Unravelling the molecular mechanisms underlying mitochondrial dysfunction in metabolic diseases

Mitochondria are the powerhouses of the cell and their function is often disturbed in disease, especially in metabolic diseases, like myopathies and non-alcoholic steatohepatitis (NASH). The cause-consequence relationship herein is however poorly understood. In this thesis, molecular mechanisms are studied that underlie mitochondrial dysfunction in unexplained myopathies as well as in NASH. Moreover, experimental therapies making use of carbon monoxide-releasing molecules (CORMs) are explored to improve mitochondrial health. The effects of mitochondrial DNA (mtDNA) methylation on mitochondrial gene expression points to a layer of epigenetic regulation that may play a role in disease initiation and/or progression. In this thesis, we study the effects of mtDNA methylation in NASH and myopathy. Increase in mtDNA methylation is associated with a decrease in energy production and this sets out a possible cause for mitochondrial dysfunction. Additional work presented in this thesis shows that mitochondrial function can be improved and enhanced using compounds such as carbon monoxide (CO). As CO can potentially alleviate mitochondrial respiratory impairment and is known to promote liver regeneration, it can be used to treat chronic diseases like NASH.In conclusion, this thesis supports a role for mtDNA methylation in promoting mitochondrial dysfunction, impaired lipid metabolism and loss of ATP-generating capacity and highlights potential therapeutic interventions based on CO that may potentially attenuate the development of metabolic diseases

Accessing Freedom: Culturally Responsive Restorative Justice Practice in Schools

Restorative justice in schools is becoming an essential set of practices and strategies taken on by schools and school districts to address the disproportionate academic and social-emotional outcomes among students within individual schools and across districts. Restorative justice in schools supports building healthy and supportive relationships among students and adults that serve as the bedrock of growth and development for students, their families and practitioners. While aiming to develop and restore positive and relationships among the most vulnerable and marginalized students (and their families), educators and schools bear the heaviest burden of re-visioning how these students gain access to rigorous academic content and experiences, as well as opportunities to develop behaviorally, socially and emotionally. While restorative justice in schools offers a sturdy foundation for teachers and school leaders from which to begin this complex endeavor, this paper argues that culturally responsive practice must be an essential part of restorative justice practice in schools. The paper also offers insights from my experiences as an educator and school leader in a Massachusetts Charter School that support this assertion

Restorative Approach in Schools: Systemic Approaches to Building Positive School Climates

The release of new federal guidance for developing positive school climate and equitable discipline practices has created a window of opportunity for schools to revisit their approaches to developing the conditions for student achievement and success. (U.S. Department of Education, January 2014) Recent education leadership literature notes that many school districts’ current discipline policies do not lend themselves to more equitable access to learning opportunities and positive school experiences for many students. Recent education leadership literature suggests that restorative approaches to building positive school climate are more likely to lead to more equitable academic and social-emotional outcomes for students of color and students with special needs. This paper argues that such successes are outcomes of restorative approaches to building positive school climates that focus on the development of school connectedness and culturally responsive practice of educators. One of the greatest insights of the restorative movement in schools has been that positive climate and discipline outcomes, as well as academic achievement, will result from whole systems approaches to positive climate initiatives. Further, while recent discussion about restorative practices in schools has focused primarily on school discipline programs, developing fair and equitable school climates through the use of restorative approaches can only be accomplished by leveraging continuous improvement of whole school change efforts, as well as long-term investments in educator learning and development

Heterogeneous Nitrogen Losses: Cost-Effectiveness Analysis of Changes in Management Across South Dakota

