2 resultados para Interleukine-6, Multiple Sclerosis, regulatory T cells, humanized mice
em Universidad Politécnica de Madrid
Resumo:
Differences in gene expression patterns have been documented not only in Multiple Sclerosis patients versus healthy controls but also in the relapse of the disease. Recently a new gene expression modulator has been identified: the microRNA or miRNA. The aim of this work is to analyze the possible role of miRNAs in multiple sclerosis, focusing on the relapse stage. We have analyzed the expression patterns of 364 miRNAs in PBMC obtained from multiple sclerosis patients in relapse status, in remission status and healthy controls. The expression patterns of the miRNAs with significantly different expression were validated in an independent set of samples. In order to determine the effect of the miRNAs, the expression of some predicted target genes of these were studied by qPCR. Gene interaction networks were constructed in order to obtain a co-expression and multivariate view of the experimental data. The data analysis and later validation reveal that two miRNAs (hsa-miR-18b and hsa-miR-599) may be relevant at the time of relapse and that another miRNA (hsa-miR-96) may be involved in remission. The genes targeted by hsa-miR-96 are involved in immunological pathways as Interleukin signaling and in other pathways as wnt signaling. This work highlights the importance of miRNA expression in the molecular mechanisms implicated in the disease. Moreover, the proposed involvement of these small molecules in multiple sclerosis opens up a new therapeutic approach to explore and highlight some candidate biomarker targets in MS
Resumo:
El crecimiento económico ha producido mejoras en el nivel de vida de la población que muchas veces tienen efectos medioambientales negativos en el largo plazo. Ante esta problemática, surge la necesidad a nivel empresarial de enmarcarse en un modelo de desarrollo sostenible que combine los objetivos de crecimiento económico con los de protección medioambiental. Esta situación puede representar altos costes para las empresas del sector petroquímico venezolano, debido al elevado riesgo de sus operaciones y al conjunto de regulaciones legales vigentes en materia medioambiental. Por lo tanto, el objetivo de la presente investigación ha sido proponer un modelo para la gestión de costes medioambientales de dicho sector fundamentado en la ecoeficiencia. Se planteó una investigación proyectiva, desde un enfoque holístico. Se utilizó un diseño de investigación univariable, transeccional contemporáneo, de fuente mixta. Univariable, porque se enfoca en la gestión de costes medioambientales como único evento a modificar. Transeccional contemporáneo, porque el evento se estudia en la actualidad y la medición de los datos se realiza en un solo momento. De fuente mixta, porque se combinó un diseño documental con un diseño de campo. Se utilizó un diseño documental para el análisis comparativo de las normativas de registro y control de costes medioambientales propuestas por organismos internacionales, mediante la aplicación de una matriz de análisis de categorías emergentes. Para el diagnóstico de la gestión de costes medioambientales en el sector petroquímico venezolano, se utilizó un diseño de campo en las empresas del sector que operan en la región zuliana. Para ello se aplicó un cuestionario con 100 ítems en escala Likert y 6 preguntas de opción múltiple. Dicho cuestionario fue validado mediante la revisión de expertos y se determinó su confiablidad a través del coeficiente alfa de Cronbach. Los resultados muestran que los principales asuntos tratados por las normativas analizadas pueden agruparse en seis temas: alcance de la contabilidad de gestión medioambiental, clasificación, tratamiento contable, asignación, informes de costes medioambientales e indicadores de gestión. Se evidenció que las guías de aplicación de la contabilidad de gestión medioambiental abordan todos los temas identificados pero no hay uniformidad en los criterios asumidos. Por el contrario, las normativas en el ámbito de la contabilidad financiera consideran principalmente los aspectos relacionados con el tratamiento contable de los costes medioambientales y su inclusión en los estados financieros. En cuanto a la gestión de costes medioambientales que realizan las empresas del sector petroquímico venezolano, se evidenció su limitación por la escasa consideración de criterios de ecoeficiencia y la poca aplicación de herramientas de contabilidad de gestión, que dificultan la determinación y el control de costes medioambientales. Tomando como base los resultados obtenidos, se diseñó el modelo de Gestión de Costes Medioambientales Ecoeficiente (GCME). Dicho modelo plantea como deben incorporarse los criterios de ecoeficiencia y las herramientas de contabilidad de gestión medioambiental para la planificación, coordinación y control en la gestión de costes medioambientales. Se plantea que estas etapas deben desarrollarse permanentemente para asegurar la mejora continua del proceso y su adaptación a los cambios tecnológicos y a las regulaciones legales. Se hace énfasis en las directrices que deben seguir las empresas del sector petroquímico venezolano para la aplicación del modelo GCME. Sin embargo, por su generalidad y adaptación a las Normas Internacionales de Contabilidad vigentes en Venezuela, dicho modelo es aplicable a diversos sectores industriales que requieran mejorar su desempeño económico-medioambiental. ABSTRACT Economic growth has led to improvements in the standard of living of the population that often have negative environmental effects over the long term. Faced with this problem, at the enterprise-level, the need to be framed in a sustainable development model that combines the goals of economic growth with environmental protection arises. This situation may represent high costs for the Venezuelan petrochemical companies due to the high risk of their operations and to all the applicable legal regulations on environmental matters. Therefore, this research aims to propose a model for the environmental costs management of these companies based on eco-efficiency. A projective research was performed from a holistic approach. An univariate, contemporary cross-sectional and mixed source research design was used. It is univariate, because it focuses on environmental costs management as the single event to change. It is contemporary cross-sectional, because the event is currently studied and the data measurement is performed in a single moment. It relies on mixed source, because it combines a documentary design with a field design. A documentary design was used for the comparative analysis of the standards of registration and control of environmental costs proposed by international organizations, by applying an analysis matrix of emerging categories. For the diagnosis of the environmental costs management in the Venezuelan petrochemical industry, a field design was applied in the companies that operate in the Zulia region. A questionnaire with 100 items on a Likert scale and 6 multiple-choice questions was used. The questionnaire was validated by peer review and internal consistency reliability was determined using Cronbach's alpha coefficient. The results show that the main issues addressed in the analyzed regulations can be grouped into six themes: scope of environmental management accounting, classification, accounting, allocation, reporting of environmental costs and performance indicators. It was evident that implementation guides of environmental management accounting address all issues identified but there is no uniformity in the assumed criteria. Meanwhile, regulations in the financial accounting field mainly consider aspects related to the accounting treatment of environmental costs and their inclusion in the financial statements. Regarding the environmental costs management performed by Venezuelan petrochemical companies, its limitations were made evident by the low status of eco-efficiency criteria and insufficient application of management accounting tools, which hinder the identification and control of environmental costs. Based on the results, the model of eco-efficient environmental costs management (EECM) was designed. This model indicates how eco-efficiency criteria and tools of environmental management accounting for planning, coordination and control in the environmental costs management should be incorporated. It argues that these stages must be continually developed to ensure a continuous process improvement and its adaptation to technological and legal regulatory changes. The guidelines which the Venezuelan petrochemical companies should follow for the EECM model application have been emphasized. However, due to its generality and adaptation to the International Accounting Standards enforced in Venezuela, this model is applicable to various industries that require an improvement of their economic and environmental performance.