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.     

Improved Working Memory but No Effect on Striatal Vesicular Monoamine Transporter Type 2 after Omega-3 Polyunsaturated Fatty Acid Supplementation

Studies in rodents indicate that diets deficient in omega-3 polyunsaturated fatty acids (n–3 PUFA) lower dopamine neurotransmission as measured by striatal vesicular monoamine transporter type 2 (VMAT2) density and amphetamine-induced dopamine release. This suggests that dietary supplementation with fish oil might increase VMAT2 availability, enhance dopamine storage and release, and improve dopamine-dependent cognitive functions such as working memory. To investigate this mechanism in humans, positron emission tomography (PET) was used to measure VMAT2 availability pre- and post-supplementation of n–3 PUFA in healthy individuals. Healthy young adult subjects were scanned with PET using [¹¹C]-(+)-α-dihydrotetrabenzine (DTBZ) before and after six months of n–3 PUFA supplementation (Lovaza, 2 g/day containing docosahexaenonic acid, DHA 750 mg/d and eicosapentaenoic acid, EPA 930 mg/d). In addition, subjects underwent a working memory task (n-back) and red blood cell membrane (RBC) fatty acid composition analysis pre- and post-supplementation. RBC analysis showed a significant increase in both DHA and EPA post-supplementation. In contrast, no significant change in [¹¹C]DTBZ binding potential (BP_ND) in striatum and its subdivisions were observed after supplementation with n–3 PUFA. No correlation was evident between n–3 PUFA induced change in RBC DHA or EPA levels and change in [¹¹C]DTBZ BP_ND in striatal subdivisions. However, pre-supplementation RBC DHA levels was predictive of baseline performance (i.e., adjusted hit rate, AHR on 3-back) on the n-back task (y = 0.19+0.07, r² = 0.55, p = 0.009). In addition, subjects AHR performance improved on 3-back post-supplementation (pre 0.65±0.27, post 0.80±0.15, p = 0.04). The correlation between n-back performance, and DHA levels are consistent with reports in which higher DHA levels is related to improved cognitive performance. However, the lack of change in [¹¹C]DBTZ BP_ND indicates that striatal VMAT2 regulation is not the mechanism of action by which n–3 PUFA improves cognitive performance.     

Acute Effects of Typical and Atypical Antipsychotic Drugs on the Release of Dopamine from Prefrontal Cortex, Nucleus Accumbens, and Striatum of the Rat: An In Vivo Microdialysis Study

In vivo microdialysis has been used to study the acute effects of antipsychotic drugs on the extracellular level of dopamine from the nucleus accumbens, striatum, and prefrontal cortex of the rat. (-)-Sulpiride (20, 50, and 100 mg/kg i.v.) and haloperidol (0.1 and 0.5 mg/kg i.v.) enhanced the outflow of dopamine in the striatum and nucleus accumbens. In the medial prefrontal cortex, (-)-sulpiride at all doses tested did not significantly affect the extracellular level of dopamine. The effect of haloperidol was also attenuated in the medial prefrontal cortex; 0.1 mg/kg did not increase the outflow of dopamine and the effect of 0.5 mg/kg haloperidol was of shorter duration in the prefrontal cortex than that observed in striatum and nucleus accumbens. The atypical antipsychotic drug clozapine (5 and 10 mg/kg) increased the extracellular concentration of dopamine in all three regions. In contrast to the effects of sulpiride and haloperidol, that of clozapine in the medial prefrontal cortex was profound. These data suggest that different classes of antipsychotic drugs may have distinct effects on the release of dopamine from the nigrostriatal, mesolimbic, and mesocortical terminals.     

Excitatory Amino Acid Receptors in the Ventral Tegmental Area Regulate Dopamine Release in the Ventral Striatum

Abstract: The role of excitatory amino acid (EAA) receptors located in the ventral tegmental area (VTA) in tonic and phasic regulation of dopamine release in the ventral striatum was investigated. Microdialysis in conscious rats was used to assess dopamine release primarily from the nucleus accumbens shell region of the ventral striatum while applying EAA antagonists or agonists to the VTA. Infusion of the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (25 and 100 µ M ) into the VTA did not affect dopamine release in the ventral striatum. In contrast, intra-VTA infusion of the NMDA receptor antagonist 2-amino-5-phosphopentanoic acid (100 and 500 µ M ) dose-dependently decreased the striatal release of dopamine. Intra-VTA application of the ionotropic EAA receptor agonists NMDA and AMPA dose-dependently (10 and 100 µ M ) increased dopamine efflux in the ventral striatum. However, infusion of 50 or 500 µ M trans -(±)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD), a metabotropic EAA receptor agonist, did not significantly affect these levels. These data suggest that NMDA receptors in the VTA exert a tonic excitatory influence on dopamine release in the ventral striatum. Furthermore, dopamine neurotransmission in this region may be enhanced by activation of NMDA and AMPA receptors, but not ACPD-sensitive metabotropic receptors, located in the VTA. These data further suggest that EAA regulation of dopamine release primarily occurs in the VTA as opposed to presynaptically at the terminal level.     