The loss of nitrogen fertilizer into the atmosphere and waterways is of increasing concern for citizens and policy makers. This is particularly relevant for hypoxia in rivers, lakes, and oceans, but also relevant for policy makers in reducing the increasing concentration of greenhouse gases (GHG) in the atmosphere. GHGs trap heat in the atmosphere and include: carbon dioxide, methane, nitrous oxide and fluorinated gases. Overall, the estimated contribution from the agricultural sector to GHG emissions was 9% in 2013 (EPA, 2013). Further, the addition of nitrogen to the soil through the use of synthetic fertilizers is a main contributor to nitrous oxide (N20) emissions. Approximately 74% of U.S. N2O emissions were from synthetic fertilizer applications according to the EPA (2013). However, these emissions are not spatially homogenous, nor homogenous across crop production systems. The objective of this study is to begin to spatially account for the heterogeneous nitrogen losses from nitrogen fertilizer applications on South Dakota farms. This study conducts a cost-effectiveness analysis (CEA) to determine the best strategies, and areas, to reduce GHG emissions from nitrogen application in South Dakota. This form of analysis is done by spatially comparing the amount of emissions reductions per acre across the state, assuming alternative mitigation strategies and adoption rates. Using the environmental factors (climate type, soil texture, soil organic carbon, soil drainage, soil pH and crop type), and management decisions (no till, conventional till, and reduced till, crop rotations, and application timing), we assess the areas and methods in South Dakota that can be targeted for considering management changes to gain the most cost effective continuous improvement in stemming nitrogen losses. The purpose is to minimize costs from changes in management, but provide the maximum reduction in nitrogen losses. Spatial heterogeneity in GHG Emissions can vary considerably. For example, the coefficient of variation for N2O emission measurements typically range between 100 to 300% (Thornton and Valente, 1996; Snyder, C.S. et al., 2009). A switch from conventional tillage to reduced tillage and to no-till is expected to mitigate GHG emissions across all areas. However, it is important to spatially examine the heterogeneous effect on emissions reduction from mitigation efforts, given factors that contribute to heterogeneous GHG flux. This is particularly relevant in light of efforts to develop standardized metrics for determining GHG rates, and reductions from baseline, that may be used by agri-businesses and retailers for sourcing agricultural inputs. The intent of such effort is to provide an efficient method to promote food products and verifiable, sustainable marketing claims to consumers (Field to Market 2012 V2). Consequently, universally accepted management mitigation metrics may result in heterogeneous impacts to reducing emissions and costs, depending on site-specific environmental and soil factors that cannot be altered. Findings from this study will aid land grant extension personnel in targeting educational programs to areas where it is cost effective to enhance sustainable agriculture and mitigate GHG emissions from nitrogen fertilizer application. Results of the study will also inform stakeholders of the costs and trade-offs of changes in management decisions, such as timing of fertilizer application and fertilizer efficiency improvement methods (e.g. Brink et al., 2005). Management techniques, yields, and fertilizer applications data used for this study have been retrieved from USDA-ARMS data. Soil characteristics were obtained from NRCS soil data (GSSURGO), and crop rotations and locations were derived from USDA-FSA certified acres and the National Land Cover Database (NLCD). Arc-GIS software was used to combine the multiple data sets, into spatially homogenous response units. The Environmental Policy Integrated Climate (EPIC) model was used to simulate the homogenous response units to calculate all emission values. Simetar was then used to derive certainty equivalence values for changes in management and nitrogen runoff, which helped determine most effective management practices and the costs from our management control

Ecology of Water Relations in Plants

Water is an important resource for plant growth. Availability of water in the soil determines the niche, distribution and competitive interaction of plants in the environment

La Revisoría Fiscal en el sector público: una nueva forma de control fiscal

La presente reflexión se centra en la ausencia total de medidas legales que justifiquen la NO participación, dentro de las labores propias del control fiscal ejercido desde las Contralorías (General de la República, Departamentales, Distritales y Municipales) y aplicadas en las Empresas de inferencia estatal, de la legal institución de la Revisoría Fiscal. La cual “... tiene su origen y se sustenta en el modelo de control de fiscalización, puesto que lleva a cabo un examen integrado e integral de los objetos materia de su supervisión y vigilancia…” (Consejo Técnico de la Contaduría Pública,[CTCP], 2008). En el desarrollo posterior del presente artículo se observa como la sinergia existente entre el Estado y las tareas de fiscalización que se materializan en el desarrollo de la función de Control de fiscalización histórica transversalmente inherente a la institución de la Revisoría Fiscal, se ciernen en razón a que éste se entiende como “un sistema compuesto por un conjunto de procesos, estructurados de manera lógica y organizada, por medio del cual se supervisa, inspecciona, vigila y constata la ejecución idónea y secuencial de los hechos económicos en todos sus ámbitos en un determinado ente, conforme a parámetros preestablecidos” (CTCP, 2008)