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

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• An atlas of early human mandibular endochondral and osteogenic paracrine signaling regions of Meckel's cartilage AI翻译
  作者：Shen, Zongshan; Zhang, Ran; Chen, Xinyue; Yang, Guan; Si, Yuanchun; Yan, Tianxing; Chen, Suwen; Cheng, Bin; Wu, Xiaoshan; Chen, Di; Zhang, Dong; Xiao, Guozhi; Zhu, Jian-Kang; Wang, Songlin
  作者单位：Capital Medical University; Capital Medical University; Sun Yat Sen University; Peking University; Capital Medical University; Central South University; Shenzhen University of Advanced Technology; Southern University of Science & Technology; Southern University of Science & Technology; Southern University of Science & Technology; Southern University of Science & Technology
  摘要：The mandible, also known as the lower jaw, is the only bone in the skull that can move and is essential for speaking and chewing. Meckel's cartilage (MC) is a temporary structure that supports the formation of the mandible, but how MC is involved in the ossification of the mandible is poorly understood. Through the use of single-cell RNA sequencing and single-cell spatial transcriptomics analyses, a spatiotemporal atlas of MC in human fetuses from 7 to 15 wk postconception was established, hig...
• Decoding in- cell respiratory enzyme dynamics by label- free in situ electrochemistry AI翻译
  作者：Tokunou, Yoshihide; Yamazaki, Tomohiko; Fujikawa, Takashi; Okamoto, Akihiro; Gierasch, Lila M.
  作者单位：University of Tsukuba; National Institute for Materials Science; Hokkaido University; National Institute for Materials Science; Hokkaido University
  摘要：Deciphering metabolic enzyme catalysis in living cells remains a formidable challenge due to the limitations of in vivo assays, which focus on enzymes isolated from respiration. This study introduces an innovative whole-cell electrochemical assay to reveal the Michaelis-Menten landscape of respiratory enzymes amid complex molecular interactions. We controlled the microbial current generation's rate-limiting step, extracting in vivo kinetic parameters (Km, Ki, and kcat) for the periplasmic nitr...
• Integrative spatiotemporal modeling of biomolecular processes: Application to the assembly of the nuclear pore complex AI翻译
  作者：Latham, Andrew P.; Zhang, Wanlu; Tempkin, Jeremy O. B.; Otsuka, Shotaro; Ellenberg, Jan; Sali, Andrej
  作者单位：University of California System; University of California San Francisco; University of California System; University of California San Francisco; European Molecular Biology Laboratory (EMBL); Medical University of Vienna; University of Vienna; Vienna Biocenter (VBC); Max F. Perutz Laboratories (MFPL); Medical University of Vienna
  摘要：Dynamic processes involving biomolecules are essential for the function of the cell. Here, we introduce an integrative method for computing models of these processes based on multiple heterogeneous sources of information, including time-resolved experimental data and physical models of dynamic processes. First, for each time point, a set of coarse models of compositional and structural heterogeneity is computed (heterogeneity models). Second, for each heterogeneity model, a set of static integ...
• Identification of a ligand-binding site on tubulin mediating the tubulin-RB3 interaction AI翻译
  作者：Li, Yong; Zhang, Chufeng; Tang, Dongmei; Wang, Tao; Yan, Wei; Yang, Linyu; Bai, Peng; Tang, Minghai; Pei, Heying; Chen, Lijuan; Chen, Qiang; Yang, Jianhong
  作者单位：Sichuan University; Sichuan University; Sichuan University; Sichuan University; Sichuan University; Sichuan University
  摘要：For decades, microtubules-composed of alpha beta- tubulin dimers-have been primary targets for cancer chemotherapy. While eight binding sites on the tubulin dimer have been structurally characterized, this study reveals a ninth. We found that the tubulin inhibitor Tumabulin-1 (TM1, a BML284 derivative) binds simultaneously to the well-known colchicine site and a previously unknown site, designated as Tumabulin site. This site resides at the interface of alpha 1-tubulin, beta 1-tubulin, and RB3...
• Epstein-Barr virus and the immune microenvironment in multiple sclerosis: Insights from high- dimensional brain tissue imaging AI翻译
  作者：Orr, Noga; Steinman, Lawrence
  作者单位：Stanford University; Stanford University
  摘要：Epstein-Barr virus (EBV) is strongly implicated in the pathogenesis of multiple sclerosis (MS), yet its exact role in disease progression remains unclear. Using high-dimensional CO-detection by indexing, a technology for spatial imaging, this study examines the cellular microenvironment of MS lesions in secondary progressive MS and primary progressive MS. We analyzed immune, glial, neuronal, and endothelial cell interactions within MS lesions and normal-appearing white matter across two indepe...
