Título: “Efecto del aceite de quinoa (Chenopodium quinoa) en la activación de NF-κB y Nrf2 y en los niveles de TNF-α y HO-1 inducidos por lipopolisacárido en hepatocitos humanos HepG2”.

The proposal focuses on understanding the neuro-vascular aging mechanisms associated with alterations in fetal growth by intrauterine hypoxia using molecular biology and physiology as an area.
The aim of the study is to demonstrate that impaired fetal growth conditions are associated with epigenetic programming of aging-related DNA methylation, chromatin remodeling, and miRNA-omic profile of junctional complex genes in the neuroendothelium, which can alter BBB integrity and permeability, increasing cerebral damage which impacts the juvenile and adulthood neurocognitive function.

Retinal vascular diseases are major causes of vision loss in the United States and around the world. To better treat these disorders, we need to understand the signaling pathways that control the growth and integrity of retinal blood vessels. Our recent publications and preliminary data detail a novel angiogenic signaling system centered around heme, a co-factor critical for oxygen transport, metabolism, and gene transcription. We found that heme promotes angiogenic growth in the retina by regulating tip/stalk selection, and that reduced heme production or import leads to reduced retinal vascularization and tissue hypoxia, similar to other retinal vasculopathies including retinopathy of prematurity, choroidal neovascularization, and the rare but important exudative vitreoretinopathies. Furthermore, we found that VEGF suppresses, while Norrin-bCatenin promotes, the expression of the obligate endothelial heme importer, Flvcr2. Based on these data, we hypothesize that heme, is involved in retinal angiogenesis and retinal vasculopathies. The Specific Aims of this proposal are to (1) determine how heme intersects with Notch signaling to control angiogenic tip/stalk selection, (2) characterize the role for Flvcr2/heme in VEGF-induced angiogenic proliferation and neo-vascularization, and (3) determine whether induction of Flvcr2/heme signaling is sufficient and necessary to reverse the vascular defects and downstream vision changes observed in mouse models of exudative vitreoretinopathy. To accomplish these aims, we developed new tools to directly manipulate heme in cultured retinal endothelial cells and assess heme transport and intracellular trafficking in vitro. We also generated new conditional knock-in and knock-out alleles to manipulate endothelial heme transport in vivo. Our studies will fundamentally impact our understanding of how endothelial heme levels are controlled, and the role of heme in retinal angiogenesis and vascular disease.

The brain is an energy intensive organ that requires a robust supply of nutrients and oxygen. The vasculature irrigating the brain is a huge and complex network of blood vessels fulfilling this requirement, while also protecting the neural tissue from blood-borne toxic substances. This regulated nutrient supply is accomplished by the formation of a highly selective molecular barrier, termed the blood-brain barrier (BBB). Dysfunction of the BBB or malformations of the vascular network are associated with pathological conditions that impair brain function, and can lead to death. Thus, appropriate morphogenesis and establishment of the brain vasculature is necessary for a healthy life.
The brain vasculature forms during intrauterine development, matching brain growth in this same period. Anatomically, blood vessels grow first surrounding the brain primordium and then penetrate the parenchyma until they vascularize the periventricular zone. The molecular regulation of this patterned growth is not completely understood. Several signaling pathways are known to be involved in brain angiogenesis, including WNT, TGF-β, Hh, and NOTCH, which differentially regulate vascular growth. Recently, cholesterol has been shown to modulate angiogenic growth in other vascular beds by regulating the activity of the NOTCH pathway, suggesting that cholesterol levels could influence developmental angiogenesis in the brain. Interestingly, cholesterol is also required for signal transduction of the Hh pathway. In preliminary in vitro experiments, we have observed that brain endothelial cells activate an angiogenic program after cholesterol depletion. Here, we will extend those studies to in vivo models to determine the role of cholesterol in developmental brain angiogenesis. We propose that an increase in vascular cell cholesterol activates NOTCH and attenuates Hh signaling pathways, restricting sprouting angiogenesis and blood-brain barrier formation in mouse embryo brain vasculature.
To test this hypothesis, we will study mouse embryos with altered cholesterol levels by dietary, pharmacological, and genetic manipulations. We expect these manipulations to induce a reduction or an increase in cholesterol levels in the brain vasculature during embryonic development, which we will evaluate by measuring cholesterol content in isolated vascular fragments.
In all these models, we will (Specific aim 1) study vascularization in the brain during intrauterine development using immunofluorescence with specific antibodies against endothelium proteins. In addition, we will measure the levels of transcript and proteins of general key regulators of angiogenesis in isolated vascular fragments, using qPCR and Western blot. We will (Specific aim 2) also evaluate the state of the BBB in the brain vasculature of these models at a fetal stage when the barrier is already formed and functional. For this, we will use immunofluorescence to detect the presence of marker proteins of the BBB in vascular fragments, and we will measure their levels by Western blot. Further, we will test the functionality of the barrier by injecting a fluorescent tracer and evaluating its extravasation in the brain. Finally, we will (Specific aim 3) determine the activation of the NOTCH and Hh pathways in the brain vasculature of the models at the stage of maximal angiogenesis. We will use qPCR and Western blot to measure the levels of marker genes and proteins for these two pathways in vascular fragments, and Proximity Ligation In Situ Hybridization in tissue sections to evaluate the transcript levels of those markers in situ.
We expect that the different models of dietary, pharmacological, and genetic interventions will increase or reduce cholesterol levels in the brain vasculature. These changes are expected to correlate with opposing effects on angiogenesis in the brain during development (i.e. low cholesterol will increase angiogenesis, while high cholesterol will inhibit it). In the same way, we expect that distinct cholesterol levels will have opposing effects on the integrity of the BBB. These changes in angiogenesis and BBB function are expected to be associated with concomitant disruption of the NOTCH and Hh pathways.
In summary, in this proposal we aim to cover a knowledge gap regarding the role of cholesterol in the regulation of developmental angiogenesis in the brain. These experiments may uncover new mechanisms driving vascular growth and barrier establishment in the brain, which could lead to new strategies for the prevention and treatment of pathologies involving the brain vasculature.

