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作者：Radakovic, Aleksandar; Lewicka, Anna; Todisco, Marco; Aitken, Harry R. M.; Weiss, Zoe; Kim, Shannon; Bannan, Abdullah; Piccirilli, Joseph A.; Szostak, Jack W.
作者单位：University of Chicago; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; University of Chicago; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University
摘要：Coded ribosomal peptide synthesis could not have evolved unless its sequence and amino acid-specific aminoacylated tRNA substrates already existed. We therefore wondered whether aminoacylated RNAs might have served some primordial function prior to their role in protein synthesis. Here, we show that specific RNA sequences can be nonenzymatically aminoacylated and ligated to produce amino acid-bridged stem- loop RNAs. We used deep sequencing to identify RNAs that undergo highly efficient glycin...
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作者：Deng, Ming-Zhi; Liu, Qingyun; Cui, Shu-Jun; Wang, Yi-Xin; Zhu, Guoliang; Fu, Han; Gan, Mingyu; Xu, Yuan - Yuan; Cai, Xia; Wang, Sheng; Sha, Wei; Zhao, Guo-Ping; Fortune, Sarah M.; Lyu, Liang-Dong
作者单位：Fudan University; Harvard University; Harvard T.H. Chan School of Public Health; Fudan University; Chinese Academy of Sciences; Center for Excellence in Molecular Plant Sciences, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Fudan University; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine
摘要：The removal of mis- incorporated nucleotides by proofreading activity ensures DNA replication fidelity. Whereas the 8- exonuclease DnaQ is a well- established proofreader in the model organism Escherichia coli, it has been shown that proofreading in a majority of bacteria relies on the polymerase and histidinol phosphatase (PHP) domain of replicative polymerase, despite the presence of a DnaQhomolog that is structurally and functionally distinct from E. coli DnaQ. However, the biological funct...
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作者：Lipsh-Sokolik, Rosalie; Fleishman, Sarel J.
作者单位：Weizmann Institute of Science
摘要：Mutations in protein active sites can dramatically improve function. The active site, however, is densely packed and extremely sensitive to mutations. Therefore, some mutations may only be tolerated in combination with others in a phenomenon known as epistasis. Epistasis reduces the likelihood of obtaining improved functional variants and dramatically slows natural and lab evolutionary processes. Research has shed light on the molecular origins of epistasis and its role in shaping evolutionary...
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作者：Illibauer, Jennifer; Clodi- Seitz, Tamara; Zoufay, Alexander; Aberle, Judith H.; Weninger, Wolfgang J.; Foedinger, Manuela; Elsayad, Kareem
作者单位：Medical University of Vienna; Medical University of Vienna; Medical University of Vienna
摘要：Blood plasma viscosity (PV) is an established biomarker for numerous diseases. Measurement of the shear PV using conventional rheological techniques is, however, time consuming and requires significant plasma volumes. Here, we show that Brillouin light scattering (BLS) and angle- resolved spectroscopy measurements of the longitudinal PV from microliter- sized plasma volumes can serve as a proxy for the shear PV measured using conventional viscometers. This is not trivial given the distinct fre...
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作者：Yu, Guoyu; Corn, Paul G.; Mak, Celia Sze Ling; Liang, Xin; Zhang, Miao; Troncoso, Patricia; Song, Jian H.; Lin, Song - Chang; Song, Xingzhi; Liu, Jingjing; Zhang, Jianhua; Logothetis, Christopher J.; Melancon, Marites P.; Panaretakis, Theocharis; Wang, Guocan; Lin, Sue - Hwa
作者单位：University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center
摘要：Immune checkpoint therapy has limited efficacy for patients with bone- metastatic castration- resistant prostate cancer (bmCRPC). To improve immunotherapy for bmCRPC, we aimed to identify the mechanism of bmCRPC- induced changes in the immune microenvironment. Among bmCRPC patients, higher levels of a 32- gene M2- like macrophage signature in bone metastasis samples correlated with shorter overall survival. Immunohistochemistry showed that CD206- positive (CD206+) macrophages were enriched in ...
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作者：Kirby, Duncan
作者单位：University of Toronto
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作者：Samajdar, Rajarshi; Meigooni, Moeen; Yang, Hao; Li, Jialing; Liu, Xiaolin; Jackson, Nicholas E.; Mosquera, Martin A.; Tajkhorshid, Emad; Schroeder, Charles M.
作者单位：University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; Montana State University System; Montana State University Bozeman; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
摘要：Proteins play a key role in biological electron transport, but the structure-function relationships governing the electronic properties of peptides are not fully understood. Despite recent progress, understanding the link between peptide conformational flexibility, hierarchical structures, and electron transport pathways has been challenging. Here, we use single- molecule experiments, molecular dynamics (MD) simulations, nonequimachine learning to understand the role of secondary structure on ...
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作者：Sharp, Phillip A.; Bonvillian, William B.; Brand, Amy; Goldston, David; Stebbins, Michael
作者单位：Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
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作者：Barkley, Anne E.; Winckler, Gisela; Recasens, Cristina; Kaplan, Michael R.; Koffman, Bess G.; Calabozo, Fernando; Middleton, Jennifer L.; Anderson, Robert F.; Cai, Yue; Bolge, Louise; Longman, Jack; Goldstein, Steven L.
作者单位：United States Environmental Protection Agency; Columbia University; Columbia University; Colby College; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); National University of Cordoba; Cicterra; Chinese Academy of Sciences; Chinese Academy of Sciences; Carl von Ossietzky Universitat Oldenburg; Northumbria University
摘要：Disentangling inputs of aeolian dust, ice- rafted debris (IRD), and eroded continental detritus delivered by ocean currents to marine sediments provide important insights into Earth System processes and climate. This study uses Sr-Nd-Pb isotope ratios of the continent- derived (lithogenic) fraction in deep- sea core TN057-6 from the subantarctic Southern Ocean southwest of Africa over the past 150,000 y to identify source regions and quantify their relative contributions and fluxes utilizing a...
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作者：Choi, Jung-Hyun; Marsal-Garcia, Laura; Peraldi, Eve; Walters, Caleb; Huang, Ziying; Gantois, Ilse; Sonenberg, Nahum
作者单位：McGill University
摘要：Fragile X syndrome (FXS) is the most common genetic cause of autism spectrum disorder engendered by transcriptional silencing of the fragile X messenger ribonucleoprotein 1 ( FMR1 ) gene. Given the early onset of behavioral and molecular changes, it is imperative to know the optimal timing for therapeutic intervention. Case reports documented benefits of metformin treatment in FXS children between 2 and 14 y old. In this study, we administered metformin from birth to Fmr1-/y mice which correct...
