Physiology
Metabolic dysregulation contributes to the development of dysferlinopathyDysferlin deficiency causes metabolic dysregulation, characterized by mitochondrial abnormalities, death signaling, and elevated glucose uptake and excessive glycogen accumulation in muscle.
NAD+ depletion is central to placental dysfunction in an inflammatory subclass of preeclampsiaInflammatory preeclampsia exhibits a decline in placental NAD+ levels along with mitochondrial impairment, which could be ameliorated by supplementing with NAD+ boosters during pregnancy.
Laminin-α2 chain deficiency in skeletal muscle causes dysregulation of multiple cellular mechanismsThis work reveals the defects caused by the absence of laminin-α2, including impaired myoblast proliferation and differentiation, DNA damage, oxidative stress, and mitochondrial dysfunction, highlighting its important role in muscle development and cellular homeostasis.
Activation mechanism and novel binding sites of the BKCa channel activator CTIBDCTIBD relieves overactive bladder in animal models by activating BKCa channels through extracellular binding, independent of calcium and membrane depolarization; key residues include W22, W203, and F266.
C/EBPβ deletion in macrophages impairs mammary gland alveolar budding during the estrous cycleMacrophage C/EBPβ contributes to alveolar budding during the estrous cycle by providing critical signaling to mammary epithelial cells.
Frataxin deficiency shifts metabolism to promote reactive microglia via glucose catabolismFrataxin depletion triggers reactive microglia with increase glucose catabolism. Butyrate treatment reinstates immunometabolic balance, potentially offering neuroprotection.
Metabolic and circadian inputs encode anticipatory biogenesis of hepatic fed microRNAsUnravelling molecular and physiological mechanisms that couple circadian and metabolic cues to regulate anticipatory miR biogenesis during fed-fast-refed cycles in the liver.
IMPA1 dependent regulation of phosphatidylinositol 4,5-bisphosphate and calcium signalling by lithiumThis study demonstrates that lithium that is used to treat bipolar disorder acts via IMPA1 to regulate calcium signalling and neuronal excitability.
Endothelial cells adopt a pro-reparative immune responsive signature during cardiac injuryscRNA-seq uncovers an endothelial cell (EC) subpopulation with immune responsive signatures in cardiac injury. Profiling of human heart failure samples reveals EC-specific immune responsive signatures in adult and pediatric heart failure. ECs can adopt immune responsive signatures during cardiac stress.
A dual-targeted drug inhibits cardiac ryanodine receptor Ca2+ leak but activates SERCA2a Ca2+ uptakeOur study identified a first multi-targeted compound (GM1869) inhibiting RyR2-mediated Ca2+ leak together with activating SERCA2a function that may represent a critical breakthrough for treatment of diastolic Ca2+ leak in heart failure.