Inbreeding and the incidence of childhood genetic disorders in Karnataka, South India

Consanguineous marriages are strongly favoured among the populations of South India. In a study conducted on 407 infants and children, a total of 35 genetic diseases was diagnosed in 63 persons: 44 with single gene defects, 12 with polygenic disorders, and seven with Down's syndrome. The coefficient of inbreeding of the total study group, F = 0.0414, was significantly higher than that previously calculated for the general population, F = 0.0271, and autosomal recessive disorders formed the largest single disease category diagnosed. The results suggest that long term inbreeding may not have resulted in appreciable elimination of recessive lethals and sub-lethals from the gene pool.

Helix-coil stability constants for amino acids in nonaqueous solvents. Studies of random poly(-benzyl-L-glutamate-co-L-alanine) and poly(-benzyl-L-glutamate-co-L-leucine) in a mixed solvent

The host-guest technique has been applied to the determination of the helix-coil stability constants of two naturally occurring amino acids, L-alanine and L-leucine, in a nonaqueous solvent system. Random copolymers containing L-alanine and L-leucine, respectively, as guest residues and -benzyl-L-glutamate as the host residue were synthesized. The polymers were fractionated and characterized for their amino acid content, molecular weight, and helix-coil transition behavior in a dichloroacetic acid (DCA)-1,2-dichloroethane (DCE) mixture. Two types of helix-coil transitions were carried out on the copolymers: solvent-induced transitions in DCA-DCE mixtures at 25°C and thermally induced transitions in a 82:18 (wt %) DCA-DCE mixture. The thermally induced transitions were analyzed by statistical mechanical methods to determine the Zimm-Bragg parameters, and s, of the guest residues. The experimental data indicate that, in the nonaqueous solvent, the L-alanine residue stabilizes the -helical conformation more than the L-leucine residue does. This is in contrast to their behavior in aqueous solution, where the reverse is true. The implications of this finding for the analysis of helical structures in globular proteins are discussed.

Dry sliding wear behaviour of magnesium alloy based hybrid composites in the longitudinal direction

In the present investigation, the wear behaviour of a creep-resistant AE42 magnesium alloy and its composites reinforced with Saffil short fibres and SiC particles in various combinations is examined in the longitudinal direction i.e., the plane containing random fibre orientation is perpendicular to the steel counter-face. Wear tests are conducted on a pin-on-disc set-up under dry sliding condition having a constant sliding velocity of 0.837 m/s for a constant sliding distance of 2.5 km in the load range of 10-40 N. It is observed that the wear rate increases with increase in load for the alloy and the composites, as expected. Wear rate of the composites is lower than the alloy and the hybrid composites exhibit a lower wear rate than the Saffil short fibres reinforced composite at all the loads. Therefore, the partial replacement of Saffil short fibres by an equal volume fraction of SiC particles not only reduces the cost but also improves the wear resistance of the composite. Microstructural investigation of the surface and subsurface of the worn pin and wear debris is carried out to explain the observed results and to understand the wear mechanisms. It is concluded that the presence of SiC particles in the hybrid composites improves the wear resistance because these particles remain intact and retain their load bearing capacity even at the highest load employed, they promote the formation of iron-rich transfer layer and they also delay the fracture of Saffil short fibres to higher loads. Under the experimental conditions used in the present investigation, the dominant wear mechanism is found to be abrasion for the AE42 alloy and its composites. It is accompanied by severe plastic deformation of surface layers in case of alloy and by the fracture of Saffil short fibres as well as the formation of iron-rich transfer layer in case of composites.

Methylenetetrahydrofolate reductase gene polymorphisms and risk of acute lymphoblastic leukemia in children

Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. Genetic polymorphisms of this enzyme have been shown to impact several diseases, including cancer. Leukemias are malignancies arising from rapidly proliferating hematopoietic cells having great requirement of DNA synthesis. This case-control study was undertaken to analyze the association of the MTHFR gene polymorphisms 677 C"T and 1298 A"C and the risk of acute lymphoblastic leukemia in children. Materials and Methods: Eighty-six patients aged below 15 years with a confirmed diagnosis of acute lymphoblastic leukemia (ALL) and 99 matched controls were taken for this study. Analysis of the polymorphisms was done using the polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) method. Results: Frequency of MTHFR 677 CC and CT were 85.9% and 14.1% in the controls, and 84.9% and 15.1% in the cases. The 'T' allele frequency was 7% and 7.5% in cases and controls respectively. The frequency of MTHFR 1298 AA, AC, and CC were 28.3%, 55.6% and 16.1% for controls and 23.3%, 59.3% and 17.4% for cases respectively. The 'C' allele frequency for 1298 A→C was 43.9% and 47% respectively for controls and cases. The odds ratio (OR) for C677T was 1.08 (95% CI 0.48- 2.45, p = 0.851) and OR for A1298C was 1.29(95% CI 0.65-2.29, p = 0.46) and OR for 1298 CC was 1.31 (95% CI 0.53-3.26, p =0.56). The OR for the combined heterozygous status (677 CT and 1298 AC) was 1.94 (95% CI 0.58 -6.52, p = 0.286). Conclusion: The prevalence of 'T' allele for 677 MTHFR polymorphism was low in the population studied. There was no association between MTHFR 677 C→T and 1298 A→C gene polymorphisms and risk of ALL, which may be due to the small sample size.

