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Approximately 18 million people die of cardiovascular disease (CVD) around the world each year, making CVDs the number one cause of death in the world1. The extracellular signal-regulated protein kinase 5 (ERK5) has been found to play an essential role in cell growth and survival in heart disease, however, its role in other cell functions is still under investigation. Therefore, the objective of this study was to uncover the potential participation of ERK5 in cardiac metabolism, particularly under pathological conditions. In the setting of high-fat diet (HFD)-induced obesity, it was demonstrated that ERK5 regulates peroxisome proliferator-activated receptor gamma co-activator alpha (PGC1alpha) expression through myocyte enhancer factor 2 a (MEF2A) and MEF2D, this way maintaining mitochondrial biogenesis, fatty acid oxidation (FAO), and oxidative stress control. Mimicking HFD stress, saturated fatty acid treatment in adult rat cardiomyocytes (ARCMs) showed that the oxidative stress produced by GP91PHOX activates calpain1, which degrades ERK5. Preventing ERK5 loss by Gp91phox or Calpain- 1 inhibition preserved mitochondrial function and FAO. Similarly, restoring ERK5 expression in ERK5-deficient hearts using adeno-associated virus 9 (AAV9) prevented the development of heart failure after HFD feeding. In the context of myocardial infarction (MI), it was established that ERK5 loss leads to a dampened cardiac insulin response, increased apoptosis and accelerated cardiac dysfunction through an increased inhibition of the insulin receptor substrate 1 (IRS1) by miR128-3p. Subjecting ARCMs and human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to hypoxia, it was discovered that ERK5 regulates miR128-3p by activation of the CAMP responsive element binding protein (CREB)-CCAAT/enhancer-binding protein beta (CEBPbeta) pathway. Consistent with these observations, ERK5 restoration, CEBPbeta overexpression, or miR128-3p inhibition in ERK5-deficient mice by AAV9 injection normalized IRS1 level and cardiac function after MI. These results indicate that the ERK5-CEBPbeta pathway is essential for the prevention of insulin resistance after an ischaemic insult by protecting IRS1. ERK5 was found to be a cardioprotective regulator of lipid and glucose metabolism under stress; therefore, indicating its potential as a treatment to prevent heart failure.

This dissertation analyzes differences found in Spanish-speaking middle school and high school students in algebra-based problem solving. It identifies the accuracy differences between word problems presented in English, Spanish and numerically based problems. The study also explores accuracy differences between each subgroup of Spanish-speaking students in each category. It identifies specific strategies used by successful students when solving algebra problems. The study also sought to identify factors that could serve to predict Spanish-speaking students' ability to accurately solve algebra word problems presented in English and Spanish. A heterogeneous urban sample composed of one hundred and fifty two middle school and high school students were given an assessment composed of pre-approved algebra-based problems and a biographical information sheet. Specific students were then chosen for individual interviews in which researcher sought to gain more in depth information about student's reaction to assessment. The study found that the average accuracy rate for Hispanics non-ELL and non-Hispanic students was significantly higher for numerically based problems than Spanish word problems. Similarly, the average accuracy rate for Hispanics non-ELL and non-Hispanic students was significantly higher in English word problems that in Spanish word problems. Results showed that there was a significant difference in the overall performance of the assessment between Hispanic ELL and Hispanic non-ELL students. On one particular set, set C (Spanish word problems), findings showed that Hispanic ELL students performed better than Hispanic non-ELL students and non-Hispanic students. All other subgroup comparisons did not show a significant difference. The study found that students who were most successful in the assessment: (a) used previous linguistics knowledge and memory of previously seen mathematical problems properly; (b) highlighted the question being asked; (c) used key words to identify mathematical principles and to aid in the translation process; (d) used diagrams, tables and graphs to organize data; (e) showed work and had all processes laid out clearly; and (f) displayed a clear verification process for their answer as strategies for successfully answering the problems. As it was evident through the study, the diversity in the Spanish speaking population and their needs exposes the need for teaching methods, which are inclusive of all populations. Schools must be sensitive to the diversity in which students learn and aim to individualize the teaching for every student. As Hispanics become the largest minority in the United States, understanding the diverse needs of Spanish speaking students in the classroom will be necessary for the development of a better educated society. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]