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作者:West, Jevin D.; Bergstrom, Carl T.
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作者:Carlier, Florian; Ramirez, Sebastian Castro; Kilani, Jaafar; Chehboub, Sara; Loiodice, Isabelle; Taddei, Angela; Gladyshev, Eugene
作者单位:Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Sorbonne Universite; UNICANCER; Universite PSL; Institut Curie; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB)
摘要:In eukaryotes, repetitive DNA can become silenced de novo, either transcriptionally or post- transcriptionally, by processes independent of strong sequence- specific cues. The mechanistic nature of such processes remains poorly understood. We found that in the fungus Neurospora crassa, de novo initiation of both transcriptional and post- transcriptional silencing was linked to perturbed chromatin, which was produced experimentally by the aberrant activity of transcription factors at the tetO o...
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作者:Gaglione, Stephanie A.; Rosales, Tatiana J.; Schmidt-Hong, Laura; Baker, Brian M.; Birnbaum, Michael E.
作者单位:Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); University of Notre Dame; University of Notre Dame; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute
摘要:dren, which resembles superantigen- induced toxic shock syndrome. Recent work has suggested that the SARS- CoV- 2 spike (S) protein could act as a superantigen by binding T cell receptors (TCRs) and inducing broad antigen- independent T cell sites near the S receptor- binding domain, in addition to a site with homology to known neurotoxins. We experimentally examined the mechanism underpinning this resonance of recombinantly expressed S protein and TCR revealed no detectable wild- type and pre...
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作者:Nourisanami, Farahdokht; Sobol, Margarita; Li, Zhuoran; Horvath, Matej; Kowalska, Karolina; Kumar, Atul; Vlasak, Jonas; Koupilova, Nicola; Luginbuhl, David J.; Luo, Liqun; Rozbesky, Daniel
作者单位:Charles University Prague; Czech Academy of Sciences; Institute of Molecular Genetics of the Czech Academy of Sciences; Stanford University; Howard Hughes Medical Institute
摘要:The precise assembly of a functional nervous system relies on axon guidance cues. Beyond engaging their cognate receptors and initiating signaling cascades that modulate cytoskeletal dynamics, guidance cues also bind components of the extracellular matrix, notably proteoglycans, yet the role and mechanisms of these interactions remain poorly understood. We found that Drosophila secreted semaphorins bind specifically to glycosaminoglycan (GAG) chains of proteoglycans, showing a preference based...
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作者:Rodrigues, Matthew J.; Tejero, Oliver; Muhle, Jonas; Pamula, Filip; Das, Ishita; Tsai, Ching - Ju; Terakita, Akihisa; Sheves, Mordechai; Schertler, Gebhard F. X.
作者单位:Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Swiss Federal Institutes of Technology Domain; ETH Zurich; Weizmann Institute of Science; Osaka Metropolitan University; Osaka Metropolitan University
摘要:Animal vision depends on opsins, a category of G protein-coupled receptor (GPCR) that achieves light sensitivity by covalent attachment to retinal. Typically binding as an inverse agonist, 11-cis retinal photoisomerizes to the all-trans isomer and activates the receptor, initiating downstream signaling cascades. Retinal bound to bistable opsins isomerizes back to the 11-cis state after absorption of a second photon, inactivating the receptor. Bistable opsins are essential for invertebrate visi...
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作者:Vincent, Philippe F. Y.; Young, Eric D.; Edge, Albert S. B.; Glowatzki, Elisabeth; Fettiplace, Robert
作者单位:Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts Eye & Ear Infirmary; Harvard University; Harvard Medical School; Harvard University
摘要:Ribbon synapses between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs) in the inner ear are damaged by noise trauma and with aging, causing synaptopathy and hearing loss. Cocultures of neonatal denervated organs of Corti and newly introduced SGNs have been developed to find strategies for improving IHC synapse regeneration, but evidence of the physiological normality of regenerated synapses is missing. This study utilizes IHC optogenetic stimulation and SGN recordings, showi...
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作者:Vlimmeren, Anne E. van; Voleti, Rashmi; Chartier, Cassandra A.; Jiang, Ziyuan; Karandur, Deepti; Humphries, Preston A.; Lo, Wan- Lin; Shah, Neel H.
作者单位:Columbia University; Columbia University; Vanderbilt University; Utah System of Higher Education; University of Utah
摘要:Mutations in the tyrosine phosphatase Src homology- 2 domain- containing protein tyrosine phosphatase-2 (SHP2) are associated with a variety of human diseases. Most mutations in SHP2 increase its basal catalytic activity by disrupting autoinhibitory interactions between its phosphatase domain and N- terminal SH2 (phosphotyrosine recognition) domain. By contrast, some disease- associated mutations located in the ligand- binding pockets of the N- or C- terminal SH2 domains do not increase basal ...
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作者:Wang, Yihang; Wu, Jiangbo; Zsolnay, Vilmos; Pollard, Thomas D.; Voth, Gregory A.
作者单位:University of Chicago; University of Chicago; Yale University; Yale University; Yale University
摘要:After ATP- actin monomers assemble filaments, the ATP's y- phosphate is hydrolyzedwithin seconds and dissociates over minutes. We used all- atom molecular dynamics simulations to sample the release of phosphate from filaments and study residues that gate release. Dissociation of phosphate from Mg2+is 2+ is rate limiting and associated with an energy barrier of 20 kcal/mol, consistent with experimental rates of phosphate release. Phosphate then diffuses within an internal cavity toward a gate f...
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作者:Wang, Ke; Rees, Vaughan W.; Dorison, Charles A.; Kawachi, Ichiro; Lerner, Jennifer S.
作者单位:Harvard University; Harvard University; Harvard T.H. Chan School of Public Health; Georgetown University; Harvard University
摘要:Meta- analyses have concluded that positive emotions do not reduce appetitive risk behaviors (risky behaviors that fulfill appetitive or craving states, such as smoking and excessive alcohol use). We propose that this conclusion is premature. Drawing on the Appraisal Tendency Framework and related theories of emotion and decision- making, we hypothesized that gratitude (a positive emotion) can decrease cigarette smoking, a leading cause of premature death globally. A series of multimethod stud...
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作者:Yang, Heeseung; Lee, Daehan; Kim, Heekyeong; Cook, Daniel E.; Paik, Young - Ki; Andersen, Erik C.; Lee, Junho
作者单位:Seoul National University (SNU); Northwestern University; Sungkyunkwan University (SKKU); Yonsei University; Seoul National University (SNU); Johns Hopkins University
摘要:Phoresy is an interspecies interaction that facilitates spatial dispersal by attaching to a more mobile species. Hitchhiking species have evolved specific traits for physical contact and successful phoresy, but the regulatory mechanisms involved in such traits and their evolution are largely unexplored. The nematode Caenorhabditis elegans displays a hitchhiking behavior known as nictation during its stress- induced developmental stage. Dauer- specific nictation behavior has an important role i...