A novel guanine-inspired 2-hydrazinyl-4(3H)-quinazolinone derivative (HL) has been synthesized and characterized. The reaction of HL with Cu(II) in a 11 ML ratio and with Cu(II), Ni(II) and Zn(II) in a 12 ML ratio resulted in the formation of complexes, [Cu(L)(H2O)2](NO3), 1 and [M(L)2] (M = Cu for 2, Ni for 3 and Zn for 4), respectively. In all these complexes, the ligand L is tridentately bound to the corresponding metal. The affinity of the complexes for calf-thymus DNA was examined by diverse techniques and the complexes can intercalate between the DNA-bases. The cleavage ability of the complexes towards supercoiled circular pBR322 plasmid DNA was examined via agarose gel electrophoresis experiments in the absence or presence of UVA, UVB or visible light and the DNA-cleavage was found to depend on the concentration and light wavelength used. The binding of the complexes for bovine and human serum albumins was also investigated in order to determine the binding constants and the binding subdomain. The scavenging activity of the compounds was evaluated towards free radicals 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid). Naphthalene sulfonic acids (NSAs) are used as additives in lubricants, dyes, and greases and commonly act as surfactants in many industrial processes. The calcium salt of dinonyl NSA (calcium dinonylnaphthalenesulfonate; CaDNS) is listed among thousands of chemicals identified as priorities for assessment by the Government of Canada's Chemical Management Plan due to the limited toxicity data. The purpose of this study was two-fold 1) to establish the toxicity of CaDNS to Western clawed frog (Silurana tropicalis) embryos and 2) to assess the sub-lethal effects and mechanisms of toxicity of CaDNS in amphibians through targeted gene expression and metabolite analyses. Frog embryos were exposed to water overlying sand spiked with a range of concentrations of CaDNS (17-1393 μg/g) over a 72-h period. Results indicated significantly higher mortality and presence of malformations in frog larvae exposed to over 672 μg/g CaDNS in the sand (14 ng/mL CaDNS in the water) compared to control treatments. An overall decrease in the glutathione redox cycle was observed, including decreases in relative mRNA levels of enzymes (glutathione S-transferase (gst), glutathione reductase (gsr), glutathione peroxidase (gpx)) and decreases in the glutathione (GSH) and glutathione disulfide (GSSG) metabolite concentrations. In addition, transcript levels of genes involved in antioxidant capacity and essential amino acid metabolites decreased significantly in embryos exposed to low levels of CaDNS. This is the first study to assess the toxicity of NSAs in amphibians, contributing important data to aid in the assessment of NSAs. Crown All rights reserved.The production of coenzyme B12 using well-characterized microorganisms, such as Escherichia coli, has recently attracted considerable attention to meet growing demands of coenzyme B12 in various applications. In the present study, we designed an auxotrophic selection strategy and demonstrated the enhanced production of coenzyme B12 using a previously engineered coenzyme B12-producing E. coli strain. To select a high producer, the coenzyme B12-independent methionine synthase (metE) gene was deleted in E. coli, thus limiting its methionine synthesis to only that via coenzyme B12-dependent synthase (encoded by metH). Following the deletion of metE, significantly enhanced production of the specific coenzyme B12 validated the coenzyme B12-dependent auxotrophic growth. Further precise tuning of the auxotrophic system by varying the expression of metH substantially increased the cell biomass and coenzyme B12 production, suggesting that our strategy could be effectively applied to E. coli and other coenzyme B12-producing strains. Activation of the hexosamine pathway (HP) through gain-of-function mutations in its rate-limiting enzyme glutamine fructose-6-phosphate amidotransferase (GFAT-1) ameliorates proteotoxicity and increases lifespan in Caenorhabditis elegans. Here, we investigate the role of the HP in mammalian protein quality control. In mouse neuronal cells, elevation of HP activity led to phosphorylation of both PERK and eIF2α as well as downstream ATF4 activation, identifying the HP as a modulator of the integrated stress response (ISR). Increasing uridine 5'-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc) levels through GFAT1 gain-of-function mutations or supplementation with the precursor GlcNAc reduces aggregation of the polyglutamine (polyQ) protein Ataxin-3. Blocking PERK signaling or autophagy suppresses this effect. In C. elegans, overexpression of gfat-1 likewise activates the ISR. Consistently, co-overexpression of gfat-1 and proteotoxic polyQ peptides in muscles reveals a strong protective cell-autonomous role of the HP. Thus, the HP has a conserved role in improving protein quality control through modulation of the ISR. HYPOTHESIS Monitoring progression of biochemical processes is required for medical and industrial applications. Spatiotemporal changes in fluid properties can be measured to determine progress of biochemical processes like blood coagulation. Localised electrowetting-on-dielectric (EWOD) actuates a part of droplet contact line, allowing local measurement of fluid properties without inducing bulk fluid motion, which is unlike full droplet oscillation-based techniques. EXPERIMENTS In this work, narrow electrodes (50-450 μm) were used to actuate a portion of drop interface. Dynamics of interface actuation and relaxation was used to estimate the local visco-elastic properties of the droplet. FINDINGS For local interface motion, theory predicts a generic dispersion relation ω=cqn. In agreement with theory, decay time was found to be proportional to viscosity and inversely proportional to surface tension. Interface displacement remained almost constant for different viscosities, but it decreased with increase in surface tension. Capability to measure spatiotemporal dynamics of chemical process was demonstrated for sugar dissolution in a droplet of water.  https://www.selleckchem.com/products/otx015.html  For full droplet oscillation-based techniques, the induced bulk flows adversely affect the monitored process. Localised EWOD reduces bulk flows in the sample. So, this technique was applied to study blood coagulation dynamics, enlightening the future prospect of developing biomedical sensors.