Increasing the versatility of an ex vivo model in nanosafety studies and fibrosis

Nanomaterials are materials in the size range of 1-100 nm, although their classifcation remains still debated in the field. Despite their small size, nanotechnology applications are many and their number is continuously growing in the industry sector as well as in the biomedical field. Nanomedicine field combines chemical and mechanical properties of nanomaterials to prepare e.g. new drugs that may reach the intended target with higher efficiency than standard drugs. However, nanomaterials are everywhere and humans can be exposed to them via external (air, water, food, etc.) and/or internal sources, therefore exposed to them also unintentionally. For this reason it is pivotal to investigate their potential toxicity in cells and organism. Nanosafety, it is the discipline that studies the potential hazards of nanomaterials and their interference with biological systems. One of the major problem in this field, it is to find reliable advanced in vitro models. In this thesis, Precision-Cut Tissue Slices, 3D model, derived from mice, rat and importantly human are explored as alternative to in vivo and in vitro models to study nanoparticles behavior and potential toxicity ex vivo using real pieces of liver, lung and kidney. Tissue slices have the great advantage to maintain intact the cell ratio and architecture of the organ from where they are extracted. Briefly, we demonstrate that it is possible to reproduce ex vivo key features of in vivo biodistribution, e.g. nanoparticles are preferentially accumulated in macrophages. Furthermore, this ex vivo model has been used in the second part of the thesis to study the expression of Vanin 1 protein, in fibrosis

IGF-I Receptor-induced Cell-Cell Adhesion of MCF-7 Breast Cancer Cells Requires the Expression of Junction Protein ZO-1

Hyperactivation of the insulin-like growth factor I receptor (IGF-IR) contributes to primary breast cancer development, but the role of the IGF-IR in tumor metastasis is unclear. Here we studied the effects of the IGF-IR on intercellular connections mediated by the major epithelial adhesion protein, E-cadherin (E-cad). We found that IGF-IR overexpression markedly stimulated aggregation in E-cad-positive MCF-7 breast cancer cells, but not in E-cad-negative MDA-MB-231 cells. However, when the IGF-IR and E-cad were co-expressed in MDA-MB-231 cells, cell-cell adhesion was substantially increased. The IGF-IR-dependent cell-cell adhesion of MCF-7 cells was not related to altered expression of E-cad or alpha-, beta-, or gamma-catenins but coincided with the up-regulation of another element of the E-cad complex, zonula occludens-1 (ZO-1). ZO-1 expression (mRNA and protein) was induced by IGF-I and was blocked in MCF-7 cells with a tyrosine kinase-defective IGF-IR mutant. By co-immunoprecipitation, we found that ZO-1 associates with the E-cad complex and the IGF-IR. High levels of ZO-1 coincided with an increased IGF-IR/alpha-catenin/ZO-1-binding and improved ZO-1/actin association, whereas down-regulation of ZO-1 by the expression of an anti-ZO-1 RNA inhibited IGF-IR-dependent cell-cell adhesion. The results suggested that one of the mechanisms by which the activated IGF-IR regulates E-cad-mediated cell-cell adhesion is overexpression of ZO-1 and the resulting stronger connections between the E-cad complex and the actin cytoskeleton. We hypothesize that in E-cad-positive cells, the IGF-IR may produce antimetastatic effects

“En los márgenes”: Curanderas y adivinas. Una aproximación historiográfica a través de la literatura dramática y las artes visuales (Argentina, 1880-1940)

El análisis de un centenar de obras teatrales argentinas del período 1880-1950 me ha permitido indagar en personajes femeninos “marginales” insertos en el ámbito laboral. El abordaje propuesto tomará como punto de partida el examen exhaustivo de dichas obras, con un método histórico elaborado por la propia autora, y algunas notas sobre su relación con obras artísticas del momento, específicamente pinturas custodiadas por el Museo Nacional de Bellas Artes (Buenos Aires, Argentina). Mi atención se centrará en las curanderas y en las adivinas, trabajadoras sin residencia fija y/o con un pasado “dudoso”. Desde el punto de vista histórico, se advertirá la relación entre las percepciones artísticas y el proyecto modernizador impulsado políticamente a partir de la generación del ochenta. Dicho vínculo será especialmente visible con respecto a las curanderas, asociadas con prácticas tradicionales de la medicina que era necesario desterrar, y se advertirá tácitamente en la marginación social hacia las adivinas

Spectroscopic Evidence of Work Function Alterations Due to Photoswitchable Monolayers on Gold Surfaces

