Vitamin D Represses Retinoic Acid-Dependent Transactivation of the Retinoic Acid Receptor-ß2 Promoter: The AF-2 Domain of the Vitamin D Receptor Is Required for Transrepression

10 pages, 8 figures.Retinoic acid (RA)-dependent activation of the RA receptor ß2 (RARß2) gene in embryonal carcinoma cells is mediated by binding of retinoid receptor heterodimers (RAR/RXR) to a RA response element (RARE) located closely to the TATA box. We have analyzed the effect of vitamin D on the response of the RARß2 promoter to RA in pituitary GH4C1 cells that coexpress receptors for retinoids and vitamin D. Incubation with vitamin D markedly reduced the response to RA caused by transcriptional interference of the vitamin D receptor (VDR) on the RARE. This DNA element binds VDR/RXR heterodimers with high affinity, and these inactive heterodimers can displace active RAR/RXR from the RARE. Overexpression of RXR in GH4C1 cells, as well as incubation with BMS649 (a RXR-specific ligand), increased the inhibitory effect of vitamin D, suggesting that the VDR/RXR heterodimer is the repressive species and that titration of RXR is not responsible for this inhibition. Although DNA binding could be required for full potency of the inhibitory activity of VDR, it is not absolutely required because a truncated receptor (VDR {Delta}1–111), lacking the DNA binding domain, also displays repressor activity. Furthermore, the ability to mediate transrepression by vitamin D was strongly decreased when a mutant VDR in which the last 12 C-terminal aminoacids have been deleted (VDR {Delta}AF-2) was used. Because this region contains the domain responsible for ligand-dependent recruitment of coactivators, titration of common coactivators for VDR and RAR could be involved in the inhibitory effect of vitamin D. In agreement with this hypothesis, overexpression of E1A, which can act as a RARß2 promoter-specific coactivator, significantly reversed repression by vitamin D.This work was supported by Grants PM94–0094 and PM97–0135 from the Direccion General de Enseñanza Superior e Investigación Científica.Peer reviewe

Retinoic acid protects human breast cancer cells against etoposide-induced apoptosis by NF-kappaB-dependent but cIAP2-independent mechanisms

<p>Abstract</p> <p>Background</p> <p>Retinoids, through their cognate nuclear receptors, exert potent effects on cell growth, differentiation and apoptosis, and have significant promise for cancer therapy and chemoprevention. These ligands can determine the ultimate fate of target cells by stimulating or repressing gene expression directly, or indirectly through crosstalking with other signal transducers.</p> <p>Results</p> <p>Using different breast cancer cell models, we show here that depending on the cellular context retinoids can signal either towards cell death or cell survival. Indeed, retinoids can induce the expression of pro-apoptotic (i.e. TRAIL, TNF-Related Apoptosis-Inducing Ligand, Apo2L/TNFSF10) and anti-apoptotic (i.e. cIAP2, inhibitor of apoptosis protein-2) genes. Promoter mapping, gel retardation and chromatin immunoprecipitation assays revealed that retinoids induce the expression of this gene mainly through crosstalk with NF-kappaB. Supporting this crosstalk, the activation of NF-kappaB by retinoids in T47D cells antagonizes the apoptosis triggered by the chemotherapeutic drugs etoposide, camptothecin or doxorubicin. Notably apoptosis induced by death ligands (i.e. TRAIL or antiFAS) is not antagonized by retinoids. That knockdown of cIAP2 expression by small interfering RNA does not alter the inhibition of etoposide-induced apoptosis by retinoids in T47D cells reveals that stimulation of cIAP2 expression is not the cause of their anti-apoptotic action. However, ectopic overexpression of a NF-kappaB repressor increases apoptosis by retinoids moderately and abrogates almost completely the retinoid-dependent inhibition of etoposide-induced apoptosis. Our data exclude cIAP2 and suggest that retinoids target other regulator(s) of the NF-kappaB signaling pathway to induce resistance to etoposide on certain breast cancer cells.</p> <p>Conclusions</p> <p>This study shows an important role for the NF-kappaB pathway in retinoic acid signaling and retinoic acid-mediated resistance to cancer therapy-mediated apoptosis in breast cancer cells, independently of cIAP2. Our data support the use of NF-kappaB pathway activation as a marker for screening that will help to develop novel retinoids, or retinoid-based combination therapies with improved efficacy.</p

Alkaline activation of metakaolin. Effect of the soluble silicate addition and curing temperature

