DISC1 gene polymorphisms and the risk of schizophrenia in an Iranian population: A preliminary study

Background: Schizophrenia, schizoaffective disorder, and bipolar illness are common psychological disorders with high heritability and variable phenotypes. The disrupted in schizophrenia 1 ( DISC1) gene, on chromosome 1q42, has an essential role in neurite outgrowth and cell signaling. The purpose of this study was to investigate the association of three single-nucleotide polymorphisms (SNPs; rs6675281, rs2255340, and rs2738864) with schizophrenia disorder. These three SNPs were chosen as they had been used in most of the previous studies. Methods: In a case-control study of Iranian population for the first time 778 blood samples were collected including, 402 schizophrenic patients and 376 healthy controls. Genomic DNA was extracted from peripheral blood using DNA extraction kit (BioFlux Co). The genotypes of rs6675281, rs2255340, and rs2738864 were detected by nested allele-specific multiplex polymersae chain reaction (PCR). Results: Our data revealed that the three SNPs are significantly associated with schizophrenia (rs2255349 C>T: confidence interval (CI), 2.115 to 3.268; P = 0.0000 OR: 2.629; rs2738864 C>T: CI, 1.538 to 2.339; P = 0.0000 OR: 1.897; rs6675281 C>T: CI, 2.788 to 4.662; P = 0.0009241 OR: 3.605). Through applying the expectation-maximization (EM) algorithm, we calculated the haplotype frequency, and finally performed haplotype analysis with Bonferroni correction and data preprocessing methods and the results showed rs66875281 to have the highest association. Discussion: Our findings primarily showed that DISC1 gene polymorphisms contribute to schizophrenia risk and have a significant association with this disorder among Iranian population. The strategy was found to be easy, rapid, specific, and consistent for the co-occurring detection of the DISC1 polymorphisms. We could finally confirm that the polymorphisms are related to schizophrenia studied in Iranian population.     

A comparative study of the characteristics of eIF-2 and eIF-2-ancillary factor activities from yeast Saccharomyces cerevisiae and rabbit reticulocytes

The characteristics of yeast eukaryotic initiation factor 2 (eIF-2) and Co-eIF-2A have been studied and compared with those of the corresponding factors from rabbit reticulocytes. 1) Unlike eIF-2r, purified eIF-2y did not contain bound GDP. 2) Purified eIF-2y preparation contained GTPase activity and dephosphorylated GTP to GDP. 3) An anti-eIF-2r preparation which predominantly precipitated the gamma-subunit (Mr 54,000) of eIF-2r also precipitated the larger subunit (Mr 54,000) of eIF-2y. 4) Unlike eIF-2r, ternary complex formation by eIF-2y was not inhibited by Mg2+. 5) Both Co-eIF-2A20y and Co-eIF-2r significantly enhanced Met-tRNAf binding to eIF-2y and, again, Mg2+ did not have any effect on this stimulated Met-tRNAf binding to eIF-2y. 6) Both Co-eIF-2A20y and Co-eIF-2r were similarly effective in stimulating Met-tRNAf binding to eIF-2r in the absence of Mg2+. However, in the presence of Mg2+, Co-eIF-2A20y was significantly less effective than Co-eIF-2r as Co-eIF-2A20y did not promote displacement of GDP from eIF-2r X GDP. 7) eIF-2y bound [3H]GDP and this binding was significantly enhanced in the presence of Mg2+. Also, [3H]GDP in the preformed eIF-2y X [3H]GDP complex was rapidly exchanged with exogenously added unlabeled GDP in the presence of Mg2+. Co-eIF-2A20y had no effect on GDP binding to eIF-2y nor on GDP exchange reactions. 8) Reticulocyte heme-regulated protein synthesis inhibitor, which phosphorylated almost completely (in excess of 80%) the alpha-subunit (Mr 38,000) of eIF-2r, also phosphorylated similarly the smaller subunit (Mr 36,000) of eIF-2y. However, such phosphorylation had no significant effect on ternary complex formation, GDP binding, and GDP exchange reactions.     

