“Butylbenzyl phthalate (BBzP) is used as a plasticizer
to import flexibility to polyvinylchloride plastics. In this study, hydrolysis of BBzP to monobutyl phthalate (MBP) and monobenzyl phthalate (MBzP) in liver microsomes of humans, monkeys, dogs, rats and mice was examined. The kinetics for MBP formation by human, dog and mouse liver microsomes followed the Michaelis-Menten model, whereas the kinetics by monkey and rat liver microsomes fitted the Hill model. The kinetics for MBzP formation fitted the Hill model for all liver microsomes. The V-max and in vitro clearance (CLint CLmax) ratios of MBP/MBzP formation varied among animal species, although the Km for MBP and MBzP formation in each liver microsomes were generally comparable. The hydrolysis of BBzP to monoester phthalates in mammalian liver microsomes could be classified into two types: MBzP bigger than MBP type for Crenolanib in vitro humans and dogs, and MBP bigger than MBzP type for monkeys, rats and mice. These findings suggest that the formation profile of MBzP and MBP from BBzP by liver microsomes differs extensively among animal species.”
“One of the unique characteristics of cellular signaling pathways is that a common signaling pathway can selectively regulate multiple
cellular functions of a hormone; however, this selective downstream control through a common signaling pathway is poorly understood. Here we show that the insulin-dependent AKT pathway uses temporal selleckchem patterns multiplexing for selective regulation of downstream molecules. Pulse and sustained insulin stimulations were simultaneously encoded into transient Pinometostat and sustained AKT phosphorylation, respectively. The downstream molecules, including ribosomal protein S6 kinase (S6K), glucose-6-phosphatase (G6Pase), and glycogen
synthase kinase-3 beta (GSK3 beta) selectively decoded transient, sustained, and both transient and sustained AKT phosphorylation, respectively. Selective downstream decoding is mediated by the molecules’ network structures and kinetics. Our results demonstrate that the AKT pathway can multiplex distinct patterns of blood insulin, such as pulse-like additional and sustained-like basal secretions, and the downstream molecules selectively decode secretion patterns of insulin.”
“For many years, it was generally accepted that mRNA is too unstable to be efficiently used for gene therapy purposes. In the last decade, however, several research groups faced this challenge and not only proved the feasibility of mRNA-mediated transfection with surprising results regarding transfection efficiency and duration of protein expression, but also were able to demonstrate major advantages over the use of pDNA. These advantages will be the first issue discussed in this review, which first of all addresses the notions that mRNA does not need to cross the nuclear barrier to exert its biological activity and in addition lacks CpG motifs, which reduces its immunogenicity.