Molecular dynamics simulation of lactate dehydrogenase adsorption onto pristine and carboxylic-functionalized graphene

ABSTRACT

Lactate dehydrogenase (LDH) is a tetrameric enzyme which is composed of two subunits known as LDHA and LDHB, which are encoded by the LDHA and LDHB genes respectively. LDH catalyses the last step in anaerobic glycolysis through the reversible conversion of pyruvate to lactate via coupled oxidation of NADH cofactor. The LDHA plays an important regulatory role in anaerobic glycolysis, by catalysing the final step of the process. Therefore, it is likely that increases in the expression level of LDHA in cancer cells could facilitate the efficiency of anaerobic glycolysis. Measuring the level of serum LDHA is a key step in the diagnosis of many cancer types. In this study, the adsorption, stability, and dynamics of LDHA on the surface of pristine graphene (PG) and carboxylated graphene (COOH-Graphene) were investigated using its molecular dynamics simulation. Variations in root mean square deviation, root mean square fluctuation, solvent accessible surface area and adsorption energy of the LDHA during the simulation were calculated to analyse the effect of PG and COOH-Graphene on the overall conformation of LDHA. Results showed that the adsorption of LDHA on COOH-Graphene is mostly mediated by electrostatic interactions, whereas on the PG, both Van der Waals and π-π interactions are prominent.     

Copper Concentration in a Healthy Urban Adult Population of Southern Iran

Nutritional deficiencies are important and widespread problems in most developing countries. Preventing and correcting micronutrient deficiencies are important because of the multiple negative consequences of these deficiencies. This study was designed to determine the prevalence of copper deficiency in an adult population in Shiraz, southern Iran. We also determined the association between copper status and other factors such as age, sex, and body mass index (BMI). In this cross-sectional study, 416 adults residing in Shiraz were selected by two-stage sampling. Serum copper was measured by flame-atomic absorption spectrometry. The data were analyzed with SPSS software. Mean age in our sample was 39.33?±?15.06 years, and mean BMI was 26.17?±?4.81 kg/m(2). Mean serum copper concentration was 118.15?±?54.33 μg/dL in the whole sample, 109.74?±?56.22 μg/dL in men, and 122.15?±?53.04 μg/dL in women. The overall prevalence of copper deficiency was 24%. The prevalence of copper deficiency differed significantly between men and women but not between different age groups. Serum copper concentration correlated significantly with BMI (p?相似文献   

Cloning,expression and dynamic simulation of TRYP6 from <Emphasis Type="Italic">Leishmania major</Emphasis> (MRHO/IR/75/ER)

Leishmania, a digenetic protozoan parasite causes severe diseases in human and animals. Efficient evasion of toxic microbicidal molecules, such as reactive oxygen species and reactive nitrogen species is crucial for Leishmania to survive and replicate in the host cells. Tryparedoxin peroxidase, a member of peroxiredoxins family, is vital for parasite survival in the presence of antioxidant, hence it is one of the most important molecules in Leishmania viability and then, it may be an appropriate goal for challenging against leishmaniasis. After cloning and sub-cloning of TRYP6 from Leishmania major (MRHO/IR/75/ER), homology modeling of the LmTRYP6 was proposed to predict some functional property of this protein. The refined model showed that the core structure consists of a seven β stranded β-sheet and five α helices which are organized as a central 7-stranded β2-β1-β5-β4-β3-β6-β7 surrounded by 2-stranded β-hairpin, α helices A and D on one side, and α helices B, C and E on the other side. The peroxidatic active site is located in a pocket formed by the residue Pro45, Met46, Thr49, Val51, Cys52, Arg128, Met147 and Pro 148. The catalytic Cys52, located in the first turn of helix αB, is in van der Waals with a Pro45, a Thr49 and an Arg128 that are absolutely conserved in all known Prx sequences. In this study, an attractive molecular target was studied. These results might be used in designing of drugs to fight an important human pathogen.     

Nano silver treatment is effective in reducing bacterial contaminations of Araucaria excelsa R. Br. var. glauca explants

The downside of plant tissue culture techniques is an unwanted microbial contamination. Elimination of contaminants is the first step of any successful investigation on plant tissue culture. Preliminary experiments on Araucaria excelsa R. Br. var. glauca (Norfolk-Island pine) (syn.: A. heterophylla) showed that most common decontaminants could not successfully eliminate the contamination. Therefore, nano silver (NS) colloids were evaluated for controlling contamination. Treatments were included soaking the explants in NS solution or adding NS to the culture medium. Explants were cultured on MS medium supplemented with appropriate growth regulators for their establishment. Results showed that surface sterilization followed by treatment with 200 mg l-1 of NS with soaking time of 180 min reduced the bacterial contamination from 61.5% to 11.3% and adding 400 mg l-1 NS to the medium reduced the bacterial contamination from 81.25% to 18.75%. Nano silver could be applied without adverse effects on plant growth and development. This is the first report on in vitro establishment of A. excelsa R. Br. using NS to reduce bacterial infections.     

