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作者:Tanaka, Hiroki; Dias, Joao Diogo; Jay, Basile; Kita, Shunsuke; Sasaki, Mina; Takeda, Hiroyuki; Kishimoto, Naoki; Sasaki, Shunsuke; Misumi, Shogo; Mizokami, Masashi; Neuveut, Christine; Sumikama, Takashi; Shibata, Mikihiro; Maenaka, Katsumi; Machida, Shinichi
作者单位:Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); Hokkaido University; Ehime University; Kumamoto University; Japan Institute for Health Security (JIHS); National Center for Global Health & Medicine - Japan; Kanazawa University; Kanazawa University; Hokkaido University; Hokkaido University; Hokkaido University; Kumamoto University
摘要:A cure for chronic hepatitis B requires eliminating or permanently silencing covalently closed circular DNA (cccDNA). A pivotal target of this approach is the hepatitis B virus (HBV) X protein (HBx), which is a key factor that promotes transcription from cccDNA. However, the HBx structure remains unsolved. Here, we present the cryoelectron microscopy structure of HBx in complex with DDB1, which is an essential complex for cccDNA transcription. In this structure, hydrophobic interactions within...
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作者:Turesky, Ted K.; Escalante, Elizabeth S.; Loh, Megan; Gaab, Nadine
作者单位:Harvard University
摘要:Reading is one of the most complex skills that we utilize daily, and it involves the early development and interaction of various lower- level subskills, including phonological processing and oral language. These subskills recruit brain structures, which begin to develop long before the skill manifests and exhibit rapid development during infancy. However, how longitudinal trajectories of early brain development in these structures support long- term acquisition of literacy subskills and subse...
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作者:Brezner, Shelly; Garushyants, Sofya K.; Wolf, Yuri I.; Koonin, Eugene V.; Snir, Sagi
作者单位:University of Haifa; National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM); Division of Intramural Research (DIR)
摘要:Evolution of bacterial and archaeal genomes is highly dynamic, including extensive gene gain via horizontal gene transfer (HGT) and gene loss as well as different types of genome rearrangements, such as inversions and translocations, so that gene order is not highly conserved even among closely related organisms. We sought to quantify the contributions of different genome dynamics processes to the evolution of the gene order in prokaryote genomes, relying on the recently developed, simple, sto...
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作者:Lin, Wenwu; Nagy, Peter D.
作者单位:University of Kentucky
摘要:Positive-strand RNA viruses are important pathogens of humans and plants. These viruses built viral replication organelles (VROs) with the help of co-opted host proteins and intracellular membranes to support robust virus replication in infected cells. Tomato bushy stunt virus (TBSV), a model (+)RNA virus, assembles membranous VROs, which are associated with vir-condensate substructures driven by TBSV p33 replication-associated protein. In this work, we provide evidence that the peroxisome-ass...
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作者:Tran, Quang D.; Lenz, Martin; Lamour, Guillaume; Paty, Lilian; Varela-Salgado, Maritzaida; Campilo, Clemen; Wioland, Hugo; Jegou, Antoine; Romet-Lemonne, Guillaume; Leduc, Cecile
作者单位:Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Universite Paris Cite; Sorbonne Universite; Universite PSL; Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI); CY Cergy Paris Universite; Centre National de la Recherche Scientifique (CNRS); Institut Universitaire de France; Brandeis University
摘要:Intermediate filaments are key regulators of cell mechanics. Vimentin, a type of intermediate filament expressed in mesenchymal cells and involved in migration, forms a dense network in the cytoplasm that is constantly remodeling through filament transport, elongation/shortening, and subunit exchange. While it is known that filament elongation involves end-to-end annealing, the reverse process of filament shortening by fragmentation remains unclear. Here, we use a combination of in vitro recon...
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作者:Das, Lahari; Chen, Bing; Rajagopalan, Saranathan; Vilcheze, Catherine; Mullholland, Claire V.; Berney, Michael; Andrews, Patrick K.; Edwards, Ashley; Lahiri, Ramanuj; Jacobs Jr, William R.
作者单位:Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; United States Health Resources & Service Administration (HRSA)
摘要:Mycobacterium leprae, the causative agent of leprosy, has never been cultured in vitro, posing significant challenges for genetic manipulation and drug discovery. Current antileprosy drug screening methods relying on microscopic count, radiorespirometry, and qPCR are time consuming and require the use of radioactive elements. We demonstrate mycobacteriophage-mediated introduction of foreign DNA using the broad-host range mycobacteriophage TM4 and the application of the luciferase reporter myco...
