Respiratory syncytial virus infection activates STAT signaling in human epithelial cells

Acute respiratory syncytial virus (RSV) infection causes airway inflammation and exacerbates asthma, but the mechanism of inflammation is poorly understood. The role of the STAT-signaling pathway in RSV infection in epithelial cells was examined in this study. DNA microarray analyses of RSV-infected human alveolar type II (A549) epithelial cells identified several genes whose expression was altered from -5.5 to +56.4-fold. Four of the highly expressed genes contained STAT-binding elements. In A549 and normal human bronchial epithelial cells (NHBE), RSV induced phosphorylation and nuclear translocation of STAT-1alpha that was abrogated when RSV attachment was blocked. Treatment with a JAK-2 inhibitor or transfection with dominant-negative STAT-1alpha blocked STAT-1alpha activation and RSV infection. RSV also activated STAT-3 and IL-6 specific antibodies blocked this activation. Thus, activation of the STAT-1alpha and STAT-3 pathways play a role in RSV infection.     

Airborne fungal spores in an industrial area: seasonal and diurnal periodicity

Qualitative and quantitative studies of atmospheric fungal spores at a chloralkali factory, Jayashree Chemicals. were made during 1993 employing culture plate and rotorod methods. A total of 57 sporulating fungal types, including three sterile mycelial forms, were recorded by the culture plate method and 51 spore types, including the hyphal fragments and unidentified spores, were recorded by the rotorod method. As to the seasonal variation, winter was found to be the greatest contributor of fungal spores as compared to the summer and rainy season. Instead, when considering the hour of the day, the peak number of fungal propagules was recorded at noon (12.00 h) followed by evening and morning values, an exception being recorded in winter months, when maximum CFUs ofCladosporium were monitored in the morning. The seasonal variation in fungal concentration and composition was found to be influenced by temperature, rainfall and relative humidity, whereas diurnal incidence was the effect of varying temperature and relative humidity during day time only. Moderate temperature and relative humidity favoured the maximum fungal spore load in the atmosphere.Cladosporium, Nigrospora, Alternaria, Lasiodiplodia, Drechslera, Pestalotia, Curvularia, Epicoccum, Aspergillus, Penicillium andChaetomium were the commonest fungal spores in the factory area.     

From LC-MS/MS metabolomics profiling of Kanchanara Guggulu to molecular docking and dynamics simulation of quercetin pentaacetate with aldose reductase

Kanchanara Guggulu (KG) is an important traditional medicine that is prescribed by the Ayurveda physicians for the treatment of swellings in various organs such as the thyroid, and lymph nodes. High-resolution mass-spectrometry-based metabolomics found metabolites in KG. LC-MS/MS-based metabolomics analysis of KG identified 2,579 compounds including quercetin and kaempferol derivatives. The molecular docking and dynamics analysis of quercetin pentaacetate with aldose reductase is documented for further consideration in drug discovery.     

Phenotypic plasticity can potentiate rapid evolutionary change

Using a computational model of string-like haploid genotypes, we verify the conjecture (J. Theor. Biol. 188 (1997) 153) that phenotypic plasticity can speed up evolution. The corresponding real-life situation was realized by Waddington in experiments carried out on the fruit fly Drosophila. Waddington found that after selecting for an environmentally induced trait over a number of generations, a new, true-breeding phenotype resulted that was absent in the starting population. The phenomenon, termed 'genetic assimilation', continues to attract interest because of the rapidity of the effect and because of its seemingly Lamarckian implications. By making use of a genetic algorithm-based approach developed previously, we show that conventional Darwinian selection acting on regulatory genes can account for genetic assimilation. The essential assumption in our model is that a structural gene can be in either of three allelic states. These correspond to its being (a) 'on' or 'off' constitutively or (b) in a plastic state in which the probability that it is 'on' or 'off' is influenced by regulatory loci in a dosage-dependent manner.     

Recurrent respiratory syncytial virus infections in allergen-sensitized mice lead to persistent airway inflammation and hyperresponsiveness

Respiratory syncytial virus (RSV) infection is considered a risk factor for bronchial asthma; however, the synergy between allergen sensitization and RSV infection in the development of pulmonary inflammation and asthma has been controversial. In this study the effects of primary and recurrent RSV infection on allergic asthma were examined in a group of control, RSV-infected, Dermatophagoides farinae (Df) allergen-sensitized, and Df allergen-sensitized plus RSV-infected BALB/c mice. Primary RSV infection in Df-sensitized mice transiently increases airway responsiveness, which is accompanied by increases in eosinophilic infiltration, the expression of ICAM-1, and macrophage inflammatory protein-1alpha (MIP-1alpha) in the lung tissue. A secondary RSV infection persistently enhances airway responsiveness in Df-sensitized mice, with a concomitant increase in MIP-1alpha and RSV Ag load in lung tissues. Bulk cultures of thoracic lymph node mononuclear cells demonstrate that acute RSV infection augments both Th1- and Th2-like cytokines, whereas secondary and tertiary infections shift the cytokine profile in favor of the Th2-like cytokine response in Df-sensitized mice. The elevated total serum IgE level in the Df-sensitized mice persists following only RSV reinfection. Thus, recurrent RSV infections in Df-sensitized mice augment the synthesis of Th2-like cytokines, total serum IgE Abs, and MIP-1alpha, which are responsible for persistent airway inflammation and hyperresponsiveness, both of which are characteristics of asthma.     

