24,044 research outputs found
The activation of glucose 6-phosphate dehydrogenase as a source of substrate for NADPH oxidase in the failing heart.
No full textRole of oxidative-nitrosative stress and downstream pathways in various forms of cardiomyopathy and heart failure.
No full textImpact of glucose-6-phosphate dehydrogenase deficiency on the pathophysiology of cardiovascular disease.
No full textGlucose-6-phosphate dehydrogenase (G6PD) catalyzes the rate-determining step in the pentose phosphate pathway and produces NADPH to fuel glutathione recycling. G6PD deficiency is the most common enzyme deficiency in humans and affects over 400 million people worldwide; however, its impact on cardiovascular disease is poorly understood. The glutathione pathway is paramount to antioxidant defense, and G6PD-deficient cells do not cope well with oxidative damage. Limited clinical evidence indicates that G6PD deficiency may be associated with hypertension. However, there are also data to support a protective role of G6PD deficiency in decreasing the risk of heart disease and cardiovascular-associated deaths, perhaps through a decrease in cholesterol synthesis. Studies in G6PD-deficient (G6PDX) mice are mixed and provide evidence for both protective and deleterious effects. G6PD deficiency may provide a protective effect through decreasing cholesterol synthesis, superoxide production, and reductive stress. However, recent studies indicate that G6PDX mice are moderately more susceptible to ventricular dilation in response to myocardial infarction or pressure overload-induced heart failure. Furthermore, G6PDX hearts do not recover as well as nondeficient mice when faced with ischemia-reperfusion injury, and G6PDX mice are susceptible to the development of age-associated cardiac hypertrophy. Overall, the limited available data indicate a complex interplay in which adverse effects of G6PD deficiency may outweigh potential protective effects in the face of cardiac stress. Definitive clinical studies in large populations are needed to determine the effects of G6PD deficiency on the development of cardiovascular disease and subsequent outcomes
The construction of Karen Karnak: The multi-author-function
No full textThis thesis is situated within the comparatively recent developments of Web 2.0 and the emergence of interactive WikiMedia, and explores the mode of authorship within a Read/Write culture compared to that of a Read/Only tradition. The hypothesis of this study is that the role of the audience has become merged with the author, and as such, represents new functions and attributes, distinct from a more conventional concept of authorship, in which the roles of audience and author are more separate. Read/Write and participatory culture, as defined by this study, is focused on collaboration, and includes the influences of D.I.Y. culture, Open-Source practices and the production of text by multiple authors. Multi-authorship presents a re-thinking of several concepts which support the notion of the individual author, since the focus of multi-authorship is not on attribution and ownership of a finished text, but on the continued malleability of a text. Modes of multi-authorship, demonstrated in the use of the pseudonyms Alan Smithee and Karen Eliot, represent declarative authors whose names signify multiple origins, whilst concurrently indicating a distinct body of work. The function of these names form an important context to this study, since primary research involves the construction of an experimental mode of multi-authorship utilising WikiMedia technology and the interaction of thirty nine participants, who are invited to create a body of work under the collective pseudonym Karen Karnak. The data generated by this experiment is analysed using aspects of Michel Foucault's author-function to identify and determine power structures inherent in the WikiMedia context. The interplay of power structures, including concepts such as identity, ownership and the body of work, affect the resulting mode of authorship and contribute to the construction of Karen Karnak, suggesting further areas of research into the emerging multi-author
Superoxide production by NAD(P)H oxidase and mitochondria is increased in genetically obese and hyperglycemic rat heart and aorta before the development of cardiac dysfunction. The role of glucose-6-phosphate dehydrogenase-derived NADPH.
No full textReverse changes in cardiac substrate oxidation in dogs recovering from heart failure.
