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作者:Sun, Gangyu; Li, Xiang; Hu, Jiaojiao; Yang, Tianbin; Liu, Cong; Wang, Zhizhi; Li, Dan; Xu, Wenqing
作者单位:ShanghaiTech University; Shanghai Jiao Tong University; Shanghai Jiao Tong University; Chinese Academy of Sciences; Shanghai Institute of Organic Chemistry, CAS; Fudan University
摘要:Pathological aggregation of transactive response DNA binding protein of 43 kDa (TDP-43), primarily driven by its low-complexity domain, is closely associated with various neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite the therapeutic potential of preventing TDP-43 aggregation, no effective small molecule or biomacromolecule therapeutics have been successfully developed so far. Here, we introduce a protein design s...
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作者:Zhang, Shijie; Fei, Chenyi; Dunkel, Jorn
作者单位:Massachusetts Institute of Technology (MIT)
摘要:Regulation of cell growth and division is essential to achieve cell-size homeostasis. Recent advances in imaging technologies, such as mother machines for bacteria or yeast, have allowed long-term tracking of cell-size dynamics across many generations, and thus have brought major insights into the mechanisms underlying cell-size control. However, understanding the governing rules of cell growth and division within a quantitative dynamical-systems framework remains a major challenge. Here, we i...
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作者:Zhang, Zhifen; Zhang, Minquan; Burnap, Robert L.
作者单位:Oklahoma State University System; Oklahoma State University - Stillwater
摘要:Cyanobacteria achieve highly efficient photosynthesis using a CO2-concentrating mechanism relying on specialized Type I (NDH-1) complexes. Among these, NDH-1(3) and NDH-1(4) catalyze redox-coupled hydration of CO2 to bicarbonate, supporting carbon fixation in carboxysomes. The mechanism of coupling electron transfer to CO2-hydration by these variant NDH-1 complexes remains unknown. We engineered a Synechococcus PCC7942 strain that expresses exclusively the high flux/low affinity NDH-1(4) compl...
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作者:Hoxha, Isabelle; Sperber, Leo; Palminteri, Stefano
作者单位:Universite PSL; Ecole Normale Superieure (ENS); Institut National de la Sante et de la Recherche Medicale (Inserm)
摘要:The tendency to repeat past choices more often than expected from the history of outcomes has been repeatedly empirically observed in reinforcement learning experiments. It can be explained by at least two computational processes: asymmetric update and (gradual) choice perseveration. A recent meta-analysis showed that both mechanisms are detectable in human reinforcement learning. However, while their descriptive value seems to be well established, they have not been compared regarding their p...
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作者:Liu, Hang; Tse, Chun Mong; Dang, Shangyu
作者单位:Hong Kong University of Science & Technology; Hong Kong University of Science & Technology
摘要:Membrane proteins play crucial roles in numerous biological processes and are important drug targets. However, structural studies of membrane proteins often rely on solubilization with detergents, which may not accurately reflect their native states in a cellular context. Additionally, identifying suitable detergents for individual membrane proteins can be a detailed and time-consuming process. Here, we developed a vesicle-based method that preserves the native lipid environment for subsequent...
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作者:Ninomiya, Taihei
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作者:Pasiliao, Clarissa C.; Thomas, Evan C.; Yung, Theodora; Zhu, Min; Tao, Hirotaka; Sun, Yu; Goyal, Sidhartha; Hopyan, Sevan
作者单位:University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of Toronto; University of Toronto; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto
摘要:The ingression of neural crest cells from an ectodermal to a mesodermal layer is regulated by instructive, directional cues and potentially stochastic, biophysical parameters such as differential cell adhesion and tension heterogeneity.However, a cohesive framework in which to consider how various influences contribute to ingression remains elusive. Here, we observe the cell behaviors of the murine neural crest in three dimensions over time and apply a free energy framework to more wholly unde...
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作者:Han, Zhenyu; Huang, Chi; Luo, Taokun; Mirkin, Chad A.
作者单位:Northwestern University; Northwestern University
摘要:Genome editing with CRISPR-Cas systems hold promise for treating a wide range of genetic disorders and cancers. However, efficient delivery of genome editors remains challenging due to the requirement for the simultaneous delivery or intracellular generation of Cas proteins, guide RNAs, and, in some applications, donor DNAs. Furthermore, the immunogenicity and toxicity of delivery vehicles can limit the safety and efficacy of genetic medicines. Here, we combine two nucleic acid delivery approa...
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作者:Koleske, Benjamin; Rajagopalan, Saranathan; Schill, Courtney; Lun, Shichun; Vilcheze, Catherine; Das, Lahari; Gupta, Manish; Martinez-Martinez, Yazmin B.; Bishai, William R.; Jacobs Jr, William R.
作者单位:Johns Hopkins University; Johns Hopkins Medicine; Montefiore Medical Center; Yeshiva University; Albert Einstein College of Medicine
摘要:The ESX-5 secretion system, uniquely found in slow-growing mycobacteria, is predicted to secrete over 150 proteins across the inner membrane of Mycobacterium tuberculosis (M.tb). Although many of these substrates are believed to promote M.tb virulence, most remain poorly characterized. Here, we use a complete locus deletion strain of ESX-5 in M.tb to examine the molecular changes caused by a broad loss in ESX-5 secretory substrates. We confirmed the selective loss of PE/PPE proteins secreted b...
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作者:Qiu, Ruoyuan; Yu, Zhichao; Mills, Benjamin J. W.; Huang, Renda; Zhang, Wang; Isson, Terry; Wan, Bo; Zhang, Ruizhen; Zhao, Mingyu; Jin, Zhijun
作者单位:Chinese Academy of Sciences; Nanjing Institute of Geology & Paleontology, CAS; Institute of Geology & Geophysics, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; University of Leeds; Peking University; University of Waikato; Chinese Academy of Sciences; Nanjing Institute of Geology & Paleontology, CAS; Institute of Geology & Geophysics, CAS
摘要:Reconstructing carbon release fluxes during ancient climatic warming events is important for improving predictions of carbon cycle and climate dynamics under future anthropogenic warming scenarios. We investigate the extent of biogenic methane release and its approximately 183 million years ago. To do this, we developed a global biogeochemical simulations. Based on a high- resolution record of carbon isotope excursions from the Yorkshire section, our results indicate that a release of at least...