Genome-wide genetic association of complex traits in heterogeneous stock mice

Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits.     

Ionic effects on cyclic nucleotide accumulation in a phytophagous insect

Summary Incubation in solutions containing high potassium levels reduces specific accumulation of cyclic AMP in larval nerve cords ofManduca, sexta in vitro with or without serotonin or theophylline.Supported in part by NIH grant NS-09161-20 to R.W.N.     

A method for determining cross-measurements of motor neurons

Summary This new triangulation technique allows the investigator to make cross-measurements of individual cells quickly and easily with a high degree of accuracy and reliability.     

Primary structure of Torpedo californica acetylcholinesterase deduced from its cDNA sequence

Acetylcholinesterase, an essential enzyme of the nervous system, rapidly terminates the action of acetylcholine released into the synapse. Acetylcholinesterase is also found (in lower abundance) in extrajunctional areas of muscle and nerve and on erythrocyte membranes. Hydrodynamic analyses of the native enzyme and characterization of its dissociated subunits have revealed multiple enzyme forms which can be divided into two classes: dimensionally asymmetric forms which are usually found within the synapse and contain a collagen-like structural subunit disulphide-linked to the catalytic subunits; and globular forms which appear to be widely distributed on the outer surface of cell membranes. Both forms have been characterized in the ray Torpedo californica and, although their catalytic behaviours seem to be identical, they differ slightly in amino-acid composition, peptide maps and reactivity with certain monoclonal antibodies. Here, we report the complete amino-acid sequence of an acetylcholinesterase inferred from the sequence of a complementary DNA clone. The 575-residue protein shows significant homology with the C-terminal portion of thyroglobulin.     

Effects of centrophenoxine,piracetam and hydergine on rat brain lipid peroxidation

Summary The cerebral insufficiency improvers centrophenoxine, piracetam and hydergine were tested for their effect on lipid peroxidation of rat brain homogenates, both in vitro and in vivo. There was no effect either in vitro or after chronic 8 week dosing of animals.     

Biological effects of singlet delta oxygen on respiratory tract epithelium

Summary Exposure of hamster tracheal organ cultures to gas phase singlet delta oxygen,¹O₂, at atmospheric pressure produced significant alterations in the mucociliary epithelium resulting in changes in ciliary activity and cellular morphology.Acknowledgments. The authors acknowledge helpful conversations with Professor R.W. Murray of the University of Missouri (St. Louis). We would like to thank the National Institute of Environmental Health Sciences for supporting this work through Public Health Grant 1-RO1-ESO1-O1A1-PHTB.     

Schistosome vaccines

Summary Schistosomiasis control currently relies primarily on chemotherapy which is both expensive and temporary. There is an urgent need for an effective vaccine. Studies in animal models and man have demonstrated the existence of protective immunity. Antibody-dependent cell-mediated cytotoxicity mechanisms involving eosinophils and macrophages have been implemented in destruction of the parasites. Antigens expressed on the surface of the schistosomulum are among the targets of protective immune responses. Vaccines comprising recombinant antigens are now being tested in vivo for their capacity to evoke protective responses. Live oral vaccines based on attenuatedSalmonella expressing schistosomular surface antigens are being developed.