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

最新文章

• Engineered Un1Cas12f1 with boosted gene-editing activity and expanded genomic coverage AI翻译
  作者：Chen, Li; Zhou, Xujiao; Huang, Chengsi; Zhang, Yirou; Xin, Changchang; Hong, Jiaxu; Wang, Yu
  作者单位：Shenzhen University; Shenzhen University; Fudan University; Fudan University; Fudan University; Chinese Academy of Sciences; Shenzhen Institute of Advanced Technology, CAS
  摘要：Compact programmable nucleases provide versatile genome editing tools with therapeutic potential, particularly when delivered via adeno-associated virus (AAV) vectors. However, their limited editing efficacy and stringent protospaceradjacent motif (PAM) requirements impose significant limitations in practical application. Here, we engineered MiniCasUltra, an optimized Un1Cas12f1 variant, through rational minimal off-target effects (on/off-target ratio > 10), and an expanded PAM preference (5 '...
• Structural basis of auxin binding and transport by Arabidopsis thaliana AUX1 AI翻译
  作者：Jing, Dan; Kong, Fang; Lu, Xiaoli; Huang, Gaoxingyu; Huang, Jing; Wang, Haolin; Shi, Yigong; Wang, Chengcheng
  作者单位：Zhejiang University; Westlake University; Westlake Laboratory; Tsinghua University
  摘要：Indole-3-acetic acid (IAA), the major form of auxin, is essential for plant growth. Auxin resistant 1 (AUX1), the first identified auxin importer, plays a crucial role in polar auxin transport (PAT). Here, we present cryo-EM structures ofArabidopsis thaliana AUX1 in the IAA-free and IAA-bound states. AUX1 exists as a monomer that contains 11 trans-membrane helices (TMs). TMs 1 to 5 and 6 to 10 constitute the two halves of a classic LeuT-fold, and TM11 interacts with both halves at the interfac...
• Physics-tailored machine learning reveals unexpected physics in dusty plasmas AI翻译
  作者：Yu, Wentao; Abdelaleem, Eslam; Nemenman, Ilya; Burton, Justin C.
  作者单位：Emory University; Emory University
  摘要：Dusty plasma is a mixture of ions, electrons, and macroscopic charged particles that is commonly found in space and planetary environments. The particles interact through Coulomb forces mediated by the surrounding plasma, and as a result, the effective forces between particles can be nonconservative and nonreciprocal. Machine learning (ML) models are a promising route to learn these complex forces, yet their structure should match the underlying physical constraints to provide useful insight. ...
• The power of coalescent methods for inferring recent and ancient gene flow in endangered Bactrian camels AI翻译
  作者：Zhu, Tianqi; Wang, Zhen; Yang, Ziheng
  作者单位：Chinese Academy of Sciences; Chinese Academy of Sciences; Shanghai Institute of Nutrition & Health, CAS; University of London; University College London
  摘要：Genomic sequence data harbor valuable information concerning the history of species divergence and interspecific gene flow and may offer important insights into conservation of endangered species. However, extracting such information from genomic data requires powerful statistical inference methods. A recent analysis of genomic sequence data found little evidence for gene flow from domestic Bactrian camels into the endangered wild Bactrian species. Nevertheless, the methods used to infer gene ...
• Autophagy activator AA-20 improves proteostasis and extends Caenorhabditis elegans lifespan AI翻译
  作者：Tan, Ee Phie; Lyang, Nora; Doroodian, Saam; Sanz-Martinez, Pablo; Xu, Jin; Zaretski, Sviatlana; Nieto-Torres, Jose L.; Ebata, Hiroshi; Lim, Shaun H. Y.; Hou, William C.; Clay, Khalyd J.; Yoon, Leonard; Rhoades, Derek; Garza, Danny; Johnson, Kristen A.; To, Alan; Ambaye, Lydia; Bentley, Emily P.; Petrascheck, Michael; Stolz, Alexandra; Kelly, Jeffery W.; Hansen, Malene
  作者单位：Universidad CEU Cardenal Herrera; Sanford Burnham Prebys Medical Discovery Institute; Scripps Research Institute; Buck Institute for Research on Aging; Goethe University Frankfurt; Goethe University Frankfurt; Scripps Research Institute; Scripps Research Institute; Scripps Research Institute; Scripps Research Institute
  摘要：The degradation of cellular components through autophagy is essential for longevity and healthy aging. However, autophagy function decreases with aging, contributing to age-related diseases. In this study, we characterized a small-molecule activator of autophagy called AA-20 that enhances autophagy and lipid droplet clearance in human cells and in the nematode Caenorhabditis elegans. AA-20 reduces polyglutamine aggregation in an autophagy-dependent manner in both human cells and C. elegans, wh...
