Interaction of eNOS polymorphism with MTHFR variants increase the risk of diabetic nephropathy and its progression in type 2 diabetes mellitus patients

The present study has investigated the role of endothelial nitric oxide (eNOS) G894T polymorphism and its interaction with methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C variants on the predisposition to diabetic nephropathy and its progression. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method the eNOS G894T and MTHFR polymorphisms were detected in 72 microalbuminuric, 68 macroalbuminuric, and 72 normoalbuinuric type 2 diabetes mellitus (T2DM) patients from Western Iran. The presence of GT and GT + TT genotypes of eNOS were associated with insignificantly 1.86- and 1.68-fold increased risk of macroalbuminuria, respectively and 1.21- and 1.13-fold increased risk of microalbuminuria, respectively. However, the concomitant presence of eNOST and MTHFR 1298C alleles were significantly increased the risk of macroalbuminuria (6.6-fold, P < 0.001) and progression from micro- to macro-albuminuria (3.85 times, P = 0.011). Also, the presence of both alleles of eNOST and MTHFR 677T were significantly associated with increased risk of macroalbuminuria (4.8-fold, P = 0.005). The presence of GT + TT genotypes of eNOS was significantly associated with increased risk of coronary artery disease in micro- and macro-albuminuric patients compared to normoalbuminuric patients. The concomitant presence of three mutant alleles significantly increased the risk of macroalbuminuria and progression from micro- to macro-albuminuria 38.5- and 10.5-fold, respectively. Our study indicated that eNOS T allele interacts with MTHFR variants, especially MTHFR A1298C to increase the risk of macroalbuminuria and progression from micro-to macro-albuminuria. Also, Interaction between three alleles of eNOST, MTHFR 677T, and 1298C highly increased the risk of macroalbuminuria and progression of diabetic nephropathy in T2DM patients.     

Comparative cellular and molecular analysis of cytotoxicity and apoptosis induction by doxorubicin and <Emphasis Type="Italic">Baneh</Emphasis> in human breast cancer T47D cells

It is now widely accepted that dietary phytochemicals inhibit cancer progression and enhance the effects of conventional chemotherapy. In this report, we comparatively studied the cellular and molecular aspects of apoptosis induction by the methanolic extract of Baneh fruit skin in comparison to Doxorubicin (Dox), a well-known anticancer drug, in human breast cancer T47D cells. The MTT assay was used to determine the antiproliferative effects. The flow cytometric and microscopic analyses were done to evaluate the apoptosis induction. Furthermore, western blot analyses have been done to study the role of key molecular players of apoptosis including caspase 3 and PARP. The Baneh extract showed strong antiproliferative activity against T47D cells in a dose- and time-dependent manner that was comparable to and even stronger than Dox in certain concentrations. Analysis of Baneh-treated cells by flow cytometry and fluorescence microscopy indicated strong apoptosis induction and nuclear morphological alterations similar to or greater than Dox. Finally, molecular analysis of apoptosis by western blotting proved activation of caspase 3 followed by poly ADP ribose polymerase (PARP) cleavage more efficiently in Baneh than in Dox treated cancer cells. These findings indicate that Baneh extract contains phytochemicals which act as inhibitor of cell proliferation and inducer of apoptosis in human breast cancer T47D cells that makes it a potentially good candidate for new anticancer drug development.     

A chemiluminescent metalloimmunoassay based on copper‐enhanced gold nanoparticles for quantification of human growth hormone

A chemiluminescence (CL) immunoassay was developed to determine human growth hormone (hGH) based on copper‐enhanced gold nanoparticles. In this method, gold nanoparticles were deposited on polystyrene wells for adsorption of human growth antibodies as well as catalyst for reducing of copper ions from the copper enhancer solution. The reduction of copper ions was prevented where the gold nanoparticles were covered by the antibody–antigen immunocomplex. The deposited copper on Au nanoparticles was then dissolved in HNO₃ solution and quantified using the CL method. The CL intensity response was logarithmically dependent on the hGH concentrations over the range 0.2–50 ng/mL, with a detection limit (3σ) of 0.036 ng/mL. Copyright © 2012 John Wiley & Sons, Ltd.     

