Small molecule tertiary amines as agonists of the nuclear hormone receptor Rev-erbα

The structure-activity relationship study of a small molecule Rev-erbα agonist is reported. The potency and efficacy of the agonists in a cell-based assay were optimized as compared to the initial lead. Modest mouse pharmacokinetics coupled with an improved in vitro profile make 12e a suitable in vivo probe to interrogate the functions of Rev-erbα in animal models of disease.     

Regulation of apoptosis by vasoactive peptides

Although originally discovered because of their ability to affect hemodynamics, vasoactive peptides have been found to function in a variety of capacities including neurotransmission, endocrine functions, and the regulation of cell proliferation. A growing body of evidence describes the ability of vasoactive peptides to regulate cell death by apoptosis in either a positive or negative fashion depending on the peptide and the type of target cell. The available evidence to date is strongest for the peptides endothelin, angiotensin II, vasoactive intestinal peptide, atrial natriuretic peptide, and adrenomedullin. Each of these peptides is discussed, with specific regard to apoptosis, in terms of regulatory activity, target cell specificity, and potential role in pulmonary physiology.     

The relationship of age, body mass index and waist circumference with blood pressure in Bengalee Hindu male jute mill workers of Belur, West Bengal, India

A cross-sectional study of 150 adult Bengalee Hindu male jute mill workers of Belur, a suburb of Kolkata, West Bengal, India, was undertaken to study the relationship of age, body mass index (BMI) and waist circumference (WC) with systolic (SBP), diastolic (DBP) and mean arterial (MAP) blood pressure. The mean age and the BMI of the subjects were 40.7 years (S.D. = 15.2) and 23.2 kg/m2 (S.D. = 3.2), respectively. The mean SBP, DBP and MAP were 124.7 mmHg (S.D. = 7.8), 81.5 mmHg (S.D. = 5.7) and 95.9 mmHg (S.D. = 6.1), respectively. Age had similar significant (p < 0.001) correlations with BMI and WC. Age and WC were significantly correlated (p < 0.001) with all the three blood pressure variables. In general, the correlations of BMI with SBP (r = 0.24, p < 0.01), DBP (r = 0.15, n.s.) and MAP (r = 0.19, p < 0.05) were weaker. Age controlled multiple regression analyses demonstrated that BMI did not have a significant effect of any blood pressure variable. However, WC had a significant impact (p < 0.0001) on SBP (t = 7.068), DBP (t = 5.190) and MAP (t = 6.387), even after adjusting for the effect of age. Moreover, even after age adjustment, percent variations in SBP (20.7%), DBP (12.5%) and MAP (17.2%) explained by WC were high. This significant impact (p < 0.0001) of WC on SBP (t = 9.426), DBP (t = 8.349) and MAP (t = 9.642) remained even after controlling for the combined effects of age and BMI.     

Pre-clinical toxicity evaluation of leaf-stalk extractive of Piper betle Linn. in rodents

Studies on pre-clinical toxicity were undertaken to determine the haematological and biochemical changes after administration of alcoholic extract of leaf-stalk of P. betle in rats and mice. Acute and chronic toxicity experiments were performed on mice and rats according to WHO protocol. Different doses of plant extractive were administered for toxicity studies on short and long term basis. Haematological, biochemical profiles and enzymatic studies (transaminases and phosphatases) indicated that the drug (plant extractive) was devoid of toxicity.     

Dual doped biocompatible multicolor luminescent carbon dots for bio labeling,UV‐active marker and fluorescent polymer composite

We report on metal–non‐metal doped carbon dots with very high photoluminescent properties in solution. Magnesium doping to tamarind extract associated with nitrogen‐doping is for the first time reported here which also produce very high quantum yield. Our aim is to develop such dual doped carbon dots which can also serve living cell imaging with easy permeation towards cells and show non‐cytotoxic attributes. More importantly, the chemical signatures of the carbon dots unveiled in this work can support their easy solubilization into water; even in sub‐ambient temperature. The cytotoxicity assay proves the almost negligible cytotoxic effect against human cell lines. Moreover, the use of carbon dots in UV‐active marker and polymer composites are also performed which gave clear distinguishable features of fluorescent nanoparticles. Hitherto, the carbon dots can be commercially prepared without adopting any rigorous methods and also can be used as non‐photo‐bleachable biomarkers of living cells.     

Nonparametric bayesian estimation of positive false discovery rates

We propose a Dirichlet process mixture model (DPMM) for the P-value distribution in a multiple testing problem. The DPMM allows us to obtain posterior estimates of quantities such as the proportion of true null hypothesis and the probability of rejection of a single hypothesis. We describe a Markov chain Monte Carlo algorithm for computing the posterior and the posterior estimates. We propose an estimator of the positive false discovery rate based on these posterior estimates and investigate the performance of the proposed estimator via simulation. We also apply our methodology to analyze a leukemia data set.