Transcription factor NFE2L2/NRF2 modulates chaperone-mediated autophagy through the regulation of LAMP2A

Chaperone-mediated autophagy (CMA) is a selective degradative process for cytosolic proteins that contributes to the maintenance of proteostasis. The signaling mechanisms that control CMA are not fully understood but might involve response to stress conditions including oxidative stress. Considering the role of CMA in redoxtasis and proteostasis, we sought to determine if the transcription factor NFE2L2/NRF2 (nuclear factor, erythroid derived 2, like 2) has an impact on CMA modulation. In this work, we identified and validated 2 NFE2L2 binding sequences in the LAMP2 gene and demonstrated in several human and mouse cell types that NFE2L2 deficiency and overexpression was linked to reduced and increased LAMP2A levels, respectively. Accordingly, lysosomal LAMP2A levels were drastically reduced in nfe2l2-knockout hepatocytes, which also displayed a marked decrease in CMA activity. Oxidant challenge with paraquat or hydrogen peroxide, or pharmacological activation of NFE2L2 with sulforaphane or dimethyl fumarate also increased LAMP2A levels and CMA activity. Overall, our study identifies for the first time basal and inducible regulation of LAMP2A, and consequently CMA activity, by NFE2L2. Abbreviations: ACTB: actin, beta, ARE: antioxidant response element; ATG5: autophagy related 5; BACH1: BTB domain and CNC homolog 1; ChIP: chromatin immunoprecipitation; CMA: chaperone-mediated autophagy; DHE: dihydroethidium; DMF: dimethyl fumarate; ENCODE: Encyclopedia of DNA elements at the University of California, Santa Cruz; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GBA: glucosylceramidase beta; GFP: green fluorescent protein; HMOX1: heme oxygenase 1; H2O2: hydrogen peroxide; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; KEAP1: kelch like ECH associated protein 1; LAMP2A: lysosomal associated membrane protein 2A; LAMP2B: lysosomal associated membrane protein 2B; LAMP2C: lysosomal associated membrane protein 2C; LAMP1: lysosomal associated membrane protein 1; MAFF: MAF bZIP transcription factor F; MAFK: MAF bZIP transcription factor K; NFE2L2/NRF2: nuclear factor, erythroid derived 2, like 2; NQO1: NAD(P)H quinone dehydrogenase 1; PQ: paraquat; PI: protease inhibitors; qRT-PCR: quantitative real-time polymerase chain reaction; RNASE: ribonuclease A family member; SFN: sulforaphane; SQSTM1/p62: sequestosome 1; TBP: TATA-box binding proteinThis paper was funded by the Spanish Ministry of Economy and Competitiveness under the grant SAF2016-76520-R and by grants from the National Institute of Health/National Institute on Aging P01 AG031782. M.P. is recipient of a FPU fellowship of Autonomous University of Madrid. E.A. was supported by NIH/NIA AG038072 P&

Comprehension of energy efficiency in popular urban areas of the city of Barranquilla

All settlement in development with leads analyze concepts of habitability and energy efficiency. This topic of interest contributes information to the plans and programs for local development allowing timely interventions, especially in neighborhoods with environmental deficiencies, basic services and urban equipment. The work is based on a qualitative - quantitative approach of research, developing statistical samples, which allowed to recognize the lack of planning and sustainability, which are debatable enough to realize an understanding of energy efficiency in these areas.Todo asentamiento en desarrollo conlleva analizar conceptos de habitabilidad y eficiencia energética. Este tema de interés aporta información a los planes y programas para el desarrollo local permitiendo intervenciones oportunas, especialmente en barrios con deficiencias ambientales, servicios básicos y equipamiento urbano. El trabajo se fundamenta en un enfoque cualitativo - cuantitativo de investigación desarrollando muestras estadísticas, que permitió reconocer la carencia de planificación y sostenibilidad bastantes discutibles para realizar una comprensión de la eficiencia energética en estas áreas

Factors affecting the big data adoption as a marketing tool in SMEs

The change brought by Big Data about the way to analyze the data is revolutionary. The technology related to Big Data supposes a before and after in the form of obtaining valuable information for the companies since it allows to manage a large volume of data, practically in real time and obtain a great volume of information that gives companies great competitive advantages. The objective of this work is evaluating the factors that affect the acceptance of this new technology by small and medium enterprises. To that end, the technology acceptance model called Unified Theory of Technology Adoption and Use of Technology (UTAUT) was adapted to the Big Data context to which an inhibitor was added: resistance to the use of new technologies. The structural model was assessed using Partial Least Squares (PLS) with an adequate global adjustment. Among the results, it stands out that a good infrastructure is more relevant for the use of Big Data than the difficulty of its use, accepting that it is necessary to make an effort in its implementation.Universidad Peruana de Ciencias Aplicadas, Universidad de la Costa, Fundación Universitaria Popayán, Corporación Universitaria Latinoamericana, Corporación Universitaria Reformada

Lectura de contexto y abordaje psicosocial desde los enfoques narrativos. Turbo.

