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作者:Gu, Bowen; Le, Gia-Han; Herrera, Sebastian; Blair, Steven J.; Meissner, Torsten B.; Strominger, Jack L.
作者单位:Harvard University; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School
摘要:The distinct human leukocyte antigen (HLA) class I expression pattern of human extravillous trophoblasts (EVT) endows them with unique tolerogenic properties that enable successful pregnancy. Nevertheless, how this process is elaborately regulated remains elusive. Previously, E74 like ETS transcription factor 3 (ELF3) was identified to govern high- level HLA- C expression in EVT. In the present study, ELF3 is found to bind to the enhancer region of two adjacent NOD- like receptor (NLR) genes, ...
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作者:Itoh, Masayuki; Piot, Laura; Mony, Laetitia; Paoletti, Pierre; Yuzaki, Michisuke
作者单位:Keio University; Universite PSL; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm)
摘要:Delta receptors (GluD1 and GluD2), members of the large ionotropic glutamate receptor (iGluR) family, play a central role in numerous neurodevelopmental and psychiatric disorders. The amino- terminal domain (ATD) of GluD orchestrates synapse formation and maturation processes through its interaction with the Cbln family of synaptic organizers and neurexin (Nrxn). The transsynaptic triad of Nrxn-Cbln-GluD also serves as a potent regulator of synaptic plasticity, at both excitatory and inhibitor...
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作者:Touchon, Justin C.; Mcmillan, W. Owen; Ibanez, Roberto; Lessios, Harilaos A.
作者单位:Vassar College; Smithsonian Institution; Smithsonian Tropical Research Institute
摘要:Among vertebrates, nearly all oviparous animals are considered to have either obligate aquatic or terrestrial oviposition, with eggs that are specialized for developing in those environments. The terrestrial environment has considerably more oxygen but is dry and thus presents both opportunities and challenges for developing embryos, particularly those adapted for aquatic development. Here, we present evidence from field experiments examining egg- laying behavior, egg size, and egg jelly funct...
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作者:Metz, Daniel C. G.; Hechinger, Ryan F.
作者单位:University of California System; University of California San Diego; University of Nebraska System; University of Nebraska Lincoln
摘要:We show that the globally invasive, human- infectious flatworm, Haplorchis pumilio, possesses the most physically specialized soldier caste yet documented in trematodes. Soldiers occur in colonies infecting the first intermediate host, the freshwater snail Melanoides tuberculata, and are readily distinguishable from immature and mature reproductive worms. Soldiers possess a pharynx five times absolutely larger than those of immature and mature reproductives, lack a germinal mass, and have a di...
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作者:Mabry, Alexander R.; Singh, Arnima; Mulrooney, Brianna; Gorman, James; Thielbar, Abigail R.; Wolf, Eric R.; Mayo, Lindsey D.
作者单位:Indiana University System; Indiana University Indianapolis; Indiana University System; Indiana University Bloomington; Indiana University System; Indiana University Indianapolis; Indiana University System; Indiana University Indianapolis
摘要:The tumor suppressor von Hippel-Lindau, pVHL, is a multifaceted protein. One function is to dock to the hypoxia- inducible transcription factor (HIF) and recruit a larger protein complex that destabilizes HIF via ubiquitination, preventing angiogenesis and tumor development. pVHL also binds to the tumor suppressor p53 to activate specific p53 target genes. The oncogene Mdm2 impairs the formation of the p53-pVHL complex and activation of downstream genes by conjugating nedd8 to pVHL. While Mdm2...
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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...