Genetic association of Glutathione peroxidase-1 (GPx-1) and NAD(P)H:Quinone Oxidoreductase 1(NQO1) variants and their association of CAD in patients with type-2 diabetes

Coronary artery disease (CAD) is a major health concern and the leading cause of death in individuals with type-2 diabetes mellitus (T2DM). Glutathione peroxidase-1 (GPx-1) and NAD(P)H: quinone oxidoreductase (NQO1) are known for its broad range of detoxification. The role of functional variants of these genes in the development of various disorders is proven. Hereby, we investigated the possible role of these variants in the development of CAD in T2DM patients of South Indian population. In this case-control study, a total of 539 patients (T2DM = 241; T2DM-CAD = 298) and 285 controls were included. The C198T GPx-1 and C609T NQO1 single-nucleotide polymorphisms were analyzed by PCR-RFLP. Further, these genotypes were correlated with blood lipid profile. Regression analysis showed that GPx1-C/T genotype is associated with a 1.35-fold increase (95% CI = 1.000-1.824; P = 0.048) and GPx1-T/T genotype is associated with a 1.76-fold increase (95% CI = 1.011 to 3.066; P = 0.046) to the T2DM development. Increased odds ratio showed that NQO1-T/T genotype had a higher occurrence of CAD in diabetic patients with CAD (95% CI = 1.003-2.674, P = 0.049) than T2DM patients without CAD. The level of triglycerides alone showed significant increase for GPx-1-C/T and -T/T genotypes in Tukey's Post hoc analysis (177.1 ± 19.2 vs. 184 ± 23.5; P = 0.039 and 177.1 ± 19.2 vs. 190 ± 22.4; P = 0.006) among the patients with T2DM-CAD. Our work concludes that GPx-1 variants might contribute to the development of diabetes and both GPx-1 and NQO1 variants confirm the association of CAD in people with T2DM of South Indian population.     

Rapid degradation of lindane (��-hexachlorocyclohexane) at low temperature by Sphingobium strains

Bioremediation of anthropogenic organic pollutants in cold climates is often limited by lower microbial or enzyme activity induced by low temperature. The present study addressed this issue through the degradation of ??-hexachlorocyclohexane (??-HCH) by three Sphingobium strains (S. indicum B90A, S. japonicum UT26 and S. francense Sp+) under low temperature (4 °C). After 5 days incubation at 4 °C, 79.7% and 43.8% of 5 and 25 mg L⁻¹ of ??-HCH added were degraded, respectively by the inoculation of 1.75 × 10⁷ cells mL⁻¹ of S. indicum B90A. An increase in inoculum concentration to 1.72 × 10⁸ cells mL⁻¹ significantly increased the degradation to 98.1 ± 1.7% of 5 mg L⁻¹ within 24 h. Further, S. indicum B90A and S. japonicum UT26 can rapidly degrade ??-HCH at 4 °C, while the degradation capability of S. francense Sp+ is relatively low. At 4 °C, ??-HCH is transformed to extremely low amounts of 1,2,4-trichlorobenzene (1,2,4-TCB) and 2,5-dichlorophenol (2,5-DCP) by S. indicum B90A, but most of ??-HCH were transformed to 2,5-Dichloro-2,5-cyclohexadiene-1,4-diol (2,5-DDOL) by S. japonicum UT26. These results revealed that haloalkane dehalogenases in some Sphingobium species are very active at temperature as low as 4 °C and S. indicum B90A might be a good candidate for developing novel bioremediation techniques for cold regions to decontaminate ??-HCH from soils/waters.     

Synthesis and antibacterial activity of some novel imidazole-based dicationic quinolinophanes

Synthesis of novel quinoline based dicationic benzimidazolophanes and imidazolophanes incorporating various spacer units is described. Some of the quinolinophanes 1b, 3a, 3b and 4a exhibit good antibacterial activity against most of the human pathogenic bacteria in the tested concentrations as compared to the other cyclophanes as well as the test control, streptomycin.     

Adaptive and cross resistance to cadmium (II) and zinc (II) by Pseudomonas aeruginosa BC15

Cadmium and zinc appear in the combined forms and they are co-pollutants. Cd is the most hazardous metal ion for human beings and causes renal dysfunction, liver and lungs damage, bone degeneration and blood damage. Though Zn is an essential nutrient, excess of Zn is toxic. Biological process was more important because conventional methods fail to remediate these pollutants due to high costs and less affordability. The screening and understanding of the functioning of microorganism plays an important role in removal and recovery of metals from heavy-metal-polluted water and soil. In our study, the strain Pseudomonas aeruginosa BC15 was isolated from oil-mill-treated waste water and it showed to be highly resistant to 6 mM Cd and 20 mM Zn in the solid and liquid media. The growth studies of BC15 strain in the medium without induction exhibited high tolerable capacity when compared to other microbes. Pretreatment of P. aeruginosa BC15 with sub-lethal concentrations of Cd induced adaptive resistance to lethal doses of Cd. Cadmium-induced cells also showed cross resistance to lethal concentration of zinc. The organism had high resistance against Cd and Zn. This has been clearly proven through biosorption studies: Cd was absorbed up to 62% and Zn about 60% in single solution, whereas in binary solution Cd was biosorbed up to 82% and Zn 85%. In conclusion, this study reveals the significance of using the strain P. aeruginosa BC15 in the bioremediation of Cd and Zn from industrial waste water and contaminated soil.     