Dual conformation of H2H3 domain of prion protein in mammalian cells

The concept of prion is applied to protein modules that share the ability to switch between at least two conformational states and transmit one of these through intermolecular interaction and change of conformation. Although much progress has been achieved through the understanding of prions from organisms such as Saccharomyces cerevisiae, Podospora anserina, or Aplysia californica, the criteria that qualify a protein module as a prion are still unclear. In addition, the functionality of known prion domains fails to provide clues to understand the first identified prion, the mammalian infectious prion protein, PrP. To address these issues, we generated mammalian cellular models of expression of the C-terminal two helices of PrP, H2 and H3, which have been hypothesized, among other models, to hold the replication and conversion properties of the infectious PrP. We found that the H2H3 domain is an independent folding unit that undergoes glycosylations and glycosylphosphatidylinositol anchoring similar to full-length PrP. Surprisingly, in some conditions the normally folded H2H3 was able to systematically go through a conversion process and generate insoluble proteinase K-resistant aggregates. This structural switch involves the assembly of amyloid structures that bind thioflavin S and oligomers that are reactive to A11 antibody, which specifically detects protein oligomers from neurological disorders. Overall, we show that H2H3 is a conformational switch in a cellular context and is thus suggested to be a candidate for the conversion domain of PrP.     

Estimating climate change,CO2 and technology development effects on wheat yield in northeast Iran

Wheat is the main food for the majority of Iran’s population. Precise estimation of wheat yield change in future is essential for any possible revision of management strategies. The main objective of this study was to evaluate the effects of climate change, CO₂ concentration, technology development and their integrated effects on wheat production under future climate change. This study was performed under two scenarios of the IPCC Special Report on Emission Scenarios (SRES): regional economic (A2) and global environmental (B1). Crop production was projected for three future time periods (2020, 2050 and 2080) in comparison with a baseline year (2005) for Khorasan province located in the northeast of Iran. Four study locations in the study area included Mashhad, Birjand, Bojnourd and Sabzevar. The effect of technology development was calculated by fitting a regression equation between the observed wheat yields against historical years considering yield potential increase and yield gap reduction as technology development. Yield relative increase per unit change of CO₂ concentration (1 ppm^?1) was considered 0.05 % and was used to implement the effect of elevated CO₂. The HadCM3 general circulation model along with the CSM-CERES-Wheat crop model were used to project climate change effects on wheat crop yield. Our results illustrate that, among all the factors considered, technology development provided the highest impact on wheat yield change. Highest wheat yield increase across all locations and time periods was obtained under the A2 scenario. Among study locations, Mashhad showed the highest change in wheat yield. Yield change compared to baseline ranged from ?28 % to 56 % when the integration of all factors was considered across all locations. It seems that achieving higher yield of wheat in future may be expected in northeast Iran assuming stable improvements in production technology.     

Endothelial cadherins in cancer

Cadherins are cell adhesion receptors that play important roles in embryogenesis and tissue homoeostasis. Endothelial cells express various members of the cadherin superfamily, in particular vascular endothelial (VE-) cadherin, which is the main adhesion receptor of endothelial adherens junctions and neural (N-) cadherin, which is normally localized outside the junctions and may mediate adhesion between endothelial cells and non-endothelial cells. Dysregulation of cadherin expression has been implicated in tumor progression, in particular the loss of epithelial (E-) cadherin expression or function and the gain of N-cadherin. Moreover, more recently, aberrant expression of VE-cadherin was observed in certain cancer types. In breast carcinoma, VE-cadherin was shown to promote tumor cell proliferation and invasion through enhancing TGF-β signaling. Thus, in breast cancer, the cadherin switch involves another player, vascular endothelial cadherin, which is part of an intricate interplay of classical cadherins in breast cancer progression.     