No full textQanud K, Mamdani M, Pepe M, Khairallah RJ, Gravel J, Lei B, Gupte SA, Sharov VG, Sabbah HN, Stanley WC, Recchia FA. Reverse changes in cardiac substrate oxidation in dogs recovering from heart failure. Am J Physiol Heart Circ Physiol 295: H2098-H2105, 2008. First published September 26, 2008; doi: 10.1152/ajpheart.00471.2008.-When recovering from heart failure (HF), the myocardium displays a marked plasticity and can regain normal gene expression and function; however, recovery of substrate oxidation capacity has not been explored. We tested whether cardiac functional recovery is matched by normalization of energy substrate utilization during post-HF recovery. HF was induced in dogs by pacing the left ventricle (LV) at 210-240 beats/min for 4 wk. Tachycardia was discontinued, and the heart was allowed to recover. An additional group was studied in HF, and healthy dogs served as controls (n = 8/group). Cardiac free fatty acids (FFAs) and glucose oxidation were measured with [3H] oleate and [14C] glucose. At 10 days of recovery, hemodynamic parameters returned to control values; however, the contractile response to dobutamine remained depressed, LV end-diastolic volume was 28% higher than control, and the heart mass-to-body mass ratio was increased (9.8 +/- 0.4 vs. 7.5 +/- 0.2 g/kg, P < 0.05). HF increased glucose oxidation (76.8 +/- 19.7 nmol.min(-1).g(-1)) and decreased FFA oxidation (20.7 +/- 6.4 nmol.min(-1).g(-1)), compared with normal dogs (24.5 +/- 6.3 and 51.7 +/- 9.6 nmol.min(-1).g(-1), respectively), and reversed to normal values at 10 days of recovery (25.4 +/- 6.0 and 46.6 +/- 6.7 nmol.min(-1).g(-1), respectively). However, similar to HF, the recovered dogs failed to increase glucose and fatty acid uptake in response to pacing stress. The activity of myocardial citrate synthase and aconitase was significantly decreased during recovery compared with that in control dogs (58 and 27% lower, respectively, P < 0.05), indicating a persistent reduction in mitochondrial oxidative capacity. In conclusion, cardiac energy substrate utilization is normalized in the early stage of post-HF recovery at baseline, but not under stress conditions
Language Change and SA-OT: The case of sentential negation
No full textSimulated Annealing for Optimality Theory (SA-OT) updates Optimality Theory by adding a model of performance to a theory of linguistic competence. Our aim is to show that SA-OT can contribute to language change simulations. Performance "errors" are considered to be one of the causes of variation and change. We have chosen to model the evolution of sentential negation (SN). The descriptive background adopts Jespersen's Cycle, according to which the evolution of sentential negation follows three main stages (1. pre-verbal, 2. discontinuous, and 3. post-verbal). Therefore, we advance a novel model for SN, based on SA-OT. It reproduces the three pure and the two observed mixed stages, whereas it correctly predicts the lack of an intermediate stage between 3 and 1. The success of the approach corroborates the computational, performance-based approach to the data. Finally, we employ the iterated learning paradigm to reproduce historical changes in a "simulated corpus study". This enterprise turns out to be more difficult than one would naively believe.Appeared open access as: Computational Linguistics in the Netherlands Journal (CLIN), vol. 1 (2011), pp. 21-40, and is available at http://www.clinjournal.org/sites/default/files/Lopopolo.pdfA. Lopopolo and Biró, T., “Language Change and SA-OT. The case of sentential negation”, Computational Linguistics in the Netherlands Journal, vol. 1, pp. 21-40, 2011.Peer Reviewe
Stakeholder research CoVE Water SA: CoVE Water SA the umbrella for all stakeholders
No full textThe water and sanitation sector faces well-documented issues that are challenging to address, leading to the establishment of the Platform of Vocational Excellence (PoVE) Water. This platform brings together five regional Centers of Vocational Excellence (CoVE) Water in Europe and South Africa to ensure high-quality skills and competencies in the water sector. These CoVEs facilitate collaboration among stakeholders, enabling the development of vocational education and training programs to increase awareness, responsiveness to industry needs, and address sector challenges. A few months ago, CoVE Water SA was established in South Africa to achieve the previously mentioned goals. Therefore, it is important that the following research question is answered in this initial set-up phase: What actions need to be taken to enhance the effectiveness of the CoVE Water SA? To answer this research question, several important stakeholders were interviewed. Subsequently, the interviews were analysed thematically in order to extract the most important themes and quotes, PI grids were created to assess power and interest dynamics among stakeholders, and a Social Network Analysis was conducted to understand the CoVE Water SA network and potential clusters.The research findings have unveiled key aspects for enhancing the effectiveness of CoVE Water SA. The current network in the water sector has a low density, implying that many collaborations are lacking. This leads to a high degree of interdependence within the network, resulting in a non dynamic system. The lack of collaborations, such as connections with TVET colleges, schools, farmers and local communities, results in a lack of knowledge, funding and