Mechanism of Oxidation of Brilliant Cresyl Blue with Acidic Chlorite and Hypochlorous Acid. A Kinetic Approach

The kinetics and mechanism of oxidation of brilliant cresyl blue (7-amino-3-diethylamino-8-methyl-phenoxazine chloride) (BB+) by chlorite in the presence of acid is reported. Under [H+]0>[ClO2–]0>[BB+]0 conditions, the oxidation reaction followed pseudo first-order kinetics with respect to BB+. During the reaction, chlorite ion disproportionates, resulting in accumulation of chlorine dioxide. The overall reaction is third-order with first-order dependence on both H+ and ClO2– ions. The rate coefficient for the overall reaction is (0.158 ± 0.003) l2 mol–2 s–1. The stoichiometry of the reaction is 2BB+ + 7ClO2 – + 2H+  2P + → 2CH3COOH + 4ClO2 + 3Cl– where P=7-amino-3-ethylamino-8-methyl-phenoxazine-10-N-oxide, and it varied with the initial concentrations of chlorite and acid. Near neutral pH, the hypochlorite-initiated oxidation of BB+ proceeded through two second-order pathways, one driven by OCl– ion and the other by HOCl. The latter reaction is much faster, with k=(1.26±0.04)×103 l mol–1 s–1. At low pH, the reaction was much faster and had first-order dependence on the concentrations of BB+, H+ and HOCl. Ru(III) catalysed the BB+-chlorite reaction with efficiency and the kinetics of the catalysed reaction are reported. Ru(III) had a catalytic constant, kCAT=1.2 × 106 l3 mol–3 s–1. The activation parameters for both uncatalysed and catalysed reactions were also reported. The kinetic profiles of the title reaction were computed using the proposed 11-step mechanism and Simkine software. The simulated curves agreed well with the experimental curves.Keywords: Kinetics, reaction mechanisms, dyes, water chemistry, computer chemistry

Detection of Vhe Gamma-Rays from MRK 501 with the Cat Imaging Telescope

The CAT imaging telescope on the site on the former solar plant Themis has been observing gamma-rays from Mrk501 above 220 GeV in March and April 1997. This source is shown to be highly variable and the light curve is presented. The detected gamma-ray rate for the most intense flare is in excess of 10 per minute.Comment: 5 pages, 4 figures, Tex, contribution to 25th ICRC Durba

On the Use of Variance per Genotype as a Tool to Identify Quantitative Trait Interaction Effects: A Report from the Women's Genome Health Study

Testing for genetic effects on mean values of a quantitative trait has been a very successful strategy. However, most studies to date have not explored genetic effects on the variance of quantitative traits as a relevant consequence of genetic variation. In this report, we demonstrate that, under plausible scenarios of genetic interaction, the variance of a quantitative trait is expected to differ among the three possible genotypes of a biallelic SNP. Leveraging this observation with Levene's test of equality of variance, we propose a novel method to prioritize SNPs for subsequent gene–gene and gene–environment testing. This method has the advantageous characteristic that the interacting covariate need not be known or measured for a SNP to be prioritized. Using simulations, we show that this method has increased power over exhaustive search under certain conditions. We further investigate the utility of variance per genotype by examining data from the Women's Genome Health Study. Using this dataset, we identify new interactions between the LEPR SNP rs12753193 and body mass index in the prediction of C-reactive protein levels, between the ICAM1 SNP rs1799969 and smoking in the prediction of soluble ICAM-1 levels, and between the PNPLA3 SNP rs738409 and body mass index in the prediction of soluble ICAM-1 levels. These results demonstrate the utility of our approach and provide novel genetic insight into the relationship among obesity, smoking, and inflammation

Convergent Evidence from Mouse and Human Studies Suggests the Involvement of Zinc Finger Protein 326 Gene in Antidepressant Treatment Response

OBJECTIVES: The forced swim test (FST) is a commonly used model to predict antidepressant efficacy. Uncovering the genetic basis of the model may unravel the mechanism of antidepressant treatment. METHODS: FVB/NJ (FVB) and C57BL/6J (B6) were first identified as the response and non-response strains to fluoxetine (a serotonin-specific reuptake inhibitor antidepressant) treatment in the mouse FST. Simple-interval (SIM) and composite-interval (CIM) mappings were applied to map the quantitative trait loci (QTLs) of the anti-immobility effect of fluoxetine in FST (FST(FLX)) in 865 male B6×FVB-F2 mice. The brain mRNA expressions of the gene with the maximum QTL-linkage signal for FST(FLX) after the FST were compared between B6 and FVB mice and also compared between fluoxetine and saline treatment. The association of the variants in the human homologue of the mouse FST(FLX)-QTL gene with major depressive disorder (MDD) and antidepressant response were investigated in 1080 human subjects (MDD/control = 582/498). RESULTS: One linkage signal for FST(FLX)-QTL was detected at an intronic SNP (rs6215396) of the mouse Zfp326 gene (maximal CIM-LOD = 9.36). The Zfp326 mRNA expression in the FVB thalamus was significantly down-regulated by fluoxetine in the FST, and the higher FVB-to-B6 Zfp326 mRNA expressions in the frontal cortex, striatum and hypothalamus diminished after fluoxetine treatment. Two coding-synonymous SNPs (rs2816881 and rs10922744) in the human homologue of Zfp326, ZNF326, were significantly associated with the 8-week antidepressant treatment response in the MDD patients (Bonferroni-corrected p = 0.004-0.028). CONCLUSIONS: The findings suggest the involvement of the Zfp326 and ZNF326 genes in antidepressant treatment response