[ES] El objetivo del presente trabajo es determinar el efecto que la cantidad de sílice soluble presente en la disolución activadora (relación molar SiO2/Na2O entre 0 y 0.69) y la temperatura de curado (85ºC, 150ºC y 200ºC) ejercen sobre las propiedades físico-mecánicas y las características mineralógicas y microestructurales de los productos formados por activación alcalina de metacaolín. Para ello se determinaron los valores de resistencia mecánica a compresión de los materiales objeto de estudio y se realizó un estudio mineralógico y microestructural de los mismos por DRX, SEM-EDX, 29Si RMN-MAS y porosimetría de mercurio. Los resultados obtenidos muestran que la resistencia mecánica del material guarda una estrecha relación con la naturaleza, microestructura y composición química de los productos de reacción así como con las condiciones de curado. En todos los casos se genera, como principal producto de reacción, un polímero inorgánico alcalino con propiedades cementantes (gel N-A-S-H) responsable, en mayor medida, de las propiedades mecánicas del material. Como productos secundarios se forman algunas zeolitas cuya proporción y tipo (sodalita, zeolita A, faujasita, …) dependen tanto de la naturaleza del activador como de las condiciones de curado. La presencia de sílice soluble en la disolución activadora conduce a la formación de geles con una mayor relación Si/Al y a la ralentización de la zeolitización, factores, ambos, con un efecto positivo sobre la resistencia mecánica. Con respecto a la temperatura de curado, existe un valor umbral, en función de la composición del material, a partir del cual un incremento en dicha temperatura deja de tener efectos positivos sobre la evolución de la resistencia mecánica.[EN] This study has been undertaken to determine the effect that the soluble silica content in the activating solution (molar ratio SiO2/Na2O between 0 and 0.69) and curing temperature (85ºC, 150ºC, and 200ºC) have on the physico-mechanical properties and mineralogical and microstructural characteristics of products formed by alkaline activation of metakaolin. The compression strength of the materials obtained was determined and a mineralogical and microstructural study of these materials was conducted by XRD, SEM-EDX, 29Si MAS-NMR, and mercury porosimetry. The results show that the mechanical strength of the material is closely related to the nature, microstructure, and chemical composition of the reaction products, as well as to the curing conditions. In all cases, the main reaction product that forms is an inorganic alkaline polymer with cementing properties (N-A-S-H gel), which is largely responsible for the mechanical properties of the material. Some zeolites form as by-products, whose quantity and type (sodalite, zeolite A, faujasite, etc.) depend on the nature of the activator and the curing conditions. The presence of soluble silica in the activating solution leads to the formation of gels with a larger Si/Al ratio and slower zeolitisation, these both being factors with a positive effect on mechanical strength. The curing temperature exhibits a threshold value that depends on the composition of the material, beyond which an increase in curing temperature ceases to positively affect the evolution of the material’s mechanical strength.Programa de Alta Especialización en Tecnologías Industriales “Nuevas técnicas y recubrimientos cerámicos de baja temperatura” (IMAETA/2004/15-IMAETB/2005/12-IMAETB/2006/18) financiado por el Instituto de la Pequeña y Mediana Industria de la Generalitat Valenciana (IMPIVA) y a la Uunión Europea (Fondo Social Europeo), a la Dirección General de Investigación Científica y Técnica por la financiación del proyecto BIA2004-04835 y al CSIC/Fondo Social Europeo por el contrato de investigador en prácticas REF I3P-PC2004L.Peer reviewe

Why do student perceptions of academic performance improve? The influence of acquired competences and formative assessment in a flipped classroom environment

The university system must be able to respond to the growing demand for graduates with certain skills that guarantee their employability. A key requirement of this goal is the use of different teaching-learning methods, such as the flipped classroom methodology. However, although some studies have shown the advantages of this model, more research is needed to identify the reasons for these positive effects and the contexts in which it works best. In this paper, we analyse the perceptions of students of six undergraduate subjects at the University of Jaén (Spain) concerning their acquired competences and the formative assessment received in a flipped classroom environment. In addition, we analyse whether these two variables influence these student perceptions of achieving better academic outcomes. The results show that both aspects explain student perceptions of better performance and are key elements in the provision of a better learning environment. In this way, these results contribute to the literature concerning the positive effects of a flipped classroom on the teaching-learning process in higher education.Proyecto de Innovación Docente de la Universidad de Jaén titulado ‘Aulas invertidas (Flipped Classroom): Una nueva forma de enseñar y aprender’, Financiado por la Universidad de Jaén (España) como parte del ‘Plan de Innovación y Mejora Docente’ (PIMED-UJA 2019

