Computational Quantum Chemistry Studies of the Interactions of Amino Acids Side Chains with the Guanine Radical Cation.

Guanine is generally accepted as the most easily oxidized DNA base when cells are subjected to ionizing radiation, photoionization or photosensitization. At pH 7, the midpoint reduction potential is on the order of 0.2 – 0.3 V higher than those of the radicals of e.g. tyrosine, tryptophan cysteine and histidine, so that the radical “repair” (or at least, a thermodynamically favorable reaction) involving these amino acids is feasible. Computational quantum studies have been done on tyrosine, tryptophan, cysteine and histidine side chains as they appear in histones. Density functional theory was employed using B3LYP/6-31G+ (d, p) basis set to study spin densities on these amino acids side chains as they pair with the guanine radical cation. The amino acid side chains are positioned so as not to disrupt the Watson-Crick base pairing. Our results indicate that, these side chains of amino acid with reducing properties can repair guanine radical cation through electron transfer coupled with proton transfer

Some aspects of the taxonomy, genetics, carotenogenesis and chemical composition of a red yeast Rhodotorula rubra TP1

A new strain of yeast was isolated from yogurt and tentatively identified as Rhodoturula ruhra TP1 It was reported that the yeast produced structures resembling ascospores and, hence, was the first report of a sexual stage in Rhodotorula rubra. Preliminary studies in fish feeding trials indicate that the yeast may be an attractive candidate for use in the aquaculture industry for coloring fish muscle. To exploit the potentials of the new yeast isolate, a comprehensive study was undertaken to: I) confirm the phylogenetic affinity of the new isolate using molecular, biochemical and physiological techniques; 2) identify and quantify the pigments produced by the yeast; 3) isolate mutants with increased pigment production; 4) examine the cell wall for industrially useful polysaccharides; 5) isolate and characterize the carotenogenic enzymes. Studies on the sexuality of the new isolate could not confirm the production of ascospores or any structures resembling spores. To determine the exact phylogenetic relationship of the new isolate, various biochemical and physiological tests were carried out. These tests included assimilation of various carbon and nitrogen sources, isozyme electrophoresis and analysis of cellular long-chain fatty acids. Based on the comparison of the electrophoretic mobilities (IJ) of 8 isozymes in the new isolate and 8 other yeast isolates (Rhodotontla nthra ATCC 9449, Saccharomyces cerevisiae, Phaffia rhodozyma, Rhodotontla glutinis, Rhodotontla graminis. Rhodotorula minuta, Rhodosporidium toruloides and Cryptoccocus macerans), it was concluded that the new isolate could not be distinguished from R. ruhra and should therefore be considered a variant strain. The study also suggested that cellulose acetate electrophoresis could be an invaluable taxonomic tool for the identification of isolates of yeast. Similarly, on the basis of the numerical analysis of the cellular long-chain fatty acid composition 9 isolates, assimilation patterns of various carbon sources, Diazonium blue (DBB), urease and nitrate tests, the new isolate should be confirmed as a variant strain of R. ruhra. To determine whether the phylogeny of the new isolate could be determined on the basis of other identification protocols aside from the biochemical and physiological tests, a ponion of the ribosomal DNA (rONA) and internal transcribed spacer was amplified by the polymerase chain reaction and then sequenced. Comparison ofthe DNA sequences ofthe small subunit ribosomal RNA (ISS rRNA) coding regions and the internal transcribed spacer (ITS) of the new isolate with those of other yeast isolates revealed that the new yeast isolate may be a variant strain of R. ruhra. The new isolate had 93 and lOO% sequence similarity with R. rubra ATCC 9449 tbr the ISS rRNA and ITS sequences, respectively. Furthermore, the evolutionary distances estimated from the 18S rRNA genes and the ITS sequences of the two organisms were 0.015 and 0.000, respectively. Using gas liquid chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy, it was determined that the cell wall polysaccharides of the new isolate consisted of mainly mannans with 13-( 1 ~3) and ~-(I ~4) mannopyranosyl units. The major monosaccharides of the cell wall were determined to be mannose (50.53%), glucose (25.53%), galactose (12.27%), fucose (8.6%) and rhamnose (3.2%). Characterization of pigments produced by the new isolate involved the use of column and thin layer chromatography, high performance liquid chromatography and light spectroscopy. The new isolate was found to produce P-carotene, torulene, torularhodin, phytoene and phytotluene with percentage compositions of 39.85, 30.65, 24.5, 2.2 and 3.1%, respectively. Studies on the genetics of the new isolate included mutagenesis with nitrosoguanadine. Several mutants with increased production of pigments were isolated. Some of these mutants produced the same types of pigments produced by the parental strain while others were found to be blocked at the hydrogenation step and, therefore, produced only ~- carotene. The preliminary studies on the isolation and characterization of the carotenogenic enzymes involved the solubilization and polyethylene glycol precipitation of a cell-free 40,000 x: g supernatant fraction that converted [14C]MVA to phytoene, P-carotene, torulene and torularhodin. The effects of three non-ionic detergents, Tweens 40, 60 and 80 over a 0.5 to 3 % (w/v) concentration range on enzyme activity and protein release were investigated. Enzymatic activity was retained with all three detergents, however, I% Tween 60 was found to be the least inhibitory. The efficacy of the new isolate to color the flesh of rainbow trout was demonstrated in a 16 week feeding triaL Even though a commercial canthaxanthin containing diet induced better pigmentation than the test yeast supplemented diet, the level of pigmentation obtained with the test yeast was comparable to the level reported tor rainbow trout as sufficient for adequate visual color impression. The highest growth rate was obtained with fish fed a diet containing no pigment (negative control group) and the lowest growth rate was observed in fish fed a diet supplemented with test yeast. While the proximate analysis of the flesh showed significant increases in the total protein content of fish in all groups at the end of the feeding trial, the levels were found to be lower than those reported for rainbow trout by other workers and were found to be associated with increased moisture content. Finally, it was observed that the test yeast fed fish had increased polyunsaturated fatty acids content whereas the fatty acid profile remaining relatively unchanged in all other groups