• The kinesin KIF3AC recycles endocytosed integrin to polarize new adhesion formation toward the leading edge AI翻译
  作者：Rockenbach, Johnny A. Z.; Nader, Guilherme P. F.; Antoku, Susumu; Gundersen, Gregg G.
  作者单位：Columbia University; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia
  摘要：The recycling of integrin endocytosed during focal adhesion (FA) disassembly is critical for cell migration and contributes to the polarized formation of new FAs toward the leading edge. How this occurs is unclear. Here, we sought to identify the kinesin motor protein(s) that is involved in recycling endocytosed integrin back to the plasma membrane. We show that the kinesin- 2 heterodimer, KIF3AC, and the Rab11 adaptor protein Rab coupling protein (RCP) are required for FA reformation after th...
• Active bacterial baths in droplets AI翻译
  作者：Villalobos-Concha, Cristian; Liu, Zhengyang; Ramos, Gabriel; Goral, Martyna; Lindner, Anke; Lopez-Leon, Teresa; Clement, Eric; Soto, Rodrigo; Cordero, Maria Luisa
  作者单位：Universidad de Chile; Centre National de la Recherche Scientifique (CNRS); Universite PSL; Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI); Sorbonne Universite; Universite Paris Cite; Universite PSL; Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Institut Universitaire de France
  摘要：Suspensions of self-propelled objects represent a novel paradigm in colloidal science. In such active baths, traditional concepts such as Brownian motion, fluctuation-dissipation relations, and work extraction from heat reservoirs, must be extended beyond the conventional framework of thermal baths. Unlike thermal baths, which are characterized by a single parameter, the temperature, the fundamental descriptors of an active bath remain elusive. Particularly relevant are confined environments, ...
• Optomechanical reservoir computing AI翻译
  作者：Kiyabu, Steven; Nelson, Daniel; Thomson, John; Schultz, Benjamin; Vincent, Timothy; Hertlein, Nathan; Gillman, Andrew; Criner, Amanda; Buskohl, Philip R.
  作者单位：UES, Inc.; United States Department of Defense; United States Air Force
  摘要：Nonlinear dynamics are pervasive phenomena in natural and synthetic material systems, where time-varying signals from different physical stimuli in the environment influence the material system behavior. Physical reservoir computing leverages these nonlinear dynamics to produce complex input-output mappings by interpreting the dynamical system as a physical recurrent neural network. A source of physical nonlinearity is crucial for enabling the reservoir to predict nonlinear relationships. Desp...
• Infectious disease outbreaks drive political mistrust AI翻译
  作者：Koren, Ore; Weidmann, Nils B.
  作者单位：Indiana University System; Indiana University Bloomington; University of Konstanz
  摘要：The COVID- 19 pandemic has renewed attention to the far- reaching social implications of emerging infectious diseases, an issue with historical parallels in the transformative reshape political trust and fuel instability has remained underexplored. This study leverages a novel dataset on zoonotic disease outbreaks-including Ebola, Marburg, H1N1, and the Black Plague-and geolocated Afrobarometer survey data from dozens of African states to investigate whether exposure to these deadly outbreaks ...
• Dynamic forces drive cell and organ morphology changes during embryonic development AI翻译
  作者：Manna, Raj Kumar; Retzlaff, Emma M.; Hinman, Anna Maria; Lan, Yiling; Abdel-Razek, Osama; Bates, Mike; Hehnly, Heidi; Amack, Jeffrey D.; Manning, M. Lisa
  作者单位：Syracuse University; Syracuse University; Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Kharagpur; State University of New York (SUNY) System; SUNY Upstate Medical University; Syracuse University
  摘要：Cells, tissues, and organs must change shape in precise ways during embryonic development to execute their functions. Multiple mechanisms including biochemical signaling pathways and biophysical forces help drive these morphology changes, but it has been difficult to tease apart their contributions, especially from tissue-scale dynamic forces that are typically ignored. We use a combination of mathematical models and in vivo experiments to study a simple organ in the zebrafish embryo called Ku...