18 research outputs found
The mitochondrial T1095C mutation increases gentamicin-mediated apoptosis
No full textAbstract not availableHakan Muyderman, Neil R. Sims, Masashi Tanaka, Noriyuki Fuku, Ravinarayan Raghupathi, Dominic Thyagaraja
RCAN1 regulates mitochondrial function and increases susceptibility to oxidative stress in mammalian cells
No full textPublished 9 June 2014Mitochondria are the primary site of cellular energy generation and reactive oxygen species (ROS) accumulation. Elevated ROS levels are detrimental to normal cell function and have been linked to the pathogenesis of neurodegenerative disorders such as Down's syndrome (DS) and Alzheimer's disease (AD). RCAN1 is abundantly expressed in the brain and overexpressed in brain of DS and AD patients. Data from nonmammalian species indicates that increased RCAN1 expression results in altered mitochondrial function and that RCAN1 may itself regulate neuronal ROS production. In this study, we have utilized mice overexpressing RCAN1 (RCAN1(ox)) and demonstrate an increased susceptibility of neurons from these mice to oxidative stress. Mitochondria from these mice are more numerous and smaller, indicative of mitochondrial dysfunction, and mitochondrial membrane potential is altered under conditions of oxidative stress. We also generated a PC12 cell line overexpressing RCAN1 (PC12(RCAN1)). Similar to RCAN1(ox) neurons, PC12(RCAN1) cells have an increased susceptibility to oxidative stress and produce more mitochondrial ROS. This study demonstrates that increasing RCAN1 expression alters mitochondrial function and increases the susceptibility of neurons to oxidative stress in mammalian cells. These findings further contribute to our understanding of RCAN1 and its potential role in the pathogenesis of neurodegenerative disorders such as AD and DS.Heshan Peiris, Daphne Dubach, Claire F. Jessup, Petra Unterweger, Ravinarayan Raghupathi, Hakan Muyderman, Mark P. Zanin, Kimberly Mackenzie, Melanie A. Pritchard, and Damien J. Keatin
Increased expression of the glucose-responsive gene, RCAN1, causes hypoinsulinemia, Beta-cell dysfunction, and diabetes
No full textData source: Supplementary data, https://doi.org/10.1210/en.2011-2149RCAN1 is a chromosome 21 gene that controls secretion in endocrine cells, regulates mitochondrial function, and is sensitive to oxidative stress. Regulator of calcineurin 1 (RCAN1) is also an endogenous inhibitor of the protein phosphatase calcineurin, the inhibition of which leads to hypoinsulinemia and diabetes in humans and mice. However, the presence or the role of RCAN1 in insulin-secreting β-cells and its potential role in the pathogenesis of diabetes is unknown. Hence, the aim of this study is to investigate the presence of RCAN1 in β-cells and identify its role in β-cell function. RCAN1 is expressed in mouse islets and in the cytosol of pancreatic β-cells. We find RCAN1 is a glucose-responsive gene with a 1.5-fold increase in expression observed in pancreatic islets in response to chronic hyperglycemia. The overexpression of the human RCAN1.1 isoform in mice under the regulation of its endogenous promoter causes diabetes, age-associated hyperglycemia, reduced glucose tolerance, hypoinsulinemia, loss of β-cells, reduced β-cell insulin secretion, aberrant mitochondrial reactive oxygen species production, and the down-regulation of key β-cell genes. Our data therefore identifies a novel molecular link between the overexpression of RCAN1 and β-cell dysfunction. The glucose-responsive nature of RCAN1 provides a potential mechanism of action associated with the β-cell dysfunction observed in diabetes.Heshan Peiris, Ravinarayan Raghupathi, Claire F. Jessup, Mark P. Zanin, Daisy Mohanasundaram, Kimberly D. Mackenzie, Tim Chataway, Jennifer N. Clarke, John Brealey, P. Toby Coates, Melanie A. Pritchard and Damien J. Keatin
Identification of unique release kinetics of serotonin from guinea-pig and human enterochromaffin cells
No full textThis is the accepted version of the following article: [Raghupathi, R., Duffield, M. D., Zelkas, L., Meedeniya, A., Brookes, S. J. H., Sia, T. C., Wattchow, D. A., Spencer, N. J. and Keating, D. J. (2013), Identification of unique release kinetics of serotonin from guinea-pig and human enterochromaffin cells. The Journal of Physiology, 591: 5959–5975. doi: 10.1113/jphysiol.2013.259796], which has been published in final form at [http://dx.doi.org/10.1113/jphysiol.2013.259796]. In addition, authors may also transmit, print and share copies with colleagues, provided that there is no systematic distribution of the submitted version, e.g. posting on a listserve, network or automated delivery
Carbon-fiber amperometry in the study of exocytosis
No full textPermission to archive book chapters in an institutional repository is not permitted by the publisher, Springer.Our laboratory has utilized a non-invasive method of measuring the release of oxidizable molecules from cells, known as carbon-fiber amperometry.Australian Research Counci
The Intellectual Structure of Health and Medical Informatics
No full textThis paper presents the results of an author co-citation analysis of the health and medical informatics discipline. It updates a smaller study that focused on health information systems. Drawing on such sub-fields as bio informatics, clinical decision support systems, computational genomics, e-health, health informatics, and others, this body of knowledge defines the core internal structure of the discipline and delineates its sub-fields. An author co-citation analysis was performed for a nine-year period using the members of editorial boards of several medical informatics-related journals as an initial author sample (N = 272). Several multivariate analyses, including cluster analysis, factor analysis and multidimensional scaling, were performed. The authors results confirm that several established sub-fields still stand but a number of new sub-fields are emerging. Future research can build on this work and examine other journals and additional authors to gain insights into the collaborative and interdisciplinary nature of the health and medical informatics discipline.</p
Conservation of nature : a perspective from the Bhagavadgita
No full textThis thesis was scanned from the print manuscript for digital preservation and is copyright the author.
