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Abstract: Individuals with obsessive-compulsive disorder (OCD) often experience intrusive thoughts. These intrusions may be due to biases in information processing mechanisms, including attention, memory, and learning. To examine this hypothesis, we presented a modified negative priming (NP) paradigm with idiographically selected words to 19 individuals with OCD (OCs) and 19 matched non-anxious control participants (NACs). The words included OCD-relevant threat, OCD-relevant positive, and neutral words. This paradigm typically elicits positive priming because participants may learn the contingency between the prime and probe that facilitates responding [Frings and Wentura (2006). Strategy effects counteract distractor inhibition: NP with constantly absent probe distractors. Journal of Experimental Psychology: Human Perception and Performance, 32, 854–864]. As predicted, NACs showed facilitation (i.e., positive priming) rather than NP for all word types, whereas OCs exhibited facilitation for only neutral words. For positive words, OCs exhibited no priming and for threat words they exhibited NP. These results suggest that for idiographic, OCD-relevant threat information, individuals with OCD show difficulty learning the contingency between the information in the prime and probe displays relative to the NACs. [Copyright &y& Elsevier]

Abstract In this study we examined whether the action of simvastatin affects re-differentiation of passaged chondrocytes and if so, whether this was mediated via changes in cholesterol or cholesterol intermediates. Bovine articular chondrocytes, of varying passage number, human knee chondrocytes and rat chondrosarcoma chondrocytes were treated with simvastatin and examined for changes in mRNA and protein expression of markers of the chondrocyte phenotype as well as changes in cell shape, proliferation and proteoglycan production. In all three models, while still in monolayer culture, simvastatin treatment alone promoted changes in phenotype and morphology indicative of re-differentiation most prominent being an increase in SOX9 mRNA and protein expression. In passaged bovine chondrocytes, simvastatin stimulated the expression of SOX9, ACAN, BMP2 and inhibited the expression of COL1 and α-smooth muscle actin. Co-treatment of chondrocytes with simvastatin plus exogenous cholesterol—conditions that had previously reversed the inhibition on CD44 shedding, did not alter the effects of simvastatin on re-differentiation. However, the co-treatment of chondrocytes with simvastatin together with other pathway intermediates, mevalonate, geranylgeranylpyrophosphate and to a lesser extent, farnesylpyrophosphate, blocked the pro-differentiation effects of simvastatin. Treatment with simvastatin stimulated expression of SOX9 and COL2a and enhanced SOX9 protein in human OA chondrocytes. The co-treatment of OA chondrocytes with mevalonate or geranylgeranylpyrophosphate, but not cholesterol, blocked the simvastatin effects. These results lead us to conclude that the blocking of critical protein prenylation events is required for the positive effects of simvastatin on the re-differentiation of chondrocytes. [ABSTRACT FROM AUTHOR]

Abstract: Falciparum malaria vaccine candidates have been developed using recombinant, replication-deficient serotype 5 and 35 adenoviruses (Ad5, Ad35) encoding the Plasmodium falciparum circumsporozoite surface protein (CSP) (Ad5.CS, Ad35.CS) (Crucell Holland BV, Leiden, The Netherlands). To evaluate the immunogenicity of these constructs, BALB/cJ mice were immunized twice with either Ad5.CS, Ad35.CS, empty Ad5-vector (eAd5), empty Ad35 vector (eAd35), or saline. Another group received the CSP-based RTS,S malaria vaccine formulated in the proprietary Adjuvant System AS01B (GlaxoSmithKline Biologicals, Rixensart, Belgium). Here we report that Ad5.CS, Ad35.CS, and RTS,S/AS01B, elicited both cellular and serologic CSP antigen-specific responses in mice. These adenoviral vectors induce strong malaria-specific immunity and warrant further evaluation. [Copyright &y& Elsevier]