Physiology
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.
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.
Performance and robustness analysis reveals phenotypic trade-offs in yeastThis study combines phenotypic data from yeast cultivations with quantification of robustness over a defined perturbation space, revealing trade-offs between performance and robustness.
Fn14 promotes myoblast fusion during regenerative myogenesisGenetic and molecular approaches demonstrate that Fn14 receptor–mediated signaling improves myoblast fusion during skeletal muscle regeneration in a cell-autonomous manner.
Huntingtin loss in hepatocytes is associated with altered metabolism, adhesion, and liver zonationLifelong huntingtin loss in mouse hepatocytes is associated with altered metabolism, adhesion, and liver zonation which mimics the phenotypes caused by impaired B-catenin function.
Decoding the obesity–cancer connection: lessons from preclinical models of pancreatic adenocarcinomaPreclinical models demonstrate that obesity reprograms the pretumor or tumor cell and its micro- and macro-environments to drive cancer development via altered cellular metabolism, hormone dysregulation, inflammation, and microbial dysbiosis.
ERK1/2-SOX9/FOXL2 axis regulates ovarian steroidogenesis and favors the follicular–luteal transitionERK1/2 negatively regulates estradiol synthesis while positively regulating progesterone production in ovarian granulosa cells via the ERK1/2-SOX9/FOXL2 axis.
Hypoxia controls expression of kidney-pathogenic MUC1 variantsHypoxia or pharmacological treatment with novel HIF stabilizers promotes the expression of MUC1 genetic variants that predispose to the development of chronic kidney disease in renal tubular cells.
Yolk-deprived Caenorhabditis elegans secure brood size at the expense of competitive fitnessMany egg-laying species lower fecundity when yolk is in short supply, but not C. elegans. They still produce abundant offspring, yet of decreased quality.
Local tissue mechanics control cardiac pacemaker cell embryonic patterningMicroenvironmental patterning during sinoatrial node morphogenesis is critical for sustaining cardiac pacemaker cell function.