The novel allele (3R) of the VNTR polymorphism in the XRCC5 promoter region dramatically decreases the gene expression

Polymorphism of variable number of tandem repeats (VNTR) in the promoter region of X-ray repair cross-complementing 5 (MIM: 194364, XRCC5; rs6147172) was reported. The aim of the present study is to evaluate the influence of this polymorphism on XRCC5 mRNA levels. Genotypes of XRCC5 VNTR were determined by high resolution of melting analysis (HRMA). The quantitative XRCC5 mRNA expression (compared to ß-actin expression) among 0R/1R, 1R/2R, and 1R/3R genotypes was investigated. There was a negative correlation between the overall number of tandem repeats and XRCC5 expression (r = ?0.965, df = 7, P < 0.001). The mRNA level of XRCC5 decreased as function of number of tandem repeats. The 3R allele of the VNTR polymorphism in the XRCC5 promoter region dramatically decreases the gene expression.     

Effects of silicon oxide nanoparticles on growth and physiology of wheat seedlings

The effects of silicon oxide (SiO₂) nanoparticles at concentrations of 50, 100, 200, 400, and 800 mg/L on Triticum aestivum L. seedlings were investigated. We showed that SiO₂ nanoparticles, at concentrations higher 200 mg/L, had negative impacts on wheat seedlings. At these concentrations, SiO₂ nanoparticles significantly decreased roots and shoots fresh weight, decreased roots and shoots dry weight, decreased amounts of chlorophyll a and b in leaves, decreased amount of carotenoids in leaves, increased proline content in leaves, increased lipid peroxidation in leaves, and increased catalase activity in leaves. Results of this study indicate that at lower concentrations (such as 50 and 100 mg/L), SiO₂ nanoparticles not only have negative effects on wheat seedlings, but can have even some positive effects.     

Modulation of hematology changes by polymorphism of glutathione S-transferase M1 and T1

Workers in the petroleum distribution trades experience relatively low-level exposures to gasoline vapors whose consequences have not been fully elucidated. The purpose of this study was to investigate changes in the hematological parameters among filling station workers who were occupationally exposed to gasoline. The target group for the study consisted of 41 workers from eight filling stations of Shiraz (south of Iran). The control group consisted of 27 healthy subjects matched for age and sex from general population. The complete blood count analysis was done in one laboratory. Using PCR-based method, the genotypes of glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) were determined. Workers were divided into three exposure groups according to employment history: duration less than 1 year, 1-5 years, and more than 5 years. Comparison was performed using Kruskal-Wallis test. In the individuals with the presence of both GSTT1 and GSTM1 functional alleles, comparison between four exposure groups revealed no significant difference for studied hematological variables. There were statistically significant differences between study groups, with only one functional allele, either GSTT1 or GSTM1, for relative number of lymphocytes (chi(2)=9.147, df=3, P=0.027) and neutrophils (chi(2)=9.951, df=3, and P=0.019), and absolute number of lymphocytes (chi(2)=9.135, df=3, and P=0.028), and RBC (chi(2)=10.586, df=3, and P=0.014). These findings could indicate the possible protective effect of concurrent presence of GSTM1 and GSTT1 enzymes on the hematopoietic system of filling station workers.     

Impaired striatal Akt signaling disrupts dopamine homeostasis and increases feeding

Background

The prevalence of obesity has increased dramatically worldwide. The obesity epidemic begs for novel concepts and therapeutic targets that cohesively address “food-abuse” disorders. We demonstrate a molecular link between impairment of a central kinase (Akt) involved in insulin signaling induced by exposure to a high-fat (HF) diet and dysregulation of higher order circuitry involved in feeding. Dopamine (DA) rich brain structures, such as striatum, provide motivation stimuli for feeding. In these central circuitries, DA dysfunction is posited to contribute to obesity pathogenesis. We identified a mechanistic link between metabolic dysregulation and the maladaptive behaviors that potentiate weight gain. Insulin, a hormone in the periphery, also acts centrally to regulate both homeostatic and reward-based HF feeding. It regulates DA homeostasis, in part, by controlling a key element in DA clearance, the DA transporter (DAT). Upon HF feeding, nigro-striatal neurons rapidly develop insulin signaling deficiencies, causing increased HF calorie intake.

