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    1. Structural Biology and Molecular Biophysics

    An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering

    Daniel A Keedy et al.
    By measuring how multiple conformations shift in response to temperature, a new allosteric binding site is discovered for the phosphatase PTP1B.
    1. Neuroscience

    The cerebellum linearly encodes whisker position during voluntary movement

    Susu Chen et al.
    Cerebellar Purkinje cells represent movements via bidirectional linear changes in spike rate, and activity from single cells is sufficient to reconstruct kinematic changes during bouts of free whisking.
    1. Cancer Biology

    Overcoming mutation-based resistance to antiandrogens with rational drug design

    Minna D Balbas et al.
    Mutagenesis studies identified an androgen receptor mutation that converts enzalutamide-a drug recently approved for the treatment of advanced prostate cancer-into an androgen receptor agonist, and modeling studies informed the design of novel drugs that are effective against the mutant receptor.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    Rationally derived inhibitors of hepatitis C virus (HCV) p7 channel activity reveal prospect for bimodal antiviral therapy

    Joseph Shaw et al.
    Exploiting virus-encoded ion channels as drug targets drove a multi-faceted approach to deriving potent small molecules targeting HCV p7, simultaneously providing new insights into its fundamental biology.
    1. Evolutionary Biology

    An adjunctive therapy administered with an antibiotic prevents enrichment of antibiotic-resistant clones of a colonizing opportunistic pathogen

    Valerie J Morley et al.
    Cholestyramine, an FDA-approved bile acid sequestrant, can be repurposed to inactivate the antibiotic daptomycin in the gut, which prevents the emergence of transmissible antibiotic resistance in gastrointestinal Enterococcus faecium populations.
    1. Cell Biology
    2. Computational and Systems Biology

    Development, calibration, and validation of a novel human ventricular myocyte model in health, disease, and drug block

    Jakub Tomek et al.
    A computer model of human cardiomyocyte was produced and validated on independent datasets, overcoming shortcomings of its predecessors, also yielding broadly relevant insights and results on major ionic currents.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    The human gut chemical landscape predicts microbe-mediated biotransformation of foods and drugs

    Leah Guthrie et al.
    A network of the gut chemical landscape predicts microbe-mediated biotransformation of foods and drugs and supports the generation of mechanistic hypotheses of microbiome metabolic phenotypes that shape human biology.
    1. Neuroscience

    Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein

    Ismael Al-Ramahi et al.
    This work validates PIP4K gamma as pharmacological target to ameliorate Huntington's disease.
    1. Neuroscience

    Stimulus-dependent relationships between behavioral choice and sensory neural responses

    Daniel Chicharro et al.
    New stimulus-dependencies of choice-related signals in sensory neurons uncovered by new analytical results and methods.
    1. Microbiology and Infectious Disease
    2. Physics of Living Systems

    Inhibition of SARS-CoV-2 polymerase by nucleotide analogs from a single-molecule perspective

    Mona Seifert et al.
    High-throughput and ultra-stable magnetic tweezers reveal that Remdesivir induces a long-lived backtrack pause upon incorporation by the coronavirus polymerase, and SARS-CoV-2 is able to evade interferon-induced antiviral ddhCTP.