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作者:Gorelik, Andrii; Paulo, Joao A.; Schroeter, Christina B.; Lad, Melanie; Shurr, Abigail; Mastrokalou, Chara; Siddiqi, Samrah; Suyari, Osamu; Brognard, John; Walter, David; Matthews, Jason; Palmer, Timothy M.; Gygi, Steven P.; Ahel, Ivan
作者单位:University of Oxford; Harvard University; Harvard Medical School; Heinrich Heine University Dusseldorf; Heinrich Heine University Dusseldorf; Heinrich Heine University Dusseldorf Hospital; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Oslo; University of Toronto; University of York - UK; University of Hull
摘要:PARP7 is an enzyme that uses donor substrate NAD+ to attach a single ADP-ribose moiety onto proteins related to immunity, transcription, and cell growth and motility. Despite the importance of PARP7 in these processes, PARP7 signaling networks remain underresearched. Here, we used genome-wide CRISPR screens and multiplex quantitative proteomics in distinct lung cancer cell lines treated with a PARP7 inhibitor to better understand PARP7 molecular functions. We find that manipulating the aryl hy...
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作者:Vilchez, Victoria; Zhou, Shitong; Bouville, Florian
作者单位:Imperial College London
摘要:Spatial ordering of matter elicits exotic properties sometimes absent from a material's constituents. A few highly mineralized natural materials achieve high toughness through delocalized damage, whereas synthetic particulate composites must trade toughness for mineral content. We test whether ordering the mineral phase in particulate composites through the formation of macroscopic colloidal crystals can trigger the same damage resistance found in natural materials. Our macroscopic silica rod-...
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作者:Zhai, Jingjing; Gokaslan, Aaron; Schiff, Yair; Berthel, Ana; Liu, Zong - Yan; Lai, Wei - Yun; Miller, Zachary R.; Scheben, Armin; Stitzer, Michelle C.; Romay, M. Cinta; Buckler, Edward S.; Kuleshov, Volodymyr
作者单位:Cornell University; Cornell University; Cornell University; Cold Spring Harbor Laboratory; United States Department of Agriculture (USDA)
摘要:Interpreting function and fitness effects in diverse plant genomes requires transferable models. Language models (LMs) pretrained on large-scale biological sequences can capture evolutionary conservation and offer cross-species prediction better than supervised models through fine-tuning limited labeled data. We introduce PlantCaduceus, a plant DNA LM that learns evolutionary conservation patterns in 16 angiosperm genomes by modeling both DNA strands simultaneously. When fine-tuned on a small ...
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作者:Tien, Jean Ching-Yi; Zhai, Yali; Wu, Rong; Zhang, Yuping; Chang, Yu; Cheng, Yunhui; Todd, Abigail J.; Wheeler, Christina E.; Li, Shuqin; Mannan, Rahul; Cheng, Caleb; Magnuson, Brian; Cruz, Gabriel; Cao, Yizhi; Mahapatra, Somnath; Stolfi, Carmine; Cao, Xuhong; Su, Fengyun; Wang, Rui; Yang, Jianzhang; Zhou, Licheng; Qiao, Yuanyuan; Xiao, Lanbo; Cieslik, Marcin; Wang, Xiaoju; Wang, Zhen; Chou, Jonathan; Fearon, Eric R.; Ding, Ke; Cho, Kathleen R.; Chinnaiyan, Arul M.
作者单位:University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Chinese Academy of Sciences; Shanghai Institute of Organic Chemistry, CAS; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; University of California System; University of California San Francisco; University of Michigan System; University of Michigan; Howard Hughes Medical Institute; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
摘要:Ovarian cancer is the sixth leading cause of cancer death among American women, with most fatalities attributable to tubo-ovarian high-grade serous carcinoma (HGSC). This malignancy usually develops resistance to conventional chemotherapy, underscoring the need for robust preclinical models to guide the development of novel therapies. Here, we introduce an HGSC mouse model generated via Ovgp1-driven Cre recombinase effecting CRISPR/Cas9-mediated deletion of Trp53, Rb1, and Nf1 tumor suppressor...