Structure and regulation of type 2 transglutaminase in relation to its physiological functions and pathological roles

This chapter contains sections titled: Introduction Structure and Regulation Physiologic Functions of TG2 Disruption of TG2 Functions in Pathologic Conditions Perspectives for Pharmacologic Interventions Concluding Comments Acknowledgements References

Common variants in left/right asymmetry genes and pathways are associated with relative hand skill

Humans display structural and functional asymmetries in brain organization, strikingly with respect to language and handedness. The molecular basis of these asymmetries is unknown. We report a genome-wide association study meta-analysis for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)] (n = 728). The most strongly associated variant, rs7182874 (P = 8.68×10-9), is located in PCSK6, further supporting an association we previously reported. We also confirmed the specificity of this association in individuals with RD; the same locus was not associated with relative hand skill in a general population cohort (n = 2,666). As PCSK6 is known to regulate NODAL in the development of left/right (LR) asymmetry in mice, we developed a novel approach to GWAS pathway analysis, using gene-set enrichment to test for an over-representation of highly associated variants within the orthologs of genes whose disruption in mice yields LR asymmetry phenotypes. Four out of 15 LR asymmetry phenotypes showed an over-representation (FDR≤5%). We replicated three of these phenotypes; situs inversus, heterotaxia, and double outlet right ventricle, in the general population cohort (FDR≤5%). Our findings lead us to propose that handedness is a polygenic trait controlled in part by the molecular mechanisms that establish LR body asymmetry early in development. © 2013 Brandler et al.

A survey of some small firms in the rural areas of England: their structure and functions, with special reference to factors that affect their development

This study was concerned with the structure, functions and development, especially the performance, of some rural small firms associated with the Council for Small Industries in Rural Areas (C?SIRA) of England. Forty firms were used as the main basis of analysis. For some aspects of the investigation, however, data from another 54 firms, obtained indirectly through nine CoSIRA Organisers, were also used. For performance-analysis, the 40 firms were firstly ranked according to their growth and profitability rates which were calculated from their financial data. Then each of the variables hypothesised to be related to performance was tested to ascertain its relationship with performance, using the Spearman's Rank Correlation technique. The analysis indicated that each of the four factors .. the principal, the firm itself, its management, and the environment - had a bearing upon the performance of the firm. Within the first factor, the owner-manager's background and attitudes were found to be most important; in the second, the firm's size, age and scope of activities were also found to be correlated with performance; with respect to the third, it was revealed that firms which practised some forms of systems in planning, control and costing performed better than those which did not and, finally with respect to the fourth factor, it was found that some of the services provided by CoSIRA, especially credit finance, were facilitative to the firm's performance. Another significant facet of the firms highlighted by the study was their multifarious roles. These, meeting economic, psychological, sociological and political needs, were considered to be most useful to man and his society. Finally, the study has added light to the structural characteristics of the sampled firms, including various aspects of their development, orientation and organisation, as well as their various structural strengths and weakness. ' .