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作者:Blecher, Ronen; Zelzer, Elazar
作者单位:Ben-Gurion University of the Negev; Samson Assuta Ashdod University Hospital; Weizmann Institute of Science
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作者:Glaser, Andrew W.; Padua, Ricardo A. P.; Ojoawo, Adedolapo M.; Sullivan, Camille; Kern, Dorothee
作者单位:Brandeis University; Howard Hughes Medical Institute; Scripps Research Institute; Howard Hughes Medical Institute
摘要:SH2 domains are critical mediators of cellular signaling, although the molecular mechanisms by which they bind their phosphopeptide ligands remain incompletely understood. We investigate the atomic mechanisms underlying both healthy regulation and dysregulation of the human protein tyrosine phosphatase SHP2, a key regulator of cellular signaling. While most pathogenic mutations cluster near the PTP/N-SH2 interface, the E139D and T42A mutations are located within the regulatory SH2 domains, and...
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作者:Otten, Kasper
作者单位:Erasmus University Rotterdam; Erasmus University Rotterdam - Excl Erasmus MC
摘要:In an increasingly interconnected world, prosociality across group boundaries becomes ever more important. Yet, a common premise in the behavioral and social sciences is that people are prosocial mainly toward their ingroup and not outgroups. So far, evidence for this premise comes mostly from studies in which people must choose between ingroup and outgroup prosociality, thereby precluding positive associations between the two types of prosociality. We study situations in which people make sep...
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作者:Tian, Heng -Ci; Zhang, Chi; Li, Wen -Jun; Xue, Dingshuai; Wang, Jing; Yang, Wei; Liu, Yan -Hong; Lin, Yangting; Li, Xian -Hua; Wu, Fu -Yuan
作者单位:Chinese Academy of Sciences; Institute of Geology & Geophysics, CAS; Chinese Academy of Sciences; Institute of Geology & Geophysics, CAS
摘要:Recent studies suggest that the lunar farside experienced a magma ocean evolution similar to that of the nearside. Thus, the nearside-farside dichotomy, such as volcanism and crustal thickness, is likely related to the South Pole-Aitken (SPA) basin-forming impact. Although the noritic clasts found in Chang'e-6 (CE6) samples may originate from crustal remelting induced by the SPA impact, how (and whether) the lunar mantle was modified by this event remains unclear. Here, we present the first hi...
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作者:Ayuso-Fernandez, Ivan; Emrich-Mills, Tom Z.; Golten, Ole; Forsberg, Zarah; Hall, Kelsi R.; Nagy, Laszlo G.; Sorlie, Morten; Rohr, Asmund Kjendseth; Eijsink, Vincent G. H.
作者单位:Norwegian University of Life Sciences; Consejo Superior de Investigaciones Cientificas (CSIC); University of Canterbury; University of Canterbury; Korea University
摘要:Enzymes known as lytic polysaccharide monooxygenases (LPMOs) are exceptionally powerful small redox enzymes that master the controlled generation and productive use of potentially damaging hydroxyl radicals in what is essentially a H2O2 -driven peroxygenase reaction. We have used ancestral sequence reconstruction and enzyme resurrection to unravel evolutionary steps leading to this exceptional catalytic ability. Real-time monitoring of copper reoxidation and amino acid radical formation showed...
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作者:Mackay, Euan D.; Bebbington, Aimee; Januschke, Jens; Kursawe, Jochen; Bischoff, Marcus; Sknepnek, Rastko
作者单位:University of Dundee; University of St Andrews; University of St Andrews; University of St Andrews; University of Dundee
摘要:The apicomedial actomyosin network is crucial for generating mechanical forces in cells. Oscillatory behavior of this contractile network is commonly observed before or during significant morphogenetic events. For instance, during the development of the Drosophila adult abdominal epidermis, larval epithelial cells (LEGs) undergo pulsed contractions before being replaced by histoblasts. These contractions involve the formation of contracted regions of concentrated actin and myosin. The emergenc...
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作者:Singh, Krishna Kumar; Jin, Yang; Hu, Ming -Wen; Palazzo, Isabella; Cano, Marisol; Hoang, Thanh; Bhutto, Imran; Wang, Shusheng; Sinha, Debasish; Blackshaw, Seth; Qian, Jiang; Handa, James T.
作者单位:Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Tulane University; Tulane University; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine
摘要:Cigarette smoking induces epigenetic changes that can cause degenerative heterogeneity with aging and disease. In disease such as age--related macular degeneration (AMD), the leading worldwide cause of blindness among the elderly, retinal pigment epithelial (RPE) cell heterogeneity is a key change. Since smoking is a powerful risk factor for AMD, we hypothesized that smoke induces epigenetic--mediated degenerative RPE heterogeneity. We administered cigarette smoke condensate (CSC) to young and...
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作者:Turcotte, Elizabeth A.; Kim, Kyungsub; Eislmayr, Kevin D.; Goers, Lisa; Mitchell, Patrick S.; Lesser, Cammie F.; Vance, Russell E.
作者单位:University of California System; University of California Berkeley; Harvard University; Harvard Medical School; Tufts University; University of Washington; University of Washington Seattle; University of Washington; Howard Hughes Medical Institute; University of Washington Seattle; Tufts University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Howard Hughes Medical Institute; University of California System; University of California Berkeley
摘要:The NAIP-NLRC4 inflammasome senses pathogenic bacteria by recognizing the cytosubunits. In mice, the NAIP-NLRC4 inflammasome provides robust protection against bacterial pathogens that infect intestinal epithelial cells, including the gastrointestinal pathogen Shigella flexneri. By contrast, humans are highly susceptible to Shigella, Why the NAIP-NLRC4 inflammasome protects mice but not humans against Shigella infection remains unclear. We previously found that human THP-1 cells infected with ...
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作者:Ishizawa, Kenichi; Kaseda, Ken; Fujii, Wataru; Tomomitsu, Yoshihiro; Hirohama, Daigoro; Yamazaki, Osamu; Kochi, Yuta; Shibata, Shigeru
作者单位:Teikyo University; Institute of Science Tokyo; Teikyo University
摘要:The maintenance of potassium (K+) balance is a fundamental biological process involving multiple tissues. However, the roles of intertissue crosstalk in K+homeosta-sis remain poorly understood. Here, we demonstrate that the mechanosensor Piezo1 dictates extracellular K+ homeostasis by orchestrating the ubiquitin ligase Kelch-like 3 (KLHL3) activity in red blood cells (RBCs; erythrocytes) and the kidney. Genetic variants within KLHL3 with expression quantitative trait locus effects are associat...
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作者:Anadon, Jose D.; Sala, Osvaldo E.
作者单位:Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto Pirenaico de Ecologia (IPE); Arizona State University; Arizona State University-Tempe; Arizona State University; Arizona State University-Tempe
摘要:Managed grazing is the most extensive land use on Earth. The prevailing narrative is that global rangelands, from grasslands to deserts, are being degraded by overgrazing due to overstocking. This perception arises from scientific literature, which contains an order of magnitude more studies on overstocking than on reductions in stocking rates. In contrast, over the past 25 y, regions representing almost half (42%) of global livestock have experienced reductions in stocking rates rather than t...