Mediatorless voltammetric oxidation of NADH and sensing of ethanol

A simple, selective and sensitive method for the detection of NADH and ethanol is presented. Self-assembled monolayers (SAMs) of mercaptopyrimidine (MPM) and their derivatives, thiocytosine (TC) and 4,6-diamino-2-mercaptopyrimidine (DMP) on gold (Au) electrode are used for the voltammetric detection of NADH and ethanol in neutral aqueous solution. A decrease of 200-300 mV in the overpotential associated with an observable increase in the peak current was obtained for the oxidation of NADH on MPM and TC monolayer-modified electrodes without any redox mediator. The facilitated electron transfer for the oxidation of NADH at the TC monolayer is ascribed to the existence of stable cationic p-quinonoid form of TC. The electrode modified with DMP monolayer could not exhibit stable response for NADH owing to the fouling of electrode surface. The MPM and TC monolayer-modified electrodes show high selectivity and excellent sensitivity (MPM: 0.633+/-0.005 microA cm(-2) microM(-1); TC: 0.658+/-0.008 microA cm(-2) microM(-1)) towards NADH with detection limit (3sigma) of 2.5 and 0.5 microM, respectively. Presence of large excess of ascorbate (AA) does not interfere the detection of NADH and the monolayer-modified electrode shows individual voltammetric peaks for AA and NADH. Voltammetric sensing of ethanol using alcohol dehydrogenase on MPM and TC monolayer-modified electrode is successfully demonstrated and these electrode can detect as low as 0.5 mM ethanol in neutral pH. The sensitivity of the MPM and TC monolayer-modified electrodes toward ethanol was found to be 3.24+/-0.03 and 3.435+/-0.04 microA cm(-2) mM(-1), respectively.     

Genotoxic effect of isoproturon (herbicide) as revealed by three mammalian in vivo mutagenic bioassays

Genotoxic effect of isoproturon was assessed by employing in vivo chromosomal aberration, micronucleus and sperm-shape abnormality assays. A significant dose-responsive mutagenic effect was observed in chromosome aberration and sperm-shape abnormality tests whereas in micronucleus assay the effect was significant only at the highest dose (200 mg/kg). Only the result for the chronic dose and the two different fixation times (6 and 48 hr) were not statistically significant. The results indicate the genotoxic property of isoproturon in mammalian in vivo test system.     

Prevalence of Pulmonary Tuberculosis among Adults in a North Indian District

BackgroundRecent population prevalence estimates of pulmonary tuberculosis (PTB) are not available for several areas in India. We conducted a field-based population survey at a north Indian district to estimate point prevalence of bacteriologically positive PTB.MethodsA stratified cluster sampling design was used to conduct the survey in both urban and rural areas within the district. All adults aged more than 15 years, in 18 rural and 12 urban clusters of 3000 subjects each, were interviewed using a symptom card. Two sputum samples were collected from all persons having symptoms suggestive of PTB, or history of antitubercular treatment, for smear microscopy for acid-fast bacilli and mycobacterial culture. Those having at least one sputum specimen positive on microscopy and/or culture were categorized as having PTB. Prevalence was estimated after adjusting for cluster sampling and incomplete data (through individual level analysis with robust standard error).ResultsOf 91,030 eligible adult participants (47,714 men and 43,316 women), 85,770 (94.2%) completed the symptom cards. Of them, 2,898 persons were considered eligible for sputum examination and 2,839 (98.0%) provided at least one sample. Overall, 21 persons had bacteriologically positive PTB, and cluster level prevalence was estimated at 24.5 per 100,000 population (95% CI 12.8–36.2). Individual level analysis with robust standard error yielded a prevalence estimate of 24.1 per 100,000 populations (95% CI 12.8–35.4).ConclusionThe observed prevalence of bacteriologically positive PTB in this district is lower than empiric national estimates, probably as a result of successful implementation of tuberculosis control measures in the area.     

Role of miRNAs in the pathogenesis of T2DM,insulin secretion,insulin resistance,and β cell dysfunction: the story so far

Journal of Physiology and Biochemistry - Diabetes, the most common endocrine disorder, also known as a silent killer disease, is characterized by uncontrolled hyperglycemia. According to the...