Molecular Characterization of Circulating Respiratory Syncytial Virus (RSV) Genotypes in Gilgit Baltistan Province of Pakistan during 2011-2012 Winter Season

Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract infections in young children, but very little is known about its epidemiology and circulating genotypes in Pakistan. This study analyzed the epidemiological and molecular characteristics of RSV genotypes detected in Pakistani children less than 2 years of age with acute respiratory tract infections (ARIs) in a tertiary care hospital in Gilgit Baltistan (GB) province during 2011-12 winter season. RSV was detected in 75 out of 105 children presenting with acute respiratory infection. Male infants between 2-6 months age made up the highest percentage of RSV positive cases. Epidemiological factors such as pre-maturity, mean weight, clinical features and diagnosis when compared between RSV positive and negative groups were found to be statistically insignificant. Phylogenetic analysis classified all 75 of the RSV strains into 71 strains of subgroups A and 4 strains of subgroup B, respectively. Strains belonging to subgroups A and B were further subdivided into NA1/GA2 and BA, respectively. The nucleotide and deduced amino acid sequence identities were relatively high among these strains (>90%). Both RSV-A and RSV-B isolates had two potential N-glycosylation sites in HVR2 of G protein and with heavy O-glycosylation of serine and threonine residues (G scores of 0.5-0.7). This report highlights the significance of RSV as a dominant viral etiologic agent of pediatric ARIs, and need for continued molecular epidemiological surveys for early detection of prevalent strains and newly emerging genotypes to understand epidemiology of RSV infections in various regions of Pakistan.     

The c.42_52del11 Mutation in TPRN and Progressive Hearing Loss in a Family from Pakistan

The DFNB79 locus harbors TPRN mutations in which have been reported in a few families with deafness. Four frameshift mutations in TPRN have been described to cause severe or severe-to-profound hearing loss in Moroccan and Pakistani families, and a single frameshift mutation was associated with progressive hearing loss in deaf individuals in a Dutch family. We identified a Pakistani family in which the affected individuals were homozygous for a pathogenic mutation, c.42_52del11, in TPRN (p.G15Afs150X). In contrast to the previously reported individuals affected by the same mutation, hearing loss is likely to be progressive in this family. Thus the same mutation of TPRN can be associated with different thresholds of hearing as well as differences in the stability of the phenotype.     

Speciation of antimony in natural waters : the determination of Sb(III) and Sb(V) by continuous flow hydride generation-atomic absorption spectrometry

Abstract

A new procedure for the speciation of dissolved antimony is described. This makes use of complexation with citrate to prevent, preferentially, the formation of hydride from Sb(V) and allow the selective determination of Sb(III) to be made by continuous flow hydride generation - atomic absorption spectrometry. When the citric acid (12% m/V) is replaced by potassium iodide (3% m/V), total antimony is determined and the concentration of Sb(V) can be obtained by difference. The determination of the antimony species is dominated in this new procedure by the complexation of Sb(V) with citrate and the effect of pH is limited to a minor, re-inforcing role. This permits acidification to be made with hydrochloric acid. The principal interfering species in the determination of total antimony and Sb(III) is Fe³⁺, with Fe²⁺, Cu²⁺ and Ni²⁺ showing lesser effects on Sb(III). The technique is applied successfully to synthetic mixtures and to natural waters from the environment of a disused antimony mine.

The characteristic concentration obtained for antimony was 0.7 ng mL^–1 and the detection limit 1 ng mL^–1.     

Ultrasonic synthesis of tyramine derivatives as novel inhibitors of α-glucosidase in vitro

Tyramine derivatives 3–27 were synthesized by using conventional and environmental friendly ultrasonic techniques. These derivatives were then evaluated for the first time for their α-glucosidase (Sources: Saccharomyces cerevisiae and mammalian rat-intestinal acetone powder) inhibitory activity by using in vitro mechanism-based biochemical assays. Compounds 7, 14, 20, 21 and 26 were found to be more active (IC₅₀?=?49.7?±?0.4, 318.8?±?3.7, 23.5?±?0.9, 302.0?±?7.3 and 230.7?±?4.0?μM, respectively) than the standard drug, acarbose (IC₅₀?=?840.0?±?1.73?μM (observed) and 780?±?0.028?μM (reported)) against α-glucosidase obtained from Saccharomyces cerevisiae. Kinetic studies were carried out on the most active members of the series in order to determine their mode of inhibition and dissociation constants. Compounds 7, 20 and 26 were found to be the competitive inhibitors of α-glucosidase. These compounds were also screened for their protein antiglycation, and dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. Only compounds 20, 22 and 27 showed weak antiglycation activity with IC₅₀ values 505.27?±?5.95, 581.87?±?5.50 and 440.58?±?2.74?μM, respectively. All the compounds were found to be inactive against DDP-IV enzyme. Inhibition of α-glucosidase, DPP-IV enzymes and glycation of proteins are valid targets for the discovery of antidiabetic drugs. Cytotoxicity of compounds 3–27 was also evaluated by using mouse fibroblast 3T3 cell lines. All the compounds were found to be noncytotoxic. The current study describes the synthesis α-glucosidase inhibitory activity of derivatives, based on a natural product tyramine template. The compounds reported here may serve as the starting point for the design and development of novel α-glucosidase inhibitors as antidiabetic agents.     

