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作者：Carlson, Maryn O.; Andrews, Bryan L.; Simons, YuvalB.
作者单位：University of Chicago; University of Chicago; University of Chicago; University of Chicago; University of Chicago; University of Chicago
摘要：The phenotypic effect of a mutation may depend on the genetic background in which it occurs, a phenomenon referred to as epistasis. One source of epistasis in proteins is direct interactions between residues in close physical proximity to one another. However, epistasis may also occur in the absence of specific interactions between amino acids if the genotype-to-phenotype map is nonlinear. Disentangling the contributions of these two phenomena-specific and global epistasis-from noisy, high-thr...
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作者：V. Vasylyev, Dmytro; Zhao, Peng; Schulman, Betsy R.; Waxman, Stephen G.
作者单位：Yale University; Yale University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Connecticut Healthcare System
摘要：Voltage-gated sodium channel Nav1.8 plays a crucial role in regulating excitability of small dorsal root ganglion (DRG) neurons and is an emerging target for pain therapeutics. Using dynamic clamp, we systematically manipulated Nav1.8 conductance to assess its impact on action potential (AP) electrogenesis, rheobase, and repetitive firing in native rat DRG neurons and those expressing the gain-of-function Nav1.7L858H mutation which underlies inherited erythromelalgia, a human genetic pain diso...
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作者：van Gestel, Jordi; Koo, Byoung-Mo; Sturmer, Vanessa S.; Garriga-Canut, Mireia; Wagner, Jonas; Zanon, Andrea; Gross, Carol A.
作者单位：University of California System; University of California San Francisco; European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL); Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg
摘要：Single-cell eukaryotic predators in the soil are a primary cause of bacterial cell death. Yet, most functional genomic studies on soil bacteria have been performed without predation, thereby selecting for phenotypes impacting growth rather than survival and biasing our view on the ecological factors driving genomic evolution. Here, we study how predation by the ubiquitous amoebal predator Dictyostelium discoideum affects Bacillus subtilis' growth and survival using both a genome-scale mutant s...
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作者：Yu, Jie; Lakey, Pascale S. J.; Ditto, Jenna C.; Huynh, Han N.; Link, Michael F.; Poppendieck, Dustin; Zimmerman, Stephen M.; Wang, Xing; Farmer, Delphine K.; Vance, Marina E.; Abbatt, Jonathan P. D.; Shiraiwa, Manabu
作者单位：University of Toronto; University of California System; University of California Irvine; Washington University (WUSTL); University of Colorado System; University of Colorado Boulder; National Oceanic Atmospheric Admin (NOAA) - USA; National Institute of Standards & Technology (NIST) - USA; University of Toronto; Colorado State University System; Colorado State University Fort Collins; University of Colorado System; University of Colorado Boulder
摘要：The total partitioning capacity of indoor surface reservoirs determines the mechanism by which humans receive nondietary exposure to organic contaminants, via inhalation, dermal uptake, and dust ingestion. And yet, this capacity is largely unknown. Surface organic films are ubiquitously present but have very low partitioning volume being only 10's of nanometer thick, whereas other surface reservoirs such as building materials and furnishings can be permeable or porous with large surface areas ...
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作者：Gonzalez, Brenda Martinez-; Soria, Maria Eugenia; Avila, Ana Isabel de; Somovilla, Pilar; Sabido, Claudia Aguilar-; Minguez, Pablo; Orta, Cristina Ferrer-; Vidal, Llanos Salar-; Lorenzo-Redondojk, Ramon; Delgado, Soledad; Moran, Federico; Verdaguer, Nuria; Gadea, Ignacio; Domingo, Esteban; Perales, Celia
作者单位：Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Biologia Molecular Severo Ochoa (CBM); Autonomous University of Madrid; Autonomous University of Madrid; Autonomous University of Madrid; Autonomous University of Madrid; Instituto de Salud Carlos III; CIBER - Centro de Investigacion Biomedica en Red; CIBERER; Autonomous University of Madrid; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Biologia Molecular de Barcelona (IBMB); Instituto de Salud Carlos III; Northwestern University; Feinberg School of Medicine; Northwestern University; Universidad Politecnica de Madrid; Complutense University of Madrid
摘要：RNA virus populations consist of complex and dynamic mutant spectra in which most individual genomes differ in one or more positions from the other genomes of the same population. This behavior, known as quasispecies dynamics, applies to SARS-CoV-2 which exhibits intrahost genetic and functional heterogeneity while evolving at a high rate in the human population. In the present study, we describe a remarkable reduction in mutant spectrum complexity (intrahost viral genome heterogeneity) in SAR...
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作者：O'Donnell, Andrew J.; Pellatz, Preston J.; Nichols, Caroline S.; Gershenzon, Jonathan; Peters, Reuben J.; Schmidt, Axel
作者单位：Max Planck Society; Iowa State University; University of Iowa
摘要：A long-standing question in biology is what makes evolution more or less repeatable. Although evolution seems repeatable when observing convergent phenotypic outcomes, each episode of convergence could have been contingent on an idiosyncratic history that is not expected to repeat. Overlooking events that preceded convergent episodes therefore risks overestimating repeatability. Here, we demonstrate using resurrected ancestral proteins that the evolution of a characteristic diterpene resin aci...
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作者：Qin, Sanbo; Zhou, Huan- Xiang
作者单位：University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital
摘要：The small-angle scattering (SAS) profile of a dense protein solution contains rich information about interprotein interactions, but extracting this information has been extremely challenging. In previous studies, we developed a fast Fourier transform-based method, FMAPB2, to compute protein pair interactions at the all-atom level. Here, we use FMAPB2 to precompute pair interaction energies and then use the latter to drive simulations of dense protein solutions. The resulting MAEPPI (many-prote...
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作者：Su, Yapeng; Thelen, Ashley; Wirth, Lena V.; Jenkins, Cody M.; Mak, Sam R.; Chen, Daniel G.; Gottardo, Raphael; Greenberg, Philip D.
作者单位：Fred Hutchinson Cancer Center; Fred Hutchinson Cancer Center; Wellcome Trust Sanger Institute; University of Cambridge; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Lausanne; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
摘要：Adoptive T cell therapies have shown limited efficacy against solid tumors due in part to immunosuppressive cues such as from TGF-f3 and insufficient survival/proliferative signals within the tumor microenvironment (TME). We engineered chimeric immunomodulatory fusion proteins (IFPs) that convert immunosuppressive TGF-f3 signals into proliferative/survival Interleukin 2 (IL-2) signals in T cells. Chimeric TGF-f3R/IL-2R IFPs were constructed by fusing extracellular domains of the TGF-f3 recepto...
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作者：Cooke, Dylan F.
作者单位：Simon Fraser University; Simon Fraser University
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作者：Ruiz, Nestor; Hendrixson, David R.
作者单位：University of California System; University of California Los Angeles
摘要：Canonical bacterial two-component signal transduction systems (TCSs) detect cues by sensors with opposing kinase and phosphatase activities to alter the level of phosphorylation of cognate response regulators to mediate responses. We previously identified the Campylobacter jejuni BumSR TCS as the founding member of a bacterial TCS family in which the sensor solely functions as a phosphatase. Sensing specific intestinal metabolites inhibits BumS dephosphorylation of phospho-BumR (P-BumR) to imp...
