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作者:Powell, Nathaniel J.; Hein, Bettina; Kong, Deyue; Elpelt, Jonas; Mulholland, Haleigh N.; Kaschube, Matthias; Smith, Gordon B.
作者单位:University of Minnesota System; University of Minnesota Twin Cities; Columbia University; Goethe University Frankfurt
摘要:In order to deal with a complex environment, animals form a diverse range of neural representations that vary across cortical areas, ranging from largely unimodal sensory input to higher - order representations of goals, outcomes, and motivation. The developmental origin of this diversity is currently unclear, as representations could arise through processes that are already area- specific from the earliest developmental stages or alternatively, they could emerge from an initially common funct...
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作者:Duan, Ye; Li, Li; Panzade, Ganesh Prabhakar; Piton, Amelie; Zinovyeva, Anna; Ambros, Victor
作者单位:University of Massachusetts System; UMass Chan Medical School; University of Massachusetts Worcester; Harvard University; Kansas State University; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg
摘要:MicroRNAs (miRNA) associate with Argonaute (AGO) proteins and repress gene expression by base pairing to sequences in the 3 ' untranslated regions of target genes. De novo coding variants in the human AGO genes AGO1 and AGO2 cause neurodevelopmental disorders (NDD) with intellectual disability, referred to as Argonaute syndromes. Most of the altered amino acids are conserved between the miRNA- associated AGO in Homo sapiens and Caenorhabditis elegans, suggesting that the human mutations could ...
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作者:Dasgupta, Anirban
作者单位:Purdue University System; Purdue University
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作者:Dore, Hugo; Eisenberg, Amy R.; Junkins, Emily N.; Leventhal, Gabriel E.; Ganesh, Anakha; Cordero, Otto X.; Paul, Blair G.; Valentine, David L.; O'Malley, Michelle A.; Wilbanks, Elizabeth G.
作者单位:Ifremer; Universite de Bretagne Occidentale; University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; Massachusetts Institute of Technology (MIT); Marine Biological Laboratory - Woods Hole; University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; Marine Biological Laboratory - Woods Hole
摘要:Diversity - generating retroelements (DGRs) are used by bacteria, archaea, and viruses as a targeted mutagenesis tool. Through error - prone reverse transcription, DGRs introduce random mutations at specific genomic loci, enabling rapid evolution of these targeted genes. However, the function and benefits of DGRdiversified proteins in cellular hosts remain elusive. We find that 82% of DGRs from one of the major monophyletic lineages of DGR reverse transcriptases are encoded by multicellular ba...
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作者:Ilker, Efe; Hinczewski, Michael
作者单位:Max Planck Society; University System of Ohio; Case Western Reserve University
摘要:Noise control, together with other regulatory functions facilitated by microRNAs (miRNAs), is believed to have played important roles in the evolution of multicellular eukaryotic organisms. miRNAs can dampen protein fluctuations via enhanced degradation of messenger RNA (mRNA), but this requires compensation by increased mRNA transcription to maintain the same expression levels. The overall mechanism is metabolically expensive, leading to questions about how it might have evolved in the first ...
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作者:Li, Zhangqiang; Wu, Qiurong; Huang, Gaoxingyu; Jin, Xueqin; Li, Jiaao; Pan, Xiaojing; Yan, Nieng
作者单位:Tsinghua University; Westlake University; Shenzhen Medical Academy of Research & Translation (SMART)
摘要:Voltage - gated sodium channels (Nav) undergo conformational shifts in response to membrane potential changes, a mechanism known as the electromechanical coupling. To delineate the structure-function relationship of human Nav channels, we have performed systematic structural analysis using human Nav1.7 as a prototype. Guided by the structural differences between wild - type (WT) Nav1.7 and an eleven mutation- containing variant, designated Nav1.7-M11, we generated three additional intermediate...
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作者:Mangeol, Pierre; Harroche, Dominique Massey-; Sebbagh, Michael; Richard, Fabrice; Le Bivic, Andre; Lenne, Pierre- Francois
作者单位:Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Aix-Marseille Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Aix-Marseille Universite; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB)
摘要:Cell-cell apical junctions of epithelia consist of multiprotein complexes that organize as belts regulating cell-cell adhesion, permeability, and mechanical tension: the tight junction (zonula occludens), the zonula adherens (ZA), and the macula adherens. The prevailing dogma is that at the ZA, E- cadherin and catenins are lined with F - actin bundles that support and transmit mechanical tension between cells. Using super- resolution microscopy on human intestinal biopsies and Caco-2 cells, we...
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作者:Abel, Nikolaj B.; Norgaard, Malita M. M.; Hansen, Simon B.; Gysel, Kira; Diez, Ignacio Arribas; Jensen, Ole N.; Stougaard, Jens; Andersen, Kasper R.
作者单位:Aarhus University; University of Southern Denmark
摘要:Symbiosis receptor- like kinase SYMRK is required for root nodule symbiosis between legume plants and nitrogen- fixing bacteria. To understand symbiotic signaling from SYMRK, we determined the crystal structure to 1.95 angstrom and mapped the phosphorylation sites onto the intracellular domain. We identified four serine residues in a conserved alpha- I motif, located on the border between the kinase core domain and the flexible C- terminal tail, that, when phosphorylated, drives organogenesis....
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作者:Chadwick, Sarah R.; Barreda, Dante; Wu, Jing Ze; Ye, Gang; Yusuf, Bushra; Ren, Dejian; Hilgemann, Donald
作者单位:University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of Toronto; University of Pennsylvania
摘要:Phagocytes promptly resolve ingested targets to replenish lysosomes and maintain their responsiveness. The resolution process requires that degradative hydrolases, solute transporters, and proteins involved in lipid traffic are delivered and made active in phagolysosomes. It also involves extensive membrane remodeling. We report that cation channels that localize to phagolysosomes were essential for resolution. Specifically, the conductance of Na+ by two - pore channels (TPCs) and the presence...
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作者:Keum, Byeong - Rak; Kim, Hong Jin; Lee, Juhun; Lee, Minji; Hong, Sin - Hyoung; Chang, Ha Kyun; Han, Jin - Kwan; Kim, Sanguk; Chang, Dong - Gune; Kim, Gun - Hwa
作者单位:Pohang University of Science & Technology (POSTECH); Inje University; Korea Basic Science Institute (KBSI); University of Science & Technology (UST); Korea University; Korea University Medicine (KU Medicine); Yonsei University; Chungnam National University
摘要:Postmenopausal osteoporosis arises from imbalanced osteoclast and osteoblast activity, and mounting evidence suggests a role for the osteoimmune system in bone homeostasis. Bisphosphonate (BP) is an antiresorptive agent, but its treatment failure rate can be as high as 40%. Here, we performed single - cell RNA sequencing on peripheral immune cells from carefully selected postmenopausal women: non- osteoporotic, osteoporosis improved after BP treatment, and BP- failed cases. We found an increas...