Researchers can access this thesis by asking their local university, institution or public library to
make a request on their behalf. Monash staff and postgraduate students can use the link in the References field
The relation between big data and informational privacy in the context of the healthcare
No full textBig data is a broad term that is related to the collection, storage and analysis of large volumes of data. The term big data is often associated with the popular 3V’s model, which defined that data is growing significantly in the characteristics volume, variety and velocity. In this research we defined big data as: the collection, storage and transformation of structured and unstructured data from multiple sources into useful information (or knowledge) to improve decision-making within organizations. The significant growth of data is also occurring in the health care sector. A lot of these scattered data sources, possessing large volumes of personal health data of patients, are present in the health care. Big data have shown potential to support health care, by combining and transforming health data. Big data can be used to support medical and healthcare functions, including among others clinical decision support, disease surveillance, and population health (Raghupathi & Raghupathi, 2014). The increasing availability of large data sets from various sources in combination with the development of more advanced analytical tools for big data makes it more and more difficult to ensure privacy. Big data in its current form is still relatively new, and the knowledge on the implications on the security and privacy issues that it brings is still limited. This study explores the relation between big data and privacy in the health care. The research objective of this study is to gather knowledge on how big data affects privacy in the health care. In order to reach this objective, semi-structured interviews have been conducted with eight experts in either big data, health care or privacy in the Netherlands. In this research, a conceptual model of privacy has been created based on existing theories of privacy (e.g. nonintrusion theory, seclusion theory, control theory and restricted access theory). The conceptual model of privacy defines privacy in the elements: natural privacy, normative privacy, control aspect of privacy and the condition of privacy and has been used as a structure to analyze the relation between big data and privacy.Management of TechnologyICTTechnology, Policy and Managemen
Variáveis associadas ao desempenho cognitivo tardio de pacientes com traumatismo crânio-encefálico grave
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde. Programa de Pós-Graduação em Ciências MédicasObjetivos: O trauma cranioencefalico (TCE) e uma das principais causas de mortalidade e morbidade. Ha raros estudos prospectivos que investigam a associacao de variaveis clinicas e laboratoriais da fase aguda do TCE e o prognostico cognitivo tardio dos pacientes vitimas de TCE. Este estudo tem como objetivo identificar variaveis clinicas, laboratoriais e biomarcadores de lesao tecidual associados ao prognostico cognitivo em pacientes vitimas de TCE. Metodos: Foram coletadas prospectivamente as variaveis da internacao hospitalar de 234 pacientes consecutivos com TCE grave (GCS admissao . 8). Dos 172 sobreviventes, uma amostra representada de 46 pacientes realizaram avaliacao cognitiva (composta de 15 testes neuropsicologicos) em media 3 (+ - 1,8) anos apos a hospitalizacao. Um sub-grupo de 22 pacientes que foram avaliados cognitivamente realizaram analise dos niveis plasmaticos de TBARS (indicativo de dano por estresse oxidativo a lipideos) e Carbonil (indicador de dano por estresse oxidativo a proteinas) em amostras de sangue coletadas na fase aguda de TCE (mediana de 10, 30 e 70 horas apos o impacto do TCE). Um grupo controle (n=23) pareado por sexo, idade e nivel socio-educacional foi avaliado cognitivamente para comparacao com os pacientes. Resultados: A media de idade dos pacientes foi 34 (+ - 13) anos sendo 85% do sexo masculino, com escolaridade media de 9 (+ - 4,7) anos. Os pacientes apresentaram um desempenho inferior em todos os testes neuropsicologicos. A analise por regressao linear evidenciou uma forte associacao independente (R coeficiente = 0,6 a 0,8) entre maior escolaridade e menor idade e o desempenho cognitivo em 14 dos 15 testes neuropsicologicos avaliados. O desempenho nos testes cognitivos nao esteve associado ao genero, escore de admissao na Escala de Coma de Glasgow (ECG), exame das pupilas, presenca de trauma em outros orgaos, e classificacao da escala de Marshall na tomografia computadorizada na admissao (TC). Niveis elevados de glicose e presenca de hemorragia sub-aracnoide na TC mostraram-se independentemente associados a um menor desempenho no teste de Retencao de Aprendizagem de Rey e de Memoria Logica respectivamente. Embora os niveis plasmaticos de TBARS e Carbonil tenham sido significativamente elevados na fase aguda do TCE, estes biomarcadores nao se mostraram associados ao desempenho cognitivo dos pacientes. Conclusoes: Baixa escolaridade e idade mais avancada sao preditores independentes de pior desempenho cognitivo tardio apos o TCE grave. O exame de TC e glicemia mostraram limitada capacidade de predicao do desempenho cognitivo enquanto que o exame das pupilas, ECG na admissao, presenca de trauma associado nao foram preditores do desempenho em nenhum dos testes neuropsicologicos avaliados. A medida dos niveis plasmaticos de TBARS e Carbonil tambem nao se mostrou associada com o desempenho cognitivo dos pacientes. A identificacao de variaveis clinicas e laboratoriais associadas ao prognostico cognitivo apos o TCE grave permanece um desafio para a area de neuropsicologia clinica
