Greg Markby
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View article: Autophagy regulates cellular senescence by mediating the degradation of CDKN1A/p21 and CDKN2A/p16 through SQSTM1/p62-mediated selective autophagy in myxomatous mitral valve degeneration
Autophagy regulates cellular senescence by mediating the degradation of CDKN1A/p21 and CDKN2A/p16 through SQSTM1/p62-mediated selective autophagy in myxomatous mitral valve degeneration Open
Myxomatous mitral valve degeneration (MMVD) is one of the most important age-dependent degenerative heart valve disorders in both humans and dogs. It is characterized by the aberrant remodeling of extracellular matrix (ECM), regulated by s…
View article: TGF-β phospho antibody array identifies altered SMAD2, PI3K/AKT/SMAD, and RAC signaling contribute to the pathogenesis of myxomatous mitral valve disease
TGF-β phospho antibody array identifies altered SMAD2, PI3K/AKT/SMAD, and RAC signaling contribute to the pathogenesis of myxomatous mitral valve disease Open
Background TGFβ signaling appears to contribute to the pathogenesis of myxomatous mitral valve disease (MMVD) in both dogs and humans. However, little is known about the extent of the downstream signaling changes that will then affect cell…
View article: <scp>TGF‐β</scp>‐induced <scp>PI3K</scp>/<scp>AKT</scp>/<scp>mTOR</scp> pathway controls myofibroblast differentiation and secretory phenotype of valvular interstitial cells through the modulation of cellular senescence in a naturally occurring in vitro canine model of myxomatous mitral valve disease
<span>TGF‐β</span>‐induced <span>PI3K</span>/<span>AKT</span>/<span>mTOR</span> pathway controls myofibroblast differentiation and secretory phenotype of valvular interstitial cells through the modulation of cellular senescence in a naturally occurring in vitro canine model of myxomatous mitral valve disease Open
PI3K/AKT/mTOR signalling contributes to several cardiovascular disorders. The aim of this study was to examine the PI3K/AKT/mTOR pathway in myxomatous mitral valve disease (MMVD). Double‐immunofluorescence examined expression of PI3K and T…
New Insights into Molecular Mechanisms Mediating Adaptation to Exercise; A Review Focusing on Mitochondrial Biogenesis, Mitochondrial Function, Mitophagy and Autophagy Open
Exercise itself is fundamental for good health, and when practiced regularly confers a myriad of metabolic benefits in a range of tissues. These benefits are mediated by a range of adaptive responses in a coordinated, multi-organ manner. T…
Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965 Open
SBI-0206965, originally identified as an inhibitor of the autophagy initiator kinase ULK1, has recently been reported as a more potent and selective AMP-activated protein kinase (AMPK) inhibitor relative to the widely used, but promiscuous…
View article: Osteoblast‐specific deficiency of ectonucleotide pyrophosphatase or phosphodiesterase‐1 engenders insulin resistance in high‐fat diet fed mice
Osteoblast‐specific deficiency of ectonucleotide pyrophosphatase or phosphodiesterase‐1 engenders insulin resistance in high‐fat diet fed mice Open
Supraphysiological levels of the osteoblast‐enriched mineralization regulator ectonucleotide pyrophosphatase or phosphodiesterase‐1 (NPP1) is associated with type 2 diabetes mellitus. We determined the impact of osteoblast‐specific Enpp1 a…
Expression of Calcification and Extracellular Matrix Genes in the Cardiovascular System of the Healthy Domestic Sheep (Ovis aries) Open
The maintenance of a healthy cardiovascular system requires expression of genes that contribute to essential biological activities and repression of those that are associated with functions likely to be detrimental to cardiovascular homeos…
Transcription factor EB and TFE3: new metabolic coordinators mediating adaptive responses to exercise in skeletal muscle? Open
In response to the increased energy demands of contractions, skeletal muscle adapts remarkably well through acutely regulating metabolic pathways to maintain energy balance and in the longer term by regulating metabolic reprogramming, such…
Comparative transcriptomic profiling of myxomatous mitral valve disease in the Cavalier King Charles Spaniel Open
Background. Almost all elderly dogs develop myxomatous mitral valve disease by the end of their life, but the Cavalier King Charles Spaniel (CKCS) has a heightened susceptibility, frequently resulting in death at a young age and suggesting…
Severe perinatal hydrops fetalis in genome edited pigs with a biallelic five base pair deletion of the Marfan syndrome gene, <i>FBN1</i> Open
This paper describes a genome editing project using CRISPR-Cas9. The objective was to create a large animal model of human Marfan syndrome by targeting the FBN1 gene of the pig, Sus scrofa , using a single guide and non-homologous end join…
Comparative transcriptomic profiling of myxomatous mitral valve disease in the Cavalier King Charles Spaniel Open
Background. Almost all elderly dogs develop myxomatous mitral valve disease by the end of their life, but the Cavalier King Charles Spaniel (CKCS) has a heightened susceptibility, frequently resulting in death at a young age and suggesting…
Comparative transcriptomic profiling of myxomatous mitral valve disease in the Cavalier King Charles Spaniel Open
Background. All dogs develop myxomatous mitral valve disease by the end of their life, but the Cavalier King Charles Spaniel (CKCS) has a heightened susceptibility, frequently resulting in death at a young age and suggesting that there is …
Disease Severity-Associated Gene Expression in Canine Myxomatous Mitral Valve Disease Is Dominated by TGFβ Signaling Open
Myxomatous mitral valve disease (MMVD) is the most common acquired canine cardiovascular disease and shares many similarities with human mitral valvulopathies. While transcriptomic datasets are available for the end-stage disease in both s…
Gene expression in the cardiovascular system of the domestic sheep ( <i>Ovis aries</i> ); a new tool to advance our understanding of cardiovascular disease Open
Large animal models are of increasing importance in cardiovascular disease research as they demonstrate more similar cardiovascular features (in terms of anatomy, physiology and size) to humans than do rodent species. The maintenance of a …
Beyond mineralisation: metabolic functions for matrix mineralisation regulators Open
The physiological mineralisation of skeletal tissues, as well as the pathological mineralisation of soft tissues involves a fine balance between regulators that either promote or inhibit the process. In recent years, several studies have a…
CKCS CEL data Open
The dataset is microrarray data collected from canine RNA samples. The experimental design of this project is to perform comparative analysis (unpaired one-way ANOVA) between normal canine mitral valves, late stage Myxomatous mitral valves…
Evaluation of canine 2D cell cultures as models of myxomatous mitral valve degeneration Open
The utility of cells cultured from the mitral valve as models of myxomatous diseases needs to be properly validated. In this study valve interstitial cells (VICs) and valve endothelial cells (VECs) were cultured from normal and diseased ca…
Isolation and Characterization of Primary Rat Valve Interstitial Cells: A New Model to Study Aortic Valve Calcification Open
Calcific aortic valve disease (CAVD) is characterized by the progressive thickening of the aortic valve leaflets. It is a condition frequently found in the elderly and end-stage renal disease (ESRD) patients, who commonly suffer from hyper…
Comparative Transcriptomic Profiling and Gene Expression for Myxomatous Mitral Valve Disease in the Dog and Human Open
Myxomatous mitral valve disease is the single most important mitral valve disease in both dogs and humans. In the case of the dog it is ubiquitous, such that all aged dogs will have some evidence of the disease, and for humans it is known …