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Background Recent studies have revealed sexually dimorphic associations between the carbamoyl-phosphate synthase 1 locus, intermediates of the metabolic pathway leading from choline to urea, and risk of coronary artery disease ( CAD ) in women. Based on evidence from the literature, the atheroprotective association with carbamoyl-phosphate synthase 1 could be mediated by the strong genetic effect of this locus on increased circulating glycine levels. Methods and Results We sought to identify additional genetic determinants of circulating glycine levels by carrying out a meta-analysis of genome-wide association study data in up to 30 118 subjects of European ancestry. Mendelian randomization and other analytical approaches were used to determine whether glycine-associated variants were associated with CAD and traditional risk factors. Twelve loci were significantly associated with circulating glycine levels, 7 of which were not previously known to be involved in glycine metabolism ( ACADM , PHGDH , COX 18- ADAMTS 3, PSPH , TRIB 1, PTPRD , and ABO ). Glycine-raising alleles at several loci individually exhibited directionally consistent associations with decreased risk of CAD . However, these effects could not be attributed directly to glycine because of associations with other CAD -related traits. By comparison, genetic models that only included the 2 variants directly involved in glycine degradation and for which there were no other pleiotropic associations were not associated with risk of CAD or blood pressure, lipid levels, and obesity-related traits. Conclusions These results provide additional insight into the genetic architecture of glycine metabolism, but do not yield conclusive evidence for a causal relationship between circulating levels of this amino acid and risk of CAD in humans.

In murine models of alcoholism, the glutamate receptor scaffolding protein Homer2 bidirectionally regulates alcohol intake. Although chronic alcohol drinking increases Homer2 expression within the core subregion of the nucleus accumbens (NAc) of alcohol-preferring P rats, the relevance of this neuroadaptation for alcohol intake has yet to be determined in rats. Thus, the present study employed an adeno-associated viral vector (AAV) strategy to over-express and knock down the major rodent isoform Homer2b within the NAc of both P and outbred Wistar rats to examine for changes in alcohol preference and intake (0-30% v/v) under continuous-access procedures. The generalization of AAV effects to non-drug, palatable, sweet solutions was also determined in tests of sucrose (0-5% w/v) and saccharin (0-0.125% w/v) intake/preference. No net-flux in vivo microdialysis was conducted for glutamate in the NAc to relate Homer2-dependent changes in alcohol intake to extracellular levels of glutamate. Line differences were noted for sweet solution preference and intake, but these variables were not affected by intra-NAc AAV infusion in either line. In contrast, Homer2b over-expression elevated, while Homer2b knock-down reduced, alcohol intake in both lines, and this effect was greatest at the highest concentration. Strikingly, in P rats there was a direct association between changes in Homer2b expression and NAc extracellular glutamate levels, but this effect was not seen in Wistar rats. These data indicate that NAc Homer2b expression actively regulates alcohol consumption by rats, paralleling this previous observation in mice. Overall, these findings underscore the importance of mesocorticolimbic glutamate activity in alcohol abuse/dependence and suggest that Homer2b and/or its constituents may serve as molecular targets for the treatment of these disorders.

Examines the point at which children develop negative attitudes toward science and whether the adoption of the National Curriculum in England and Wales has influenced student attitudes. Results indicate that although unpopular, students do not necessarily have negative attitudes toward science. Contains 32 references. (DDR)

Explored the perceptions of primary school students in Wales (United Kingdom) with regard to science since its introduction as a compulsory component of the curriculum. In samples of 120 students a year for three years, both boys and girls viewed science positively, but their science preferences were different. (SLD)

Issues concerning the use of physicist's tools to enhance understanding of the properties of earth materials and earth processes are presented. Reference is made to the use of synchrotron radiation and neutron radiation.

Research was conducted to examine the role of sliding scales and wage flexibility in early 1920s Britain. The objective was to take into account their possible contribution using cross-sectional industry data. Data were taken from wage level information for 49 industries for 1920 and 1924 and supplemented with data from the Labour Gazette and the UK 1924 Census of Production on industry characteristics. Results indicate that sliding scales had little effect on wage-setting during the rapid deflation of the early 1920s.

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1468-0289.2007.00401_14.x Byline: nicholas woodward (1) Author Affiliation: (1)University of Swansea

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1468-0289.2007.00394_16.x Byline: nicholas woodward (1) Author Affiliation: (1)University of Swansea