Effect of organic carbon sources and environmental factors on cell growth and lipid content of Pavlova lutheri

The present study aimed to investigate the effects of organic carbon sources, cultivation methods, and environmental factors on growth and lipid content of Pavlova lutheri for biodiesel production. In the 250-mL flask bioreactors, P. lutheri was cultivated in the modified artificial seawater (ASW) medium containing glucose, glycerol, sodium acetate, or sucrose as an organic carbon substrate. The effects of different growth conditions (phototrophic, mixotrophic, and heterotrophic) and environmental factors such as photoperiod, light intensity, and salinity were evaluated. Growth of P. lutheri was inhibited under heterotrophy but was enhanced in mixotrophy as compared to phototrophy. Biomass and lipid content of P. lutheri were significantly (p < 0.05) affected by changing photoperiod, light intensity, and salinity. Higher biomass concentration and lipid content were observed at a light intensity of 100 ± 2 μmol photons m−2 s−1, 18 h photoperiod, and 30% salinity, in a modified ASW medium supplemented with 10 mmol sucrose. An increase in biomass concentration from 320 ± 25.53 to 1106 ± 18.52 mg L−1 and high lipid content of 31.11 ± 1.65% (w/w) were observed with the optimized culture conditions, demonstrating a significant (p < 0.05) enhancement in biomass and lipid content due to the improved culture conditions. The present study emphasizes the possible use of sucrose for biomass and lipid production with P. lutheri under the optimized culture conditions. Using low-cost and relatively easy accessible feedstock such as sucrose would be a valuable alternative for growing microalgae with enhanced lipid content.     

Extremely stable indole-3-glycerol-phosphate synthase from hyperthermophilic archaeon Pyrococcus furiosus

Extremophiles - The gene-encoding Indole-3-glycerol phosphate synthase, a key enzyme involved in the cyclization of 1-(o-carboxyphenylamino)-1-deoxyribulose 5-phosphate, from Pyrococcus furiosus...     

Swine generated by somatic cell nuclear transfer have increased incidence of intrauterine growth restriction (IUGR)

While somatic cell nuclear transfer (SCNT) has been successful in several species, many pregnancies are lost and anomalies are found in fetal and perinatal stages. In this study SCNT and artificial inseminations (AI) populations were compared for litter size, average birth weight, piglets alive at birth, stillborn, mummies, dead at the first week, intrauterine growth restriction (IUGR) and large for gestational age (LGA). Twenty-three SCNT litters (143 individuals) were compared to 112 AI litters (1300 individuals). Litter size average was 11.5 for AI and 6.2 for SCNT. Litter weight and average birth weight adjusted by litter size were significantly (p < 0.05) higher in AI than in SCNT litters. The SCNT population had a significant (p < 0.01) increase in the number of IUGRs per litter with LSmeans 7.2 +/- 1.4 versus 19.4 +/- 3.5 and means 8.0 +/- 10.8 versus 15.5 +/- 24.5 for AI and SCNT, respectively. Additionally, there was a trend for higher postnatal mortality and stillbirths in the SCNT population. These findings demonstrate that there are some differences between SCNT-derived and AI litters. SCNT-derived pigs are excellent models to study epigenetic factors and genes involved in IUGRs, and to develop effective means to improve fetal growth in humans and animals.     

Tackling the plant proteome: practical approaches, hurdles and experimental tools

The study of complex biological questions through comparative proteomics is becoming increasingly attractive to plant biologists as the rapidly expanding plant genomic and expressed sequence tag databases provide improved opportunities for protein identification. This review focuses on practical issues associated with comparative proteomic analysis, including the challenges of effective protein extraction and separation from plant tissues, the pros and cons of two-dimensional gel-based analysis and the problems of identifying proteins from species that are not recognized models for functional genomic studies. Specific points are illustrated using data from an ongoing study of the tomato and pepper fruit proteomes.     

Synthesis and antihyperglycemic activity profiles of novel thiazolidinedione derivatives

A number of thiazolidine-2,4-diones derivatives having carboxylic ester appendage at N-3 were synthesized and their antihyperglycemic activity was evaluated. Many of these derivatives as well as their corresponding carboxylic acid showed significant improvement on post-prandial hyperglycemia in normal rats, in contrast to their poor agonist activity at PPARgamma.