Strategies for anti-fibrotic therapies.

The fibrotic diseases encompass a wide spectrum of entities including such multisystemic diseases as systemic sclerosis, nephrogenic systemic fibrosis and sclerodermatous graft versus host disease, as well as organ-specific disorders such as pulmonary, liver, and kidney fibrosis. Collectively, given the wide variety of affected organs, the chronic nature of the fibrotic processes, and the large number of individuals suffering their devastating effects, these diseases pose one of the most serious health problems in current medicine and a serious economic burden to society. Despite these considerations there is currently no accepted effective treatment. However, remarkable progress has been achieved in the elucidation of their pathogenesis including the identification of the critical role of myofibroblasts and the determination of molecular mechanisms that result in the transcriptional activation of the genes responsible for the fibrotic process. Here we review the origin of the myofibroblast and discuss the crucial regulatory pathways involving multiple growth factors and cytokines that participate in the pathogenesis of the fibrotic process. Potentially effective therapeutic strategies based upon this new information are considered in detail and the major challenges that remain and their possible solutions are presented. It is expected that translational efforts devoted to convert this new knowledge into novel and effective anti-fibrotic drugs will be forthcoming in the near future. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease

La construcción de la Argentina como país proliferador

La Argentina pertenece a la categoría de países que autores como Emmanuel Wallerstein definen como semiperiferia. Los países semiperiféricos son aquellos que poseen capacidad industrial e impulsan procesos de desarrollo dependientes. Desde esta perspectiva, se analizan algunos ejemplos del variado y tenaz arsenal de estrategias de presión que fueron desplegadas desde la arena internacional (aunque principalmente impulsadas por los Estados Unidos) para obstaculizar el desarrollo de capacidades autónomas de la Argentina en el área nuclear.Fil: Hurtado de Mendoza, Diego Fabian. Universidad Nacional de San Martín. Escuela de Humanidades. Centro de Estudios de Historia de la Ciencia y de la Técnica "José Babini"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Stimulation of Transforming Growth Factor-β1-Induced Endothelial-To-Mesenchymal Transition and Tissue Fibrosis by Endothelin-1 (ET-1): A Novel Profibrotic Effect of ET-1.

TGF-β-induced endothelial-to-mesenchymal transition (EndoMT) is a newly recognized source of profibrotic activated myofibroblasts and has been suggested to play a role in the pathogenesis of various fibrotic processes. Endothelin-1 (ET-1) has been implicated in the development of tissue fibrosis but its participation in TGF-β-induced EndoMT has not been studied. Here we evaluated the role of ET-1 on TGF-β1-induced EndoMT in immunopurified CD31+/CD102+ murine lung microvascular endothelial cells. The expression levels of α-smooth muscle actin (α-SMA), of relevant profibrotic genes, and of various transcription factors involved in the EndoMT process were assessed employing quantitative RT-PCR, immunofluorescence histology and Western blot analysis. TGF-β1 caused potent induction of EndoMT whereas ET-1 alone had a minimal effect. However, ET-1 potentiated TGF-β1-induced EndoMT and TGF-β1-stimulated expression of mesenchymal cell specific and profibrotic genes and proteins. ET-1 also induced expression of the TGF-β receptor 1 and 2 genes, suggesting a plausible autocrine mechanism to potentiate TGF-β-mediated EndoMT and fibrosis. Stimulation of TGF-β1-induced skin and lung fibrosis by ET-1 was confirmed in vivo in an animal model of TGF-β1-induced tissue fibrosis. These results suggest a novel role for ET-1 in the establishment and progression of tissue fibrosis

Protein purification of SETD8: a structure and inhibition study

https://openworks.mdanderson.org/sumexp21/1215/thumbnail.jp

Changes in Risk Appreciation, and Short Memory of House Buyers When the Market is Hot, a Case Study of Christchurch, New Zealand

In this paper house prices in Christchurch are analyzed over three distinct periods of time: post-2011 earthquake, pre-COVID-19 lockdown, and post-COVID-19 lockdown using the well-established hedonic price model. Results show that buyers, in periods that are temporally distant from the 2011 Christchurch earthquake, value the risk of potential earthquake damage to a property differently from buyers soon after the earthquake. We find that there are observable shifts in hedonic prices across the different time periods, specifically for section size pre and post COVID-19 lockdown

A prospective observational study of mycophenolate mofetil treatment in progressive diffuse cutaneous systemic sclerosis of recent onset.

