Population structure, differential bias and genomic control in a large-scale, case-control association study

The main problems in drawing causal inferences from epidemiological case-control studies are confounding by unmeasured extraneous factors, selection bias and differential misclassification of exposure. In genetics the first of these, in the form of population structure, has dominated recent debate. Population structure explained part of the significant +11.2% inflation of test statistics we observed in an analysis of 6,322 nonsynonymous SNPs in 816 cases of type 1 diabetes and 877 population-based controls from Great Britain. The remainder of the inflation resulted from differential bias in genotype scoring between case and control DNA samples, which originated from two laboratories, causing false-positive associations. To avoid excluding SNPs and losing valuable information, we extended the genomic control method by applying a variable downweighting to each SNP.     

Wolbachia variability and host effects on crossing type in Culex mosquitoes

Wolbachia is a common maternally inherited bacterial symbiont able to induce crossing sterilities known as cytoplasmic incompatibility (CI) in insects. Wolbachia-modified sperm are unable to complete fertilization of uninfected ova, but a rescue function allows infected eggs to develop normally. By providing a reproductive advantage to infected females, Wolbachia can rapidly invade uninfected populations, and this could provide a mechanism for driving transgenes through pest populations. CI can also occur between Wolbachia-infected populations and is usually associated with the presence of different Wolbachia strains. In the Culex pipiens mosquito group (including the filariasis vector C. quinquefasciatus) a very unusual degree of complexity of Wolbachia-induced crossing-types has been reported, with partial or complete CI that can be unidirectional or bidirectional, yet no Wolbachia strain variation was found. Here we show variation between incompatible Culex strains in two Wolbachia ankyrin repeat-encoding genes associated with a prophage region, one of which is sex-specifically expressed in some strains, and also a direct effect of the host nuclear genome on CI rescue.     

Adenyl cyclase activity of mouse liver membranes after incubation with endotoxin and epinephrine

Summary Adenyl cyclase activity in isolated mouse liver cell membranes was stimulated two-fold by endotoxin. Furthermore, endotoxin inhibited epinephrine induction of adenyl cyclase activity, apparently through interruption of the phospholipid moiety of the enzyme complex.     

Effect of cyproheptadine on the octopamine-induced responses in the mammalian central nervous system

Summary Extracellular recordings have been made from rat thalamic neurones anaesthetized with urethane, 1.5–2 g/kg i.p. Iontophoretically applied octopamine excited certain thalamic neurones in the ventral basal complex while inhibiting others. Both effects were reversibly antagonized by iontophoretically applied cyproheptadine without affecting responses to noradrenaline and dopamine.Acknowledgment. We are grateful to Merck, Sharp and Dohme for a gift of cyproheptadine HCl.