Violacein: Properties and Production of a Versatile Bacterial Pigment

Violacein-producing bacteria, with their striking purple hues, have undoubtedly piqued the curiosity of scientists since their first discovery. The bisindole violacein is formed by the condensation of two tryptophan molecules through the action of five proteins. The genes required for its production, vio ABCDE, and the regulatory mechanisms employed have been studied within a small number of violacein-producing strains. As a compound, violacein is known to have diverse biological activities, including being an anticancer agent and being an antibiotic against Staphylococcus aureus and other Gram-positive pathogens. Identifying the biological roles of this pigmented molecule is of particular interest, and understanding violacein's function and mechanism of action has relevance to those unmasking any of its commercial or therapeutic benefits. Unfortunately, the production of violacein and its related derivatives is not easy and so various groups are also seeking to improve the fermentative yields of violacein through genetic engineering and synthetic biology. This review discusses the recent trends in the research and production of violacein by both natural and genetically modified bacterial strains.open0

Susceptibility to Oxidative Stress is Greater in Korean Patients with Coronary Artery Disease than Healthy Subjects

There are some evidences that the increased oxidative stress and thus increased oxidizability of lipoproteins and DNA can contribute to the development of certain human diseases, such as cardiovascular disease. To confirm the association of DNA damage with cardiovascular disease, we investigated susceptibility of DNA to oxidation in lymphocytes and oxidative stress related parameters in blood of patients with coronary artery disease (CAD). Subjects were consisted of 42 patients (27 men, 15 women) with documented CAD and 49 apparently healthy subjects (33 men, 16 women) as controls. Cellular DNA damage induced by 100 µM H2O2 was measured using Comet assay and quantified by TL. There were no differences in age (61.4 ± 1.7 years vs 62.0 ± 2.2 years) between the two groups. All the findings were shown to be independent of either sex or smoking habit. The patients showed significantly higher TL (87.3 ± 1.6 µm) compared to the control (79.3 ± 1.7 µm, p<0.01). Plasma TRAP, vitamin C, γ-tocopherol, and α-carotene levels in patients group were lower than those of control groups, while erythrocytic catalase activity increased in patients group. In conclusion, we observed that reduced overall antioxidant status was closely connected to higher susceptibility of DNA damage in CAD patients

Correlation of the Rates of Solvolysis of i-Butyl Fluoroformate and a Consideration of Leaving-Group Effects

The specific rates of solvolysis of isobutyl fluoroformate (1) have been measured at 40.0 °C in 22 pure and binary solvents. These results correlated well with the extended Grunwald-Winstein (G-W) equation, which incorporated the NT solvent nucleophilicity scale and the YCl solvent ionizing power scale. The sensitivities (l and m-values) to changes in solvent nucleophilicity and solvent ionizing power, and the kF/kCl values are very similar to those observed previously for solvolyses of n-octyl fluoroformate, consistent with the additional step of an addition-elimination pathway being rate-determining. The solvent deuterium isotope effect value (kMeOH/kMeOD) for methanolysis of 1 was determined, and for solvolyses in ethanol, methanol, 80% ethanol, and 70% TFE, the values of the enthalpy and the entropy of activation for the solvolysis of 1 were also determined. The results are compared with those reported earlier for isobutyl chloroformate (2) and other alkyl haloformate esters and mechanistic conclusions are drawn

Potential redox-sensitive Akt activation by dopamine activates Bad and promotes cell death in melanocytes

Dopamine (DA) is a well known oxidative neurotoxin. In addition, Akt has been reported to deliver a survival signal that inhibits apoptosis. However, it has also been reported that chronic Akt activation leads to apoptosis in response to oxidative stress. The objective of the present study was to investigate the possible role of the Akt pathway in vitiligo and its possible relationship with DA-induced cell death using Mel-Ab cells. Cultured Mel-Ab cells were treated with DA with and without N-Acetyl-L-cysteine (NAC), which is known to have antioxidative properties. Cell viability was then assessed by a crystal violet assay and Annexin staining was performed. The changes in the expression of Akt were analyzed by western blot analysis. The cell viability was reduced by approximately 60% in response to treatment with 500 µM DA, and NAC effectively prevented this cytotoxic effect. Likewise, treatment with DA produced numerous Annexin positive cells, while treatment with NAC prevented this apoptotic cell death. Akt was slowly phosphorylated after treatment with DA, while NAC clearly inhibited the DA-induced Akt activation. Western blot analysis also showed that treatment with DA induced the activation of Bad. Finally, LY294002 exerted a protective effect against DA-induced apoptotic cell death. DA may induce redox-sensitive Akt activation and increase the level of Bad, which can promote cell death by heterodimerization with survival proteins. Moreover, NAC effectively protects against DA-induced melanocyte death via inhibition of DA-induced Akt activation

