Neutralization potential of the plasma of HIV-1 infected Indian patients in the context of anti-V3 antibody content and antiretroviral theraphy

We assessed the anti-V3 antibody content and viral neutralization potential of the plasma of 63 HIV-1-infected patients (antiretroviral naïve=39, treated=24) against four primary isolates (PIs) of clade C and a tier 1 clade B isolate SF162. Depletion and inhibition of anti-V3 antibodies in the plasma of five patients with high titers of anti-V3 antibodies led to modest change in the neutralization percentage against two PIs (range 0–21%). The plasma of antiretroviral-treated patients exhibited higher neutralization potential than that of the drug-naïve plasmas against the four PIs tested which was further evidenced by a follow-up study.     

Is There Any Association between Use of Smokeless Tobacco Products and Coronary Heart Disease in Bangladesh?

Background

Most epidemiological studies exploring the association between smokeless tobacco (SLT) use and coronary heart disease (CHD) have been in Western populations, and have focused on SLT products used in those countries. Few studies come from South Asian countries. Our objective was to determine the association between SLT use and CHD among non-smoking adults in Bangladesh.

Methods

A matched case-control study of non-smoking Bangladeshi adults aged 40–75 years was conducted in 2010. Incident cases of CHD were selected from two cardiac hospitals. Community controls, matched to CHD cases, were selected from neighbourhoods, and hospital controls were selected from outpatient departments of the same hospitals. The Rose Angina Questionnaire (RAQ) was also used to re-classify cases and controls.

Results

The study enrolled 302 cases, 1,208 community controls and 302 hospital controls. Current use was higher among community controls (38%) compared to cases (33%) and hospital controls (32%). Current use of SLT was not significantly associated with an increased risk of CHD when community controls were used (adjusted OR 0.87, 95% CI 0.63–1.19), or when hospital controls were used (adjusted OR 1.00, 95% CI 0.63–1.60), or when both control groups were combined (adjusted OR 1.00, 95% CI 0.74–1.34). Risk of CHD did not increase with use of individual types except gul, frequency, duration, past use of SLT products, or using the RAQ to re-classify cases and controls. There was a significant association between gul use and CHD when both controls were combined (adjusted OR 2.93, 95% CI 1.28–6.70).

Conclusions

There was no statistically significant association between SLT use in general and CHD among non-smoking adults in Bangladesh. Further research on the association between gul use and CHD in Bangladesh along with SLT use and CHD in other parts of the subcontinent will guide public health policy and interventions that focus on SLT-related diseases.     

Heterotrophic nitrification by <Emphasis Type="Italic">Achromobacter xylosoxidans</Emphasis> S18 isolated from a small-scale slaughterhouse wastewater

Heterotrophic carbon utilizing microbes were acclimatized in the laboratory by inoculating sludge collected from the waste discharge pond of a small-scale rural abattoir in India in a nutrient solution intermittently fed with glucose and ammonium chloride. Cultures of 10 well-developed isolates were selected and grown in a basal medium containing glucose and ammonium chloride. Culture supernatants were periodically analyzed for ammonium nitrogen (NH₄ ⁺-N) and chemical oxygen demand (COD). Polyphasic taxonomic study of the most active nitrifier (S18) was done. Half saturation concentration (K _s), maximum rate of substrate utilization (k), yield coefficient (Y) and decay coefficient (K _d) were determined from the Lineweaver–Burk plot using the modified Monod equation. S18 was able to remove 97 ± 2% of (NH₄ ⁺-N) and 88 ± 3% of COD. Molecular phylogenetic study supported by physiological and biochemical characteristics assigned S18 as Achromobacter xylosoxidans. Nitrification activity of A. xylosoxidans was demonstrated for the first time, while interestingly, the distinctive anaerobic denitrification property was preserved in S18. K _s values were determined as 232.13 ± 1.5 mg/l for COD reduction and 2.131 ± 1.9 mg/l for NH₄ ⁺-N utilization. Yield coefficients obtained were 0.4423 ± 0.1134 mg of MLVSS/mg of COD and 0.2461 ± 0.0793 mg of MLVSS/mg of NH₄ ⁺-N while the decay coefficients were 0.0627 ± 0.0013 per day and 0.0514 ± 0.0008 per day, respectively. After a contact period of 24 h, 650 ± 5 mg/l solids were produced when the initial concentration of COD and NH₄ ⁺-N were 1820 ± 10 mg/l and 120 ± 5.5 mg/l, respectively. This is the first report on the kinetic coefficients for carbon oxidation and nitrification by a single bacterium isolated from slaughterhouse wastewater.     