CFD tools in engineering design studies and medical sciences

In the recent time CFD tools have become increasingly useful in the engineering design studies especially in the area of aerospace vehicles. This is largely due to the advent of high speed computing platforms in addition to the development of new efficient algorithms. The algorithms based on kinetic schemes have been shown to be very robust and further meshless methods offer certain advantages over the other methods. Preliminary investigations of blood flow visualization through artery using CFD tool have shown encouraging results which further needs to be verified and validated.

In-situ crystallization studies of gels in the ZrO2---SiO2 system

The in-situ investigation of amorphous gels is important in understanding the evolution of structures and the influence of environmental factors on crystallization. In this paper, the ZrO2---SiO2 system has been studied in-situ under electron beam heating. The study reveals that both the size of the ZrO2 particles and the presence of hydroxyl ions influence the nature of the crystalline phase of the ZrO2 particles formed.

Topology of wolfgram proteins and 2?, 3?-cyclic nucleotide 3?-phosphodiesterase in CNS myelin: Studies with proteases

The topological disposition of Wolfgram proteins (WP) and their relationship with 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in human, rat, sheep, bovine, guinea pig and chicken CNS myelin was investigated. Controlled digestion of myelin with trypsin gave a 35KDa protein band (WP-t) when electrophoresed on dodecyl sulfate-polyacrylamide gel in all species. Western blot analysis showed that the WP-t was derived from WP. WP-t was also formed when rat myelin was treated with other proteases such as kallikrein, thermolysin and leucine aminopeptidase. Staining for CNPase activity on nitrocellulose blots showed that WP-t is enzymatically active. Much of the CNPase activity remained with the membrane fraction even after treatment with high concentrations of trypsin when WP were completely hydrolysed and no protein bands with M.W > 14KDa were detected on the gels. Therefore protein fragments of WP with M.W < 14KDa may contain CNPase activity. From these results, it is suggested that the topological disposition of all the various WP is such that a 35KDa fragment is embedded in the lipid bilayer and the remaining fragment exposed at the intraperiod line in the myelin structure which may play a role in the initiation of myelinogenesis.

In situ structural studies on orthorhombic SnS micro-crystals

In situ powder X-ray diffraction (XRD) studies on 3D micro-crystalline tin (II) sulfide (SnS) were carried out at different temperatures. While increasing temperature, the crystal structure of SnS remains stable as orthorhombic, whereas its lattice parameters and unit-cell volume are considerably varied. Further, these 3D micro-crystalline structures have showed a negative thermal expansion along the a-axis and positive expansion along the b- and c-axes. However, the overall drop along the a-axis of SnS crystals is nearly equal to their expansion along the c-axis. The observed changes in the structural properties of SnS micro-crystallites with temperature are discussed and reported.

Non-polio enteroviruses and their association with acute diarrhea in children in India

A causative agent in approximately 40% of diarrhea] cases. still remains unidentified. Though many enteroviruses (EVs) are transmitted through fecal-oral route and replicate in the intestinal cells, their association with acute diarrhea has not so far been recognized due to lack of detailed epidemiological investigations. This long-term, detailed molecular epidemiological study aims to conclusively determine the association of non-polio enteroviruses (NPEVs) with acute diarrhea in comaparison with rotavirus (RV) in children. Diarrheal stool specimens from 2161 children aged 0-2 years and 169 children between 2 and 9 years, and 1800 normal stool samples from age-matched healthy children between 0 and 9 years were examined during 2008-2012 for enterovirus (oral polio vaccine strains (OPVs) and NPEVs). Enterovirus serotypes were identified by complete VP1 gene sequence analysis. Enterovirus and rotavirus were detected in 19.01% (380/2330) and 13.82% (322/2330) diarrheal stools. During the study period, annual prevalence of EV- and RV-associated diarrhea ranged between 8% and 22%, but with contrasting seasonal prevalence with RV predominating during winter months and NPEV prevailing in other seasons. NPEVs are associated with epidemics-like outbreaks during which they are detected in up to 50% of diarrheic children, and in non-epidemic seasons in 0-10% of the patients. After subtraction of OPV-positive diarrheal cases (1.81%), while NPEVs are associated with about 17% of acute diarrhea, about 6% of healthy children showed asymptomatic NPEV excretion. Of 37 NPEV serotypes detected in diarrheal children, seven echovirus types 1, 7, 11, 13, 14, 30 and 33 are frequently observed, with Ell being more prevalent followed by E30. In conclusion, NPEVs are significantly associated with acute diarrhea, and NPEVs and rotavirus exhibit contrasting seasonal predominance. This study signifies the need for a new direction of research on enteroviruses involving systematic analysis of their contribution to diarrheal burden. (C) 2013 Elsevier B.V. All rights reserved.