On A Model For The Cross Protection Of Two Infectious Diseases

This paper studies the effects of the spread of two similarly transmitted infectious diseases with cross protection in an unvaccinated population using a basic SEIR model with vital dynamics (births and deaths). A basic Mathematical model is built-up to study the joint transmission dynamics of diseases in the population. The equilibriums of these models as well as their stabilities are studied. Specifically, the stability results for disease-free and endemic steady states are proven. Finally, numerical simulations of the models are carried out with Matlab / Mathematica to study the behavior of the solutions in different regions of the parameter space. Keywords: cross protection, infectious diseases, disease-free and endemic equilibria, numerical simulations, joint modelin

Knowledge of HIV/AIDS among older adults (50 years and above) in a peri-urban setting: A descriptive cross-sectional study

Background: In the absence of vaccine or cure, public knowledge about Human Immune Virus (HIV) is a central tool for curbing HIV epidemic. This study sought to assess the knowledge of HIV among older adults (50 years and above) at the Methodist Faith Healing hospital, Ankaase, Ghana. Methods: Using a descriptive study design, older adults (50 years and above) who visited the Ankaase Methodist Faith Healing hospital were randomly sampled for the study. A structured questionnaire was administered to collect data which was analyzed quantitatively using Statistical Package for Social Sciences (SPSS version 16.0). Results: A total of 100 respondents who were aged 50 to 68 (54 ± 2.3) were recruited. Most of the respondents had average knowledge of the mode of HIV transmission (62%) as well as HIV prevention (58%) and signs and symptoms of HIV (60%). HIV status was significantly associated with HIV knowledge among older adults as HIV positive respondents were 2.25 times more knowledgeable in terms of signs and symptoms, mode of transmission and prevention of HIV [AOR (95% CI) 2.25(1.02-8.68)]. Conclusion: Most older adults (50 years and above) have average knowledge of the mode of transmission, prevention as well as signs and symptoms of HIV. The National Commission for Civic Education should collaborate with various key stakeholders to educate older adults on issues related to HIV/AIDS

Cultural Profile as Determinant of Work Outcomes in a Collectivist Context

Extant research evidence shows that interpersonal bonds—the bond to the immediate supervisor and work team—have an incremental predictive effect in western settings, neglecting emerging economic and cultural environments. This study, thus, examines the impact of cultural profiles on interpersonal bonds and related performance in an emerging market context. Specifically, the study examines the emergence of profiles based on micro-level psychological collectivism (individualism) and power distance orientations. The study further examines the effect of the emerged profiles on interpersonal bonds and the performance of activities related to the targets of the bonds. A survey questionnaire was used to collect data from 148 multiple public and private organizations of varied industries (banking, manufacturing, education, and local government) in an emerging market. Using the MANOVA analytic procedure, the study finds that the supervisor-oriented and team-involved profile rather than the team-alienated profile demonstrates a significantly higher level of work outcomes involving interpersonal commitment to the supervisor and substantially higher task performance. The outcome suggests that power distance cultural value may have a negative psychological effect while collectivism has a positive psychological effect on work outcomes in this context. The implication of the outcome for theory and policy in the collectivist context is discussed

