing proteins including RIPK1, TRIF, and ZBP1. Whether necroptosis can be activated independent of the upstream signaling pathways leading to inflammatory pathogenesis remains ambiguous. Here, we revealed a mechanism in which a viral protein mediates direct RIPK3 activation resulting in severe inflammatory pathogenesis in patients. The nonstructural protein N...
• The GRAS protein RAM1 interacts with WRI transcription factors to regulate plant genes required for arbuscule development and function AI翻译
  作者：Paries, Michael; Hobecker, Karen; Luelmo, Sofia Hernandez; Binci, Filippo; Guercio, Angelica; Uslaender, Annika; Cardoso, Catarina; Si, Yang; Wankner, Lotta; Bashyal, Sagar; Troycke, Philip; Brueckner, Franziska; Pimprikar, Priya; Shabek, Nitzan; Gutjahr, Caroline
  作者单位：Technical University of Munich; Max Planck Society; University of California System; University of California Davis; University of Munich; University of Padua; University of Freiburg; University of California System; University of California San Diego; Salk Institute
  摘要：During arbuscular mycorrhiza (AM) symbiosis AM fungi form tree-shaped structures called arbuscules in root cortex cells of host plants. Arbuscules and their host cells are central for reciprocal nutrient exchange between the symbionts. REQUIRED FOR ARBUSCULAR MYCORRHIZATION1 (RAM1) encodes a GRAS protein crucial for transcriptionally regulating plant genes needed for arbuscule development and nutrient exchange. Similar to other GRAS proteins, RAM1 likely does not bind to DNA and how RAM1 activ...
• Estrogen- related receptors regulate innate and adaptive muscle mitochondrial energetics through cooperative and distinct actions AI翻译
  作者：Fan, Weiwei; Oh, Tae Gyu; Wang, Hui J.; Crossley, Lillian; He, Mingxiao; Robbins, Hunter; Koopari, Chandra; Dai, Yang; Truitt, Morgan L.; Liddle, Christopher; Yu, Ruth T.; Atkins, Annette R.; Downes, Michael; Evans, Ronald M.
  作者单位：Salk Institute; University of Oklahoma System; University of Oklahoma Health Sciences Center; University of Sydney; Westmead Institute for Medical Research; University of Sydney
  摘要：Mitochondrial energy metabolism is vital for muscle function and is tightly controlled at the transcriptional level, both in the basal state and during adaptive muscle remodeling. The importance of the transcription factors estrogen-related receptors (ERRs) in controlling innate mitochondrial energetics has been recently demonstrated. However, whether different ERR isoforms display distinct functions in glycolytic versus oxidative myofibers is largely unknown. Moreover, their roles in regulati...
• Kernels of selfhood: GPT-4o shows humanlike patterns of cognitive dissonance moderated by free choice AI翻译
  作者：Lehr, Steven A.; Saichandran, Ketan S.; Harmon-Jones, Eddie; Vitali, Nykko; Banaji, Mahzarin R.
  作者单位：Boston University; University of New South Wales Sydney; Harvard University
  摘要：Large language models (LLMs) show emergent patterns that mimic human cognition. We explore whether they also mirror other, less deliberative human psychological processes. Drawing upon classical theories of cognitive consistency, two preregistered studies tested whether GPT-4o changed its attitudes toward Vladimir Putin in the direction of a positive or negative essay it wrote about the Russian leader. Indeed, GPT displayed patterns of attitude change mimicking cognitive dissonance effects in ...
• Split genetically encoded calcium indicators for interorganellar junctions AI翻译
  作者：Olszakier, Shunit; Hussein, Wessal; Heinrich, Ronit; Andreyanov, Michael; Blau, Achinoam; Otor, Yara; Schiller, Jackie; Kellner, Shai; Berlin, Shai
  作者单位：Technion Israel Institute of Technology; Rappaport Faculty of Medicine
  摘要：Genetically encoded calcium indicators (GECIs) have revolutionized the study of cellular calcium signaling, offering powerful tools for real-time optical monitoring of calcium dynamics. Although contemporary GECIs can be targeted to various organelles, there are no means to obtain active and functional GECIs exclusively at interorganellar junctions. To address this gap, we have developed a toolbox of split versions of green and red GECIs designed to reassemble only when the two halves come int...
• Shared host genetic landscape of respiratory viral infection AI翻译
  作者：Soriaga, Leah B.; Balce, Dale R.; Bartha, Istvan; Park, Arnold; Wong, Emily; McAllaster, Michael; Mueller, Elizabeth A.; Barauskas, Ona; Carabajal, Esteban; Kowalski, Beatriz; Lee, Sooyoung; Lo, Gary; Mahoney, Tara F.; Metruccio, Matteo; Sahakyan, Anna; Somasundaram, Logeshwaran; Steinfeld, Tod; Wang, Lisha; Wedel, Laura; Yim, Samantha S.; Yin, Li; Zhou, Jiayi; Newby, Zach; Tse, Winston; Grosse, Johannes; Virgin, Herbert W.; Hwang, Seungmin; Telenti, Amalio
  作者单位：Washington University (WUSTL); University of Texas System; University of Texas Southwestern Medical Center; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
  摘要：Respiratory viruses represent a major global health burden. Although these viruses have different life cycles, they may depend on common host genetic factors, which could be targeted by broad-spectrum host-directed therapies. We used genome-wide CRISPR screens and advanced data analytics to map a network of host genes that support infection by nine human respiratory viruses [influenza A virus, parainfluenza virus, human rhinovirus, respiratory syncytial virus, human coronavirus (HCoV)-229E, HC...