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One Variant (one + variant)
Selected AbstractsADH1B*3 and Response to Alcohol in African-AmericansALCOHOLISM, Issue 7 2010Denis M. McCarthy Background: Variations in the alleles for the alcohol-metabolizing enzymes have been shown to influence risk for alcohol dependence. One variant, ADH1B*3, is observed almost exclusively in populations of African ancestry and has been shown to be associated with reduced rates of alcohol dependence. We conducted an alcohol challenge study to test whether ADH1B*3 is associated with differences in subjective and physiological response to alcohol. Method: We administered a moderate dose of alcohol (0.72 g/kg for males, 0.65 g/kg for females) to a sample of African-American young adults (n = 91; ages 21 to 26). Participants were genotyped for ADH1B, as well as additional polymorphisms that might contribute to alcohol response. Breath alcohol concentration, self-reported sedation and stimulation, and pulse rate were assessed prior to alcohol administration and for 2.5 hours following administration. Results: ADH1B*3 was associated with higher levels of sedation and a sharper increase in pulse rate immediately following alcohol consumption. Conclusions: These findings suggest that the lower rates of alcohol dependence in those with ADH1B*3 alleles may be because of differences in alcohol response, particularly increased sedation. [source] HSQC pulse sequences for 19FMAGNETIC RESONANCE IN CHEMISTRY, Issue 4 2008Bruce Adams Abstract Heteronuclear single quantum coherence (HSQC) sequences using adiabatic (or composite) 180° pulses, suitable for applications requiring wide spectral widths in F2, are described. The sequences can be used with or without multiplicity editing. One variant will work even in the presence of homonuclear couplings that are equal to the heteronuclear 1-bond coupling. Copyright © 2008 John Wiley & Sons, Ltd. [source] Designed protein G core variants fold to native-like structures: Sequence selection by ORBIT tolerates variation in backbone specificationPROTEIN SCIENCE, Issue 2 2001Scott A. Ross Abstract The solution structures of two computationally designed core variants of the ,1 domain of streptococcal protein G (G,1) were solved by 1H NMR methods to assess the robustness of amino acid sequence selection by the ORBIT protein design package under changes in protein backbone specification. One variant has mutations at three of 10 core positions and corresponds to minimal perturbations of the native G,1 backbone. The other, with mutations at six of 10 positions, was calculated for a backbone in which the separation between G,1's ,-helix and ,-sheet was increased by 15% relative to native G,1. Exchange broadening of some resonances and the complete absence of others in spectra of the sixfold mutant bespeak conformational heterogeneity in this protein. The NMR data were sufficiently abundant, however, to generate structures of similar, moderately high quality for both variants. Both proteins adopt backbone structures similar to their target folds. Moreover, the sequence selection algorithm successfully predicted all core ,1 angles in both variants, five of six ,2 angles in the threefold mutant and four of seven ,2 angles in the sixfold mutant. We conclude that ORBIT calculates sequences that fold specifically to a geometry close to the template, even when the template is moderately perturbed relative to a naturally occurring structure. There are apparently limits to the size of acceptable perturbations: In this study, the larger perturbation led to undesired dynamic behavior. [source] Investigation of Adducin 2 (beta) DNA polymorphisms in genetic predisposition to diabetic nephropathy in Type 1 diabetesDIABETIC MEDICINE, Issue 8 2008D. Currie Abstract Aims Adducin 2 (beta) (ADD2) is a biological and positional candidate gene proposed to confer genetic risk for diabetic nephropathy. This study aimed to comprehensively investigate all common and putatively functional polymorphisms in the genomic region encompassing this gene. Methods Tag single nucleotide polymorphisms (n = 23) derived from phase II of the International HapMap Project and in silico functional variants (n = 2) were genotyped in 1467 White individuals from the British Isles (cases, n = 718; control subjects, n = 749) by a combination of Sequenom iPLEX and TaqMan technologies. Results ,2 analysis of genotype and allele frequencies in cases vs. control subjects revealed weak evidence for association of one variant at the 5% level of significance (rs10164951, P = 0.02). Adjusting for multiple testing