In humans, lack of phenylalanine hydroxylase (Pah) activity results in phenylketonuria (PKU), which is associated with the development of severe mental retardation after birth. The underlying mechanisms, however, are poorly understood. Mutations of the Pah gene in Pah(enu2)/c57bl6 mice result in elevated levels of phenylalanine in serum similar to those in humans suffering from PKU. In our stud...

Rationale: Traumatic brain injury (TBI) leads to neurological impairment, with no satisfactory treatments available. Classical ketogenic diets (KD), which reduce reliance on carbohydrates and provide ketones as fuel, have neuroprotective potential, but their high fat content reduces compliance, experimental evidence suggests they protect juvenile against TBI, not adult brain, would strongly lim...

Cardiometabolic alterations are frequent in patients with heart failure preserved ejection fraction (HFpEF). We recently demonstrated sinoatrial node (SAN) dysfunction limits the chronotropic response two distinct animal models of HFpEF; however, our new findings suggest a relationship between metabolism and SAN dysfunction. To identify metabolically-driven changes that facilitate HFpEF. Male C...

Idiopathic pulmonary fibrosis (IPF) is a disease that causes scarring and destruction of lung tissue ultimately fatal. There need to develop improved treatments for IPF. One problem with identifying novel IPF the poor predictability current preclinical models. Few model investigate function changes, rather relying on histological changes which doesn't adequately reflect complete clinical situat...

OBJECTIVE The role of fibroblast growth factors (FGFs) in the development of vascular diseases remains incompletely understood. The objective of this study was to examine the effects of a new small-molecule multi-FGF receptor blocker with allosteric properties, SSR128129E, on neointimal proliferation after a vein graft procedure in mice and on the development of atherosclerosis in atheroscleros...

To maximize the sensitivity of detecting affects of genetic variants in mice, variables have been minimized through the use of inbred mouse lines, by eliminating infectious organisms and controlling environmental variables. However, the impact of standard animal husbandry and experimental procedures on the validity of experimental data is under appreciated. In this study we monitored the impact...

The 5TGM1 multiple myeloma transplanted C57BL6/KaLwRij model recapitulates many disease features including monoclonal paraprotein production as well as the development of osteolytic bone lesions. Since a significant association between serum parathyroid hormone PTH variations, bone anabolism and myeloma progression in patients receiving proteasome inhibitors exists, this study investigated the ...

BACKGROUND Cancer cachexia is largely irreversible, at least via nutritional means, and responsible for 20-40% of cancer-related deaths. Therefore, preventive measures are of primary importance; however, little is known about muscle perturbations prior to onset of cachexia. Cancer cachexia is associated with mitochondrial degeneration; yet, it remains to be determined if mitochondrial degenerat...