Molecular basis for ATP/2,3-bisphosphoglycerate control switch-over (poikilotherm/homeotherm) an intermediate amino-acid sequence in the hemoglobin of the great Indian rhinoceros (Rhinoceros unicornis, Perissodactyla)

The complete primary structure of the two hemoglobin components of the Great Indian Rhinoceros (Rhinoceros unicornis) is presented. The ratio for the two components B(alpha 2 beta I2): A(alpha 2 beta II2) is 6:4. Polypeptide subunits were separated by chromatography on CM-cellulose in a buffer containing 8M urea. The sequence was studied by degradation of the tryptic and hydrolytic cleavage products in a liquid phase sequencer. At position beta NA2 component B has Asp, whereas component A has Glu, an ATP-binding site in fish and reptilian hemoglobins. The other phosphate binding sites i.e. beta NA1 Val, beta EF6 Lys and beta H21 His are identical with 2,3-bisphosphoglycerate-(DPG)binding sites in mammalian hemoglobins, whereby rhinoceros hemoglobin resembles both ATP-sensitive poikilotherm hemoglobin and DPG-sensitive mammalian hemoglobin. The two components (beta I/beta II) additionally differ by exchange of Glu----Gly at position beta A3 and Gln----Lys at position beta GH3. The significance of these changes is discussed. Oxygenation properties of the two hemoglobins components and their dependence on ATP and DPG are given. The structure and function of Rhinoceros hemoglobin may give an insight into the evolution of the organic phosphate binding in vertebrate hemoglobins.     

Primary structure of hemoglobin β-chain fromColumba livia (gray wild pigeon)

Primary structure of -chain of pigeon is presented. It was determined by amino acid sequence analysis of intact -chain and its peptides obtained by the enzymatic and chemical cleavage. Comparison of amino acid sequence of the chain with other available data shows 14 Ile, 61 Lys, and 113 Ile as residues specific to pigeon. One important replacement at ₁₁ contact is 55 MetSer.     

The primary structure of hemoglobin from amur-leopard (Panthera pardus orientalis)

The complete amino acid sequence of the major component of hemoglobin from amur-leopard (Panthera pardus orientalis) is presented. The major component accounts for more than 90% of the total hemoglobin. Separation of the globin subunits was achieved by ion-exchange chromatography on CM-cellulose in urea. The sequence was studied by automatic Edman degradation of tryptic and hydrolytic peptides. Alignment was carried out with human hemoglobin sequence. The NH₂ terminus is blocked with Ac-serine. The data are compared with other mammalian hemoglobins and results are discussed with respect to sequence and physiology.85th communication on hemoglobin.     

Isolation purification and properties of a site-specific proteolytic enzyme "valyl-proteinase" from Candida tropicalis

A highly specific proteolytic enzyme cleaving at the carboxyl group of valine has been isolated from Candida tropicalis. Its specificity has been determined by digesting beta-lactoglobulin and a number of synthetic peptides. The enzyme a glycoprotein, has a molecular mass of 40 +/- 7 kDa on the basis of sodium dodecyl sulphate polyacrylamide gel electrophoresis. Its optimum activity occurs at 37 degrees C at a pH between 8-9. It has been named "Valyl-proteinase" because of its selective cleavage.     

Primary structure of hemoglobin β-chain fromColumba livia (gray wild pigeon)

Primary structure of β-chain of pigeon is presented. It was determined by amino acid sequence analysis of intact β-chain and its peptides obtained by the enzymatic and chemical cleavage. Comparison of amino acid sequence of the chain with other available data shows β 14 Ile, β61 Lys, and β113 Ile as residues specific to pigeon. One important replacement at α₁β₁ contact is β55 Met→Ser.     

Potent beta-adrenergic antagonist possessing chemically reactive group

A highly potent beta-adrenergic antagonist based on the structure of alprenolol has been prepared by replacement of the isopropylamine residue of alprenolol by 1, 8-diamino-p-menthane (AlpM). The resulting mixture of isomers (AlpM) competes for occupancy of beta-adrenergic receptors in frog erythrocycte membranes with an apparent K_D of 210 pM. The bromoacetylated derivative of AlpM (BrAlpM) leads to an irreversible inactivation of the [³H]dihydroalprenolol ([³H]DHA) binding sites. Various adrenergic agonists and antagonists afford specific and stereoselective protection of the receptor against inactivation by BrAlpM. Tritiation of AlpM followed by bromoacetylation and chromatographic separation yielded two isomers, Br-1-AlpM and Br-8-AlpM of high specific radioactivity (～ 40 Ci/mmol). Both radiolabelled isomers interacted specifically and with high affinity with the beta-adrenergic receptor, but only a small amount of the ligands could be covalently incorporated into the receptor subunit. This agent provides a powerful new probe for studies of beta-adrenergic receptors in analogy with bungarotoxin for the nicotinic cholinergic receptor.