The current study explored the nuanced associations between components of executive functioning (EF) and subtypes of aggression, using a latent variable approach. Participants were racially diverse undergraduate students who completed a self-report of reactive (RA) and proactive aggression (PA), and traditional neuropsychological tasks of EF. The appropriateness of using a nested bifactor model of EF was confirmed, and this bifactor model of EF was used to examine the specific associations between components of EF and RA and PA. Results revealed components of EF are differentially associated with RA and PA, such that impulsive, provoked aggression is associated with lower levels of goal-oriented inhibition and higher levels of flexibility, whereas planned, goal-oriented aggression is associated with higher levels of working memory. Findings from the current study underscore the importance of considering the multidimensional nature of EF as well as aggression when examining their associations with external constructs of interest.

Atherosclerosis is a complex cardiovascular disease characterized by chronic progressive inflammation of the arteries. The progression of atherosclerosis from fatty streak to advance atherosclerotic plaque involves the development of a necrotic core region consists of cholesterol, lipids, calcium (Ca²⁺), dead cells and other cellular debris. Macrophage infiltrations occurred in all stages of atherosclerotic progression and they are abundantly found in atherosclerotic plaques. Oxidised low density lipoprotein (oxLDL) plays a vital role in the initiation and development of atherosclerosis. OxLDL is present within atherosclerotic plaque and has been shown to be cytotoxic to various types of cells including macrophages. This research initially examined the cytotoxic effects of copper oxidised LDL on U937, human monocytes and HMDM cells. As expected oxLDL was cytotoxic; causing rapid, concentration and time dependent cell viability loss in all types of cells examined. Examination of the cell morphology showed that oxLDL caused a necrotic like cell death characterised by cell swelling and lysis. Flow cytometric assay coupled with propidium iodide (PI) staining of necrotic cells was compared to MTT reduction assays of cell viability. The flow cytometric technique had the advantage over the MTT reduction assay of being rapid and showing both the live and dead cell levels at an individual cell level. The progression of oxLDL-induced cell death correlated with the rapid increased in intracellular ROS production in the cytosol and the mitochondria. Immunoblotting results showed that oxLDL induced NADPH oxidase (NOX) activation and increased p47phox expression. This suggests NOX as the generator of reactive oxygen species (ROS) induced by oxLDL in these cells. However, apocynin and VAS2870, the two NOX inhibitors used in this study, were unable to inhibit the ROS generation caused by the oxLDL. This suggests that either these inhibitors are unable to inhibit the targeted NOX or other sources of ROS might exist and contributed to the overall increase in oxidative flux. OxLDL caused a rapid increase in cytosolic Ca²⁺ level. This was contributed by the extracellular Ca²⁺ source as well as Ca²⁺ mobilisation from the intracellular stores such as endoplasmic reticulum (ER). OxLDL-induced intracellular Ca²⁺ increase also correlated with the increase in intracellular ROS. Nevertheless, blocking of oxLDL-induced intracellular Ca²⁺ elevation by Ca²⁺ chelator, EGTA, did not reduce intracellular ROS generation. Accordingly, this suggests that oxLDL-induced intracellular Ca²⁺ increase is not the cause for oxLDL-induced cell death. Additionally, oxLDL may also initiate a Ca²⁺-independent cell death pathway. The excess cytosolic Ca²⁺ taken up by the mitochondria may be detrimental and could result in mitochondrial Ca²⁺ overload. This will increase mitochondrial ROS production and initiate mitochondrial permeability transition (MPT) pores opening. Consequently, this could collapse the mitochondrial membrane potential ( m) due to the rupture of outer mitochondrial membrane (OMM) and resulted in cell death. Blocking of Ca²⁺ uptake into the mitochondria by ruthenium red protected cells from oxLDL-mediated cell death, possibly by reducing ROS production and preventing MPT activation. This study also demonstrated the protective effect of 7,8-dihydroneopterin (7,8-NP) on oxLDL-induced oxidative stress. 7,8-NP protected cells from oxLDL-induced intracellular ROS generation and cell viability loss. Intracellular Ca²⁺ increase was also reduced by 7,8-NP in particular after 3 hours incubation with oxLDL. The action of 7,8-NP was better than that of apocynin in protecting U937 cells from oxLDL suggests its potential ability to scavenge ROS from various sources. Studies have implicated the involvement of H₂S in various biological processes including atherosclerosis. Thus, the disruption of H₂S homeostasis may contribute to the progression of atherosclerosis. Slow releasing H₂S molecules (H₂S donors) have been developed for a controlled and stable delivery of H₂S to cells. In this study, specific H₂S donors, including one which targets the mitochondria, were found to be protective against oxLDL-induced cell death in U937, human monocytes and HMDM cells. Although the exact mechanism is yet to be elucidated, these H₂S donors were shown to block the elevation of intracellular Ca²⁺ and ROS production mediated by oxLDL. Therefore, these H₂S donors could be the potential candidates for future development of therapeutics in treating atherosclerosis.

