Sex-specific quantitative trait loci linked to autoresuscitation failure in SWR/J mice.

Autoresuscitation (AR) is a highly conserved response among mammals, which allows survival from transient extreme hypoxia. During hypoxia, bradycardia, and hypoxic gasping develop after a brief period of hyperactivity. Normally, AR occurs if oxygen is restored during the gasping period where an initial heart rate increase is rapidly followed resumption or eupneic breathing. Humans and other mammals can survive multiple immediately repeated AR. A defective AR capacity has been implicated in Sudden Infant Death Syndrome. We had reported earlier that inbred strains of mice such as BALB/cJ could survive a characteristic number of immediately repeated AR trials, but that SWR/J mice failed to AR from a single hypoxic episode. We now report that strains closely related to SWR/J, FVB/N and SJL/J exhibit partial resuscitation defects relative to BALB/cJ or other mouse strains, establishing a genetic basis for variation in AR failure. The AR trial phenotype of BALB/cJ x SWR/J intercross F(1) and F(2) mice was consistent with BALB/cJ dominance and a discrete number of loci. Genome-wide mapping conducted with 60 intercross F(2) animals linked two loci to the number of AR trials survived, including one sex-specific locus with male expression, consistent with the observed 50% male bias for Sudden Infant Death Syndrome in humans. A locus carried on SWR/J chromosome 10 seems to be particularly important in AR failure and was confirmed in a partial consomic line. These results establish a genetic basis for AR failure phenotype in mice, with relevance to Sudden Infant Death Syndrome.

Outcomes and lessons from a pilot RCT of a community-based HIV prevention multi-session group intervention for gay men.

This paper presents the first outcome evaluation of multi-session groupwork for HIV prevention among gay men in the UK. This community-based RCT recruited 50 men, of whom 42% were HIV-positive or untested, and 32% reported status unknown or serodiscordant UAI in the previous 12 months. No knowledge, skills, attitudinal or behavioural differences were detected between intervention and control at baseline. At eight weeks, those attending the group reported significant gains over their control in making sexual choices, physical safety, HIV and STI transmission knowledge, and sexual negotiation skills. At 20 weeks, significant differences remained for HIV and STI transmission knowledge and comfort with sexual choices. Although no behavioural differences were detected, the aims of the National Prevention Strategy were met. This pilot RCT is appraised in the light of modest sample size and attrition, and recommendations for establishing behavioural outcomes are presented. This study has demonstrated that high-risk community samples can be recruited to multi-session interventions, and has provided feasibility data for future rigorous evaluation designs.

Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense.

Precursors of alpha-defensin peptides require activation for bactericidal activity. In mouse small intestine, matrilysin colocalized with alpha-defensins (cryptdins) in Paneth cell granules, and in vitro it cleaved the pro segment from cryptdin precursors. Matrilysin-deficient (MAT-/-) mice lacked mature cryptdins and accumulated precursor molecules. Intestinal peptide preparations from MAT-/- mice had decreased antimicrobial activity. Orally administered bacteria survived in greater numbers and were more virulent in MAT-/- mice than in MAT+/+ mice. Thus, matrilysin functions in intestinal mucosal defense by regulating the activity of defensins, which may be a common role for this metalloproteinase in its numerous epithelial sites of expression.