TFor the first time in the present study the effects of vanillin, vanillyl alcohol, vanillic acid, as well as the newly synthesized vanillin derivative, bis-vanillin, were investigated on the oxidation of dopamine hydrochloride by mushroom tyrosinase. Among them, vanillin and bis-vanillin act as activators, while vanillyl alcohol and vanillic acid exhibited inhibitory effects, the IC50 values being estimated 1.5 and 1.0 mM, respectively. These compounds were mixed inhibitors. The presence of aldehyde and metoxy groups at the meta position of aromatic compounds seems to cause them to react as tyrosinase activators, as observed in the case of vanillin and bis-vanillin. The presence of both groups in bis-vanillin results in a stronger activation effect compared to vanillin. The results indicate that the electron-withdrawing capacity of the functional group at the C-1 position is essential for the inhibitory potency of vanillin derivatives. In comparison with other benzoic acid derivatives, the results obtained in this study suggest that the relative positioning of hydroxy and methoxy groups at meta and para positions plays an important role in the inhibition effects of benzoic acids and their inhibition potency.

Mental retardation (MR) is one of the most frequently found major genetic disorders around the world, affecting 1-3% of the people in the general population. The recent advancement in molecular biology and cytogenetic study has made possible the identification of new genes for a variety of genetic disorders including autosomal recessive MR. Recessive genetic disorders are common in Pakistan due to the high rate of consanguinity. A central focus of the present study was to map and identify the disease causing gene in a mentally retarded consanguineous Pakistani family with speech disorder. The study comprises of 20 individuals including 10 patients. Genetic analysis of autosomal recessive MR and speech disorders was carried out for eight known fundamental loci sorted out on the basis of clinical features. These loci including 3p26.2, 3p21.3, 7q22, 8p22, 11p15, 14q11.2-q12, 19p13.12, and 22p13 were screened using polymorphic microsatellite markers. To identify the disease locus, genomic DNA from each individual was genotyped for homozygosity analysis. Microsatellite markers were amplified using PCR. The study provided valuable data to exclude linkage of the above mentioned loci. The absence of any linkage of the Pakistani family with autosomal recessive MR to the eight well known loci, confirms the genetic heterogeneity of MR. These results need to be verified and the candidate gene be found by a complete genome scan, which may help us in establishing the genotype-phenotype correlation of MR, improving genetic counseling, carrier screening, DNAbased prenatal diagnosis and the opportunity to develop appropriate animal models to test new forms of cell or gene therapies.

Pythium irregulare oomycetes adapts with environmental changes including crude oil concentration by changing the composition of lipids in the cytoplasmic membrane and providing the required characteristics for adaptation in improper and stressful environmental situations. It was found that cultivation of Pythium irregulare LX oomycetes in the nutrient media with different concentrations of crude oil with 1.0, 2.0, 3.0, 5.0 and 10.0 (%), incubated for 5 days at 26-28°C on a rotary shaker (200 rpm) in aerobic conditions and deep culturing caused an increase in the lipid content and the unsaturation degree of fatty acids, confirming the correspondence between the increase of polar lipid/free sterol in the composition of membrane lipids’ ratio and that of polar lipids in general lipid fractions. Represented data shows that the process of adaptation of oomycetes to a stressful situation created with crude oil motivated the increase of the rate of membrane phospholipids with a high quantity of unsaturated fatty acids.

Kinetics of bacterial growth and protease production were monitored on a novel isolated moderately halophilic bacterium, Salinivibrio sp. strain MS-7, and maximum growth and protease activity was achieved after 48 hours at 30°C and 180 rpm. To determine the effect of various carbon sources on protease production, glucose, lactose, sucrose and maltose were investigated and maximum production of the enzyme was obtained in a basal medium (pH 8.0) containing maltose as a carbon source (494 U/ml). The protease was isolated from a stationary phase culture, purified 3.6-fold with 56% yield by a simple procedure and characterized biochemically. The enzyme revealed a monomeric structure with a relative molecular mass of 21 KDa by running on SDS-PAGE. Maximum caseinolytic activity of the enzyme was observed at 50°C, pH 8.0 and 0–0.5 M NaCl with a high tolerance to salt concentrations of up to 3 M. The effect of various metal ions and inhibitors on caseinolytic activity of the purified protease revealed that it probably belongs to the subclass of serine metalloproteases. These findings suggest that the protease secreted by Salinivibrio sp. strain MS-7 can be introduced as a candidate for biotechnological applications based on its haloalkaline properties.

Disposition and transportation of anticancer drugs by human serum albumin (HSA) affects their bioavailability, distribution and elimination. In this study, the interaction of a set of anticancer drugs with HSA was investigated by molecular dynamics and molecular docking simulations. The drugs' activities were analyzed according to their docking scores, binding sites and structural descriptors. The results displayed the ability of cavity 1, located in the cleft between domains I and III, to potentiate as the principal binding site of all tested drugs. This cavity provides a large space without any effective steric hindrance and induces the stability of the drugs in their binding sites by short and long ranged interactions with the accessible residues. Yet, specific structural features may lead some drug configurations to advance stronger interactions with cavities other than cavity 1. Also, the small volume and position of some cavities i.e. cavities 3, 5-10 involve penetration, small molecular volume and specific geometry which consequently force most drugs out of the corresponding binding sites. Therefore, the steric factor seems to play the most important role in the transportation of drugs by HSA.

To establish a comprehensive picture of the relationship between glutathione S-transferase omega 2 (GSTO2; MIM: 612314) gene N142D variant (rs. 156697) and breast cancer risk, the present meta-analysis was carried out. Studies published up to July 2012 with information about GSTO2 polymorphism and breast cancer risk were identified using several electronic databases. We identified 4 eligible studies, including 2678 subjects (1316 patients, and 1362 healthy controls) in relation to the N142D polymorphism of GSTO2 and risk of breast cancer. There was no heterogeneity between studies. Considering all of the studies, the DD (OR=1.29, 95%CI: 0.99-1.67, P=0.055) and ND (OR=1.03, 95%CI: 0.88-1.21, P=0.697) genotypes, did not alter the risk of breast cancer in comparison with the NN genotype. Therefore, it is suggested that if the number of studies increased, finding a significant association between N142D polymorphism of GSTO2 and susceptibility to breast cancer would be very probable.

NF-?B pathway is a link between inflammation and cancer and is involved in cellular responses to different stimuli. Gastrointestinal lumen is exposed to many inflammatory agents such as foods, free radicals and bacterial or viral antigens. The aim of the present study was to evaluate the possible role of NF-?B1in gastric adenocarcinoma. To detect the relative level of NF-?B1transcript, total RNA was extracted from tissue specimens, a cDNA library was generated, and quantitative RT-PCR was performed for thirty human gastric adenocarcinoma tissue samples and thirty matched normal gastric tissue samples. NF-?B1 expression showed two-sidedness, which means that a group of 11 sample pairs showed up-regulation and a group of 16 sample pairs showed down-regulation. No histopathologic characteristics of samples could justify the observed two-sidedness. The NF-?B1 two-sidedness expression indicates the involvement of NF-?B1 and in a larger scale, NF-?B signaling pathway in gastric carcinogenesis. Our results show the complexity of regulatory mechanisms involved in developing and controlling the process of gastric cancer pathogenesis.