Cryptic association of B7‐2 molecules and its implication for clustering

T‐cell co‐stimulation through CD28/CTLA4:B7‐1/B7‐2 axis is one of the extensively studied pathways that resulted in the discovery of several FDA‐approved drugs for autoimmunity and cancer. However, many aspects of the signaling mechanism remain elusive, including oligomeric association and clustering of B7‐2 on the cell surface. Here, we describe the structure of the IgV domain of B7‐2 and its cryptic association into 1D arrays that appear to represent the pre‐signaling state of B7‐2 on the cell membrane. Super‐resolution microscopy experiments on heterologous cells expressing B7‐2 and B7‐1 suggest, B7‐2 form relatively elongated and larger clusters compared to B7‐1. The sequence and structural comparison of other B7 family members, B7‐1:CTLA4 and B7‐2:CTLA‐4 complex structures, support our view that the observed B7‐2 1D zipper array is physiologically important. This observed 1D zipper‐like array also provides an explanation for its clustering, and upright orientation on the cell surface, and avoidance of spurious signaling.     

Molecular modeling studies of repandusinic acid as potent small molecule for hepatitis B virus through molecular docking and ADME analysis

Background: Hepatitis B virus (HBV) has affected over 300 million people worldwide which causes to induce mostly liver disease and liver cancer. It is a member of the family Hepadnaviridae which is a small DNA virus with unusual characters like retroviruses. Generally, hepatoprotective drugs provoke some side effects in human beings. For the reason, this study aims to identify alternative drug molecules from the natural source of medicinal plants with smaller quantity of side effects than those conventional drugs in treating HBV. Methods: We developed computational methods for calculating drug and target binding resemblance using the Maestro v10.2 of Schrodinger suite. The target and ligand molecules were obtained from recognized databases. Ligand molecules of 40 phytoconstituents were retrieved from variety of plants after we executed crucial analyses such as molecular docking and absorption, distribution, metabolism, and excretion (ADME) analysis.Results: In the docking analysis, the natural analogues repandusinic acid showed better docking scores of –14.768 with good binding contacts. The remaining bioactive molecules corilagin, furosin, nirurin, iso-quercetin and gallocatechin also showed better docking scores.Conclusion: This computational analysis reveals that repandusinic acid is a suitable drug candidate for HBV. Therefore, we recommend that this analogue is suitable in further exploration using in vitro studies.     

Effect of Ash Pond Soil and Amendments on the Growth and Arbuscular Mycorrhizal Colonization of Allium cepa and Germination of Arachis hypogaea,Lycopersicon esculentum,and Vigna mungo Seeds

The effect of fly ash pond soil on the growth and yield of onion (Allium cepa var. microaggregatum) plants grown in pots was investigated. The fly ash pond soil was amended with combinations of red soil and press mud, a waste product from sugar mills. Water-holding capacity of ash pond soil amended with press mud increased; however, addition of press mud delayed onion bulb development. Onion bulb germination took place rapidly in ash pond soil; however, subsequent bulb development declined. The addition of red soil and press mud increased the growth and yield of onion plants. In all the soils and amendments, onion plant roots were colonized by native arbuscular mycorrhizal species. Both vesicles and arbuscules were present in the roots. Colonization was low in ash pond soil but increased with the addition of red soil. Effect of fly ash pond soil on germination of groundnut (Arachis hypogaea), tomato (Lycopersicon esculentum), and black gram (Vigna mungo) seeds was evaluated and compared with red soil in the laboratory. Ash pond soil increased the germination of tomato seeds but did not affect the germination of groundnut and black gram seeds.     

Prediction of protein structure from ideal forms

For many years it has been accepted that the sequence of a protein can specify its three-dimensional structure. However, there has been limited progress in explaining how the sequence dictates its fold and no attempt to do this computationally without the use of specific structural data has ever succeeded for any protein larger than 100 residues. We describe a method that can predict complex folds up to almost 200 residues using only basic principles that do not include any elements of sequence homology. The method does not simulate the folding chain but generates many thousands of models based on an idealized representation of structure. Each rough model is scored and the best are refined. On a set of five proteins, the correct fold score well and when tested on a set of larger proteins, the correct fold was ranked highest for some proteins more than 150 residues, with others being close topological variants. All other methods that approach this level of success rely on the use of templates or fragments of known structures. Our method is unique in using a database of ideal models based on general packing rules that, in spirit, is closer to an ab initio approach.