No description available.

Mitochondria serve as the major source of reactive oxygen species (ROS) production in cells resulting in antioxidant systems and cell signaling pathways that are unique to mitochondria. Thioredoxin-2 (Trx-2) is the mitochondrial member of the thioredoxin superfamily, and acts specifically to reduce the mitochondrial peroxidase, peroxiredoxin-3. It has been proposed that Trx-2 associates with cytochrome c, which functions in mitochondrial respiration and apoptosis. Homozygous Trx-2 deletion in mice is embryonic lethal and it is hypothesized here that Trx-2 lethality is caused by loss of mitochondrial function and oxidative stress. Results of experiments investigating mitochondrial integrity, cell viability, and ROS levels in Trx-2(-/-) mouse embryonic fibroblasts (MEFs), and results from Trx-2 siRNA MEFs, are similar to findings of knockouts in previously reported proteins that function in mitochondrial respiration and support the involvement of Trx-2 in this process. Mitochondrial ROS have also been implicated as major secondary messengers in cell signaling. Results reported here using cancer cells and cancer cells depleted of mitochondrial DNA, which consequently produce few ROS, have indicated that mitochondrial ROS produced in hypoxia are necessary for HRE and ARE activation, and are fundamental in the activation of SP-1 during reoxygenation. However, mitochondrial ROS are not required for HIF-1α protein expression in hypoxia, indicating a unique relationship between HIF-1α, hypoxia, and mitochondrial ROS.

Chitin, chitosan recovered from fly crabs shells have been investigated by the elemental analysis, potentiometric titraton and FT–IR spectrometry methods. The molecular weght of chitosan was determined by measuring their viscosity. The adsorption kinetics of reactive dye and equilibrium conditions has been investigated. The adsorption of reactive dye on chitin and chitosan proceeds according to pseudo – second – order kinetic equation. Adsorption investigations under equilibrium conditions showed that. Theses results were fitted by both Langmuir and Freudlich models.

Dissolving multicomponent NAPL as a source of contamination in subsurface water is considered. In particular, two processes are analyzed with regard to how they alter inter-species concentration ratios at remote monitoring locations relative to inter-species molar ratios in the NAPL: nonlinear dissolution governed by Raoult’s Law and differential sorption during subsurface transport. An analytic solution for Raoult’s Law-governed dissolution is presented. Separately, it is shown how a variety of 1D analytic transport models for simple boundary conditions may be adapted to use arbitrary time-varying concentrations by use of some properties of Laguerre series. This is combined with the analytic solution so that Raoult’s Law-governed multicomponent NAPL dissolution may be employed as the boundary condition for analytic transport models. A new computer model implementing this technique in an environment of discrete, parallel fractures is presented, and its accuracy verified for specific conditions against an existing code. The new code is applied to a parametric study on the plume separation of PAH and phenolic compounds from the dissolution of creosote. Narrow fracture spacing as well as significant values of matrix organic carbon are seen as particularly conducive to separation of these types of plumes, which in some circumstances may be entirely disjoint. Concentration ratios downgradient are shown largely unrelated to concentration ratios at the source. Finally, a study of PCB speciation is undertaken in fractured rock with known parameters, for which a rigorous, least squares speciation approach is developed. Even at distances of 5 m from the source, given perfect information about the subsurface, it is found not possible to chemically fingerprint a source PCB mixture from a list of three absent a model of the weathering of the NAPL. Both the PCB and creosote studies demonstrate that forensic inference of source compositions from field data is unreliable and the need for coupled dissolution and transport models like the one developed here. / Thesis (Ph.D, Civil Engineering) -- Queen's University, 2012-09-25 21:43:29.04

No description available.

No description available.

