Accurate and Fast Multiple-Testing Correction in eQTL Studies

In studies of expression quantitative trait loci (eQTLs), it is of increasing interest to identify eGenes, the genes whose expression levels are associated with variation at a particular genetic variant. Detecting eGenes is important for follow-up analyses and prioritization because genes are the main entities in biological processes. To detect eGenes, one typically focuses on the genetic variant with the minimum p value among all variants in cis with a gene and corrects for multiple testing to obtain a gene-level p value. For performing multiple-testing correction, a permutation test is widely used. Because of growing sample sizes of eQTL studies, however, the permutation test has become a computational bottleneck in eQTL studies. In this paper, we propose an efficient approach for correcting for multiple testing and assess eGene p values by utilizing a multivariate normal distribution. Our approach properly takes into account the linkage-disequilibrium structure among variants, and its time complexity is independent of sample size. By applying our small-sample correction techniques, our method achieves high accuracy in both small and large studies. We have shown that our method consistently produces extremely accurate p values (accuracy > 98%) for three human eQTL datasets with different sample sizes and SNP densities: the Genotype-Tissue Expression pilot dataset, the multi-region brain dataset, and the HapMap 3 dataset.     

Improvement of antioxidant and defense properties of Tomato (var. Pusa Rohini) by application of bioaugmented compost

Nutrient management practices play a significant role in improving the nutritional quality of tomato. The present study deals with the evaluation of compost prepared using Effective Microorganisms (EM), on antioxidant and defense enzyme activities of Tomato (Lycopersicon esculentum). A field experiment with five treatments (control, chemical fertilizer and EM compost alone and in combination) was conducted in randomized block design. An increment of 31.83% in tomato yield was recorded with the combined use of EM compost and half recommended dose of chemical fertilizers (N₅₀P₃₀K₂₅ + EM compost at the rate of 5 t ha⁻¹). Similarly, fruit quality was improved in terms of lycopene content (35.52%), antioxidant activity (24–63%) and defense enzymes activity (11–54%), in tomatoes in this treatment as compared to the application of recommended dose of fertilizers. Soil microbiological parameters also exhibited an increase of 7–31% in the enzyme activities in this treatment. Significant correlation among fruit quality parameters with soil microbiological activities reveals the positive impact of EM compost which may be adopted as an eco-friendly strategy for production of high quality edible products.     

Detection of cholesterol by digitonin conjugated gold nanoparticles

Functionalized colloidal gold is widely used for qualitative and quantitative detection of specific analytes. We report here a novel modification of gold nanoparticles by digitonin, a glycoside used for precipitating membrane cholesterol. The specific molecular recognition of cholesterol by digitonin gold nanoparticles (DGNP), make it an attractive alternative to the existing enzymatic methods for cholesterol sensing. To enable cholesterol binding, we modified mercapto modified GNPs with digitonin, by a simple esterification reaction. The blue shift in the plasmon absorption spectra of DGNP with different cholesterol concentrations accompanied by a decrease in the absorbance is the principle applied here for the estimation. The observed size reduction followed by cholesterol binding is reasoned due to the enhanced hydophobicity of the surface which in turn expels the water layers associated with the particles prior to cholesterol binding. The method exhibited linearity between concentration of cholesterol and the corresponding absorbance of the plasmon peak, in the range of 160-600 ng/mL with a detection limit of 100±9 ng/mL. Other steroids did not show any binding affinity towards DGNP. The method depicted here has potential for development as an enzyme free sensor for cholesterol although many factors need to be addressed to transform it for assaying samples like blood.     

Rapid detection of Salmonella enterica serovars by multiplex PCR

A multiplex PCR based assay was developed for the identification of the genus Salmonella. Five sets of primers from different genomic sequences such as fimA, himA, hns, invA and hto genes were selected for the identification of serogroups of Salmonella enterica such as S. Typhi, S. ParatyphiA, S. Typhimurium, S. Enteritidis and S. Weltevreden. The selected primers amplified products with the sizes of 85, 123, 152, 275 and 496 bp, respectively, for the genus Salmonella. This assay was found to be highly sensitive, as it could detect 5 cells of Salmonella and 1,000 fg of genomic DNA. Amplification of DNA extracted from other genera viz. V. cholerae and E. coli yielded negative results. This assay provides specific and reliable results and allows for the cost–effective detection of Salmonella in one reaction tube in mixed bacterial communities.     

Antiplasmodial and cytotoxicity evaluation of 3-functionalized 2-azetidinone derivatives

3-Azido-, 3-amino- and 3-(1,2,3-triazol-1-yl)-β-lactams were synthesized and evaluated for their antiplasmodial activity against four strains of Plasmodium falciparum and KB cells for their cytotoxicity profiles. The presence of a cyclohexyl substituent at N-1 and a phenyl group on the triazole ring markedly improved the activity profiles of triazole-tethered β-lactam exhibiting IC₅₀ values of 1.13, 1.21 and 1.00 μM against 3D7, K1 and W2 strains respectively.     

N-(1,3-Diaryl-3-oxopropyl)amides as a new template for xanthine oxidase inhibitors

A series of forty two N-(1,3-diaryl-3-oxopropyl)amides were synthesized via an efficient, modified Dakin-West reaction and were evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Structure-activity relationship analyses have been presented. Selected active xanthine oxidase inhibitors (3r, 3s, and 3zh) were assessed in vivo to study their anti-hyperuricemic effect in potassium oxonate induced hyperuricemic mice model. Compound 3s emerged as the most potent xanthine oxidase inhibitor (IC(50)=2.45 μM) as well as the most potent anti-hyperuricemic agent. The basis of significant inhibition of xanthine oxidase by 3s was rationalized by its molecular docking into catalytic site of xanthine oxidase.