The stochasticity of p53 regulation, introduced at the levels of gene expression, DNA damage and repair, leads to high heterogeneity of cell responses and causes cell population split after irradiation into subpopulations of apoptotic and surviving cells, with fraction of apoptotic cells growing with the irradiation dose. (C) 2008 Elsevier Ltd. All rights reserved.”
“Nitric oxide production in the colon has been linked to inflammatory https://www.selleckchem.com/products/tucidinostat-chidamide.html bowel disease (IBD) and increased risk for colon
cancer. However, measurements of NO concentration in the inflamed colon have not been available and it is not known what NO levels are pathophysiological. A computational model, based on anatomical length scales and rates of NO production measured in cell cultures, was used to predict spatially varying NO concentrations within a colonic crypt under inflammatory conditions. A variety of scenarios were considered, including different spatial distributions of macrophages and a range of possible macrophage and epithelial synthesis rates for NO. Activated macrophages arranged as a monolayer at the base of the crypt elicited Selleckchem Lapatinib maximum NO concentrations of approximately 0.3 mu M. The epithelial contribution to NO synthesis was calculated to be
negligible. Assuming a uniform macrophage layer, NO synthesis rates greater than 20 mu M/s, or more than three times that measured in vitro, would be necessary to achieve maximum NO concentrations of 1 mu M in the crypt, Thus, unless NO synthesis rates in macrophages and/or epithelial cells greatly exceed those measured in cell cultures, NO concentrations will remain submicromolar in the crypt during inflammation. Additionally, the results were used to predict the range of NO concentrations (< 0.3 mu M) and cumulative NO dose (560 mu M min) experienced by a
given epithelial cell migrating from the base to the top of the crypt. These estimates of NO concentrations in inflamed crypts should facilitate efforts to elucidate the molecular biological linkage between NO exposure and carcinogenesis in IBD. (c) 2008 Elsevier Inc. All rights reserved.”
“The malate-aspartate (M-A) shuttle provides an important mechanism to regulate glycolysis and lactate metabolism in the Selleck KU-60019 heart by transferring reducing equivalents from cytosol into mitochondria. However, experimental characterization of the M-A shuttle has been incomplete because of limitations in quantifying cytosolic and mitochondrial metabolites. In this study, we developed a multicompartment model of cardiac metabolism with detailed presentation of the M-A shuttle to quantitatively predict non-observable fluxes and metabolite concentrations under normal and ischemic conditions in vivo. Model simulations predicted that the M-A shuttle is functionally localized to a subdomain that spans the mitochondrial and cytosolic spaces.