“The long-term consequences of early environmental experiences for development have been explored extensively in animal models to better understand the mechanisms mediating risk of psychopathology in individuals exposed to childhood adversity. One common feature https://www.selleckchem.com/products/E7080.html of these models is disruption of the mother-infant relationship which is associated with impairments in stress responsivity and maternal
behavior in adult offspring. These behavioral and physiological characteristics are associated with stable changes in gene expression which emerge in infancy and are sustained into adulthood. Recent evidence suggests that these long-term effects may be mediated click here by epigenetic modification to the promoter regions of steroid receptor genes. In particular, DNA
methylation may be critical to maternal effects on gene expression and thus generate phenotypic differentiation of offspring and, through effects on maternal behavior of offspring, mediate the transmission of these effects across generations. In this review we explore evidence for the influence of mother-infant interactions on the epigenome and consider evidence for and the implications of such epigenetic effects for human mental health. (C) 2008 Elsevier Ltd. All rights reserved.”
“Currently there is limited information about the quality of immune responses elicited by candidate human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env)-based immunogens in primates. Here we describe a comprehensive analysis of neutralizing antibody and T-cell responses obtained in cynomolgus macaques by three selected immunization regimens. We used the previously described YU2-based gp140 protein trimers administered in an adjuvant, preceded by two distinct priming strategies: either alphavirus replicon particles expressing matched gp140 trimers or gp120 core proteins stabilized in the CD4-bound conformation. The rationale for priming with replicon particles
was to evaluate the impact of the expression platform on trimer immunogenicity. The stable core proteins were chosen in an attempt to expand selectively lymphocytes recognizing common determinants between the core and trimers Flavopiridol molecular weight to broaden the immune response. The results presented here demonstrate that the platform by which Env trimers were delivered in the priming ( either protein or replicon vector) had little impact on the overall immune response. In contrast, priming with stable core proteins followed by a trimer boost strikingly focused the T-cell response on the core sequences of HIV-1 Env. The specificity of the T-cell response was distinctly different from that of the responses obtained in animals immunized with trimers alone and was shown to be mediated by CD4(+) T cells.