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A cell-type specific approach to assess the contribution of dysregulated nutrient handling to atherosclerosis
The severity of atherosclerosis, which underlies the majority of cardiovascular disease, is determined by a wide variety of factors. Though many of these factors are well studied, a complete understanding of how to best slow or reverse development of atherosclerosis is lacking. Blood glucose is positively associated with an ...
Growth Signaling in Aging and Disease
(2013-11-14)
Nutrient sensing and growth signaling pathways are key regulators of healthspan and longevity. Caloric restriction, the most widely studied and well documented intervention in aging, functions largely through effects on nutrient sensing and growth signaling pathways. Genetic approaches to studying aging have further emphasized ...
The Cellular and Molecular Axis of Muscle Regeneration
Skeletal muscle has significant regenerative capacity, which is impaired with muscular dystrophy and aging. Muscle function and repair requires the involvement of several cellular compartments and molecular interactions. With disease cellular responses are influenced by the alteration of signaling pathways that are involved ...
Short-term rapamycin persistently improves cardiac function after cessation of treatment in aged male and female mice.
Cardiac aging is an intrinsic process that results in impaired cardiac function and dysregulation of cellular and molecular quality control mechanisms. These effects are evident in the decline of diastolic function, increase in left ventricular hypertrophy, metabolic substrate shifts, and alterations to the cardiac proteome. ...
Regulator of G-protein signaling 5 is expressed in hepatic stellate cells and moderates the fibrotic response to injury
Liver fibrosis is mediated by hepatic stellate cells (HSCs), which respond to a variety of cytokine and growth factors to moderate the response to injury and create extracellular matrix at the site of injury. G-protein coupled receptor (GPCR)-mediated signaling, via endothelin-1 (ET-1) and angiotensin II (AngII), increases ...
Molecular and Cellular Phenotypes of AUTS2 Deficiency in the Developing Mouse Cortex and Hippocampus
Variants in the gene Autism Susceptibility Candidate 2 (AUTS2) are a rare cause of intellectual disability, developmental delay and autistic features in patients. However, the mechanism by which loss of AUTS2 causes specific neurological symptoms, the underlying neuroanatomical abnormalities, and the syndrome’s pathological ...
Novel Disease Genes Underlying Rare Recessively Inherited Forms Of Osteogenesis Imperfecta
Osteogenesis imperfecta (OI) is a rare inherited connective tissue disorder affecting bone. Defining features are fragile bones that are highly susceptible to fracture (“brittle bone”) and bone deformation. There is a high degree of variability in the clinical skeletal features of OI, even sometimes within families. Presentations ...
The consequences of mutator-driven mutagenesis and analysis of lifespan extending compounds using outgrowth analysis and replicative lifespan in Saccharomyces cerevisiae
The hope of dramatically extending our lifespan has captivated humanity for millennia. Over the last two decades, the biology of aging has matured as a field of study and led to greater engagement and investment in aging as a biological problem that can be understood at the molecular level and treated. Translational Geroscience ...
Characterization of Precancerous Mutations in Ulcerative-Colitis Associated Colorectal Cancer and High-Grade Serous Ovarian Cancer via Duplex Sequencing
Humans have attempted to fight cancer since the beginning of recorded history, but advances in the early detection of cancer have begun to emerge only in the last several decades. Patient survival increases with earlier detection and cancer incidence decreases with efficacious screening tests, such as colonoscopy or the pap ...
Identifying and Characterizing Novel Targets against Rhabdomyosarcoma Disease Relapse
Rhabdomyosarcoma (RMS) is the most common soft tissue pediatric sarcoma. Patients with relapsed or metastatic disease are faced with a poor survival outlook. Self-renewal of tumor propagating cells (TPCs) is believed to be responsible for driving RMS disease relapse through resistance to conventional therapies and recapitulation ...