Con este tipo de temáticas se permite construir relaciones, conversaciones en un contexto de historias donde componemos la identidad a partir de lo que se cuenta, estas historias dejan de ser historias y moldean acciones, no son construidas individualmente, sino a través de lo social y culturalmente por el entorno por el contexto, por relaciones de poder existentes en la cultura, consiste en recontar una historia de vida haciendo visible las historias que han quedado subyugadas o que han quedado invisibles en las vivencias de una persona. Ahondando en el contexto del enfoque narrativo propuesto por Michael White. Es importante hacer relación entre lo que las personas reconocen de sí mismas con la visión que otros tienen de ella y así poner en tela de juicio la historia contra esas posiciones que influyen en lo que la persona valora. Los valores, las creencias y el conocimiento son la base para realizar el análisis de las consecuencias que tiene en su vida. Para que la persona exprese lo que siente y piense con el fin contar y recontar historias que den nuevos significados a la experiencia vivida. La historia es una serie de eventos del cumulo de vivencias, se seleccionan se dan un orden, se da una línea de tiempo y se hace en torno a un tema, podemos ser personas diferentes en contextos y momentos diferentes, la narrativa no solo describe la vida sino que la constituye e influye en cómo se vive por tanto estas historias o mapas que utilizamos para dar sentido a nuestro mundo determinan como entendemos los eventos y las accionesWith this type of topics it is possible to build relationships, conversations in a context of stories where we compose the identity from what is told, these stories stop being stories and mold actions, they are not constructed individually, but through the social and culturally by the environment through the context, by power relations existing in the culture, consists in recounting a life story making visible the stories that have been subjugated or that have remained invisible in the experiences of a person. Deepening in the context of the narrative approach proposed by Michael White. It is important to establish a relationship between what people recognize about themselves and others' view of it and thus question history against those positions that influence what the person values. Values, beliefs and knowledge are the basis for the analysis of the consequences in your life. For the person to express what they feel and think in order to tell and recount stories that give new meaning to the experience lived. The story is a series of events of the cumulative experiences, selected are given an order, given a timeline and is made around a theme, we can be different people in different contexts and times, the narrative not only describes the life but it constitutes and influences how you live so these stories or maps that we use to make sense of our world determine how we understand events and action

Immersive virtual reality application for volumetric composition learning in architectural design

En este documento se explica desempeño de una aplicación de realidad virtual inmersiva, de desarrollo propio (Crality 0.1), a los métodos de enseñanza de la composición arquitectónica, ayudando a que la educación afronte los retos que implica la enseñanza a las nuevas generaciones de estudiantes, al mismo tiempo permite que la creatividad como elemento fundamental en este proceso se potencie con el mínimo de obstáculos posibles. Se toma como marco teórico e indicadores sobre la creatividad los procesos de composición en el diseño arquitectónico y principios generadores de la forma. La evaluación se lleva cabo mediante el análisis de la forma de aprendizaje de la composición arquitectónica a través de la aplicación de realidad virtual comparada con un modelo de control manual de materialidad física. Los resultados condujeron a concluir la eficacia en el proceso de aprendizaje del acompañamiento de la realidad virtual, ya que reduce tiempos de ejecución, disminución del uso de material y una mayor afinidad con los procesos cognitivos de las nuevas generaciones.This paper explains the performance of a self-developed immersive virtual reality application (Crality 0.1) to the teaching methods of architectural composition, helping education to face the challenges of teaching new generations of students, while at the same time allowing creativity as a fundamental element in this process to be enhanced with the minimum possible obstacles. The theoretical framework and indicators of creativity are taken as a framework for the processes of composition in architectural design and the principles that generate form. The evaluation is carried out by analysing the way of learning architectural composition through the application of virtual reality compared to a manual control model of physical materiality. The results led to conclude the effectiveness in the learning process of the virtual reality accompaniment, since it reduces execution times, reduces the use of material and a greater affinity with the cognitive processes of the new generations

Effect of intravenous pulses of methylprednisolone 250 mg versus dexamethasone 6 mg in hospitalised adults with severe COVID ‐19 pneumonia: An open‐label randomised trial

Producción CientíficaBackground: The efficacy and safety of high versus medium doses of glucocorticoids for the treatment of patients with COVID-19 has shown mixed outcomes in controlled trials and observational studies. We aimed to evaluate the effectiveness of methylprednisolone 250 mg bolus versus dexamethasone 6 mg in patients with severe COVID-19. Methods: A randomised, open-label, controlled trial was conducted between February and August 2021 at four hospitals in Spain. The trial was suspended after the first interim analysis since the investigators considered that continuing the trial would be futile. Patients were randomly assigned in a 1:1 ratio to receive dexamethasone 6 mg once daily for up to 10 days or methylprednisolone 250 mg once daily for 3 days. Results: Of the 128 randomised patients, 125 were analysed (mean age 60 ± 17 years; 82 males [66%]). Mortality at 28 days was 4.8% in the 250 mg methylprednisolone group versus 4.8% in the 6 mg dexamethasone group (absolute risk difference, 0.1% [95% CI, −8.8 to 9.1%]; p = 0.98). None of the secondary outcomes (admission to the intensive care unit, non-invasive respiratory or high-flow oxygen support, additional immunosuppressive drugs, or length of stay), or prespecified sensitivity analyses were statistically significant. Hyperglycaemia was more frequent in the methylprednisolone group at 27.0 versus 8.1% (absolute risk difference, −18.9% [95% CI, −31.8 to - 5.6%]; p = 0.007). Conclusions: Among severe but not critical patients with COVID-19, 250 mg/d for 3 days of methylprednisolone compared with 6 mg/d for 10 days of dexamethasone did not result in a decrease in mortality or intubation

Talleres de propuestas y sugerencias de alumnos de Grado para la mejora del Programa Docentia

El Proyecto tiene como objetivo la implementacion de una Cultura de Calidad en los alumnos de grados de diferentes Grados de Ciencias de la Salud. Y el estudio de posibles vias y mecanismos para aumentar la implicacion de los alumnos de la UCM en el Programa Docentia

Estudio in vivo del efecto protector de los polifenoles sobre el deterioro auditivo y los mecanismos moleculares asociados al proceso de envejecimiento

Tesis inédita presentada en la Universidad Europea de Madrid. Escuela de Doctorado e Investigación. Programa de Doctorado en Biomedicina y Ciencias de la SaludUE