Rapid insulinotropic action of low doses of bisphenol-A on mouse and human islets of Langerhans: role of estrogen receptor β

Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical (EDC) used as the base compound in the manufacture of polycarbonate plastics. It alters pancreatic β-cell function and can be considered a risk factor for type 2 diabetes in rodents. Here we used ERβ-/- mice to study whether ERβ is involved in the rapid regulation of K(ATP) channel activity, calcium signals and insulin release elicited by environmentally relevant doses of BPA (1 nM). We also investigated these effects of BPA in β-cells and whole islets of Langerhans from humans. 1 nM BPA rapidly decreased K(ATP) channel activity, increased glucose-induced [Ca(2+)](i) signals and insulin release in β-cells from WT mice but not in cells from ERβ-/- mice. The rapid reduction in the K(ATP) channel activity and the insulinotropic effect was seen in human cells and islets. BPA actions were stronger in human islets compared to mouse islets when the same BPA concentration was used. Our findings suggest that BPA behaves as a strong estrogen via nuclear ERβ and indicate that results obtained with BPA in mouse β-cells may be extrapolated to humans. This supports that BPA should be considered as a risk factor for metabolic disorders in humans.     

EEG-Based Functional Brain Networks: Does the Network Size Matter?

Functional connectivity in human brain can be represented as a network using electroencephalography (EEG) signals. These networks--whose nodes can vary from tens to hundreds--are characterized by neurobiologically meaningful graph theory metrics. This study investigates the degree to which various graph metrics depend upon the network size. To this end, EEGs from 32 normal subjects were recorded and functional networks of three different sizes were extracted. A state-space based method was used to calculate cross-correlation matrices between different brain regions. These correlation matrices were used to construct binary adjacency connectomes, which were assessed with regards to a number of graph metrics such as clustering coefficient, modularity, efficiency, economic efficiency, and assortativity. We showed that the estimates of these metrics significantly differ depending on the network size. Larger networks had higher efficiency, higher assortativity and lower modularity compared to those with smaller size and the same density. These findings indicate that the network size should be considered in any comparison of networks across studies.     

A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets

Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability. In an attempt to identify additional T2D genes, we analyzed global gene expression in human islets from 63 donors. Using 48 genes located near T2D risk variants, we identified gene coexpression and protein-protein interaction networks that were strongly associated with islet insulin secretion and HbA(1c). We integrated our data to form a rank list of putative T2D genes, of which CHL1, LRFN2, RASGRP1, and PPM1K were validated in INS-1 cells to influence insulin secretion, whereas GPR120 affected apoptosis in islets. Expression variation of the top 20 genes explained 24% of the variance in HbA(1c) with no claim of the direction. The data present a global map of genes associated with islet dysfunction and demonstrate the value of systems genetics for the identification of genes potentially involved in T2D.     

RAPD Fingerprint to Appraise the Genetic Fidelity of In Vitro Propagated <Emphasis Type="Italic">Araucaria excelsa</Emphasis> R. Br. var. glauca Plantlets

Randomly amplified polymorphic DNA (RAPD) was used as a tool to assess the genetic fidelity of in vitro propagated Araucaria excelsa R. Br. var. glauca with explants taken from orthotropic stem along with their related mother plants after treatment with kinetin, 2iP, BA (0.02–0.26 mg/l) and TDZ (0.001–1 mg/l) to produce axillary shoots. TDZ and kinetin induced more shoot and higher length per explant. Results showed a total of 1,676 fragments were generated with 12 RAPD primers in micropropagated plants and their donor mother plants. The number of loci ranged from 6 in OPB 12–18 in OPY 07 with a size ranging from 250 bp in OPH 19–3500 bp in OPH 11. Cluster analysis of RAPD data using UPGMA (unweighted pair group method with arithmetic average) revealed more than 92% genetic similarities between tissue cultured plants and their corresponding mother plant measured by the Jaccard’s similarity coefficient. Similarity matrix and PCoA (two dimensional principal coordinate analysis) resulted in the same affinity. Primers had shown 36% polymorphism. However, careful monitoring of tissue culture derived plants might be needed to determine that rooted shoots are adventitious in origin.