Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function.

Background: Cardiac metabolic dysfunction is a hallmark of heart failure (HF). Estrogen-related receptors ERRα and ERRγ are essential regulators of cardiac metabolism. Therefore, activation of ERR could be a potential therapeutic intervention for HF.

Loss of the Maternal Effect Gene Nlrp2 Alters the Transcriptome of Ovulated Mouse Oocytes and Impacts Expression of Histone Demethylase KDM1B.

The subcortical maternal complex (SCMC) is a multiprotein complex in oocytes and preimplantation embryos that is encoded by maternal effect genes. The SCMC is essential for zygote-to-embryo transition, early embryogenesis, and critical zygotic cellular processes, including spindle positioning and symmetric division. Maternal deletion of Nlrp2, which encodes an SCMC protein, results in increased early embryonic loss and abnormal DNA methylation in embryos.

Assigning pathogenicity for TAB2 variants using a novel scalable functional assay and expanding TAB2 disease spectrum.

Haploinsufficiency of TGF-beta-activated kinase 1 (MAP3K7) binding protein 2 (TAB2) has been associated with congenital heart disease and more recently multiorgan structural abnormalities. Missense variant represents a major proportion of non-synonymous TAB2 variants reported in gnomAD (295/576) and Clinvar (16/73), most of which are variants of uncertain significance (VUSs). However, interpretation of TAB2 missense variants remains challenging because of lack of functional assays.

SR9009 improves heart function after pressure overload independent of cardiac REV-ERB.

The core clock component REV-ERB is essential for heart function. Previous studies show that REV-ERB agonist SR9009 ameliorates heart remodeling in the pressure overload model with transverse aortic constriction (TAC). However, it is unknown whether SR9009 indeed works through cardiac REV-ERB, given that SR9009 might target other proteins and that REV-ERB in non-cardiac tissues might regulate cardiac functions indirectly.