Initial Commitment to Pre-Exposure Prophylaxis and Circumcision for HIV Prevention amongst Indian Truck Drivers

Studies of HIV prevention interventions such as pre-exposure prophylaxis (PREP) and circumcision in India are limited. The present study sought to investigate Indian truck-drivers initial commitment to PREP and circumcision utilizing the AIDS Risk Reduction Model. Ninety truck-drivers completed an in-depth qualitative interview and provided a blood sample for HIV and HSV-2 testing. Truck-drivers exhibited low levels of initial commitment towards PREP and even lower for circumcision. However, potential leverage points for increasing commitment were realized in fear of infecting family rather than self, self-perceptions of risk, and for PREP focusing on cultural beliefs towards medication and physicians. Cost was a major barrier to both HIV prevention interventions. Despite these barriers, our findings suggest that the ARRM may be useful in identifying several leverage points that may be used by peers, health care providers and public health field workers to enhance initial commitment to novel HIV prevention interventions in India.     

EXO5-DNA structure and BLM interactions direct DNA resection critical for ATR-dependent replication restart

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Thermal stress and physiological strain in the glass bangle industry

A preliminary survey of the few units of the small-scale glass bangle industry in Firozabad, Agra District, Uttar Pradesh, indicated that the workers were exposed to severe degrees of heat stress during various operations in the manufacturing processes. A more detailed study in eight glass bangle units was therefore undertaken to make quantitative estimates of heat stress on exposed workers in the summer season. The thermal data collected confirmed that the heat stress on the workers was severe but measurement of certain physiological indicators revealed relatively low levels of strain amongst the exposed workers. The findings could be attributable to high degrees of acclimatization, but further observations in the field supplemented by studies on simulated exposures of volunteers in a climatic chamber seem to be warranted.     

Metabolic Syndrome Is Associated with Increased Oxo-Nitrative Stress and Asthma-Like Changes in Lungs

Epidemiological studies have shown an increased obesity-related risk of asthma. In support, obese mice develop airway hyperresponsiveness (AHR). However, it remains unclear whether the increased risk is a consequence of obesity, adipogenic diet, or the metabolic syndrome (MetS). Altered L-arginine and nitric oxide (NO) metabolism is a common feature between asthma and metabolic syndrome that appears independent of body mass. Increased asthma risk resulting from such metabolic changes would have important consequences in global health. Since high-sugar diets can induce MetS, without necessarily causing obesity, studies of their effect on arginine/NO metabolism and airway function could clarify this aspect. We investigated whether normal-weight mice with MetS, due to high-fructose diet, had dysfunctional arginine/NO metabolism and features of asthma. Mice were fed chow-diet, high-fat-diet, or high-fructose-diet for 18 weeks. Only the high-fat-diet group developed obesity or adiposity. Hyperinsulinemia, hyperglycaemia, and hyperlipidaemia were common to both high-fat-diet and high-fructose-diet groups and the high-fructose-diet group additionally developed hypertension. At 18 weeks, airway hyperresponsiveness (AHR) could be seen in obese high-fat-diet mice as well as non-obese high-fructose-diet mice, when compared to standard chow-diet mice. No inflammatory cell infiltrate or goblet cell metaplasia was seen in either high-fat-diet or high-fructose-diet mice. Exhaled NO was reduced in both these groups. This reduction in exhaled NO correlated with reduced arginine bioavailability in lungs. In summary, mice with normal weight but metabolic obesity show reduced arginine bioavailability, reduced NO production, and asthma-like features. Reduced NO related bronchodilation and increased oxo-nitrosative stress may contribute to the pathogenesis.     

Interesterification selectivity in lipase catalyzed reactions of low molecular weight triglycerides

Summary In the absence of an organic solvent, a buffer to enzyme weight ratio of 1 gives maximum selectivity to interesterification over hydrolysis in a lipase-catalyzed mixture of triacetin and tributyrin. Addition of hexane enhances interesterification as does a reversed micelle configuration.     

Lipid fluidity and composition of the erythrocyte membrane from healthy dogs and labrador retrievers with hereditary muscular dystrophy

Erythrocyte membranes and their liposomes were prepared from clinically normal dogs and Labrador retrievers with hereditary muscular dystrophy. The static and dynamic components of fluidity of each membrane were then assessed by steady-state fluorescence polarization techniques using limiting hindered fluorescence anisotropy and order parameter values of 1,6-diphenyl-1,3,5-hexatriene (DPH) and fluorescence anisotropy values ofdl-2-(9-anthroyl)-stearic acid anddl-12-(9-anthroyl)-stearic acid, respectively. Membrane lipids were extracted and analyzed by thin-layer chromatography and gas chromatography. The results of these studies demonstrated that the lipid fluidity of erythrocyte membranes, and their liposomes, prepared from dystrophic dogs were found to possess significantly lower static and dynamic components of fluidity than control counterparts. Analysis of the composition of membranes from dystrophic dogs revealed a higher ratio of saturated fatty acyl chain/unsaturated chains (w/w) and lower double-bond index. Alterations in the fatty acid composition such as decrease in levels of linoleic (18:2) and arachidonic (20:4) acids and increase in palmitic (16:0) and stearic (18:0) acids were also observed in the membranes of dystrophic animals. These associated fatty acyl alterations could explain, at least in part, the differences in membrane fluidity between dystrophic and control dogs.     

Incorporation of beta-fluoroasparagine into peptides prevents N-linked glycosylation. In vitro studies with synthetic fluoropeptides

Previously, we reported that incorporation of threo-beta-fluoroasparagine into cellular protein inhibits N-linked glycosylation. We now show that short synthetic peptides which contain N-acetyl-threo-beta-fluoroasparagine fail to undergo glycosylation in a cell-free system except at extremely high substrate concentrations. An N-benzoyl-threo-beta-fluoroasparagine-containing peptide has a 100-fold lower Vmax/Km than the analogous N-benzoyl-asparagine-containing peptide. Substitution of a fluorine for a hydrogen on the beta-carbon of asparagine weakens the ability of the peptide to bind the oligosaccharyltransferase. A 100-fold excess of acetyl-threo-beta-fluoroasparaginyl-leucyl-threonine methylamide over acetyl-asparaginyl-leucyl-threonine methylamide inhibited glycosylation of the latter peptide by less than 10%. Both threo-beta-fluoroasparagine and erythro-beta-fluoroasparagine-containing peptides are glycosylated at the same rate. Glycofluoropeptides generated from beta-fluoroasparagine-containing peptides were N-glycosylated. These cell-free studies with synthetic fluoropeptides suggest that incorporation of beta-fluoroasparagine into cellular protein inhibits N-linked glycosylation by rendering protein substrates ineffective for glycosylation. In the course of this work, we also demonstrate that the N-linked glycosylating enzyme acts only on L-asparagine-containing peptides and not on D-asparagine peptides.