OBJECTIVE: A prospective observational study of mycophenolate mofetil (MMF) treatment in patients with diffuse progressive cutaneous systemic sclerosis (SSc) of recent onset. METHODS: Twenty-five previously untreated consecutive patients with recent-onset (\u3c 24 mo) diffuse progressive cutaneous SSc received MMF as the only disease-modifying therapy. Modified Rodnan skin score (mRSS) and affected body surface area (BSA) were compared from initiation of MMF to study end. Pulmonary function tests performed at the same institution before therapy and at study end were available in 15 patients. Histopathology and real-time PCR assessment of fibrosis-related gene expression were performed before and after treatment in skin biopsies from 3 patients. RESULTS: At 18.2 ± 8.73 months of MMF therapy (median 2000 mg/day) the mRSS decreased from 24.56 ± 8.62 to 14.52 ± 10.9 (p = 0.0004) and the affected BSA from 36% ± 16% to 14% ± 13.3% (p = 0.00001). Pulmonary function tests remained stable from initiation of MMF to the end of the study. Skin histopathology showed a remarkable reduction in accumulation of fibrotic tissue. Real-time PCR of skin biopsies demonstrated a marked decrease in expression of fibrosis-related genes. CONCLUSION: Patients with diffuse progressive cutaneous SSc of recent onset treated with MMF experienced marked improvement in skin involvement and stabilization of pulmonary function. Skin biopsies from 3 patients demonstrated histopathological improvement and decreased expression of fibrosis-related genes

The political uses of theater. Scientific and medical sociability in the city of Buenos Aires at the end of the century (1870 -1920)

Se estudian tres ceremonias científicas organizadas en distintos teatros de la ciudad de Buenos Aires por el Círculo Médico Argentino (CMA). Como parte de las prácticas de sociabilidad de esta institución, estas ceremonias, dedicadas a conmemorar episodios e individuos centrales en la frágil comunidad médica de la segunda mitad del siglo XIX, fueron uno de los recursos utilizados por el CMA para la transmisión de sentidos, valores y representaciones acerca de la práctica médica local a la sociedad civil y el poder político de su época. Esta estrategia de amplificación de los aspectos simbólicos y culturales de la práctica profesional y científica de la medicina fue utilizada por el CMA tanto para construir audiencias mayores, ganar visibilidad y demandar legitimidad para el conjunto de prácticas médicas, como para abrir una brecha de acceso al reconocimiento político en una ciudad con tendencia a mirar como extraños a médicos y hospitales hasta bien entrado el siglo XX. En especial, los tres casos estudiados permiten ilustrar las estrechas relaciones entre las ceremonias teatrales y la puesta en circulación de un programa experimental para las ciencias médicas de la ciudad de Buenos Aires.Three scientific ceremonies organized in different theaters of the city of Buenos Aires by the Argentine Medical Circle (CMA) are studied. As part of practices of sociability of this institution, these ceremonies dedicated to commemorate episodes and central individuals in the medical community in the second half of the nineteenth century were one of the resources used by the CMA for the transmission of meanings, values and representations about the local medical practice civil society and political power. This amplification strategy of symbolic and cultural aspects of professional and scientific practice of medicine was used by the CMA both to build larger audiences, gain visibility and claim legitimacy for all medical practices, such as to open a gap in access to political recognition in a city with a tendency to look like strangers to doctors and hospitals until well into the twentieth century. In particular, the three case studies to illustrate the close relationship between the theatrical ceremonies and the circulation of a pilot program for medical sciences in Buenos Aires city.Fil: Souza, Pablo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Humanidades. Centro de Estudios de Historia de la Ciencia y de la Técnica "José Babini"; ArgentinaFil: Hurtado de Mendoza, Diego Fabian. Universidad Nacional de San Martín. Escuela de Humanidades. Centro de Estudios de Historia de la Ciencia y de la Técnica "José Babini"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Geoeconomic Uses of Global Warming: The “Green” Technological Revolution and the Role of the Semi-Periphery

While some semi-peripheral countries have seen renewable energies as an opportunity to build their industrial and technological capacities, core countries and global governance organizations have been promoting “green growth.” Since the 2008 global financial crisis, global warming has been used as a catalyst for big business. As the global economy may be entering the first stage of a “green industrial revolution,” neo-Schumpeterian economists have regained visibility. We intend to show how, as a consequence of the lack of a world-systemic perspective, crucial inconsistencies arise in neo-Schumpeterian contributions that weaken their conceptualization of the role of non-core economies in technological change. We examine the case of the tortuous trajectory of wind energy in Argentina to show the specific organizational, institutional, and macroeconomic constraints faced by a semiperipheral economy as it attempts to develop its own technological and industrial capacities. The neoSchumpeterian view of the “green industrial revolution” must be understood as valid only for the core-economy subsystem, which seems to require as well polarization of the world-system through what we call “semi-peripheral neoliberalism,” a peripheralizing force upon the semi-periphery necessary in order to rejuvenate core economies.Fil: Hurtado de Mendoza, Diego Fabian. Universidad Nacional de San Martín. Escuela de Humanidades. Centro de Estudios de Historia de la Ciencia y de la Técnica "José Babini"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Souza, Pablo Andres. Universidad Nacional de San Martín. Escuela de Humanidades. Centro de Estudios de Historia de la Ciencia y de la Técnica "José Babini"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Estrategias de sistemas pasivos de iluminación natural cenital en el diseño de un mercado de abastos mayorista en Trujillo-2019

