Proyectos

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.

Analizar los procesos de enseñanza, integración curricular, evaluación y acreditación en carreras del área de salud en grado y posgrado y su relación con la trayectoria académica de los estudiantes y la actividad docente en Argentina y Chile.

Analizar los procesos de enseñanza, integración curricular, evaluación y acreditación en carreras del área de salud en grado y posgrado y su relación con la trayectoria académica de los estudiantes y la actividad docente en Argentina y Chile.

EPIGENOMIC PROGRAMMING IN THE EARLY FETAL BLOOD-BRAIN BARRIER BY GESTATIONAL HYPOXIA: CONSEQUENCES FOR THE NEURO-ENDOTHELIAL LIFESPAN.

Los tiempos actuales han facilitado nuevos medios de expresión e interacción como son las redes sociales. Estas plataformas, desde unos orígenes que bien podrían definirse como centrados en el entretenimiento, la comunicación interpersonal y la puesta en común de nuestra imagen e intereses, han pasado a convertirse en arenas de debates polarizados y nada edificantes. En este escenario, nos parece necesario preguntarnos: ¿cómo funciona la producción y circulación cross-plataforma de discursos de odio en las redes sociales chilenas en los últimos años? Para obtener una respuesta, confiamos en que una aproximación interdisciplinar emprendida por un equipo de comunicadores, lingüistas y cientistas de datos puede proporcionar una mirada más completa y compleja sobre este problema. Nuestro objetivo general es comprender el funcionamiento cross-plataforma de los discursos de odio producidos y puestos en circulación en las redes sociales en Chile a partir de las tendencias informativas más relevantes entre 2015 y 2023. Para ello requerimos: 1) caracterizar cuantitativa y cualitativamente los tipos de discursos de odio producidos y puestos en circulación en las redes sociales en Chile a partir de las tendencias informativas más relevantes entre 2015 y 2023; 2) identificar las cuentas de origen y diseminación que hacen posible tanto la producción como la circulación cross-plataforma de los tipos de discursos de odio y sus comentarios en las redes sociales en Chile, y; 3) analizar cualitativamente las estrategias lingüísticas y semióticas usadas sistemáticamente en la producción de los tipos de discursos de odio y sus comentarios. Además, y no menos importante, proponemos diseñar un kit de recursos digitales con ejemplos y recomendaciones para fomentar estrategias de formación ciudadana que ayuden a los/as usuarios/as de estas redes sociales a leer críticamente los discursos de odio y proyectar acciones para confrontarlos o neutralizarlos. Si bien esta es una acción de divulgación científica, nos parece necesario dar un pequeño paso que proyecte incluso futuras investigaciones aplicadas.

Exploring and elucidating the interplays between dissolved organic matter and microbial communities along an aquatic continuum: from the Andes to the ocean

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.

The world's transition to using cleaner energy sources to address climate change has led to a sharp rise in the demand for base and precious metals. Consequently, discovering new ore deposits to meet this growing demand and prevent supply shortages has emerged as one of the greatest challenges of the 21st century. Discovery of new magmatic-hydrothermal ore deposits can be improved based on a fundamental understanding of the geological processes that control the flux and focusing of ore-constituting elements in the Earth’s crust, and by identifying the differences between the bulk-rock and mineral chemistry of ore-forming and ordinary—barren—granitoids. Large metal anomalies in the Earth’s upper crust, such as porphyry copper-(molybdenum) deposits (PCDs), occur in intimate association with oxidized and water-rich arc magmatism in subduction zones. However, these deposits occur in restricted crustal domains and form in response to specific tectono-magmatic events, indicating that not all arc magmas have the same ore-forming potential. Understanding why only some magmas produced large PCDs while most other arc magmas remain barren is a fundamental scientific question and key to developing efficient exploration strategies. The volatile element composition of arc magmas, including water, sulfur, and halogens such as chlorine and fluorine, as well as their oxygen fugacity, exert a critical control on their ore-forming potential (i.e., ore fertility). These components are not only key to the complexation and transport of ore metals during hydrothermal activity, but also influence the amount of ore metals transported by magmas and the efficiency to which they are transferred from magmas to exsolved fluids. Magmatic differentiation in lower crustal hot zones beneath thick crustal regions is expected to enhance the volatile element budget and oxygen fugacity of evolving magmas that are discharged to the upper crust. This occurs due to the accumulation of incompatible volatile elements during successive cycles of recharge by mafic magmas and crystallization, facilitated by the deeper and hotter conditions beneath thicker arc crusts. As such, an increasingly recognized hypothesis holds that ore-forming magmas display a particularly increased budget of volatile elements and higher oxygen fugacities when compared to barren arc magmas, and that this is largely influenced by the arc crust thickness. The proposed work will test this hypothesis by focusing on the Miocene to Mio-Pliocene magmatism and associated world-class PCD mineralization in the Andes of central Chile. From the Early Miocene to the Mio-Pliocene, the arc segment located between latitudes ~33–34.5° S in the Andes of central Chile has seen a continued increase in crustal thickness and has evolved from being barren in the Early Miocene to producing some of the largest PCDs of the world in the Mio-Pliocene, such as El Teniente and Rio Blanco-Los Bronces. This geological scenario and the spatial and age distribution of the associated outcropping intrusive rocks offer a unique opportunity to investigate the temporal evolution of the volatile composition of magmas and its consequences for ore fertility. The goal of this proposal is to examine, adopting a regional scale perspective, the evolution in the volatile composition and oxygen fugacity of magmas produced in this arc segment and its relationship to magmatic ore fertility, as well as how this may have been influenced by changes in crustal thickness. To achieve this, I will sample an extensive suite of granitoids that represent a continuum from Early Miocene to Mio-Pliocene magmas, including porphyry-forming intrusions. By combining zircon petrochronology, apatite, biotite, and amphibole mineral chemistry, in conjunction with the bulk-rock composition of intermediate to felsic intrusive rocks, I will be able to constrain relative changes in the hydration state, sulfur contents, halogen and oxygen fugacities, as well as in their associated crustal thickness during the evolution of the selected arc segment. This will be done by implementing a combination of cutting-edge analytical techniques, including synchrotron-based sulfur X-ray absorption near edge structure spectroscopy, electron probe microanalysis, (laser ablation) inductively coupled plasma mass spectrometry, and X-ray fluorescence spectrometry. I aim at (1) testing the differences in the volatile composition of barren and ore-forming intrusive rocks; (2) determining whether there is a gradual change in the volatile systematics of magmas during the evolution of the studied arc segment; and (3) analyzing the relationship between variations in crustal thickness and the volatile composition of associated magmas. The results of this proposal will lead to a better understanding of the magmatic controls underpinning the formation of giant PCDs and will provide valuable insights into identifying the differences between the bulk-rock and mineral chemistry of ore-forming and barren granitoids as tools for vectoring mineralized regions.

Proyecto de investigación que apunta al estudio de practicas sostenibles para el manejo de sistemas silvopastoril en el secano costero. El proyecto involucra el estudio de la materia orgánica del suelo, además de una serie de variables que pueden impactar el manejo de los agroecosistemas