Students’ perceptions of their learning outcomes in a flipped classroom environment

The flipped classroom model has positive effects on the educational process, and has recently become an alternative to the traditional model. However, additional research is necessary to identify the causes of those improvements and the contexts in which this methodology performs better. In this study, we analyze the perceptions of different students pursuing a bachelor’s degree at the University of Jaén (Spain) regarding flipped learning dynamics and the relationship between those perceptions and perceptions of their learning outcomes. Specifically, we investigate whether students’ acquired competences and attitude, as well as the use of formative assessment have positive effects on student perceptions on results. To accomplish this task, during the first semester of the 2020–2021 and 2021–2022 academic years, we collected the opinions of students via a questionnaire and tested those relationships using PLS. The results indicate that the three variables (acquired competences, attitude, and formative assessment) explain the perceptions of students with respect to achieving better grades, and are key elements of superior learning, that can improve students’ performance. Accordingly, this study provides evidence regarding the positive effects of flipped classroom on the teaching–learning process in higher education and explains the reasons for the resulting improvement in learning outcomes.Proyecto de Innovación Docente de la Universidad de Jaén “Aulas invertidas (Flipped Classroom): Una nueva forma de enseñar y aprender”, financiado por la Universidad de Jaén (España) (PIMED-UJA 2019)

La formación de las bibliotecarias y las bibliotecas de mujeres en España

Since the end of the 19th century, women have accessed library training and in the start of the 20th century, first women’s libraries appear are created in Spain. This study addresses access of women to library training, feminizing the profession and influencing the creation of women’s libraries. In order to do so, a review of recent history is performed. On the one hand, analyzing women’s training in Higher Education and in programs developed by different Spanish institutions. On the other hand, analyzing the creation and the increasing importance women’s libraries have had. Although these two topics had independent developments, it becomes clear that women’s inclusion in library studies training fostered the creation of women’s libraries.Desde finales del siglo XIX, las mujeres en España acceden a la formación de bibliotecaria, y a partir del XX se crean las primeras bibliotecas de mujeres. Se pretende investigar el proceso de feminización en esta profesión durante este periodo, y su posible influencia en la creación de bibliotecas de mujeres. Para ello, se presenta un recorrido histórico de la formación de las mujeres en la biblioteconomía, tanto en la enseñanza reglada como en los cursos de formación impartidos por instituciones españolas de diversa índole, así como la aparición e importancia progresiva que han venido adquiriendo estas bibliotecas a partir de entonces. Se constata, que aunque ambos recorridos se desarrollaron de manera independiente, la formación de bibliotecarias propició de forma indirecta la creación de bibliotecas de mujeres

Synergy between RA and TLR3 promotes type I IFN-dependent apoptosis through upregulation of TRAIL pathway in breast cancer cells

This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License.Due to its ability to regulate the growth, differentiation and apoptosis of cancer cells, retinoic acid (RA) is considered a signaling molecule with promising therapeutic potential in oncology. In this study, we show that RA is able to induce the intrinsic ability of breast cancer cells to recognize double-stranded RNA (dsRNA) through the upregulation of Toll-like receptor 3 (TLR3) expression. RA, co-administered with the dsRNA mimicker polyinosinic–polycytidylic acid (poly(I:C)), synergizes to mount a specific response program able to sense dsRNA through the concurrent upregulation of TLR3, the dsRNA helicases melanoma differentiation-associated antigen-5 (MDA-5) and RA-inducible gene-1 (RIG-1), and the dsRNA-activated protein kinase (PKR) expression, leading breast cancer cells to specifically express downstream transcriptional targets of dsRNA sensors, such as interferon-β (IFNβ), interleukin-8 (IL-8), chemokine (C-C motif) ligand 5 (CCL5), and C-X-C motif Chemokine 10 (CXCL10). A TLR3-dependent apoptotic program is also induced by RA and poly(I:C) co-treatment that correlates with the induction of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and contributes to block breast cancer cell proliferation. The mechanisms of apoptosis induced by RA/poly(I:C) in breast cancer cells involve type I IFN autocrine signaling, caspase-8 and caspase-3 activation, as well as TRAIL signaling. Our results reveal important links among RA, TLR3 and TRAIL and highlight the combined use of RA and poly(I:C) as a potential effective tumor therapy by improving the apoptotic response of cancer cells with low sensitivity to the action of synthetic dsRNA.This work was supported by funds from the MICINN (SAF2007-63634 and SAF2010-21195), CSIC (201120E105), and Fundación Médica Mutua Madrileña (2005 0584). ARBV was supported by funds from the MICINN. AMJ-L is a recipient of a grant from the Spanish MICINN (Ramón y Cajal Program).Peer reviewe