In vitro and in silico biological studies of novel thiazolo3,2-a]pyrimidine-6-carboxylate derivatives

In the present study, we report the synthesis, characterization of new series of thiazolo3,2-a]pyrimidine-6-carboxylate derivatives 3a-f and 4a-f. The newly synthesized compounds were screened for in vitro antimicrobial and antiviral activities. The probable mode of action of these active compounds was determined through in silico docking study by docking the receptor methionyl-tRNA synthetase and human inosine-5'-monophosphate dehydrogenase (IMPDH) for antibacterial and antiviral activities, respectively. Among the compounds, 4c exhibited excellent in vitro antimicrobial activity against all tested strains with binding and docking energies -35.6 and -12.4 kcal/mol, respectively. The antiviral studies were carried out for the selected compounds in which 4a exhibited 73.69 and 54.42 % of inhibition of buffalopox and camelpox viruses, respectively. Furthermore, compound 4a showed minimum docking and binding energy along with the maximum hydrogen/hydrophobic interaction with IMPDH. The study contributes towards identification and screening of potential antimicrobial and antiviral agent's against the pathogens.

Non-polio enterovirus association with persistent diarrhea in children as revealed by a follow-up study of an Indian cohort during the first two years of life

Background: We recently reported significant association of non-polio enteroviruses (NPEVs) with acute diarrhea in children. Persistent diarrhea (PD) remains a major cause of morbidity and mortality in infants below two years of age in developing countries. Understanding age-dependent frequency and duration of NPEV infections is important to determine their association with persistent diarrhea and disease burden. Objectives: A cohort of 140 infants was followed for 6 months to 2 years of age to determine the frequency, duration, and association with PD of NPEV infections in comparison with rotavirus and other agents. Study design: Stool samples were collected every 14 days, and diarrheal episodes and their duration were recorded. Enteroviruses were characterized by RT-PCR and VP1 gene sequence analysis, rotavirus by electropherotyping, and other agents by PCR. Results: Of 4545 samples, negative for oral polio vaccine strains, 3907 (85.96%) and 638 (14.04%) were NPEV-negative and NPEV-positive, respectively, representing 403 (8.87%) infection episodes. About 68% of NPEV infections occurred during the first year with every child having at least one episode lasting between four days and four months. Approximately 38% and 22% of total diarrheal episodes were positive for NPEV and RV, respectively. While about 18% of NPEV infection episodes were associated with diarrhea, 6% being persistent, 13% of total diarrheal episodes were persistent involving infections by monotype NPEV strains or sequential infections by multiple strains and other agents. Conclusions: This is the first report revealing NPEVs as the single most frequently and persistently detected viral pathogen in every PD episode. (C) 2014 Elsevier B.V. All rights reserved.

Synthesis, X-ray structure and in vitro cytotoxicity studies of Cu(I/II) complexes of thiosemicarbazone: special emphasis on their interactions with DNA

4-(p-X-phenyl)thiosemicarbazone of napthaldehyde {where X = Cl (HL1) and X = Br (HL2)}, thiosemicarbazone of quinoline-2-carbaldehyde (HL3) and 4-(p-fluorophenyl) thiosemicarbazone of salicylaldehyde (H2L4) and their copper(I) {Cu(HL1)(PPh3)(2)Br]center dot CH3CN (1) and Cu(HL2)(PPh3)(2)Cl]center dot DMSO (2)} and copper(II) {((Cu2L2Cl)-Cl-3)(2)(mu-Cl)(2)]center dot 2H(2)O (3) and Cu(L-4)(Py)] (4)} complexes are reported herein. The synthesized ligands and their copper complexes were successfully characterized by elemental analysis, cyclic voltammetry, NMR, ESI-MS, IR and UV-Vis spectroscopy. Molecular structures of all the Cu(I) and Cu(II) complexes have been determined by X-ray crystallography. All the complexes (1-4) were tested for their ability to exhibit DNA-binding and - cleavage activity. The complexes effectively interact with CT-DNA possibly by groove binding mode, with binding constants ranging from 10(4) to 10(5) M-1. Among the complexes, 3 shows the highest chemical (60%) as well as photo-induced (80%) DNA cleavage activity against pUC19 DNA. Finally, the in vitro antiproliferative activity of all the complexes was assayed against the HeLa cell line. Some of the complexes have proved to be as active as the clinical referred drugs, and the greater potency of 3 may be correlated with its aqueous solubility and the presence of the quinonoidal group in the thiosemicarbazone ligand coordinated to the metal.

Maintaining local displacive disorders in Na0.5Bi0.5TiO3 piezoceramics by K0.5Bi0.5TiO3 substitution

A comprehensive global and local structural characterization using X-ray and neutron diffraction, and EXAFS have been performed to investigate the effect of electrical poling on the structure of (1-x)Na0.5Bi0.5TiO3-(x)K0.5Bi0.5TiO3 compositions. While the annealed samples showed definite indication of presence of local displacive disorders in all the compositions studied (0 ing the samples. The tendency of electric field to reduce the local displacive disorder decreased with increasing K0.5Bi0.5TiO3 content in the samples. (C) 2016 Elsevier Ltd. All rights reserved.