Computational validation of 3-ammonio-3-(4-oxido- 1H-imidazol-1-ium-5-yl) propane-1, 1-bis (olate) as a potent anti-tubercular drug against mt-MetAP

The advent of Multi Drug Resistant (MDR) strain of Mycobacterium tuberculosis (TB) necessitated search for new drug targets for the bacterium. It is reported that 3.3% of all new tuberculosis cases had multidrug resistance (MDR-TB) in 2009 and each year, about 0.44 million MDR-TB cases are estimated to emerge and 0.15 million people with MDR-TB die. Keeping such an alarming situation under consideration we wanted to design suitable anti tubercular molecules for new target using computational tools. In the work Methionine aminopeptidase (MetAP) of Mycobacterium tuberculosis was considered as target and three non-toxic phenolic=ketonic compounds were considered as ligands. Docking was done with Flex X and AutoDock 4.2 separately. Ten proven inhibitors of MetAP were collected from literature with their IC50 and were correlated using EasyQSAR to generate QSAR model. Activity of ligands in question was predicted from QSAR. Pharmacophore for each docking was generated using Ligandscout 3.0. Toxicity of the ligands in question was predicted on Mobyle@rpbs portal and Actelion property explorer. Molecular docking with target showed that of all three ligands, 3-ammonio-3-(4-oxido-1H-imidazol-1-ium-5-yl) propane-1, 1-bis (olate) has highest affinity (- 37.5096) and lowest IC50 (4.46 µM). We therefore, propose that -3-ammonio-3-(4-oxido-1H-imidazol-1-ium-5-yl) propane-1,1- bis(olate) as a potent MetAP inhibitor may be a new anti-tubercular drug particularly in the context of Multi Drug Resistant Tuberculosis (MDR-TB).     

Atherogenic effect of Arecoline: A computational study

There are over 600 million people worldwide covering Asian and Oceanic countries including India have the habit of chewing areca nut as masticator in different forms. Arecoline (C(8)H(13)NO(2)) has been reported as one of the abundant constituents of areca nut. A good number of scientific publications have made Arecoline responsible for oral cancer. Based on observation from clinical situation in North East India, one of the most betel quid chewing region of the country, we suspected a link between consumption of areca nut and Cerebro Vascular Disease like stroke. Therefore, we considered Low Density Lipoprotein (LDL) receptor as target and Arecoline as ligand and studied ligand -target interaction using computational tools. Also we considered High Density Lipoprotein (HDL) receptor as another target to see if Arecoline has any binding potential with it over and above LDL receptor. Docking result indicated that Arecoline and Cholesterol both, have affinity towards extracellular domain of Human LDL receptor but affinity of Arecoline is much higher (-12.3560.) than that of Cholesterol(-0.1810). Docking of Arecoline and 1, 2-Hexyl-1- cyclopentanone thiosemicarbazone (thiosemicarbazone) with Bovine HDL receptor showed that Arecoline also has the potential (Score, -6.2690Kcal/Mol) to block HDL receptor though its potential is less than that (score, -10.0509 Kcal/Mol) of control (thiosemicarbazone). We, therefore, suggest that by inhibiting endocytosis of LDL cholesterol because of blocking LDL receptor function and also by preventing LDL cholesterol uptake by liver from blood because of interference with HDL receptor, Arecoline may contribute to atherosclerosis. The study therefore, indicates a positive correlation between chewing of betel quid and Cerebro Vascular Disease.     

Towards an efficient computational mining approach to identify EST-SSR markers

Microsatellites are the markers of choice due to their high abundance reproducibility, degree of polymorphism and co-dominant nature. These are mainly used for studying the genetic variability in different species and Marker assisted selection. Expressed Sequence Tags (ESTs) serve as the main resource for Simple Sequence Repeats (SSRs). The computational approach for detecting SSRs and developing SSR markers from EST-SSRs is preferred over the conventional methods as it reduces time and cost to a great extent. The available EST sequence databases, various web interfaces and standalone tools provide the platform for an easy analysis of the EST sequences leading to the development of potential EST-SSR Markers. This paper is an overview of in silico approach to develop SSR Markers from the EST sequence using some of the most efficient tools that are available freely for academic purpose.