193 research outputs found

    Rapid detection of pathogenic leptospires by lyophilized reagent-based Polymerase Chain Reaction.

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    A simple and reliable tool for the early diagnosis of leptospirosis is urgently needed. We report the development of a lyophilized reagent-based polymerase chain reaction (PCR) assay targeting lipL32 gene, which is present only in pathogenic leptospires. To determine the effectiveness of the newly developed assay in the early diagnosis of leptospirosis, the sensitivity and specificity was evaluated. In simulated clinical samples, the assay was able to detect 10 2 and 10 3 leptospires/ml in spiked urine and blood samples, respectively. In experimentally infected animals, leptospiral DNA could be detected in blood and lung samples as early as Day 1 post infection. This assay was also shown to be stable and remained sensitive for up to five months at ambient temperature. Hence, this lyophilized reagent-based PCR assay with high specificity, sensitivity and stability would provide a simple, rapid and reliable method in diagnosing acute leptospirosis, especially in the field of veterinary medicine

    Population differences in associations of serotonin transporter promoter polymorphism (5HTTLPR) di- and triallelic genotypes with blood pressure and hypertension prevalence

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    Based on prior research finding the 5HTTLPR L allele associated with increased cardiovascular reactivity to laboratory stressors and increased risk of myocardial infarction, we hypothesized that the 5HTTLPR L allele will be associated with increased blood pressure (BP) and increased hypertension prevalence in 2 large nationally representative samples in the United States and Singapore. Methods Logistic regression and linear models tested associations between triallelic (L′S′, based on rs25531) 5HTTLPR genotypes and hypertension severity and mean systolic and diastolic blood pressure (SBP and DBP) collected during the Wave IV survey of the National Longitudinal Study of Adolescent to Adult Health (Add Health, N = 11,815) in 2008–09 and during 2004–07 in 4196 Singaporeans. Results In US Whites, L′ allele carriers had higher SBP (0.9 mm Hg, 95% CI = 0.26-1.56) and greater odds (OR = 1.23, 95% CI = 1.10-1.38) of more severe hypertension than those with S′S′ genotypes. In African Americans, L′ carriers had lower mean SBP (−1.27 mm Hg, 95% CI = −2.53 to −0.01) and lower odds (OR = 0.78, 95% CI = 0.65-0.94) of more severe hypertension than those with the S′S′ genotype. In African Americans, those with L′L′ genotypes had lower DBP (−1.13 mm Hg, 95% CI = −2.09 to −0.16) than S′ carriers. In Native Americans, L′ carriers had lower SBP (−6.05 mm Hg, 95% CI = −9.59 to −2.51) and lower odds of hypertension (OR = 0.34, 95% CI = 0.13-0.89) than those with the S′S′ genotype. In Asian/Pacific Islanders those carrying the L′ allele had lower DBP (−1.77 mm Hg, 95% CI = −3.16 to −0.38) and lower odds of hypertension (OR = 0.68, 95% CI = 0.48-0.96) than those with S′S′. In the Singapore sample S′ carriers had higher SBP (3.02 mm Hg, 95% CI = 0.54-5.51) and DBP (1.90 mm Hg, 95% CI = 0.49-3.31) than those with the L′L′ genotype. Conclusions These findings suggest that Whites carrying the L′ allele, African Americans and Native Americans with the S′S′ genotype, and Asians carrying the S′ allele will be found to be at higher risk of developing cardiovascular disease and may benefit from preventive measures

    Perturbative Approach to Higher Derivative Theories with Fermions

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    We extend the perturbative approach developed in an earlier work to deal with Lagrangians which have arbitrary higher order time derivative terms for both bosons and fermions. This approach enables us to find an effective Lagrangian with only first time derivatives order by order in the coupling constant. As in the pure bosonic case, to the first order, the quantized Hamiltonian is bounded from below whenever the potential is. We show in the example of a single complex fermion that higher derivative interactions result in an effective mass and change of vacuum for the low energy modes. The supersymmetric noncommutative Wess-Zumino model is considered as another example. We also comment on the higher derivative terms in Witten's string field theory and the effectiveness of level truncation.Comment: Latex, 21 pages, minor modification, ref. adde

    Physical activity attenuates the influence of FTO variants on obesity risk: A meta-analysis of 218,166 adults and 19,268 children

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    Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r2>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (pinteraction= 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. Concl

    A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data

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    Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants

    Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

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    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 &times; 10-11 to 5.0 &times; 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 &times; 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation
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