Replication of the genetic effects of IFN regulatory factor 5 (IRF5) on systemic lupus erythematosus in a Korean population

Recently, two studies provided convincing evidence that IFN regulatory factor 5 (IRF5) gene polymorphisms are significantly associated with systemic lupus erythematosus (SLE) in several white populations. To replicate the association with SLE in an Asian population, we examined the genetic effects in our SLE cohort from a Korean population. A total of 1,565 subjects, composed of 593 cases and 972 controls, were genotyped using the TaqMan® (Applied Biosystems, Foster City, CA, USA) method. The genetic effects of polymorphisms on the risk of SLE were evaluated using χ2 tests and a Mantel–Haenszel meta-analysis. Statistical analysis revealed results in the Korean population were similar to the previous reports from white populations. The rs2004640 T allele had a higher frequency in SLE cases (0.385) than controls (0.321; odds ratio (OR) = 1.32, P = 0.0003). In combined analysis, including all seven independent cohorts from the three studies so far, robust and consistent associations of the rs2004640 T allele with SLE were observed. The estimate of risk was OR = 1.44 (range, 1.34–1.55), with an overall P = 1.85 × 10-23 for the rs2004640 T allele. The haplotype (rs2004640T–rs2280714T) involved in both the alternative splice donor site and the elevated expression of IRF5 also had a highly significant association with SLE (pooled, P = 2.11 × 10-16). Our results indicate that the genetic effect on the risk of SLE mediated by IRF5 variants can be generally accepted in both white and Asian populations

Phylogenetic analysis and characterization of Korean orf virus from dairy goats: case report

An outbreak of orf virus infection in dairy goats in Korea was investigated. Suspected samples of the skin and lip of affected goats were sent to the laboratory for more exact diagnosis. Orf virus was detected by electron microscopy and viral DNA was identified by PCR. To reveal the genetic characteristics of the Korean strain (ORF/09/Korea), the sequences of the major envelope protein (B2L) and orf virus interferon resistance (VIR) genes were determined and then compared with published reference sequences. Phylogenetic analysis revealed that the ORF/09/Korea strain was closest to the isolates (Taiping) from Taiwan. This is believed to be the first report on the molecular characterization of orf virus in Korea

Role of Neuronal NADPH Oxidase 1 in the Peri-Infarct Regions after Stroke

The molecular mechanism underlying the selective vulnerability of neurons to oxidative damage caused by ischemia-reperfusion (I/R) injury remains unknown. We sought to determine the role of NADPH oxidase 1 (Nox1) in cerebral I/R-induced brain injury and survival of newborn cells in the ischemic injured region. Male Wistar rats were subjected to 90 min middle cerebral artery occlusion (MCAO) followed by reperfusion. After reperfusion, infarction size, level of superoxide and 8-hydroxy-20-deoxyguanosine (8-oxo-2dG), and Nox1 immunoreactivity were determined. RNAi-mediated knockdown of Nox1 was used to investigate the role of Nox1 in I/R-induced oxidative damage, neuronal death, motor function recovery, and ischemic neurogenesis. After I/R, Nox1 expression and 8-oxo-2dG immunoreactivity was increased in cortical neurons of the peri-infarct regions. Both infarction size and neuronal death in I/R injury were significantly reduced by adeno-associated virus (AAV)-mediated transduction of Nox1 short hairpin RNA (shRNA). AAV-mediated Nox1 knockdown enhanced functional recovery after MCAO. The level of survival and differentiation of newborn cells in the peri-infarct regions were increased by Nox1 inhibition. Our data suggest that Nox-1 may be responsible for oxidative damage to DNA, subsequent cortical neuronal degeneration, functional recovery, and regulation of ischemic neurogenesis in the peri-infarct regions after stroke