Link between free radicals and protein kinase C in glucose-induced alteration of vascular dilation

Development of vascular complications in diabetes has been linked to the quality of glucose regulation and characterized by endothelial dysfunction. The exact mechanism behind vascular complications in diabetes is poorly understood. However, alteration of nitric oxide (NO) biosynthesis or bioactivity is strongly implicated and the mechanism behind such alterations is still a subject for research investigations. In the present study, we tested the hypothesis that glucose-induced attenuation of vascular relaxation involves protein kinase C (PKC)-linked generation of free radicals. Vascular relaxation to acetylcholine (ACh; 10(-9)-10(-5) M), isoproterenol (10(-9)-10(-5) M), or NO donor, sodium nitropruside (SNP; 10(-9)-10(-6) M) was determined in phenylephrine (PE, 10(-7) M) pre-constricted aortic rings from Sprague-Dawley rats in the presence or absence of 30 mM glucose (30 min), L-nitro-arginine methyl ester (L-NAME; 10(-4) M for 15 min), a NO synthase inhibitor, or xanthine (10(-5) M), a free radical generator. ACh dose-dependently caused relaxation that was attenuated by L-NAME, glucose, or xanthine. Pre-incubation (15 min) of the rings with vitamin C (10(-4) M), an antioxidant or calphostin C (10(-6) M), a PKC inhibitor, restored the ACh responses. However, high glucose had no significant effects on SNP or isoproterenol-induced relaxation. ACh-induced NO production by aortic ring was significantly reduced by glucose or xanthine. The reduced NO production was restored by pretreatment with vitamin C or calphostin C in the presence of glucose, but not xanthine. These data demonstrate that oxidants or PKC contribute to glucose-induced attenuation of vasorelaxation which could be mediated via impaired endothelial NO production and bioavailability. Thus, pathogenesis of glucose-induced vasculopathy involves PKC-coupled generation of oxygen free radicals which inhibit NO production and selectively inhibit NO-dependent relaxation.     

Reduced expressions of calmodulin genes and protein and reduced ability of calmodulin to activate plasma membrane Ca2+‐ATPase in the brain of protein undernourished rats: modulatory roles of selenium and zinc supplementation

The roles of protein undernutrition as well as selenium (Se) and zinc (Zn) supplementation on the ability of calmodulin (CaM) to activate erythrocyte ghost membrane (EGM) Ca²⁺‐ATPase and the calmodulin genes and protein expressions in rat's cortex and cerebellum were investigated. Rats on adequate protein diet and protein‐undernourished (PU) rats were fed with diet containing 16% and 5% casein, respectively, for a period of 10 weeks. The rats were then supplemented with Se and Zn at a concentration of 0.15 and 227 mg l⁻¹, respectively, in drinking water for 3 weeks. The results obtained from the study showed significant reductions in synaptosomal plasma membrane Ca²⁺‐ATPase (PMCA) activity, Ca²⁺/CaM activated EGM Ca²⁺ATPase activity and calmodulin genes and protein expressions in PU rats. Se or Zn supplementation improved the ability of Ca²⁺/CaM to activate EGM Ca²⁺‐ATPase and protein expressions. Se or Zn supplementation improved gene expression in the cerebellum but not in the cortex. Also, the activity of PMCA was significantly improved by Zn. In conclusion, it is postulated that Se and Zn might be beneficial antioxidants in protecting against neuronal dysfunction resulting from reduced level of calmodulin such as present in protein undernutrition. Copyright © 2016 John Wiley & Sons, Ltd.     

A comparative evaluation of phenotypic and molecular methods in the identification of members of the Staphylococcus sciuri group

Members of the Staphylococcus sciuri group (S. sciuri, S. lentus, and S. vitulinus) are coagulase-negative, novobiocin-resistant staphylococci that could be distinguished from other staphylococci on the basis of positive oxidase activity. In the present study, a scheme based on conventional methods and utilization of various carbohydrates was evaluated for the identification of oxidase-positive staphylococci, and validated using two molecular techniques. Of the 173 oxidase-positive staphylococcal tested strains, 161 were identified as S. sciuri, 9 as S. lentus, 2 as S. vitulinus, and one as S. fleurettii by our scheme. The level of agreement with tRNA intergenic length polymorphism analysis (tDNA-PCR) was high (97.5-100% correlation). The accuracy and ease of use of this protocol suggest that it may be useful and valuable in microbiological laboratories for the identification of members of this group.     

Immunoinformatics Design of Multiepitope Vaccine Against Enterococcus faecium Infection

International Journal of Peptide Research and Therapeutics - Enterococcus faecium has emerged as the fourth most commonly isolated nosocomial pathogen due to its resistance to commonly used...     

Three-dimensional Nuclear Telomere Organization in Multiple Myeloma

Multiple myeloma (MM) is preceded by monoclonal gammopathy of undetermined significance (MGUS). Up to date, it is difficult to predict an individual's time to disease progression and the treatment response. To examine whether the nuclear telomeric architecture will unravel some of these questions, we carried out. Three-dimensional (3D) telomere analysis on samples from patients diagnosed with MGUS and MM, as well as from patients who went into relapse. Telomere signal intensity, number of telomere aggregates, nuclear volume, and the overall nuclear telomere distribution (a/c ratio) were analyzed. The telomeric profiles allowed for the differentiation of the disease stages. The telomeric profiles of myeloma cells obtained from blood and bone marrow aspirates were identical. Based on this study, we discuss the use of 3D telomere profiling as a potential future tool for risk stratification and personalized treatment decisions.     

