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    1. Structural Biology and Molecular Biophysics
    2. Evolutionary Biology

    An atomic-resolution view of neofunctionalization in the evolution of apicomplexan lactate dehydrogenases

    Jeffrey I Boucher et al.
    The convergent evolution of unusually strict substrate specificity in apicomplexan LDHs arose by classic neofunctionalization of a duplicated MDH gene via few mutations of large effect.
    1. Medicine
    2. Neuroscience

    Self-blinding citizen science to explore psychedelic microdosing

    Balázs Szigeti et al.
    The anecdotally reported benefits of psychedelics microdosing can be explained by the placebo effect.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB

    Thomas Eicher et al.
    A transport mechanism is uncovered in the major drug-efflux system in E. coli involving two remote alternating-access conformational cycles, which could provide the basis for the development of allosteric inhibitors against multidrug resistance.
    1. Cancer Biology
    2. Structural Biology and Molecular Biophysics

    Dynamics of human protein kinase Aurora A linked to drug selectivity

    Warintra Pitsawong et al.
    Slow conformational changes after drug binding rationalize selectivity, affinity and long on-target residence time for kinase inhibitors.
    1. Cell Biology

    Reduction of elevated proton leak rejuvenates mitochondria in the aged cardiomyocyte

    Huiliang Zhang et al.
    The primary respiratory defect seen in aged cardiomyocytes is an elevated proton leak mediated by ANT1, and this is prevented by treatment with SS-31 (elamipretide).
    1. Evolutionary Biology

    Convergent changes in muscle metabolism depend on duration of high-altitude ancestry across Andean waterfowl

    Neal J Dawson et al.
    Changes in pathways of lipid oxidation, glycolysis, and mitochondrial oxidative phosphorylation are common strategies to cope with high-altitude hypoxia, but some changes require longer evolutionary time to arise.
    1. Genetics and Genomics

    A regulatory pathway that selectively up-regulates elongasome function in the absence of class A PBPs

    Yesha Patel et al.
    Balanced peptidoglycan synthesis requires regulators, including sigma-I and WalKR, that coordinate the diffusive action of class A PBPs and the directional motion of the MreB-directed elongasome.
    1. Cancer Biology
    2. Computational and Systems Biology

    A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity

    Adam C Palmer et al.
    Drugs in a curative chemotherapy regimen are independently effective and resisted by different mechanisms, so cancer cells have little chance of surviving all drugs, and this benefit occurs without synergistic interactions.
    1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    Evolutionary stability of collateral sensitivity to antibiotics in the model pathogen Pseudomonas aeruginosa

    Camilo Barbosa et al.
    Evolutionary trade-offs enhance efficacy of antibiotic therapy by constraining bacterial adaptation in dependence of drug order and trade-off effect size.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    Mouse TRPA1 function and membrane localization are modulated by direct interactions with cholesterol

    Justyna B Startek et al.
    The activation and membrane localization of the broadly-tuned noxious chemosensory cation channel TRPA1 are regulated by direct interactions with cholesterol via CRAC motifs in transmembane segments 2 and 4.