La presente tesis se enmarca al ámbito de la arquitectura sostenible, proponiendo determinar de qué manera las estrategias de sistemas pasivos de iluminación natural cenital condicionan en el diseño de un Mercado de Abastos Mayorista en Trujillo. La investigación describe la necesidad que tiene Trujillo de proponer un moderno equipamiento de carácter comercial. Además, analiza casos arquitectónicos planteando lineamientos de diseño para el nuevo objeto arquitectónico, así mismo, de la mano de los casos planteados se elabora la programación arquitectónica, que permitirá detallar los espacios, dimensiones que tendrá el nuevo Mercado de Abastos Mayorista, luego se elabora una matriz de ponderación para evaluar tres posibles terrenos para finalmente diseñar el equipamiento planteado. Al término de ello, se recomienda que el objeto arquitectónico se posicione y se emplace de acuerdo a sus condiciones climáticas del lugar, específicamente sea directamente vinculada con la radiación solar, permitiendo la ganancia de la luz solar en su totalidad y sea provechoso para cualquier tipo de equipamiento de iluminar naturalmente.This thesis is part of the field of sustainable architecture, proposing to determine how the strategies of passive systems of natural overhead lighting condition the design of a Wholesale Market in Trujillo. The investigation describes the need that Trujillo has to propose a modern commercial equipment. In addition, it analyzes architectural cases proposing design guidelines for the new architectural object, likewise, from the hand of the cases raised, the architectural programming is elaborated, which will allow detailing the spaces, dimensions that the new Wholesale Market will have, then it is elaborated a weighting matrix to evaluate three possible terrains to finally design the proposed equipment. At the end of it, it is recommended that the architectural object be positioned and located according to its climatic conditions of the place, specifically it is directly linked to solar radiation, allowing the gain of sunlight in its entirety and be beneficial for any type of of equipment to illuminate naturally

Implementación de nuevas estrategias pedagógicas para mejorar el writing en los estudiantes del grado 8° de la Institución Educativa Cristóbal Colon

Carpeta de evidencia de la practica pedagógicaEl trabajo desarrollado tuvo lugar en la escuela Cristóbal Colón, ubicada en el municipio de Morroa, con los estudiantes de octavo grado, en el cual este proceso, se identificó una problemática educativa en la asignatura de inglés, relacionada con las dificultades que los alumnos enfrentan al redactar textos en el aula de clases, en respuesta a este desafío, se ha formulado una propuesta pedagógica centrada en la creación de una secuencia didáctica. Esta secuencia incluye la implementación de ejercicios interactivos en línea diseñados específicamente para mejorar la habilidad de redacción de los estudiantes en inglés, para realizar la investigación se hizo fundamental contar con las características detalladas de los estudiantes, de tal modo que se planificaran ejercicios contextualizados tomando en cuenta sus intereses y necesidades, por otra parte, se destaca la importancia del uso del diario de campo ya que fue un instrumento vital a la hora de recoger todos los datos de manera cualitativa del contexto educativo. Conforme a lo señalado anteriormente, los resultados obtenidos después de aplicar la secuencia didáctica fueron excelentes, ya que se pudo ver como los estudiantes a través de este tipo de actividades podían escribir mucho mejor en inglés, es de esta manera que cada uno de los ejercicios creados en la secuencia didáctica permitieron que los alumnos pudieran mejorar esta habilidad en específico, mejorando sus competencias en la lengua extranjera, en síntesis, la implementación de secuencias didácticas es crucial para mejorar la calidad de la educación, abordando las necesidades individuales de los estudiantes y promoviendo un enfoque basado en competencias en la enseñanza de la escritura en inglés.The research was conducted at Cristóbal Colon School, located in the municipality of Morroa, with 8th-grade students, During the study, an educational issue related to English language instruction became evident, this issue specifically pertained to students' difficulties in composing written texts in the classroom, in response, a pedagogical solution was developed, focusing on the creation of a didactic sequence that includes interactive online writing exercises designed to enhance this specific skill. In order to effectively address the problem, it was essential to gather detailed information about the students, considering their interests and needs, to create exercises that were contextually relevant, the use of field diaries played a vital role in collecting qualitative data from the educational environment, enabling a comprehensive understanding of the students' challenges and progress. The outcomes of implementing the didactic sequence were highly favorable, the results demonstrated a significant improvement in the students' English writing abilities, Each exercise within the didactic sequence contributed to honing this particular skill, ultimately enhancing their proficiency in the foreign language, the incorporation of didactic sequences proves to be instrumental in enhancing the overall quality of education, it allows for a tailored approach to address individual student needs and fosters a competency based approach to English writing instruction