Analyzing infant mortality with geoadditive categorical regression models: a case study for Nigeria

In this paper, we analyze infant mortality in Nigeria based on the data set from the 1999 Nigeria Demographic and Health Survey (NDHS). We investigate spatial patterns at a highly disaggregated level of Nigerian states and consider non-linear effects of mother's age at birth. Time to the occurrence of a child's death can intuitively be considered to be categorical in nature and the determinants of a child's death may differ in different age groups. Thus, it may be desirable to investigate separately the death of a child in the first month and in the remaining 11 months of the first year of life. To avoid selection bias, the data set used for this case study is based on information on children who were born 12 months preceding the survey. Inference is Bayesian and is based on Markov chain Monte Carlo (MCMC) techniques. We find that spatial variation and the determinants of death indeed differ considerably for the two age groups considered.     

Integrated assessment of the heavy metal pollution status and potential ecological risk in the Lagos Lagoon,South West,Nigeria

This study was carried out to assess the heavy metal pollution status and potential ecological risk in the Lagos lagoon, Nigeria. The concentrations of twelve heavy metals commonly associated with environmental pollution were determined in the sediments of the lagoon by Atomic Absorption Spectrophotometry (AAS) and the cold vapor method was employed for Mercury (Hg). Nonempirical risk indices and empirical Sediment Quality Guidelines (SQGs) were used to assess the ecological risk associated with heavy metal in the sediments. The nonempirical risk indices showed that Hg, Arsenic (As), and Cadmium (Cd) are the major contributors to the ecological risk associated with heavy metal pollution in the ecosystem. Comparison of heavy metal concentrations to the Screening Quick Reference Table (SQuiRT) showed that mean concentration of Cd (5.22 and 4.88 mg kg^?1 in dry and rainy seasons, respectively) exceeds the effect range low (ERL) value (1.20 mg kg^?1) in effect to biota. Industries sited around the lagoon have effluent output points in the lagoon serving as a major source of heavy metals coupled with indirect discharges from other sources. Heavy metals are nonbiodegradable, toxic and have the potential to alter ecosystem health, thus pollution sources should be effectively monitored and contained.     

Mixed Feedstock Approach to Lignocellulosic Ethanol Production—Prospects and Limitations

Lignocellulosic ethanol is a promising alternative to fossil-derived fuels because lignocellulosic biomass is abundant, cheap and its use is environmentally friendly. However, the high costs of feedstock supply and the expensive processing requirements of lignocellulosic biomass hinder the development of the lignocellulosic biorefinery. Lignocellulosic ethanol production so far, has been based mainly on single feedstocks while the use of mixed feedstocks has been poorly explored. Previous studies from alternative applications of mixed lignocellulosic biomass (MLB) have shown that their use can bring about significant cost savings when compared to single feedstocks. Although laboratory-scale evaluations have demonstrated that mixed feedstocks give comparable or even higher ethanol yields compared to single feedstocks, more empirical studies are needed to establish the possibility of achieving significant cost savings in terms of pre-biorefinery logistics. In this review, some potential benefits of the use of MLB for ethanol production are highlighted. Some anticipated limitations of this approach have been identified and ways to surmount them have been suggested. The outlook for ethanol production from MLB is promising provided that revolutionary measures are taken to ensure the sustainability of the industry.     

Assessment of potential ecological disruption based on heavy metal toxicity, accumulation and distribution in media of the Lagos Lagoon

Toxicity evaluations of heavy metals against three benthic animals, Tympanotonus fuscatus, Clibanarius africanus and Sesarma huzardi of the Lagos Lagoon were carried out under laboratory conditions. On the basis of the 96hLC₅₀ values, Cd was found to be the most toxic metal tested followed by Cu, Zn and Pb, in a descending order of toxicity against T. fuscatus and S. huzardi; however, against C. africanus, Cu was the most toxic followed by Cd, Zn and Pb (least toxic). The determination of the metal concentrations in the water column and sediment of the Lagos Lagoon revealed that these media of the lagoon contained measurable concentrations of heavy metals but the levels were still several folds lower than the concentrations that will cause 50% mortality of exposed animals under laboratory conditions. The significance of the observed differences between the 96hLC₅₀ values of the test metals, the concentration of heavy metals detected in tissues of field animals and ambient levels of the metals in the Lagos lagoon were discussed in relation to the protection of aquatic lives and potential public health risks. The need to verify the possibilities of synergistic interactions between the constituent metals when acting jointly against the exposed animals was recommended.     

A role for autophagic protein beclin 1 early in lymphocyte development

Autophagy is a highly regulated and evolutionarily conserved process of cellular self-digestion. Recent evidence suggests that this process plays an important role in regulating T cell homeostasis. In this study, we used Rag1(-/-) (recombination activating gene 1(-/-)) blastocyst complementation and in vitro embryonic stem cell differentiation to address the role of Beclin 1, one of the key autophagic proteins, in lymphocyte development. Beclin 1-deficient Rag1(-/-) chimeras displayed a dramatic reduction in thymic cellularity compared with control mice. Using embryonic stem cell differentiation in vitro, we found that the inability to maintain normal thymic cellularity is likely caused by impaired maintenance of thymocyte progenitors. Interestingly, despite drastically reduced thymocyte numbers, the peripheral T cell compartment of Beclin 1-deficient Rag1(-/-) chimeras is largely normal. Peripheral T cells displayed normal in vitro proliferation despite significantly reduced numbers of autophagosomes. In addition, these chimeras had greatly reduced numbers of early B cells in the bone marrow compared with controls. However, the peripheral B cell compartment was not dramatically impacted by Beclin 1 deficiency. Collectively, our results suggest that Beclin 1 is required for maintenance of undifferentiated/early lymphocyte progenitor populations. In contrast, Beclin 1 is largely dispensable for the initial generation and function of the peripheral T and B cell compartments. This indicates that normal lymphocyte development involves Beclin 1-dependent, early-stage and distinct, Beclin 1-independent, late-stage processes.