Crystal structure and thermal characterization of cadmium oxalate [CdC2O4 · 3H2O] and barium-doped cadmium oxalate [Ba0.5Cd0.5(C2O4)2 · 5H2O] single crystals grown in silica gel

Pure cadmium oxalate trihydrate (COT) and barium added cadmium oxalate (BCO) single crystals were grown by controlled diffusion of Cd²⁺ and Ba²⁺ ions in silica gel at ambient temperature. A single test tube technique coupled with gel aging conferred maximum size crystals by controlling the nucleation rate. It was found that the pH and age of the gel greatly influenced the crystal quality, their size and transparency. Grown crystals CdC₂O₄ · 3H₂O and Ba_0.5Cd_0.5(C₂O₄)₂ · 5H₂O were characterized by X-ray diffraction, Fourier transform infrared spectroscopy and thermal analysis. Effect of barium dopant on the growth and morphology of cadmium oxalate was studied. Pure cadmium oxalate crystallized in triclinic system and the barium-doped cadmium oxalate crystallized in hexagonal system with massive changes in their unit cell parameters. The infrared spectrum revealed the presence of oxalate ligands and water of hydration in both the pure and barium-doped crystals. Thermal analysis showed that the grown crystals were dehydrated thermally even from lower temperatures and the doped crystals were found more stable.     

Chitinase production by Beauveria felinaRD 101: optimization of parameters under solid substrate fermentation conditions

Major parameters affecting the production of chitinase by Beauveria felinaRD 101 under solid substrate fermentation conditions have been optimized. Wheat bran moistened with 100 MS-HCl medium adjusted to pH 5.0, inoculated with 1 × 10¹⁰ conidia g^–1 initial dry bran and incubated at 28 °C for 6 days produced maximum chitinase activity of 6.34 U g^–1 initial dry substrate.     

Identification of avian vasotocin receptor subtype-specific antagonists involved in the stress response of the chicken,Gallus gallus

Vasotocin 1a and 1b receptors (V1aR and V1bR) have been shown to play important roles in the neuroendocrine regulation of stress responses via the anterior pituitary (AP) of birds. To identify effective subtype-specific antagonists for the chicken V1aR (cV1aR) and cV1bR, potential antagonists to the mammalian V1R were screened against the cV1aR and cV1bR 3D structural models by molecular docking analysis with determination of binding pocket/amino acid residues involved in the interaction. The antagonistic effects of the selected ligands were examined by measuring pro-opiomelanocortin (POMC) heteronuclear RNA (hnPOMC) levels following the in vitro stress administration to primary chicken AP cells. Results of in silico analysis showed that the Manning compound and several other antagonists were bound to cV1bR with higher affinity than the natural agonist, arginine vasotocin (AVT). Similarities and differences in the antagonist-receptor binding interface with receptors were characterized for each ligand. Non-peptide mammalian V1bR antagonists, SSR-149415 and L-368899, were shown to be effective and had an additive effect in blocking POMC hnRNA expression in pituitary cell culture studies. SR-49059 antagonized the effect(s) of AVT/CRH on the downregulation of the cV1aR and the upregulation of the cCRH-R2 expression but not the cV1bR and cCRH-R1. The Manning compound antagonized the downregulation of cV1aR, cV1bR and cCRH-R1 and the upregulation of cCRH-R2 expression. The specificity of antagonists apparently resulted from unique differences in the interacting residues and their binding affinities. Collectively, these results provide valuable leads for future development of novel compounds capable of blocking or attenuating the AP stress response of avian species and perhaps other non-mammalian vertebrates as well.     

Analogs of N'-hydroxy-N-(4H,5H-naphtho[1,2-d]thiazol-2-yl)methanimidamide inhibit Mycobacterium tuberculosis methionine aminopeptidases

Our previous target validation studies established that inhibition of methionine aminopeptidases (MtMetAP, type 1a and 1c) from Mycobacterium tuberculosis (Mtb) is an effective approach to suppress Mtb growth in culture. A novel class of MtMetAP1c inhibitors comprising of N'-hydroxy-N-(4H,5H-naphtho[1,2-d]thiazol-2-yl)methanimidamide (4c) was uncovered through a high-throughput screen (HTS). A systematic structure-activity relationship study (SAR) yielded variants of the hit, 4b, 4h, and 4k, bearing modified A- and B-rings as potent inhibitors of both MtMetAPs. Except methanimidamide 4h that showed a moderate Mtb inhibition, a desirable minimum inhibitory concentration (MIC) was not obtained with the current set of MtMetAP inhibitors. However, the SAR data generated thus far may prove valuable for further tuning of this class of inhibitors as effective anti-tuberculosis agents.     

Methamphetamine Self-Administration Is Associated with Persistent Biochemical Alterations in Striatal and Cortical Dopaminergic Terminals in the Rat

Methamphetamine (meth) is an illicit psychostimulant that is abused throughout the world. Repeated passive injections of the drug given in a single day or over a few days cause significant and long-term depletion of dopamine and serotonin in the mammalian brain. Because meth self-administration may better mimic some aspects of human drug-taking behaviors, we examined to what extent this pattern of drug treatment might also result in damage to monoaminergic systems in the brain. Rats were allowed to intravenously self-administer meth (yoked control rats received vehicle) 15 hours per day for 8 days before being euthanized at either 24 hours or at 7 and 14 days after cessation of drug taking. Meth self-administration by the rats was associated with a progressive escalation of daily drug intake to 14 mg/kg per day. Animals that self-administered meth exhibited dose-dependent decreases in striatal dopamine levels during the period of observation. In addition, there were significant reductions in the levels of striatal dopamine transporter and tyrosine hydroxylase proteins. There were also significant decreases in the levels of dopamine, dopamine transporter, and tyrosine hydroxylase in the cortex. In contrast, meth self-administration caused only transient decreases in norepinephrine and serotonin levels in the two brain regions, with these values returning to normal at seven days after cessation of drug taking. Importantly, meth self-administration was associated with significant dose-dependent increases in glial fibrillary acidic protein in both striatum and cortex, with these changes being of greater magnitude in the striatum. These results suggest that meth self-administration by rats is associated with long-term biochemical changes that are reminiscent of those observed in post-mortem brain tissues of chronic meth abusers.