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作者:Tao, Lianyuan; He, Peng; Ge, Jiachen; Guan, Qifei; Wang, Erpei; Mohanty, Ipsita; Bez, Cristina; Song, Won-Suk; Lan, Ling; Qi, Jingjing; Zhang, Yueqi; Zhang, Peng; Liu, Yuxiao; Mukkala, Avinash; Feng, Yechen; Zhu, Mandy; Zhou, Qiong; Ai, Tingting; Watari, Kosuke; Antonucci, Laura; Gu, Li; Huang, Li; Qin, Tao; Li, Deyu; Xiu, Dianrong; Jang, Cholsoon; Varner, Judith A.; Dorrestein, Pieter C.; Sun, Beicheng; Karin, Michael
作者单位:Anhui Medical University; University of California System; University of California San Diego; University of California System; University of California San Diego; Zhengzhou University; University of California System; University of California San Diego; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of California System; University of California San Diego; International Center for Genetic Engineering & Biotechnology (ICGEB); University of California System; University of California Irvine; Zhengzhou University; Scripps Research Institute; University of California System; University of California San Diego; Sichuan University; Zhejiang University; Peking University
摘要:primary sclerosing cholangitis (PSC) is a severe liver disease that can progress to cholangiocarcinoma. Therapeutic development has been hindered by the rarity of PSC and by its poorly understood origin, which reflects incompletely defined genetic and environmental risk factors. Here we describe a mouse model that combines two suspected environmental risk factors, hepatocyte-intrinsic ER stress and oxidative stress, which leads to activation of transcription factor NRF2 in both hepatocytes and...
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作者:Wu, Peijun; Zhou, Xiang
作者单位:University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Yale University
摘要:A critical analytical task in sc-CRISPR screening is identifying downstream genes influenced by perturbed target genes. Existing methods for this task primarily rely on traditional association-based analyses, which not only fall short in establishing causal relationships between genes but also suffer from high false positive rates and limited statistical power. To overcome these limitations, we introduce a causal inference-based framework that leverages the perturbation status of gRNAs in sing...
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作者:Yuan, Yong; Jiao, Zixian; Zhou, Jiahua; Kuwana, Camille I.; Wei, William J.; Hwang, Sooyeon; Liu, Ping; Chen, Jingguang G.
作者单位:United States Department of Energy (DOE); Brookhaven National Laboratory; State University of New York (SUNY) System; Stony Brook University; Columbia University; United States Department of Energy (DOE); State University of New York (SUNY) System; Brookhaven National Laboratory; Binghamton University, SUNY
摘要:Carbon nanotubes (CNTs) are important materials for electronics and structural composites, but their production still relies on hydrocarbon-based chemical vapor deposition, an energy-intensive and fossil-dependent process, limited by rapid catalyst deactivation. Using CO2 as a carbon feedstock offers a sustainable route for CNT synthesis, yet direct CO2 conversion to CNTs is thermodynamically unfavorable and existing CO2-to-carbon pathways mainly yield amorphous or weakly graphitized solids. H...
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作者:Galvan, Manuel J.; Payne, B. Keith; Muscatell, Keely A.; Rucker, Julian M.; Sheeran, Paschal
作者单位:University of California System; University of California Berkeley; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine
摘要:We tested whether contemporary Black-White mortality disparities in the United States may be rooted in the historical legacy of slavery and perpetuated through structural inequalities. Linking county-level data on the proportion of enslaved people in 1860 with structural inequality indicators from 1990 to 2000 and mortality outcomes from 2010 to 2020, we find that historical slavery is robustly associated with contemporary racial mortality gaps. Our model estimates similar to 22 additional dea...
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作者:Simpkins, Alison G.; Skinner, Dominic J.; Felix, Brox; Marmion, Robert A.; Schottenfeld-Roames, Jodi; Shvartsman, Stanislav Y.
作者单位:Princeton University; Simons Foundation; Flatiron Institute; Princeton University
摘要:Phenotypic variability is a hallmark of human disease. It results from a combination of genetic modifiers, environment, and stochastic effects, but their contributions are hard to disentangle. Here, we establish the specification of terminal cells in the Drosophila tracheal system as a model for phenotypic variability and phenotypic emergence in Mendelian disorders. By perturbing Fibroblast growth factor (FGF) ligand dosage, which leads to a loss of terminal cells, we find that both microenvir...
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作者:Trinh, Cao Son; Shrestha, Ruben; Mao, Pengzhi; Conner, William C.; Reyes, Andres V.; Karunadasa, Sumudu S.; Yu, Annie; Liu, Grace; Hu, Ken; Xu, Shou-Ling
作者单位:Chinese Academy of Sciences; Institute of Computing Technology, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS
摘要:Capturing molecular machines in action is essential for understanding protein complex architecture, cellular regulation, and gene function. Here, we present a large-scale structural proteomics resource for Arabidopsis thaliana generated using an optimized cross-linking mass spectrometry workflow. Using the trifunctional cross-linker PhoX, whose phosphonic acid moiety enables immobilized metal affinity chromatography-based enrichment, we selectively enriched cross-linked peptides from whole-cel...
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作者:Liu, Zheling; Ying, Zhenguang; Shen, Luoan; Ma, Weirui
作者单位:Zhejiang University; Zhejiang University
摘要:Out-of-frame translation events, arising from ribosomal frameshifting or noncanonical initiation, are an unavoidable feature of translation. Their consequences depend on the distribution of stop codons in alternative reading frames, which determines the permissiveness of those frames: whether out-of-frame translation terminates quickly or generates extended products. Using quantitative dual-fluorescence reporters, we show that these stop codons function as molecular checkpoints that terminate ...
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作者:Barza, Radu; Glaeser, Edward; Hidalgo, Cesar A.; Viarengo, Martina
作者单位:Harvard University; Communaute d'universites et etablissements de Toulouse (Comue); Universite Toulouse 1 Capitole; Toulouse School of Economics; Corvinus University Budapest; Harvard University; Leibniz Association; Ifo Institut; Leibniz Association; Ifo Institut
摘要:Are cities in emerging economies poverty traps or engines of opportunity? We use 13 y of linked employer-employee data covering all formal workers in Brazil to explore the mechanisms through which agglomeration promotes mobility for initially poor workers. We find that the cities that appear to enable more upward mobility in Brazil's south are characterized by greater mixing of skilled and unskilled labor than similarly sized cities with less mobility in the north, where skilled workers dispro...
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作者:Caulkins, Jonathan P.; Kilmer, Beau; Reuter, Peter
作者单位:Carnegie Mellon University; Carnegie Mellon University; University System of Maryland; University of Maryland College Park
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作者:Ngo, Jordan Matthew; Williams, Justin Krish; Murugupandiyan, Abinayaa; Schekman, Randy
作者单位:University of California System; University of California Berkeley; University of California System; University of California Berkeley; Memorial Sloan Kettering Cancer Center
摘要:The absence of a cell wall affords animal cells diverse functionality at the cost of acute sensitization to plasma membrane (PM) damage. Thus, animal cells tightly monitor and maintain PM integrity to prevent cell death. Genetic loss of PM repair factors is associated with human diseases such as muscular dystrophy. Despite evidence that annexin and endosomal sorting complex required for transport (ESCRT) proteins are required for PM repair, the extent to which their recruitment is coordinated ...