connection to the labour market. Governmental stakeholders, like DWS, EWSeta, and BGCMA, have been identified as influential players with extensive networks and important resources, Local Authorities and Research Organizations also play important roles. Universities exhibit substantial international links, making them crucial contributors. These stakeholders have the potential to provide knowledge, collaboration, and power. These are valuable insights for CoVE Water SA, fostering network growth and effectiveness in the water sector. Furthermore, six key themes have been derived from the conducted interviews, addressing the needs of stakeholders and where CoVE can make a valuable contribution. These themes include raising awareness, reducing the skills gap in the water sector, fostering international collaborations, mitigating the labour shortage in the water sector, improving education material and establishing desired collaborations. For each theme, the interviewed stakeholders have presented their views and numerous suggestions on how CoVE Water SA can assist in addressing these issues. Additionally, stakeholders have also mentioned possible failures of CoVE Water SA, which can aid in preventing any shortcomings of the platform. Furthermore, stakeholders mentioned ongoing initiatives related to the six themes, through which they can contribute to the platform. From the Thematic Analysis, PI Grids and the SNA, a set of actions have emerged that are essential for enhancing the effectiveness of CoVE Water SA. These actions revolve around expanding and enhancing the network, organising activities and contributing to educational improvement. In terms of broadening and strengthening the network, the platform should focus on enhancing the collaborations among educational groups, building stronger relations with international institutions in Europe and Africa, involving TVETs and schools within the water network, improving stakeholder involvement and encouraging the involvement of Local Communities to increase awareness and knowledge about water issues. Furthermore, CoVE Water SA should play a role in organising activities to raise awareness of Water Resource Management. Additionally, it should assist in improving curricula, supporting students’ preparation for the workforce and making the education more practical instead of only theoretical. CoVE Water SA should also provide training and learning resources as well as comprehensive courses.However, this study recognizes several limitations that should be considered in future research and when implementing recommendations for CoVE Water SA. These limitations encompass factors like a limited scope due to resource and time constraints, minimal varied interviewee responses, and potential biases in responses. Addressing these limitations will be crucial in guiding future research and actions for CoVE Water SA.CEGM3000Civil Engineerin
Interview with Erica Jolly - teacher, author and founding member of SA Social Studies Teachers Association
No full textErica is a teacher and author who was a founding member of the SA Social Studies Teachers Association (contributing to its text books) and the SA History Teachers Association. She took her Masters in English Literature at Flinders University and taught in Girls and Boys Technical Colleges for 40 years. Erica's published works include a history of vocational education in South Australia from 1897 - 2001, We Came to Marion 1955 - 1995 (1995), A Broader Vision: Voices of Vocational Education in SA (2001), Challenging the Divide: Approaches to Science and Poetry (2010), and Making a Stand (2015)
Beneficial effects of acute inhibition of the oxidative pentose phosphate pathway in the failing heart.
No full textIn vitro studies suggested that glucose metabolism through the oxidative pentose phosphate pathway (oxPPP) can paradoxically feed superoxide-generating enzymes in failing hearts. We therefore tested the hypothesis that acute inhibition of the oxPPP reduces oxidative stress and enhances function and metabolism of the failing heart, in vivo. In 10 chronically instrumented dogs, congestive heart failure (HF) was induced by high-frequency cardiac pacing. Myocardial glucose consumption was enhanced by raising arterial glycemia to levels mimicking post-prandial peaks, before and after intravenous administration of the oxPPP inhibitor 6-aminonicotinamide (80 mg/kg). Myocardial energy substrate metabolism was measured with radiolabeled glucose and oleic acid, and cardiac 8-isoprostane output was used as an index of oxidative stress. A group of 5 chronically instrumented, normal dogs served as control. In HF, raising glycemic levels from ~80 to ~170 mg/dL increased cardiac isoprostane output by approximately 2-fold, while oxPPP inhibition normalized oxidative stress and enhanced cardiac oxygen consumption, glucose oxidation and stroke work. In normal hearts glucose infusion did not induce significant changes in cardiac oxidative stress. Myocardial tissue concentration of 6P-gluconate, an intermediate metabolite of the oxPPP, was significantly reduced by approximately 50% in treated vs non-treated failing hearts, supporting the inhibitory effect of 6-aminonicotinamide. Our study indicates an important contribution of the oxPPP activity to cardiac oxidative stress in HF, which is particularly pronounced during common physiological changes such as post-prandial glycemic peaks
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