Nitric oxide (NO), a free radical released by macrophages (a subset of white blood cells) as a response to infection, is noxious to organisms due to its ability to disable crucial biomolecules such as lipids, proteins and DNA. Although normally effective at eradicating invading bacteria, several pathogens have developed mechanisms to detoxify NO and its toxic by-products, reactive nitrogen species (RNS). While some of these detoxification processes have been characterized, very little is known about the metabolic changes that enable microbes to survive this deleterious environment. Investigations into the effects of RNS on microbial physiology have shown that these harmful radicals inactivate the citric acid cycle and oxidative phosphorylation, the series of reactions responsible for making energy aerobically. The central aim of this thesis was to determine how the organism counteracts the detrimental effects of RNS, while bypassing the ineffective central metabolic pathways. The findings presented herein show that P. fluorescens engineers an elaborate metabolic network to generate ATP whilst withstanding the injurious effects of nitrosative stress. Crucial to this adaptation is the ability to produce energy via substrate level phosphorylation, a necessity that arises out of the cells’ inability to produce a substantial amount of ATP using the electron transport chain (ETC). The up-regulation of the enzymes citrate lyase (CL), phosphoenolpyruvate carboxylase (PEPC) and pyruvate, phosphate dikinase (PPDK) helps the organism accomplish this feat. Blue native polyacrylamide gel electrophoresis (BN-PAGE), high performance liquid chromatography (HPLC) as well as co-immunoprecipitation (CO-IP) studies were applied to demonstrate that these proteins form a metabolon, a transient complex of enzymes that ensures citrate is converted into its desired end products, pyruvate and ATP. In order to gauge the individual contributions iv of phosphoenolpyruvate-dependent kinases, a novel in-gel activity assay was developed to probe these enzymes under disparate conditions. These results suggest that the organism switches from an ATP-dependent metabolism to one based on the utilization of pyrophosphate (PPi). The rationale for this appears to be energy efficiency, as pyrophosphate-dependent glycolysis can theoretically produce five ATP rather than the two yielded by Embden-Meyerhof glycolysis. Additionally, the up-regulation in activity of the enzymes adenylate kinase, nucleoside diphosphate kinase and acetate kinase seem to ensure that ATP generated by PPDK is properly shuttled and stored when aerobic metabolism is defective. The lower activity of inorganic pyrophosphatase likely ensures an adequate supply of pyrophosphate for the activity of PPDK. Taken together, this research reveals the critical role metabolism plays in the survival of microbes under the onslaught of NO and RNS. As several of these enzymes are absent in mammalian systems, they present themselves as novel targets for the development of new antibacterial agents. A comprehensive awareness of bacterial defense systems in response to NO may lay the groundwork to developing more effective treatments to impede microbial infections.

Background: Hypertension is a pathological increase in blood pressure that affects nearly 30% of the U.S. population and is a primary modifiable risk factor for cardiovascular disease. Despite advancements in prevention and treatment, hypertension is still one of the most common conditions around the world, and for a majority of cases the causal mechanisms remain to be fully elucidated. A growing body of literature suggests that oxidative stress status may play an etiological role in many chronic conditions, including hypertension. Specifically, a systemic overabundance of reactive oxygen species may give rise to endothelial dysfunction, increased sodium and H2O retention, and alterations in sympathetic outflow, leading to an increase in blood pressure. Purpose: The main objective of this study is to investigate the prospective association between F2-isoprostanes, a validated biomarker of oxidative status, and development of hypertension in a large, multi-centered, multi-ethnic cohort of adults aged 40-69 at baseline. Methods: This is a secondary data analysis that utilized previously collected data from the Insulin Resistance Atherosclerosis Study. 844 participants were included in the analysis. Briefly, four urinary F2-isoprostane isomers (F2-IsoP1, F2-IsoP2, F2-IsoP3, and F2-IsoP4) were quantified using liquid chromatography/ tandem mass spectrometry and adjusted for urinary creatinine levels. Hypertension was assessed at baseline and follow-up visits and defined as systolic blood pressure > 140 mm Hg and/or diastolic blood pressure > 90 mm Hg and/or currently taking antihypertensive medications. Crude associations between study population characteristics and hypertensive status were analyzed with the chi-square and Wilcoxon-rank sum tests. Crude associations between study population characteristics and F2-isoprostane levels were analyzed with Wilcoxon-rank sum, Kruskal-Wallis, and Spearman’s rank correlation measures. Finally, the adjusted prospective associations between hypertensive status and F2-isoprostane concentrations were modeled using logistic regression. Results: Of the 844 participants who were included in the study, 258 (31%) were classified as hypertensive at baseline. Among the 586 participants who were normotensive at baseline, 123 (21%) developed hypertension over the five-year study period. Importantly, none of four F2-isoprostane isomers predicted a significant increase in the odds of developing hypertension, as indicated by their odds ratio 95% confidence intervals; F2-IsoP1: (0.85, 1.31), F2-IsoP2: (0.62, 1.13), F2-IsoP3: (0.80, 1.27), and F2-IsoP4: (0.84, 1.29). Conclusion: Previous studies have investigated the association between oxidative status and hypertension prevalence, however the cross sectional nature of the study designs have made it difficult to establish temporality between exposure and outcome. To our knowledge, this is the first study to model the odds of developing hypertension as a function of F2-isoprostane levels. The results of this study suggest that oxidative status is not involved in the development of hypertension.