Combined effects of hyperglycemic conditions and HIV-1 Nef: a potential model for induced HIV neuropathogenesis

Hyperglycemic conditions associated with diabetes mellitus (DM) or with the use of antiretroviral therapy may increase the risk of central nervous system (CNS) disorders in HIV-1 infected patients. In support of this hypothesis, we investigated the combined effects of hyperglycemic conditions and HIV-1 accessory protein Nef on the CNS using both in vitro and in vivo models. Astrocytes, the most abundant glial cell type required for normal synaptic transmission and other functions were selected for our in vitro study. The results show that in vitro hyperglycemic conditions enhance the expression of proinflammatory cytokines including caspase-3, complement factor 3 (C3), and the production of total nitrate and 8-iso-PGF2 α as reactive oxygen species (ROS) in human astrocytes leading to cell death in a dose-dependent manner. Delivery of purified recombinant HIV-1 Nef protein, or Nef expressed via HIV-1-based vectors in astrocytes showed similar results. The expression of Nef protein delivered via HIV-1 vectors in combination with hyperglycemia further augmented the production of ROS, C3, activation of caspase-3, modulation of filamentous protein (F-protein), depolarization of the mitochondria, and loss of astrocytes. To further verify the effects of hyperglycemia and HIV-1 Nef protein on CNS individually or in combination, in vivo studies were performed in streptozotocin (STZ) induced diabetic mice, by injecting HIV-1 Nef expressing viral particles into the sub-cortical region of the brain. Our in vivo results were similar to in vitro findings indicating an enhanced production of caspases-3, ROS (lipid oxidation and total nitrate), and C3 in the brain tissues of these animals. Interestingly, the delivery of HIV-1 Nef protein alone caused similar damage to CNS as augmented by hyperglycemia conditions. Taken together, the data suggests that HIV-1 infected individuals with hyperglycemia could potentially be at a higher risk of developing CNS related complications

Modelling Emerging Pollutants in Wastewater Treatment: A Case Study using the Pharmaceutical 17??ethinylestradiol

Mathematical modelling can play a key role in understanding as well as quantifying uncertainties surrounding the presence and fate of emerging pollutants in wastewater treatment processes (WWTPs). This paper presents for the first time a simplified emerging pollutant pathway in the WWTP that incorporates two potential pathways to sequestration. It develops de-terministic and stochastic ordinary differential equations to gain insight into the fate and behaviour of a case study pharmaceutical, with particular focus on sorption to the solid phase, as well as the nature of the experimentally measured solid parent compound. Statistical estimation and inferential procedures are developed and via a proof-of-concept examination, the study explores the transformation pathways of the bioactive chemicals (BACs) in the bioreactor, which is the heart of the WWTP. With a focus on the case study pharmaceutical 17??ethinlyestradiol (EE2), the simulation results show good agreement with the EE2 data. In addition, the results suggest that the experimentally measured solid EE2-parent concentration is very similar to the model-based sequestered EE2-parent concentration

Inhibition of endogenous reverse transcription of human and nonhuman primate lentiviruses: Potential for development of lentivirucides

AbstractIn the current study, we extended our previous works on natural endogenous reverse transcription (NERT) and further examined its potential as a virucide molecular target in sexual transmission of primate lentiviruses. HIV-1 and SIV virions were pretreated with select nucleoside (NRTIs) and nonnucleoside RT inhibitors (NNRTIs), either alone or in combination with NERT-stimulating substances. The effects of these antiretrovirals on virion inactivation were analyzed in human T cell lines and primary cell cultures. Pretreatment of HIV-1 virions with physiologic NERT-stimulants and 3′-azido-3′-deoxythymidine 5′-triphosphate (AZT-TP) or nevirapine potently inactivated cell-free HIV-1 virions and resulted in strong inhibition of the viral infectivity. Pretreatment of chimeric SHIV-RT virions with NERT-stimulating cocktail and select antiretrovirals also resulted in virion inactivation and inhibition of viral infectivity in T cell lines. Our findings demonstrate the potential clinical utility of approaches based on inhibiting NERT in sexual transmission of HIV-1, through the development of effective anti-HIV-1 microbicides, such as NRTIs and NNRTIs

