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作者:Yang, Jason; Xu, Yunhan; Ziehr, David R.; Taylor, Martin S.; Valenstein, Max L.; Frenkel, Evgeni M.; Bush, Jack R.; Rutter, Kate; Stevanovski, Igor; Shi, Charlie Y.; Kesavan, Maheswaran; Pinto, Ricardo Mouro; Deveson, Ira; Bartel, David P.; Sabatini, David M.; Chivukula, Raghu R.
作者单位:Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Brown University; Czech Academy of Sciences; Institute of Organic Chemistry & Biochemistry of the Czech Academy of Sciences; Garvan Institute of Medical Research; Murdoch Children's Research Institute; Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; Laval University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of New South Wales Sydney; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
摘要:Aggregation-prone polyglycine-containing proteins produced from expanded GGC repeats are implicated in an emerging family of neurodegenerative disorders. In this study, we showed that polyglycine itself forms aggregates that incorporate endogenous glycine-rich proteins, including FAM98B, a component of the transfer RNA (tRNA) ligase complex (tRNA-LC) that harbors the most glycine-rich sequence in the human proteome. Through this glycine-rich intrinsically disordered region (IDR), polyglycine s...
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作者:Service, Robert F.
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作者:Witte, Isaac P.; Lampe, George D.; Eitzinger, Simon; Miller, Shannon M.; Berrios, Kiara N.; McElroy, Amber N.; King, Rebeca T.; Stringham, Olivia G.; Gelsinger, Diego R.; Vo, Phuc Leo H.; Chen, Albert T.; Tolar, Jakub; Osborn, Mark J.; Sternberg, Samuel H.; Liu, David R.
作者单位:Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University; Howard Hughes Medical Institute; Harvard Medical School; Columbia University; Howard Hughes Medical Institute; Columbia University; University of Minnesota System; University of Minnesota Twin Cities; Scripps Research Institute; Vertex Pharmaceuticals
摘要:Programmable gene integration in human cells has the potential to enable mutation-agnostic treatments for loss-of-function genetic diseases and facilitate many applications in the life sciences. CRISPR-associated transposases (CASTs) catalyze RNA-guided DNA integration but thus far demonstrate minimal activity in human cells. Using phage-assisted continuous evolution (PACE), we generated CAST variants with >200-fold average improved integration activity. The evolved CAST system (evoCAST) achie...
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作者:Lin, Hui; Ma, Chuanshun; Cai, Kui; Guo, Lulu; Wang, Xuemei; Lv, Lin; Zhang, Chao; Lin, Jun; Zhang, Daolai; Ye, Chuan; Wang, Tengwei; Huang, Shenming; Han, Jifei; Zhang, Zihao; Gao, Junyan; Zhang, Mingxiang; Pu, Zhao; Li, Fengyang; Guo, Yongyuan; Zhou, Xiaojun; Qin, Chengxue; Yi, Fan; Yu, Xiao; Kong, Wei; Jiang, Changtao; Sun, Jin-Peng
作者单位:Shandong University; Shandong University; Peking University; Shandong University; Shandong University; Shandong University; Shandong University; Shandong University; Shandong Medical & Pharmaceutical University; University of Toronto; Shandong University; Shandong University; Shandong University; Peking University; Peking University; Peking University
摘要:Ceramides play a central role in human health and disease, yet their role as systemic signaling molecules remain poorly understood. In this work, we identify formyl peptide receptor 2 (FPR2) as a membrane receptor that specifically binds long-chain ceramides (C14 to C20). In brown and beige adipocytes, C16:0 ceramide binding to FPR2 inhibits thermogenesis through Gi cyclic adenosine monophosphate signaling pathways, an effect that is reversed in the absence of FPR2. We present three cryo-elect...
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作者:Lyu, Cheng; Li, Zhuoran; Xu, Chuanyun; Wong, Kenneth Kin Lam; Luginbuhl, David J.; Mclaughlin, Colleen N.; Xie, Qijing; Li, Tongchao; Li, Hongjie; Luo, Liqun
作者单位:Stanford University; Howard Hughes Medical Institute; Stanford Medicine; Stanford University; Stanford University; Stanford University
摘要:A navigating axon faces complex choices when selecting postsynaptic partners in a three-dimensional (3D) space. In this work, we discovered a principle that can establish the 3D glomerular map of the fly antennal lobe by reducing the higher dimensionality serially to 1D projections. During development, olfactory receptor neuron (ORN) axons first contact their partner projection neuron dendrites on the spherical surface of the antennal lobe, regardless of whether the adult glomeruli lie near th...
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作者:Jeon, Yong Geun; Kim, Jae Bum
作者单位:Seoul National University (SNU)
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作者:Chen, Luying; Dickerhoff, Jonathan; Zheng, Ke-wei; Erramilli, Satchal; Feng, Hanqiao; Wu, Guanhui; Onel, Buket; Chen, Yuwei; Wang, Kai-Bo; Carver, Megan; Lin, Clement; Sakai, Saburo; Wan, Jun; Vinson, Charles; Hurley, Laurence; Kossiakoff, Anthony A.; Deng, Nanjie; Bai, Yawen; Noinaj, Nicholas; Yang, Danzhou
作者单位:Purdue University System; Purdue University; Hunan University; University of Chicago; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Arizona; University of Arizona Health Sciences; Indiana University System; Indiana University Bloomington; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Pace University; Purdue University System; Purdue University; Purdue University System; Purdue University; Purdue University System; Purdue University
摘要:The MYC oncogene promoter G-quadruplex (MycG4) regulates transcription and is a prevalent G4 locus in immortal cells. Nucleolin, a major MycG4-binding protein, exhibits greater affinity for MycG4 than for nucleolin recognition element (NRE) RNA. Nucleolin's four RNA binding domains (RBDs) are essential for high-affinity MycG4 binding. We present the 2.6-angstrom crystal structure of the nucleolin-MycG4 complex, revealing a folded parallel three-tetrad G-quadruplex with two coordinating potassi...
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作者:Hou, Deyi; Jia, Xiyue; Wang, Liuwei; McGrath, Steve P.; Zhu, Yong-Guan; Hu, Qing; Zhao, Fang-Jie; Bank, Michael S.; O'Connor, David; Nriagu, Jerome
作者单位:Tsinghua University; Tsinghua University; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Rothamsted Research; Chinese Academy of Sciences; Research Center for Eco-Environmental Sciences (RCEES), CAS; Chinese Academy of Sciences; Institute of Urban Environment, CAS; Southern University of Science & Technology; Nanjing Agricultural University; Institute of Marine Research - Norway; University of Massachusetts System; University of Massachusetts Amherst; Royal Agricultural University; University of Michigan System; University of Michigan
摘要:Toxic metal pollution is ubiquitous in soils, yet its worldwide distribution is unknown. We analyzed a global database of soil pollution by arsenic, cadmium, cobalt, chromium, copper, nickel, and lead at 796,084 sampling points from 1493 regional studies and used machine learning techniques to map areas with exceedance of agricultural and human health thresholds. We reveal a previously unrecognized high-risk, metal-enriched zone in low-latitude Eurasia, which is attributed to influential clima...
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作者:Lai, Meng-Chuan
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作者:Chandrashekhar, Vaishnavi