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

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• Cystic fibrosis: Correction of a fatal disease AI翻译
  作者：Friedman, Jeffrey M.
  作者单位：Howard Hughes Medical Institute; Rockefeller University
  摘要：The 2025 Lasker similar to DeBakey Clinical Medical Research Award has been given to Michael Welsh, Jesus (Tito) Gonzalez, and Paul Negulescu for their key roles in developing a novel treatment for cystic fibrosis (CF)-a three-drug combination that saves the lives of people with this lethal genetic disease [D. Keating etal., N. Engl. J. Med. 379, 1612-1620 (2018)]. The disease is caused by mutations that disrupt the function of a gene known as CF Transmembrane Conductance Regulator which encod...
• Inflammation awakens dormant cancer cells by modulating the epithelial-mesenchymal phenotypic state AI翻译
  作者：Zhang, Jingwei; Zhang, Jingwen; Han, Longfei; Wu, Shiyi; Li, Jie; Eaton, Elinor Ng; Yuan, Bingbing; Reinhardt, Ferenc; Li, Hao; Strasser, Patrick C.; Das, Sunny; Donahera, Joana Liu; Khalila, Md Imtiaz; Jiang, Haiping; Deuschel, Alexander; Lin, Danni; Sebastiany, Carolin; Maranga, Mariana; Shubitidze, Salome; Liu, Xiaofei; Lambert, Arthur W.; Zhang, Yun; Liu, Yana; Sui, Lufei; Elmiligy, Sarah; Pozza, Umberto; Gunsay, Rauf; Mishra, Ranjan; Velarde, Jose; Iyer, Sonia; Henra, Whitney S.; Weiskopf, Kipp; Fen, Guihai; Oni, Tobiloba E.; Watnick, Randolph S.; Li, Xin; Weinberg, Robert A.
  作者单位：Massachusetts Institute of Technology (MIT); Whitehead Institute; Chinese Academy of Sciences; Institute of Zoology, CAS; Chinese Academy of Sciences; Beijing Institute for Stem Cell & Regenerative Medicine; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Nankai University; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Cancer Institute & Hospital - CAMS; Chinese Academy of Medical Sciences - Peking Union Medical College; Cancer Institute & Hospital - CAMS; Peking Union Medical College; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of Bergen; University of Bergen; Haukeland University Hospital; Massachusetts Institute of Technology (MIT)
  摘要：The awakening of dormant disseminated cancer cells appears to be responsible for the clinical relapses of patients whose primary tumors have been successfully cured months and even years earlier. In the present study, we demonstrate that dormant breast cancer cells lodged in the lungs reside in a highly mesenchymal, nonproliferative phenotypic state. The awakening of these cells is not triggered by a cancer peutic agent bleomycin effectively awakens dormant cancer cells, providing useful model...
• Scaling and mechanical optimality of bristled wings in microinsects AI翻译
  作者：Kolomenskiy, Dmitry; Farisenkov, Sergey E.; Petrov, Pyotr N.; Polilov, Alexey A.
  作者单位：Skolkovo Institute of Science & Technology; Lomonosov Moscow State University
  摘要：It is crucial for both animal evolution and engineering to optimize the relative size of structures. Animal wings are no exception, every structural design having its limits in terms of achievable size and performance. For instance, many microinsects have bristled wings, which are more efficient at small scales than the membranous wings common in larger insects. However, the limitations and the optimal characteristics of bristled wings remain largely underinvestigated. We collected morphologic...
• The edge-averaging process on graphs with random initial opinions AI翻译
  作者：Elboim, Dor; Peres, Yuval; Peretz, Ron
  作者单位：Stanford University; Bar Ilan University
  摘要：In several settings (e.g., sensor networks and social networks), nodes of a graph are equipped with initial opinions, and the goal is to estimate the average of these opinions using local operations. A natural algorithm to achieve this is the edge-averaging process, where edges are repeatedly selected at random (according to independent Poisson clocks) and the opinions on the nodes of each selected edge are replaced by their average. The effectiveness of this algorithm is determined by its con...
• Immune-responsive gene 1: The mitochondrial key to Th17 cell pathogenicity in CNS autoimmunity AI翻译
  作者：Nematullah, Mohammad; Fatma, Mena; Zhou, Guoli; Prajapati, Bharat; Rashid, Faraz; Ayasolla, Kameshwar; Ahmed, Mohammad Ejaz; She, Ruicong; Mir, Sajad; Zahoor, Insha; Hoda, Nasrul; Rattan, Ramandeep; Giri, Shailendra; Steinman, Lawrence
  作者单位：Henry Ford Health System; Henry Ford Hospital; Michigan State University; University of Gothenburg; Henry Ford Health System; Henry Ford Hospital; Henry Ford Health System; Henry Ford Hospital
  摘要：Pathogenic Th17 cells play crucial roles in CNS autoimmune diseases such as multiple sclerosis (MS), but their regulation by endogenous mechanisms remains unknown. Through RNA-seq analysis of primary brain glial cells, we identified immune-responsive gene 1 (Irg1) as one of the highly upregulated genes under inflammatory conditions. Validation in the spinal cords of animals with experimental autoimmune encephalomyelitis (EAE), a preclinical MS model, confirmed elevated Irg1 levels in myeloid, ...