Antimicrobial effects of liquid anesthetic isoflurane on Candida albicans

Candida albicans is a dimorphic fungus that can grow in yeast morphology or hyphal form depending on the surrounding environment. This ubiquitous fungus is present in skin and mucus membranes as a potential pathogen that under opportunistic conditions causes a series of systemic and superficial infections known as candidiasis, moniliasis or simply candidiasis. There has been a steady increase in the prevalence of candidiasis that is expressed in more virulent forms of infection. Although candidiasis is commonly manifested as mucocutaneous disease, life-threatening systemic invasion by this fungus can occur in every part of the body. The severity of candidal infections is associated with its morphological shift such that the hyphal morphology of the fungus is most invasive. Of importance, aberrant multiplication of Candida yeast is also associated with the pathogenesis of certain mucosal diseases. In this study, we assessed the anti-candidal activity of the volatile anesthetic isoflurane in liquid form in comparison with the anti-fungal agent amphotericin B in an in vitro culture system. Exposure of C. albicans to isoflurane (0.3% volume/volume and above) inhibited multiplication of yeast as well as formation of hyphae. These data suggest development of potential topical application of isoflurane for controlling a series of cutaneous and genital infections associated with this fungus. Elucidiation of the mechanism by which isoflurane effects fungal growth could offer therapeutic potential for certain systemic fungal infections

Suicidal behaviours among in-school adolescents in Mozambique: cross-sectional evidence of the prevalence and predictors using the Global School-Based Health Survey data

Introduction: Despite interventions by low and middle-income countries toward the achievement of the global Sustainable Development Goal (SDG) on promoting mental health and well-being of their populace by the year 2030, suicidal behaviours continue to be major causes of premature mortality, especially among young people. This study examined the prevalence and predictors of suicidal behaviours among in-school adolescents in Mozambique. Materials and methods: This was a cross-sectional study of 1918 in-school adolescents using data from the 2015 Global School-based Health Survey (GSHS) of Mozambique. The outcome variables (suicidal ideation, suicidal plan, and suicidal attempt) were measured with single items in the survey. Both bivariate and multivariate analyses were performed using chi-square test of independence and binary logistic regression respectively. Results are presented as Adjusted Odds Ratios for the binary logistic regression analysis. Statistical significance was set at p<0.05. Results: The prevalence of suicidal behaviours 12 months prior to the survey were 17.7%, 19.6% and 18.5% for suicidal ideation, suicidal plan, and suicidal attempt respectively. Adolescents who experienced anxiety had higher odds of suicidal ideation [AOR = 1.616, 95%CI = 1.148-2.275], suicidal plan [AOR = 1.507, 95%CI = 1.077-2.108], and suicidal attempt [AOR = 1.740, 95%CI = 1.228-2.467]. Adolescents who were physically attacked in school were also more likely to ideate [AOR = 1.463, 95%CI = 1.115-1.921], plan [AOR = 1.328, 95%CI = 1.020-1.728], and attempt [AOR = 1.701, 95%CI = 1.306-2.215] suicide. Having close friends was, however, an important protective factor against suicidal ideation [AOR = 0.694, 95%CI = 0.496-0.971], plan [AOR = 0.625, 95%CI = 0.455-0.860], and attempt [AOR = 0.529, 95%CI = 0.384-0.729]. Peer support also reduced the risk of suicidal ideation [AOR = 0.704, 95%CI = 0.538,0.920] and plan [AOR = 0.743, 95%CI = 0.572,0.966] among the in-school adolescents. Conclusion: Suicidal behaviours constitute major public health challenges among in-school adolescents in Mozambique. The behaviours are predominant among adolescents who are physically attacked and those who experience anxiety. Conversely, having close friends serves as a protective factor against suicidal behaviours. To ensure that Mozambique meets the SDG target of promoting the mental health of all by the year 2030, the Government of Mozambique and educational authorities should urgently design and implement innovative interventions and strengthen existing ones that seek to address physical attacks and anxiety among in-school adolescents. School administrations should also incorporate programmes that seek to congregate students and offer platforms for social interaction and cohesion