in the present case,control collection negated this association. Conclusions We selected an appropriate subset of variants suitable for genetic investigations of the ADD2 gene and report the first investigation of polymorphisms in ADD2 with diabetic nephropathy. Our results suggest that common polymorphisms and putatively functional variants in the ADD2 gene do not strongly influence genetic susceptibility to diabetic nephropathy in this White population with Type 1 diabetes. [source] TLR4 and IL-18 gene variants in aggressive periodontitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 12 2008Barbara Noack Abstract Aim: We aimed to assess the association of different genotypes with increased aggressive periodontitis susceptibility by studying functional relevant variants in the pathogen-recognition receptor Toll-like receptor 4 (TLR4) and variants in the promoter region of the pro-inflammatory cytokine interleukin-18 (IL-18). Material and Methods: One hundred and eleven patients with aggressive periodontitis and 80 periodontally healthy controls were genotyped for four functional variants in the TLR4 gene (c.896A>G and c.1196C>T) and in the IL-18 promoter (c.,368G>C and c.,838C>A). The genotype and allele frequencies, as well as the frequency of combined genotypes were compared between study groups. Results: There were no statistical differences in genotype and allele frequencies within the four variants between the groups. All study subjects were further classified into carriers and non-carriers of at least one variant of both genes. The logistic regression analysis adjusted for gender and smoking showed no association between carrier status of at least one variant of both genes and periodontal status (OR=1.41, 95% CI: 0.43,4.70). Conclusions: Our results reject the hypothesis that functionally relevant IL-18 and TLR4 gene mutations have a major effect on aggressive periodontitis susceptibility alone or in combination. [source] Our knowledge ourselves: Engineers (re)thinking technology in developmentJOURNAL OF INTERNATIONAL DEVELOPMENT, Issue 6 2008Gordon Wilson Abstract A re-conceptualisation of technology (and science) in development is claimed to be taking, or have recently taken place. There is more than one variant, but they have in common a pluralist, constructivist conception of knowledge and its importance for development. What, however, do professional practitioners of technology in development say about their values, their mindsets and their practices, and what, if anything, does this sense-making contribute to the re-conceptualisation? Based on interviews with development-related engineers from a previous research project, and analysis of engineer perspectives that are provided on a private sector company website, this exploratory paper offers some preliminary observations. These include: A positive attitude to working with others and their realities, especially but not exclusively other professional realities A concern with enhancing their professional identity The interplay between retrospective reflection and ongoing enactment through projects The motivation associated with a ,can-do mindset' and the importance of creativity for job satisfaction and enhancement The general importance of shared experience gained through working with others. Copyright © 2008 John Wiley & Sons, Ltd. [source] C-peptide microheterogeneity in type 2 diabetes populationsPROTEOMICS - CLINICAL APPLICATIONS, Issue 1 2010Paul E. Oran Abstract Purpose: The purpose of this study was to investigate naturally occurring C-peptide microheterogeneity in healthy and type 2 diabetes (T2D) populations. Experimental design: MS immunoassays capable of simultaneously detecting intact C-peptide and variant forms were applied to plasma samples from 48 healthy individuals and 48 individuals diagnosed with T2D. Results: Common throughout the entire sample set were three previously unreported variations of C-peptide. The relative contribution of one variant, subsequently identified as C-peptide (3-31), was found to be more abundant in the T2D population as compared to the healthy population. Dipeptidyl peptidase IV is suspected to be responsible for this particular cleavage product, which is consistent with the pathophysiology of T2D. Conclusions and clinical relevance: C-peptide does not exist in the human body as a single molecular species. It is qualitatively more heterogeneous than previously thought. These results lay a foundation for future studies devoted to a comprehensive understanding of C-peptide and its variants in healthy and diabetic populations. [source] | |||||||||||||