• Hierarchical network of thermal plumes and their dynamics in turbulent Rayleigh-Bénard convection AI翻译
  作者：Shevkar, Prafulla P.; Samuel, Roshan J.; Zinchenko, Georgy; Bode, Mathis; Schumacher, Jorg; Sreenivasan, Katepalli R.
  作者单位：Helmholtz Association; Research Center Julich; New York University; New York University Tandon School of Engineering; New York University
  摘要：The link between characteristic coherent structures and their statistical properties in turbulent flows remains largely unclear and is thus a central bottleneck for a better understanding of turbulent flows. Here, we demonstrate this link for the important problem of thermal convection. We show how the hierarchical plume network in the near-wall region of the flow, which becomes increasingly sparse with increasing distance away from the wall, is connected to the marginal stability of the therm...
• NIPBL and STAG1 enable loop extrusion by providing differential DNA-cohesin affinity AI翻译
  作者：van Wee, Raman; Asor, Roi; Li, Yiwen; Drechsel, David; Popova, Mariia; Litos, Gabriele; Davidson, Iain F.; Peters, Jan -Michael; Kukura, Philipp
  作者单位：University of Oxford; University of Oxford; Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP); Vienna Biocenter (VBC)
  摘要：DNA loop extrusion by cohesin has emerged as a critical pathway for chromosome organization. In vitro single-molecule experiments indicate that loop extrusion requires the assembly of a heteropentameric complex consisting of the SMC1/SMC3 heterodimer, STAG1, NIPBL, and the kleisin SCC1. The complexity of the complete extrusion machinery, consisting of multiple subunits, DNA binding sites, and ATPases poses substantial challenges for revealing the underlying biomolecular mechanism. As a result,...
• QnAs with Blake C. Meyers AI翻译
  作者：Ravindran, Sandeep; Meyers, Blake C.
• Indigenous territories and protected areas are crucial for ecosystem connectivity in the Amazon basin AI翻译
  作者：Ritter, Camila Duarte; Munoz, Jesus; Machado, Arielli Fabricio; Albert, James S.; Ribas, Camila C.; Carnaval, Ana C.; Ulloa, Carmen Ulloa; Carrillo, Juan D.; Tuomisto, Hanna; Armenteras, Dolors; Guayasamin, Juan M.
  作者单位：Institute Nacional de Pesquisas da Amazonia; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Real Jardin Botanico de Madrid; Universidade Federal do Pampa; Harvard University; University of Louisiana Lafayette; City University of New York (CUNY) System; City University of New York (CUNY) System; Missouri Botanical Gardens; University of Fribourg; Swiss Institute of Bioinformatics; University of Turku; Aarhus University; Universidad Nacional de Colombia; Universidad San Francisco de Quito
  摘要：Ecosystem connectivity-the uninterrupted flow of natural processes within and among ecosystems-is critical for maintaining healthy ecosystem functions. However, in the Amazon drainage basin, multiple anthropogenic activities are rapidly disrupting connectivity. To assess the severity of this problem, we analyzed the spatial distributions of six major anthropogenic activities: dam construction, deforestation, fire, mining, oil and gas exploitation, and roads. We examined their impacts across fo...
• Emergence of isochorismate- based salicylic acid biosynthesis within Brassicales AI翻译
  作者：Hong, Kunqi; Nakano, Masahito; Tang, Ying; Jeanguenin, Linda; Kang, Wenshang; Wang, Yongliang; Zuo, Lu; Li, Pengyue; He, Jingjng; Jiang, Wanqing; Huang, Ruidong; Matsui, Hidenori; Wang, Yiming; Nakagami, Hirofumi; Li, Bo; Li, Xia; Xie, Kabin; Fukushima, Kenji; Guo, Liang; Han, Xiaowei; Katagiri, Fumiaki; Hattori, Motoyuki; Tsuda, Kenichi
  作者单位：Huazhong Agricultural University; Hubei Hongshan Laboratory; University of Minnesota System; University of Minnesota Twin Cities; Hubei Hongshan Laboratory; Huazhong Agricultural University; RIKEN; Okayama University; Nanjing Agricultural University; Max Planck Society; Research Organization of Information & Systems (ROIS); National Institute of Genetics (NIG) - Japan; Fudan University
  摘要：Salicylic acid (SA) is a major defense phytohormone. In Arabidopsis thaliana, the isochorismate (IC) pathway is the primary route for pathogen-induced SA biosynthesis. First, the IC synthase (ICS) catalyzes the isomerization of chorismate to IC in chloroplasts. Second, the chloroplast-localized MATE transporter EDS5 appears to transport IC from chloroplasts to the cytosol. Cytosolic IC is then further converted to SA via the GH3 amino acid-conjugating enzyme PBS3. While this pathway is genetic...