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.     

Exploring Coal Biodesulfurization Potential of a Novel Organic Sulfur Metabolizing Rhodococcus spp. (Eu-32) – A Case Study

Coal is one of the most abundant nonrenewable fossil fuels, in Pakistan. However, in general, the quality of coal is too low to offset the practical, economic, and regulatory barriers to its utilization. High sulfur content comes up as one of the bottlenecks in productive usage of indigenous coal. Biotechnology can emerge as a panacea for upgrading the huge reserves of high sulfur coal. In current study, the sulfur removal potential of Rhodococcus spp. (Eu-32) was investigated using coal from Dukki, Baluchistan, Pakistan. Biodesulfurization process was optimized for various parameters and maximum decrease of 40% and 60% in total and organic sulfur contents, respectively were achieved in 15 days. The Langmuir and Brunauer–Emmett–Teller (BET) surface areas of the biotreated coal were increased by 20 and 16 times, respectively. Scanning electron microscope showed higher tendency of attachment of bacterial cells to the coal particles. Our results revealed that Eu-32 could remove significant amounts of organic sulfur from coal and could be used in the pre-combustion operations with appropriate arrangements.     

Synthesize of β‐cyclodextrin functionalized dendritic fibrous nanosilica and its application for the removal of organic dye (malachite green)

Dye removal from industrial waste water has become an important issue. The highvisibility, undesirability and recalcitrance are the significant environmental problemfor the dyes. In the present work,β‐cyclodextrin functionalized KCC‐1 (KCC‐1‐NH‐β‐CD)was synthesized and utilized to the removal of hazardous malachite green. In order to study the morphology of the synthesized nano adsorbent, Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) were obtained from the surface of the sample. Additionally, the functionalization of KCC‐1 with β‐cyclodextrin was confirmed with Furrier Transform Infrared spectroscopy (FTIR). The textural property of KCC‐1 was verified using nitrogen adsorption/ desorption analysis (BET equation). UV‐Vis spectroscopy utilized for the investigation of malachite green by KCC‐1‐NH‐β‐CD. Specific surface area of the adsorbent was calculated to be 140 m²/g and it can be stated that the synthesized nano adsorbent has high removal efficiency. It should be noted that the adsorption capacity of the employed nano adsorbent was more than 95%, which could be attributed to high porosity of β‐cyclodextrin functionalized KCC‐1.     

Iranian Strawberry crinkle cytorhabdovirus variation assessed using its movement protein (P3) gene

Background

Strawberry crinkle virus (SCV) is a member of the genus Cytorhabdovirus, family Rhabdovirida, and order Mononegavirales. SCV affects the production of various strawberry cultivars. In this study we investigated the genetic diversity of SCV in strawberry fields based on P3 (movement protein) gene.

Methods and results

The samples were collected from strawberry fields in the Kurdistan Province, Iran. P3 gene from 20 SCV isolates, representing 18 nucleic acid haplotypes, is composed of 729 nucleotides, encoding a protein with 243 amino acids. SCV-P3 sequences shared 98.77%–99.86% nucleotide and 97.5%–100% amino acid sequence identity. Phylogenetic analyses of the new P3 sequences with two previously published SCV-P3 sequences from the Czech Republic showed that there are two major phylogroups (I and II) and three minor phylogroups in the body of the phylogeny, I-1, I-2, II-1. Comparisons of P3 gene sequences revealed a mutational bias, with more differences being transitions than transversions. The ratio of non-synonymous/synonymous nucleotide changes was?<?1, indicating that SCV-P3 gene is under predominantly negative selection.

Conclusions

Phylogenetic and sequence identity analyses showed that SCV isolates from Iran are closely related and have not diverged more than 2% based on P3 gene despite geographical separation and strawberry cultivar. This is the first report of the genetic diversity of SCV worldwide.