At the cellular level, we observed rapid cellular growth arrest and less resistance to oxidative stress and DNA damage
in TR4(-/-) mouse embryonic fibroblasts (MEFs) in vitro. Restoring TR4 or supplying the antioxidant N-acetyl-L-cysteine (NAC) to TR4(-/-) MEFs reduced the DNA damage and slowed down cellular growth arrest. Focused qPCR array revealed alteration of gene profiles Fosbretabulin in the DNA damage response (DDR) and anti-reactive oxygen species (ROS) pathways in TR4(-/-) MEFs, which further supports the hypothesis that the premature aging in TR4(-/-) mice might stem from oxidative DNA damage caused by increased oxidative stress or compromised genome integrity. Together, our finding identifies a novel role of TR4 in mediating the interplay between oxidative stress defense and aging.”
“Background: Quantitative modeling of the self-assembly of DNA tiles leading either to defined end-products or distribution of biopolymers is of practical importance for biotechnology and synthetic biology.\n\nMethods: The combinatorial process describing tile assembly was implemented into a generic algorithm allowing quantitative description of the population
of significant species accumulating during the reaction course. Experimental HSP990 mouse formation and characterization by optical and electrophoresis approaches of copolymers resulting from the self-assembly of a limited number of half-complementary tiles were used to define and validate generic rules allowing definition of model parameters.\n\nResults: Factors controlling the structure and the dynamic of the oligomer population were evidenced for assemblies leading or not to defined
end-products. Primary parameters were experimentally determined using rapid mixing experiments. Adjustment of simulations to experimental profiles allowed definition of generic rules for selleck calculation of secondary parameters that take into account macro- and microenvironment of individual hybridization steps. In the case of copolymers, accurate simulation of experimental profiles was achieved for formation of linear assemblies.\n\nConclusions: Overall length of species and structure of the DNA regions flanking the hybridization sites are critical parameters for which calculation rules were defined. The computational approach quantitatively predicted the parameters affecting time-course and distribution of accumulating products for different experimental designs.\n\nGeneral significance: The computational and parameter evaluation procedures designed for the assembly of DNA tiles into large 1D-structures are more generally applicable for the construction of non-DNA polymers by extremities-specific recognition of molecular blocks. (C) 2011 Elsevier B.V. All rights reserved.