A Transient Increase in Cardiomyocyte Protein O-GlcNAcylation Enhances Susceptibility to Pressure Overload-Induced Cardiac Remodeling.

Background: The observation that diabetic patients always under tight-glycemic control consistently show better cardiovascular disease outcomes compared to patients who transition to tight-glycemic control after prior conventional glycemic control lead to the concept of metabolic memory. Mechanisms such as epigenetics possibly mediate the lasting metabolic memory effects, our understanding of the underlying mechanisms remains limited. Increased cardiac protein posttranslational O-linked β-N-acetylglucosamine (O-GlcNAc) modification is implicated in cardiac remodeling observed in diabetes, and our previous work shows chronically elevated cardiomyocyte O-GlcNAc causes adverse cardiac changes.

Sirtuin 4 accelerates heart failure development by enhancing reactive oxygen species-mediated profibrotic transcriptional signaling.

Aims: Sirtuin 4 (SIRT4) is a mitochondrially-localized stress-responsive NAD-dependent deacetylase predominantly regulating energy metabolism and reactive oxygen species (ROS) homeostasis. Overexpression of SIRT4 aggravates angiotensin-induced cardiac hypertrophy, however underlying mechanisms remain incompletely elucidated. To current study was designed to explore mechanisms underlying adverse effects of increased SIRT4 levels in the heart following pressure overload.

Pulmonary Fibrosis Ferret Model Demonstrates Sustained Fibrosis, Restrictive Physiology, and Aberrant Repair.

Rationale: The role of MUC5B mucin expression in IPF pathogenesis is unknown. Bleomycin-exposed rodent models do not exhibit sustained fibrosis or airway remodeling. Unlike mice, ferrets have human-like distribution of MUC5B expressing cell types and natively express the risk-conferring variant that induces high MUC5B expression in humans.

Sustained Increases in Cardiomyocyte Protein -Linked β-N-Acetylglucosamine Levels Lead to Cardiac Hypertrophy and Reduced Mitochondrial Function Without Systolic Contractile Impairment.

Background Lifestyle and metabolic diseases influence the severity and pathogenesis of cardiovascular disease through numerous mechanisms, including regulation via posttranslational modifications. A specific posttranslational modification, the addition of -linked β- acetylglucosamine (-GlcNAcylation), has been implicated in molecular mechanisms of both physiological and pathologic adaptations. The current study aimed to test the hypothesis that in cardiomyocytes, sustained protein -GlcNAcylation contributes to cardiac adaptations, and its progression to pathophysiology.

Cardiomyocyte ZKSCAN3 regulates remodeling following pressure-overload.

Autophagy is important for protein and organelle quality control. Growing evidence demonstrates that autophagy is tightly controlled by transcriptional mechanisms, including repression by zinc finger containing KRAB and SCAN domains 3 (ZKSCAN3). We hypothesize that cardiomyocyte-specific ZKSCAN3 knockout (Z3K) disrupts autophagy activation and repression balance and exacerbates cardiac pressure-overload-induced remodeling following transverse aortic constriction (TAC).

Heat Shock Protein 90 Regulates the Activity of Histone Deacetylase Sir2 in Plasmodium falciparum.

Sir2 protein of Plasmodium falciparum has been implicated to play crucial roles in the silencing of subtelomeric genes and rRNA. It is also involved in telomere length maintenance. Epigenetic regulation of transcription occurs through a direct participation of the molecular chaperon PfHsp90, wherein PfHsp90 acts as a transcriptional repressor.

miRNA-200b-A Potential Biomarker Identified in a Porcine Model of Cardiogenic Shock and Mechanical Unloading.

Background: Cardiogenic shock (CS) alters whole body metabolism and circulating biomarkers serve as prognostic markers in CS patients. Percutaneous ventricular assist devices (pVADs) unload the left ventricle by actively ejecting blood into the aorta. The goal of the present study was to identify alterations in circulating metabolites and transcripts in a large animal model that might serve as potential prognostic biomarkers in acute CS and additional left ventricular unloading by Impella pVAD support.

Capsule Promotes Intracellular Survival and Vascular Endothelial Cell Translocation during Invasive Pneumococcal Disease.

The polysaccharide capsule that surrounds Streptococcus pneumoniae () is one of its most important virulence determinants, serving to protect against phagocytosis. To date, 100 biochemical and antigenically distinct capsule types, i.e.

Hsp90 Is Essential for Chl1-Mediated Chromosome Segregation and Sister Chromatid Cohesion.

Recent studies have demonstrated that aberrant sister chromatid cohesion causes genomic instability and hence is responsible for the development of a tumor. The Chl1 (chromosome loss 1) protein (homolog of human ChlRl/DDX11 helicase) plays an essential role in the proper segregation of chromosomes during mitosis. The helicase activity of Chl1 is critical for sister chromatid cohesion.