2,701 results found
    1. Structural Biology and Molecular Biophysics
    2. Neuroscience

    Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons

    Pedro L Martinez-Espinosa et al.
    Sodium-activated potassium ion currents encoded by the kcnt1 gene delay action potential firing in DRG neurons by activity preceding an action potential.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    PPP1R15A-mediated dephosphorylation of eIF2α is unaffected by Sephin1 or Guanabenz

    Ana Crespillo-Casado et al.
    The notion that the drug-like small molecule Sephin1 protects against protein misfolding by selectively disrupting a cellular phosphatase is refuted.
    1. Computational and Systems Biology
    2. Human Biology and Medicine

    Unravelling druggable signalling networks that control F508del-CFTR proteostasis

    Ramanath Narayana Hegde et al.
    Analysis of the mechanism of action of cystic fibrosis corrector drugs reveals signalling pathways potently controlling the proteostasis of the main disease-relevant CFTR mutant.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Subcellular drug targeting illuminates local kinase action

    Paula J Bucko et al.
    Genetically-encoded platforms direct kinase inhibitor drugs to organelles to reveal new dimensions of local kinase signaling.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Bone-Targeting Drugs: From vesicle to cytosol

    Michael J Rogers, Marcia A Munoz
    Drugs called bisphosphonates are used to treat a range of bone diseases, but how do they reach the enzymes that are their target?
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    1. Cancer Biology
    2. Cell Biology

    The anticancer natural product ophiobolin A induces cytotoxicity by covalent modification of phosphatidylethanolamine

    Christopher Chidley et al.
    An unbiased genetic screen in human cells shows that the molecular target of a natural product with promising anticancer activity is a membrane phospholipid.
    1. Cell Biology
    2. Computational and Systems Biology

    Active machine learning-driven experimentation to determine compound effects on protein patterns

    Armaghan W Naik et al.
    In an investigation into the effects of drugs on proteins, an active machine learning algorithm chose which sets of experiments to perform and was able to learn an accurate model of the effects after doing only a fraction of the experiments.
    1. Neuroscience

    Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation

    Ming Chen et al.
    Experiments examining the actions of morphine on single neurons from one of the brain's reward centers, the VTA, reveal the mechanism by which the drug exerts its hedonic effects.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Modulation of the Erwinia ligand-gated ion channel (ELIC) and the 5-HT3 receptor via a common vestibule site

    Marijke Brams et al.
    Development of nanobodies against a model pentameric ligand-gated ion channel demonstrates they can be functionally active as negative or positive allosteric modulators and offers opportunities for future drug development.
    1. Human Biology and Medicine

    Reverse translation of adverse event reports paves the way for de-risking preclinical off-targets

    Mateusz Maciejewski et al.
    Careful analysis of adverse drug reaction reports reveals noise and biases embedded in this data and allows for systematic mitigation of these effects to produce much more robust understanding of side effects of marketed drugs.

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