Handling linkage disequilibrium in qualitative trait linkage analysis using dense SNPs: a two-step strategy

<p>Abstract</p> <p>Background</p> <p>In affected sibling pair linkage analysis, the presence of linkage disequilibrium (LD) has been shown to lead to overestimation of the number of alleles shared identity-by-descent (IBD) among sibling pairs when parents are ungenotyped. This inflation results in spurious evidence for linkage even when the markers and the disease locus are not linked. In our study, we first theoretically evaluate how inflation in IBD probabilities leads to overestimation of a nonparametric linkage (NPL) statistic under the assumption of linkage equilibrium. Next, we propose a two-step processing strategy in order to systematically evaluate approaches to handle LD. Based on the observed inflation of expected logarithm of the odds ratio (LOD) from our theoretical exploration, we implemented our proposed two-step processing strategy. Step 1 involves three techniques to filter a dense set of markers. In step 2, we use the selected subset of markers from step 1 and apply four different methods of handling LD among dense markers: 1) marker thinning (MT); 2) recursive elimination; 3) SNPLINK; and 4) LD modeling approach in MERLIN. We evaluate relative performance of each method through simulation.</p> <p>Results</p> <p>We observed LOD score inflation only when the parents were ungenotyped. For a given number of markers, all approaches evaluated for each type of LD threshold performed similarly; however, RE approach was the only one that eliminated the LOD score bias. Our simulation results indicate a reduction of approximately 75% to complete elimination of the LOD score inflation while maintaining the information content (IC) when setting a tolerable squared correlation coefficient LD threshold (r²) above 0.3 for or 2 SNPs per cM using MT.</p> <p>Conclusion</p> <p>We have established a theoretical basis of how inflated IBD information among dense markers overestimates a NPL statistic. The two-step processing strategy serves as a useful framework to systematically evaluate relative performance of different methods to handle LD.</p

Antibacterial activity and mode of action of selected glucosinolate hydrolysis products against bacterial pathogens

Plants contain numerous components that are important sources of new bioactive molecules with antimicrobial properties. Isothiocyanates (ITCs) are plant secondary metabolites found in cruciferous vegetables that are arising as promising antimicrobial agents in food industry. The aim of this study was to assess the antibacterial activity of two isothiocyanates (ITCs), allylisothiocyanate (AITC) and 2-phenylethylisothiocyanate (PEITC) against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Listeria monocytogenes. The antibacterial mode of action was also characterized by the assessment of different physiological indices: membrane integrity, intracellular potassium release, physicochemical surface properties and surface charge. The minimum inhibitory concentration (MIC) of AITC and PEITC was 100 g/mL for all bacteria. The minimum bactericidal concentration (MBC) of the ITCs was at least 10 times higher than the MIC. Both AITC and PEITC changed the membrane properties of the bacteria decreasing their surface charge and compromising the integrity of the cytoplasmatic membrane with consequent potassium leakage and propidium iodide uptake. The surface hydrophobicity was also non-specifically altered (E. coli and L. monocytogenes become less hydrophilic; P. aeruginosa and S. aureus become more hydrophilic). This study shows that AITC and PEITC have strong antimicrobial potential against the bacteria tested, through the disruption of the bacterial cell membranes. Moreover, phytochemicals are highlighted as a valuable sustainable source of new bioactive products.This work was supported by the Operational Programme for Competitiveness Factors - COMPETE and by the Portuguese Foundation for Science and Technology through Project Phytodisinfectants - PTDC/DTP-SAP/1078/2012 (COMPETE: FCOMP-01-0124-FEDER-028765), the PhD grant awarded to Ana Abreu (SFRH/BD/84393/2012), and the post-doctoral grants awarded to Anabela Borges (SFRH/BPD/98684/2013) and Lucia C. Simoes (SFRH/BPD/81982/2011). Also, this work was undertaken as part of the European Research Project SUSCLEAN (Contract no FP7-KBBE-2011-5, project number: 287514) and the COST Action FA1202. The authors are solely responsible for this work. It does not represent the opinion of the European Community, and the Community is not responsible for any use that might be made of data appearing herein

Effects of vitamin E supplementation on renal non-enzymatic antioxidants in young rats submitted to exhaustive exercise stress

<p>Abstract</p> <p>Background</p> <p>Exercise stress was shown to increase oxidative stress in rats. It lacks reports of increased protection afforded by dietary antioxidant supplements against ROS production during exercise stress. We evaluated the effects of vitamin E supplementation on renal non-enzymatic antioxidants in young rats submitted to exhaustive exercise stress.</p> <p>Methods</p> <p>Wistar rats were divided into three groups: 1) control group; 2) exercise stress group and; 3) exercise stress + Vitamin E group. Rats from the group 3 were treated with gavage administration of 1 mL of Vitamin E (5 mg/kg) for seven consecutive days. Animals from groups 2 and 3 were submitted to a bout of swimming exhaustive exercise stress. Kidney samples were analyzed for Thiobarbituric Acid Reactive Substances to (TBARS) by malondialdehyde (MDA), reduced glutathione (GSH) and vitamin-E levels.</p> <p>Results</p> <p>The group treated with vitamin E and submitted to exercise stress presented the lowest levels of renal MDA (1: 0.16+0.02 mmmol/mgprot vs. 2: 0.34+0.07 mmmol/mgprot vs. 3: 0.1+0.01 mmmol/mgprot; p < 0.0001), the highest levels of renal GSH (1: 23+4 μmol/gprot vs. 2: 23+2 μmol/gprot vs. 3: 58+9 μmol/gprot; p < 0.0001) and the highest levels of renal vitamin E (1: 24+6 μM/gtissue vs. 2: 28+2 μM/gtissue vs. 3: 43+4 μM/gtissue; p < 0.001).</p> <p>Conclusion</p> <p>Vitamin E supplementation improved non-enzymatic antioxidant activity in young rats submitted to exhaustive exercise stress.</p

Construct validity of a figure rating scale for Brazilian adolescents

<p>Abstract</p> <p>Background</p> <p>Figure rating scales were developed as a tool to determine body dissatisfaction in women, men, and children. However, it lacks in the literature the validation of the scale for body silhouettes previously adapted. We aimed to obtain evidence for construct validity of a figure rating scale for Brazilian adolescents.</p> <p>Methods</p> <p>The study was carried out with adolescent students attending three public schools in an urban region of the municipality of Florianopolis in the State of Santa Catarina (SC). The sample comprised 232 10-19-year-old students, 106 of whom are boys and 126 girls, from the 5th "series" (i.e. year) of Primary School to the 3rd year of Secondary School. Data-gathering involved the application of an instrument containing 8 body figure drawings representing a range of children's and adolescents' body shapes, ranging from very slim (contour 1) to obese (contour 8). Weights and heights were also collected, and body mass index (BMI) was calculated later. BMI was analyzed as a continuous variable, using z-scores, and as a dichotomous categorical variable, representing a diagnosis of nutritional status (normal and overweight including obesity).</p> <p>Results</p> <p>Results showed that both males and females with larger BMI z-scores chose larger body contours. Girls with higher BMI z-scores also show higher values of body image dissatisfaction.</p> <p>Conclusion</p> <p>We provided the first evidence of validity for a figure rating scale for Brazilian adolescents.</p