High-Throughput System for the Early Quantification of Major Architectural Traits in Olive Breeding Trials Using UAV Images and OBIA Techniques

The need for the olive farm modernization have encouraged the research of more efficient crop management strategies through cross-breeding programs to release new olive cultivars more suitable for mechanization and use in intensive orchards, with high quality production and resistance to biotic and abiotic stresses. The advancement of breeding programs are hampered by the lack of efficient phenotyping methods to quickly and accurately acquire crop traits such as morphological attributes (tree vigor and vegetative growth habits), which are key to identify desirable genotypes as early as possible. In this context, an UAV-based high-throughput system for olive breeding program applications was developed to extract tree traits in large-scale phenotyping studies under field conditions. The system consisted of UAV-flight configurations, in terms of flight altitude and image overlaps, and a novel, automatic, and accurate object-based image analysis (OBIA) algorithm based on point clouds, which was evaluated in two experimental trials in the framework of a table olive breeding program, with the aim to determine the earliest date for suitable quantifying of tree architectural traits. Two training systems (intensive and hedgerow) were evaluated at two very early stages of tree growth: 15 and 27 months after planting. Digital Terrain Models (DTMs) were automatically and accurately generated by the algorithm as well as every olive tree identified, independently of the training system and tree age. The architectural traits, specially tree height and crown area, were estimated with high accuracy in the second flight campaign, i.e. 27 months after planting. Differences in the quality of 3D crown reconstruction were found for the growth patterns derived from each training system. These key phenotyping traits could be used in several olive breeding programs, as well as to address some agronomical goals. In addition, this system is cost and time optimized, so that requested architectural traits could be provided in the same day as UAV flights. This high-throughput system may solve the actual bottleneck of plant phenotyping of "linking genotype and phenotype," considered a major challenge for crop research in the 21st century, and bring forward the crucial time of decision making for breeders

Students’ attitude: Key to understanding the improvement of their academic RESULTS in a flipped classroom environment

The flipped classroom model has been shown in recent years to have a positive effect on students’ motivation and academic performance. In this paper, we analyze the perception that students of six undergraduate subjects at University of Ja´en (Spain) have of the subjects’ formative assessment and their attitude towards this new teaching-learning model. In addition, we analyze whether both variables influence their perception of achieving better academic results. The results of our study show that both aspects (formative assessment perception and attitude) explain students’ perception of outcomes. It leads us to conclude that students’ attitude is a key element of fostering more and better learning that improves their performance. In this way, our results provide further evidence for the literature on the positive effects of the flipped classroom on the teaching-learning process at the university level for students, teachers and scholars.“Aulas invertidas (Flipped Classroom): Una nueva forma de enseñar y aprender”, financiado por la Universidad de Jaén en el marco del “Plan de Innovación y Mejora Docente” (PIMED-UJA 2019

Gypsum to gypsum (GtoG): The European Life+ project that aims to transform the gypsum waste market

The GtoG project is working for creating a recycling culture of gypsum products, changing the way this waste is usually treated in construction, renovation and demolition works, with the aim of achieving higher gypsum recycling rates in Europe and promoting selective deconstruction practices. For this purpose and under the leadership of Eurogypsum (the European Plaster and Plasterboard Manufacturers Association) five demolition companies, one demolition consultant, two gypsum waste processors, five plasterboard manufacturers and three academic partners, from 7 European countries, work together constituting the project consortium. A preliminary study on current practices was completed in 2013. Subsequently in 2014, a set of demonstration activities on deconstruction, processing of gypsum waste and reincorporation of recycled gypsum were conducted. Finally, during this year 2015, different results have been delivered, such as the European Handbook of best practices for controlled deconstruction of gypsum systems and the Report on best practice indicators for deconstruction, recycling and reincorporation practices. The final results will include an Inventory of best practices and the Roadmap for the future implementation of a sustainable value chain