Taking advantage of surfaces’ response to interfacial dipoles, a class of photochromophores (dihydroindolizine) is demonstrated to alter the work function of the underlying substrate (∼170 meV). This same molecule also provides spectroscopic signatures for correlating the change in molecular structure to the induced change in the surfaces’ electronic properties. Polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) allows analysis of the characteristic dihydroindolizine C═C (1559 cm–1) and pyridinium (1643 cm–1) stretch as a function of photoexcitation. Structural assignments of this photochromophore are corroborated to density function theory calculations. Conformational changes in the monolayers appear in parallel with work function changes and are consistent with both its rate and magnitude

Building a Climate That Supports and Protects Mandated Reporters: School Principals and Their Perceived Roles and Policies and Procedures in K-8 Schools

Schools are designed to be safe and healthy places for children to grow and learn, and principals are the instructional leader charged with creating this climate. The role of the mandated reporter, which is the role assigned to all individuals who work in schools, is intended to protect children. The mandated reporter is supposed to be the voice for children-not just for the child who actually speaks out against the individual who is perpetrating against them, but also for the child who does not have the words to report the abuse. A suspicion is all a mandated reporter needs to make the call to DCFS. This study sought to discover the following research questions: 1) How do building principals perceive their role in the mandated reporting process in elementary schools (K-8) in three suburban counties in Illinois? 2) What types of policies and procedures do districts have in place concerning mandated reporting and child maltreatment? 3) How do principals implement these policies in their school buildings when it comes to mandated reporting and child maltreatment detection? 4) What components do principals perceive to be essential to improve mandated reporting structures? This study was conducted within three counties in suburban Illinois and employed both qualitative and quantitative information and utilized two instruments created by the researcher, the Building Principal Mandated Reporting Questionnaire and a semi-structured principal interview protocol. Further analysis was completed post-data collection due to a finding that 26% of the respondents did not strictly adhere to the law according to one of the responses on the questionnaire. The current state of mandated reporting in schools is discussed as well as steps schools can take to better support mandated reporters. Further research on this topic is needed on a broader scale and with principals from outside of Illinois

Puerto y salubridad: La ciudad, el agua y dos proyectos inconclusos en las décadas de 1870 y 1880. Un acercamiento a la labor de John L. Bateman en Buenos Aires y sus repercusiones locales inmediatas

Se abordará, en primera instancia, el proyecto de John Bateman paradotar de un puerto moderno a la ciudad de Buenos Aires, tarea que le fueencomendada por el gobierno nacional en el año 1871. Pese a quedar suplan trunco por fallas de detalle, aunque decisivas en palabras de LuisAugusto Huergo, su figura se constituyó en referente para los miembrosde la Comisión de Aguas Corrientes que confiaron en él la concreción delas obras de salubridad en la misma ciudad. No obstante su experienciaen la construcción de desagües en Londres y el contar con varios años yrecursos suficientes –inclusive onerosos– para ejecutarlo, este segundoproyecto tampoco prosperó

El trabajo de la mujer en las obras teatrales argentinas del período 1880-1950

El lunes 26 de septiembre de 2011, Viviana E. Bartucci presentó la defensa de su tesis doctoral. El Tribunal Examinador estuvo compuesto por los doctores Daisy Rípodas Ardanaz1, Cristina Minutolo de Orsi, María Gabriela Micheletti, Adela M. Salas, Carmen Pereyra Barrancos y Abelardo Levaggi, como padrino de tesis

Water penetration profile at the protein-lipid interface in Na,K-ATPase membranes.

The affinity of ionized fatty acids for the Na,K-ATPase is used to determine the transmembrane profile of water penetration at the protein-lipid interface. The standardized intensity of the electron spin echo envelope modulation (ESEEM) from 2H-hyperfine interaction with D2O is determined for stearic acid, n-SASL, spin-labeled systematically at the C-n atoms throughout the chain. In both native Na,K-ATPase membranes from shark salt gland and bilayers of the extracted membrane lipids, the D2O-ESEEM intensities of fully charged n-SASL decrease progressively with position down the fatty acid chain toward the terminal methyl group. Whereas the D2O intensities decrease sharply at the n = 9 position in the lipid bilayers, a much broader transition region in the range n = 6 to 10 is found with Na,K-ATPase membranes. Correction for the bilayer population in the membranes yields the intrinsic D2O-intensity profile at the protein-lipid interface. For positions at either end of the chains, the D2O concentrations at the protein interface are greater than in the lipid bilayer, and the positional profile is much broader. This reveals the higher polarity, and consequently higher intramembrane water concentration, at the protein-lipid interface. In particular, there is a significant water concentration adjacent to the protein at the membrane midplane, unlike the situation in the bilayer regions of this cholesterol-rich membrane. Experiments with protonated fatty acid and phosphatidylcholine spin labels, both of which have a considerably lower affinity for the Na,K-ATPase, confirm these results