This is highly significant, as it reveals that rare mutations in the HRD motifs of protein kinases are highly penetrant and disease-causing, which provides a strong functional rationale for the R311C mutation in the HRD motif of CaMKK2 being considered a potential monogenic model of bipolar 1 disorder
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non-esterified fatty acids: NEFA) on the insulin receptor-mediated signaling pathways in adipose tissue, liver, and skeletal muscle as well as the pro-inflammatory status induced by the toxic effects of excess NEFA, principally in the liver and adipose tissues
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