Proyectos

Proyecto FIV. Facultad de Ciencias Veterinarias y Pecuarias. Universidad de Chile. Investigador Responsable

Proyecto U-Inicia. Universidad de Chile. Investigador Responsable

Asthma is a chronic disease that affects young children starting mostly in the first years of life; with a high prevalence across countries globally. In Santiago, Chile, the prevalence of asthma among children 6-7 and 13-14 years of age is 11% and 15%, respectively; and for recurrent wheezing during the first year of life is as high as 22%. Asthma is the fourth most common cause of disability-adjusted life years for children aged 10–14 yrs and an important cause of reduced quality of life and exercise tolerance, higher rates of school absenteeism and hospitalization. A recent study done in Santiago reports that 30.4% of all infants visits to the emergency department presented with wheezing and wheezing exacerbations accounted for 8.4% hospital admission. Treatment of asthma currently focuses in reducing symptoms; however the morbidity remains high due to limited curative options and the unresolved etiology of asthma. There are no well-established methods or diagnostic tools to indentify the risk to develop asthma, and the current accepted practice base the diagnosis on parental or self-reported symptoms. One of the most accepted tools to predict asthma early in the infancy was developed by our team (the Asthma Predictive Index); and has been incorporated in most asthma early diagnosis guidelines globally. However, there is growing evidence supporting that beside genetic inheritance, maternal health during gestation represents an important factor conditioning the risk of asthma in the offspring. Thus a better understanding of pathogenesis of asthma in the neonatal period throughout uncovering the mechanisms that explain the associations between fetal life cues with asthma would contribute to an early prevention and treatment. Immune function plays a central role in the development of asthma, but the relative contribution of different immune cell types (i.e. mast cells, eosinophils, lymphocytes, neutrophils and monocytes/macrophages) to this disease is still under examination. Nonetheless, it is clear that asthma presents an altered expression of pro-inflammatory molecules (IL-12, TNF-α) and anti-inflammatory mediators (IL-10, IL-4). Notably, modulation of M1-M2 polarization of monocytes and macrophages seems to be crucial for the development of altered immune response in asthma, and this process would be tightly regulated by epigenetic mechanisms (i.e. DNA methylation, histone modifications). Numerous clinical and epidemiological studies have underlined the detrimental or beneficial role of nutritional factors in complex inflammation-related disorders such as allergy and asthma. It is now progressively better established that most of this risk is influenced in the very early stages of development, by a process of “early life programming” in which epigenetic mechanisms will actively participates. Remarkably, maternal obesity during gestation associates with increased plasma levels of TNF-α at birth, and a 4-fold increased risk of asthma in the offspring. Also growing data show that epigenetic mechanisms exert an important control on the altered immune function observed in autoimmune and inflammatory controlling the expression of key genes. However, whether maternal obesity during pregnancy influences the immune function and the risk of asthma in the offspring throughout epigenetic mechanisms has not been addressed. In this context we propose that “Maternal obesity during pregnancy increases the risk of developing asthma in the offspring by an epigenetic-mediated programming of the inflammatory response in monocytes. This programmed inflammatory response is characterized by a higher expression of pro-inflammatory molecules (IL-12, TNF-α) along with a lower expression of anti-inflammatory mediators (IL-10, IL-4Rα) which occurs due to changes in the methylation status of the promoter regions of these immune response- key genes”. Studying a cohort of 400 children (0–3 years old) born from mother with or without obesity during pregnancy this proposal will address whether: a) the increased risk of asthma in children born from obese mother can be observed at 3 years of life; b) the increased asthma risk in these children associates with an altered immune reactivity in monocytes at birth; and c) the altered immune reactivity in monocytes occurs along with changes in the DNA methylation status at the promoter regions of asthma-related genes. This study would reveal new molecular markers contributing to early diagnosis of asthma during childhood, as well as establish the real effects of epigenetic mechanisms modeling the immune function and responses at long term.

Creación de Metodologías de enseñanza basadas en juegos numéricos

Se reconoce que el rasgo común a la monografía en las carreras de humanidades es que introduce a los estudiantes en la escritura de investigación. Sin embargo, la distinción entre configuraciones del género responde a rasgos sociodiscursivos que pueden ligarse a las culturas disciplinares en las que se inscribe. En este sentido, los estudios exploratorios sugieren que las monografías de la carrera de Historia parecen tener como objetivo general la puesta en relación de fuentes bibliográficas brindadas al estudiante; las monografías de Filosofía suelen centrarse en un análisis textual propio del estudiante con pocas referencias al estado de la cuestión o a las lagunas en el conocimiento sobre el tema; mientras que las monografías de Educación y de Letras seguirían más de cerca el modelo de creación de nicho de los artículos de investigación (Swales, 1990, 2004) que consiste en el aporte de conocimiento nuevo a partir del relevo bibliográfico, la identificación de problemas y la presentación de hipótesis y hallazgos. Este proyecto de investigación busca hacer aportes al conocimiento de los géneros académicos de formación en español, generar insumos para la elaboración de materiales didácticos para la alfabetización avanzada a lo largo del grado en carreras de humanidades y colaborar con la discusión sobre la reforma de los planes de estudios en la Facultad de Filosofía y Letras en relación con la formación en prácticas de lectura y escritura académicas a lo largo del grado. Para cometer este propósito se construye un corpus digital con monografías correspondientes a las carreras de Educación, Filosofía, Historia y Letras de la Facultad de Filosofía y Letras (UBA) con el objeto de i) brindar una descripción de la monografía tanto en sus rasgos comunes a las carreras como en sus rasgos específicos disciplinarmente a partir de dimensiones discursivas relevantes y ii) establecer relaciones bidireccionales entre las diferentes manifestaciones del género y las diferentes culturas disciplinares en las que se inscribe.