Perceived self-efficacy in coping with cognitive stressors and opioid activation

This experiment tested the hypothesis that perceived self-inefficacy in exercising control over cognitive stressors activates endogenous opioid systems. Subjects performed mathematical operations under conditions in which they could exercise full control over the cognitive task demands or in which the cognitive demands strained or exceeded their cognitive capabilities. Subjects with induced high perceived self-efficacy exhibited little stress, whereas those with induced low perceived self-efficacy experienced a high level of stress and autonomic arousal. Subjects were then administered either an inert saline solution or naloxone, an opiate antagonist that blocks the analgesic effects of endogenous opiates, whereupon their level of pain tolerance was measured. The self-efficacious nonstressed subjects gave no evidence of opioid activation. The self-inefficacious stressed subjects were able to withstand increasing amounts of pain stimulation under saline conditions. However, when endogenous opioid mechanisms that control pain were blocked by naloxone, the subjects were unable to bear much pain stimulation. This pattern of changes suggests that the stress-induced analgesia found under the saline condition was mediated by endogenous opioid mechanisms and counteracted by the opiate antagonist

Chromatin Remodeling Pathways in Smooth Muscle Cell Differentiation, and Evidence for an Integral Role for p300

Phenotypic alteration of vascular smooth muscle cells (SMC) in response to injury or inflammation is an essential component of vascular disease. Evidence suggests that this process is dependent on epigenetic regulatory processes. P300, a histone acetyltransferase (HAT), activates crucial muscle-specific promoters in terminal (non-SMC) myocyte differentiation, and may be essential to SMC modulation as well.We performed a subanalysis examining transcriptional time-course microarray data obtained using the A404 model of SMC differentiation. Numerous chromatin remodeling genes (up to 62% of such genes on our array platform) showed significant regulation during differentiation. Members of several chromatin-remodeling families demonstrated involvement, including factors instrumental in histone modification, chromatin assembly-disassembly and DNA silencing, suggesting complex, multi-level systemic epigenetic regulation. Further, trichostatin A, a histone deacetylase inhibitor, accelerated expression of SMC differentiation markers in this model. Ontology analysis indicated a high degree of p300 involvement in SMC differentiation, with 60.7% of the known p300 interactome showing significant expression changes. Knockdown of p300 expression accelerated SMC differentiation in A404 cells and human SMCs, while inhibition of p300 HAT activity blunted SMC differentiation. The results suggest a central but complex role for p300 in SMC phenotypic modulation.Our results support the hypothesis that chromatin remodeling is important for SMC phenotypic switching, and detail wide-ranging involvement of several epigenetic modification families. Additionally, the transcriptional coactivator p300 may be partially degraded during SMC differentiation, leaving an activated subpopulation with increased HAT activity and SMC differentiation-gene specificity

United States Department of Energy Grand Junction Office Report PGJ/F-011(82)

From Introduction: "The Saint Johns Quadrangle, Arizona and New Mexico (Fig. 1), was evaluated to identify geologic environments and delineate areas that exhibit characteristics favorable for uranium deposits.