Accumulation of Glucosylceramide in the Absence of the Beta-Glucosidase GBA2 Alters Cytoskeletal Dynamics

Glycosphingolipids are key elements of cellular membranes, thereby, controlling a variety of cellular functions. Accumulation of the simple glycosphingolipid glucosylceramide results in life-threatening lipid storage-diseases or in male infertility. How glucosylceramide regulates cellular processes is ill defined. Here, we reveal that glucosylceramide accumulation in GBA2 knockout-mice alters cytoskeletal dynamics due to a more ordered lipid organization in the plasma membrane. In dermal fibroblasts, accumulation of glucosylceramide augments actin polymerization and promotes microtubules persistence, resulting in a higher number of filopodia and lamellipodia and longer microtubules. Similar cytoskeletal defects were observed in male germ and Sertoli cells from GBA2 knockout-mice. In particular, the organization of F-actin structures in the ectoplasmic specialization and microtubules in the sperm manchette is affected. Thus, glucosylceramide regulates cytoskeletal dynamics, providing mechanistic insights into how glucosylceramide controls signaling pathways not only during sperm development, but also in other cell types.     

Age-dependent functional response of Aphidius matricariae (Hymenoptera: Braconidae) on tobacco aphid,Myzus persicae nicotianae (Hemiptera: Aphididae)

This study was performed to investigate the age-dependent functional response of Aphidius matricariae Haliday (Hymenoptera: Braconidae) at varying densities of tobacco aphid, Myzus persicae nicotianae Blackman (Hemiptera: Aphididae). Six densities (2, 4, 8, 16, 32, and 64 numbers) of third instar nymphs of M. persicae nicotianae were daily exposed to one pair of 1-day-old A. matricariae until the parasitoid female died. Each host aphid density was replicated 10 times. The experiments were conducted at constant environmental conditions (25 ± 1 °C, 70 ± 5% RH and 16:8h L:D photoperiod). The logistic regression model demonstrated that the functional response of A. matricariae was type III in the second day and type II in the first day and from third to the end of adult parasitoid lifetime. The handling time (T_h) was lowest in the first day (0.2305 h) and highest in the sixth day (2.9296 h) of the parasitoid’s life. The searching efficiency (a) values were 0.0573, 0.0649, 0.0503, 0.0229, and 0.0077 h^?1 in the first, third, fourth, fifth, and sixth days of the parasitoid’s life, respectively. Also, the b value for type III functional response was 0.0147 in the second day. The values of maximum attack rate (T/T_h) ranged from 104.12 nymphs/24 h in the first day to 19.8 nymphs/24 h in the sixth day of parasitoid’s life. Based on the results, A. matricariae showed a high potential to control the population of tobacco aphid and the highest efficiency gained in the first half of the female parasitoid life.     

Interactions of anthropometric indices,rs9939609 FTO gene polymorphism and breast cancer: A case-control study

Contradictory results were reported on the effect of fat mass- and obesity-associated (FTO) gene and anthropometric measurements on breast cancer (BC). This study aimed to assess the interactions between rs9939609 polymorphism of FTO gene, anthropometric indices and BC risk in Iranian women. This case-control study was performed on 540 women including 180 women with BC and 360 healthy women in Tehran, Iran. Physical activity and dietary intakes were assessed by validated questionnaires. Data on sociodemographic and pathologic factors of the participants as well as their blood samples were collected. The rs9939609 FTO gene polymorphism was genotyped using the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). No significant association was found between BC and risk allele of FTO rs9939609 polymorphism after adjustments for the confounders. However, there was a significant association between rs9939609 polymorphism risk allele and BC risk in females with overweight, even after adjusting for age, family history of BC, abortion, BMI and the number of pregnancies (P < .05). The association was disappeared after further adjustments for lifestyle factors including smoking, alcohol consumption, calorie and macronutrients intake, and physical activity. The FTO gene polymorphism was associated with the risk of BC in overweight individuals. This association was influenced by environmental factors including diet, alcohol consumption and smoking. Future studies are required to confirm the association between the FTO gene and BC in overweight females and to identify the underlying mechanisms.