Predictores socioeconómicos y psicobiológicos del desempeño académico en estudiantes
de primer año de pedagogía de la UOH (Programa de Formación Inicial Docente)

Clásicamente se ha descrito que el rendimiento durante la enseñanza media de los estudiantes en Chile
a través del NEM y sus resultados en las pruebas de ingreso a la universidad, además un factor
determinando son las condiciones socioeconómicas, que resultan ser un factor predictivo de
rendimiento académico durante los primeros años de educación universitaria. Paralelamente, se ha
constatado que los estudiantes a lo largo del primer semestre en la universidad sufren un deterioro en
su calidad del sueño y en los hábitos alimenticios, todo relacionado con un aumento de sus niveles de
estrés. Por otro lado, hipotetizamos una asociación de estos indicadores con el desempeño en pruebas
de memoria de trabajo, y pueden ser elementos predictivos que determinen el desempeño académico.
Nuestra investigación tiene por objetivo estudiar ciertos indicadores de higiene, tales como sueño,
estrés y alimentación, con el fin de predecir su importancia en la predicción del desempeño
académico. Contemplamos el uso de datos anonimizados en acuerdo con lo que establezca el comité
de ética institucional. En el caso específico de estudiantes de educación básica y educación especial,
determinar los principales factores que afectan el rendimiento académico, es una herramienta útil que
creemos permitirá modificar ciertos modelos con el fin de mejorar los procesos de enseñanza –
aprendizaje. Este estudio se enmarca en un proyecto de Fortalecimiento a la formación Inicial
Docente el cual apoyará con los fondos necesarios para el buen desarrollo de esta investigación. La
contribución institucional de la UOH se limita a autorizar la participación voluntaria de sus
estudiantes, que se formalizará a través de la firma del consentimiento informado por cada uno de los
estudiantes de forma voluntaria sin mediar recompensa ni perjuicio fruto de su decisión de colaborar
en el estudio. A los estudiantes de pedagogía que voluntariamente decidan participar, se les aplicará,
al inicio y al final del presente semestre académico, una encuesta online que evaluará diferentes
marcadores de estrés y mediante el uso de una aplicación, se recopilará información aleatorizada de
sus hábitos de alimentación y de descanso. Estos datos serán analizados considerando elementos de
rendimiento en la educación media y marcadores socioeconómicos. Junto con esto, al finalizar el
semestre, siempre con el consentimiento de cada participante, se solicitará al docente responsable del
curso las calificaciones y nota final de todos ellos. Estos datos serán analizados cuantitativamente y de
forma anonimizada. Finalmente se evaluarán todos los marcadores obtenidos, realizando un análisis
cuantitativo y cualitativo, combinando métodos univariados y multivariados para evaluar estos de
manera exploratoria e inferencial. Posteriormente proponemos dar punto final al estudio realizando un
análisis profundo del efecto de los diferentes componentes a través de la técnica de PCA.

Mecanismos de modulación eferente auditiva en un modelo de atención selectiva en ratones genéticamente modificados y en chinchillas: Se realizo medición de funcionamiento eferente auditivo en modelos modificados genéticamente y bajo inhibición farmacológica. Se evaluó en una prueba conductual los resultados.

EFECTO DE LA OBESIDAD INDUCIDA POR EL CONSUMO DE UNA DIETA ALTA EN GRASAS SOBRE LA ACTIVACIÓN DEL INFLAMASOMA NLRP3 EN LA CÓCLEA Y LA FUNCIÓN DEL SISTEMA AUDITIVO

Consolidar y fortalecer una nueva red de nodos de innovación social que promueva la inclusión socio laboral en personas con alguna discapacidad, personas mayores, mujeres y personas en situación de vulnerabilidad enfocada en los sectores económicos priorizados en la Estrategia de Desarrollo Regional 2011-2020 (EDRE) y de innovación, priorizando el sector turístico, y agroalimentario y la puesta en valor de la identidad cultural.