• Turbulence in the tropical stratosphere, equatorial Kelvin waves, and the quasi-biennial oscillation (vol 122, e2409791122, 2025) AI翻译
  作者：Atlas, Rachel; Podglajen, Aurelien; Wilson, Richard; Hertzog, Albert; Plougonven, Riwal
• Critical fragility in sociotechnical systems AI翻译
  作者：Moran, Jose; Pijpers, Frank P.; Weitzel, Utz; Bouchaud, Jean-Philippe; Panja, Debabrata
  作者单位：University of Oxford; University of Amsterdam; Vrije Universiteit Amsterdam; Radboud University Nijmegen; Utrecht University; Utrecht University
  摘要：Sociotechnical systems, where technological and human elements interact in a goal-oriented manner, provide important functional support to our societies. Here, we draw attention to the underappreciated concept of timeliness-i.e., system elements being available at the right place at the right time-that has been ubiquitously and integrally adopted as a quality standard in the modus operandi of sociotechnical systems. We point out that a variety of incentives, often reinforced by competitive pre...
• High spatial resolution charge sensing of quantum Hall states AI翻译
  作者：Li Chiu, Cheng-; Wang, Taige; Fan, Ruihua; Watanabe, Kenji; Taniguchi, Takashi; Liu, Xiaomeng; Zaletel, Michael P.; Yazdani, Ali
  作者单位：Princeton University; Princeton University; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; National Institute for Materials Science; National Institute for Materials Science; Cornell University
  摘要：Charge distribution offers a unique fingerprint of important properties of electronic systems, including dielectric response, charge ordering, and charge fractionalization. We develop an architecture for charge sensing in two- dimensional electronic systems in a strong magnetic field. We probe local change of the chemical potential in a proximitized detector layer using scanning tunneling microscopy, allowing us to infer the chemical potential and the charge profile in the sample. Our techniqu...
• Persistence selection between simulated biogeochemical cycle variants for their distinct effects on the Earth system AI翻译
  作者：Boyle, Richard A.; Moody, Edmund R. R.; Babcock, Gunnar; Mcshea, Daniel W.; alvarez-Carretero, Sandra; Lenton, Timothy M.; Donoghue, Philip C. J.
  作者单位：University of Exeter; University of Bristol; Cornell University; Duke University
  摘要：The average long- term impact of Darwinian evolution on Earth's habitability remains extremely uncertain. Recent attempts to reconcile this uncertainty by Darwinizing nonreplicating biogeochemical processes subject to persistence- based selection conform with the historicity of the geochemical record but lack mechanistic clarity.Here, we present a theoretical framework showing how: 1) A biogeochemical cycle- biota- variant (CBV) can be defined non- arbitrarily as one biologically facilitated p...
• Bacterial polysaccharide lyase family 33: Specificity from an evolutionarily conserved binding tunnel AI翻译
  作者：Loiodice, Melanie; Drula, Elodie; Mciver, Zak; Antonyuk, Svetlana; Basle, Arnaud; Lima, Marcelo; Yates, Edwin A.; Byrne, Dominic P.; Coughlan, Jamie; Leech, Andrew; Mesdaghi, Shahram; Rigden, Daniel J.; Drouillard, Sophie; Helbert, William; Henrissat, Bernard; Terrapon, Nicolas; Wright, Gareth S. A.; Couturier, Marie; Cartmell, Alan
  作者单位：Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; INRAE; Centre National de la Recherche Scientifique (CNRS); INRAE; University of York - UK; University of Liverpool; Newcastle University - UK; Keele University; University of York - UK; University of Liverpool; King Abdulaziz University; Technical University of Denmark; University of Essex; University of York - UK; University of York - UK
  摘要：Acidic glycans are essential for the biology of multicellular eukaryotes. To utilize them, microbial life including symbionts and pathogens has evolved polysaccharide lyases (PL) that cleave their 1,4 glycosidic linkages via a beta- elimination mechanism. PL family 33 (PL33) enzymes have the unusual ability to target a diverse range of glycosamino-glycans (GAGs), as well as the bacterial polymer, gellan gum. In order to gain more detailed insight into PL33 activities we recombinantly expressed...