Methodology/Principal Findings

We show that consumption of fat-rich food impairs striatal activation of the insulin-activated signaling kinase, Akt. HF-induced Akt impairment, in turn, reduces DAT cell surface expression and function, thereby decreasing DA homeostasis and amphetamine (AMPH)-induced DA efflux. In addition, HF-mediated dysregulation of Akt signaling impairs DA-related behaviors such as (AMPH)-induced locomotion and increased caloric intake. We restored nigro-striatal Akt phosphorylation using recombinant viral vector expression technology. We observed a rescue of DAT expression in HF fed rats, which was associated with a return of locomotor responses to AMPH and normalization of HF diet-induced hyperphagia.

Conclusions/Significance

Acquired disruption of brain insulin action may confer risk for and/or underlie “food-abuse” disorders and the recalcitrance of obesity. This molecular model, thus, explains how even short-term exposure to “the fast food lifestyle” creates a cycle of disordered eating that cements pathological changes in DA signaling leading to weight gain and obesity.     

Alterations in blood pressure due to chronic exposure to natural sour gas leakage containing sulfur compounds

In order to show the alteration of blood pressure in subjects chronically exposed to natural gas containing sulfur compounds, the present study was done. The blood pressure of 94 (43 males, 51 females) of healthy individuals living in the polluted area of Masjid-i-Sulaiman (Khozestan province, southwest of Iran) was measured. The non-parametric Sign test was applied in order to detect differences between the study subjects and the normal mean values according to the sex and age of subjects. Statistical analysis showed that the systolic blood pressure significantly decreased (Z=-2.74; P=0.0031) while the diastolic blood pressure (Z=+2.11; P=0.0174) and heart rate (Z=+3.62; P<0.001) significantly increased in individuals living in the contaminated areas compared with those of normal mean values. The systolic and diastolic blood pressure decreased and increased, respectively, in individuals chronically exposed to natural sour gas containing sulfur compounds.     

Clinical response to chemotherapy in locally advanced breast cancer was not associated with several polymorphisms in detoxification enzymes and DNA repair genes

The main aim of the present study was to investigate the association between several genetic polymorphisms (in glutathione S-transferase members and DNA repair genes) and clinical response to chemotherapy in locally advanced breast cancer. A sequential series of 101 patients were prospectively included in this study. Clinical assessment of treatment was accomplished by comparing initial tumor size with preoperative tumor size using revised RECIST guideline (version 1.1). Clinical response was regarded as a response or no response. There was no difference between non-responders and responders for the prevalence of genotypes of the study polymorphisms.     

A detailed and validated three dimensional dynamic model of the patellofemoral joint

A detailed 3D anatomical model of the patellofemoral joint was developed to study the tracking, force, contact and stability characteristics of the joint. The quadriceps was considered to include six components represented by 15 force vectors. The patellar tendon was modeled using four bundles of viscoelastic tensile elements. Each of the lateral and medial retinaculum was modeled by a three-bundle nonlinear spring. The femur and patella were considered as rigid bodies with their articular cartilage layers represented by an isotropic viscoelastic material. The geometrical and tracking data needed for model simulation, as well as validation of its results, were obtained from an in vivo experiment, involving MR imaging of a normal knee while performing isometric leg press against a constant 140 N force. The model was formulated within the framework of a rigid body spring model and solved using forth-order Runge-Kutta, for knee flexion angles between zero and 50 degrees. Results indicated a good agreement between the model predictions for patellar tracking and the experimental results with RMS deviations of about 2 mm for translations (less than 0.7 mm for patellar mediolateral shift), and 4 degrees for rotations (less than 3 degrees for patellar tilt). The contact pattern predicted by the model was also consistent with the results of the experiment and the literature. The joint contact force increased linearly with progressive knee flexion from 80 N to 210 N. The medial retinaculum experienced a peak force of 18 N at full extension that decreased with knee flexion and disappeared entirely at 20 degrees flexion. Analysis of the patellar time response to the quadriceps contraction suggested that the muscle activation most affected the patellar shift and tilt. These results are consistent with the recent observations in the literature concerning the significance of retinaculum and quadriceps in the patellar stability.     

T and B-cell epitopes prediction of Iranian saffron (Crocus sativus) profilin by bioinformatics tools

Plant profilins form a well-known panallergen family responsible for cross-sensitization between plant foods and pollens. We sought to map T and B-cell epitopes on the Iranian Crocus sativus profilin by bioinformatics tools. The predicted peptides are useful for further vaccine development.