Degradation of IF1 controls energy metabolism during osteogenic differentiation of stem cells

Differentiation of human mesenchymal stem cells (hMSCs) requires the rewiring of energy metabolism. Herein, we demonstrate that the ATPase inhibitory factor 1 (IF1) is expressed in hMSCs and in prostate and colon stem cells but is not expressed in the differentiated cells. IF1 inhibits oxidative phosphorylation and regulates the activity of aerobic glycolysis in hMSCs. Silencing of IF1 in hMSCs mimics the metabolic changes observed in osteocytes and accelerates cellular differentiation. Activation of IF1 degradation acts as the switch that regulates energy metabolism during differentiation. We conclude that IF1 is a stemness marker important for maintaining the quiescence stateThis work was supported by grants from the Ministerio de Educación y Ciencia (BFU2010-18903), the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, and Comunidad de Madrid (S2011/BMD-2402), Spai

Propuesta de innovación docente en educación superior a través del uso de las redes sociales

La capacidad de las redes sociales (RRSS) para comunicar y poner en contacto a millones de personas ha provocado que éstas se usen con fines muy distintos. El mundo educativo no puede permanecer ajeno ante fenómenos sociales como este, por lo que su inclusión en la educación formal es fundamental. Aunque se puede vislumbrar el potencial comunicador y educativo de las RRSS, esto está todavía por descubrir y debe ser estudiado más en profundidad. De este modo, la presente propuesta educativa tiene el foco de atención en las RRSS como herramienta innovadora, comunicativa y de enseñanza-aprendizaje en el marco educativo superior

Propuesta de innovación metodológica en la enseñanza superior: flipped classroom, práctica reflexiva y evaluación formativa

Actualmente se ha demostrado que el aprendizaje es fruto de lo que el alumno hace y no tanto de lo que hace el profesor. La creciente incorporación de metodologías activas en la enseñanza pretende desplazar a la pedagogía tradicional, convirtiendo al alumnado en  (verdadero) protagonista activo de su proceso de enseñanza- aprendizaje. El objetivo de este trabajo es presentar una propuesta de innovación metodológica para la enseñanza superior en la que la acción pedagógica del profesor se enfoque como una orientación dentro de un proceso significativo y constructivo donde el trabajo del alumno tome protagonismo. De esta forma se minimizará el actual déficit entre créditos ECTS y horas reales, en consonancia con las pretensiones del sistema acumulado de transferencia de créditos y nos aproximaremos a una adquisición real de competencias y aprendizajes funcionales por parte del alumnado

Dynamics of CaCdc10, a septin of Candida albicans, in living cells and during infection

The morphogenetic program in the pathogenic fungus Candida albicans , including the dimorphic transition, is an interesting field of study, not only because it is absent in the commonly used model yeast Saccharomyces cerevisiae, but because of the close relationship between hyphal development and virulence of C. albicans. We studied one of the most important aspects of fungal morphogenesis-the septin ring–in C. albicans. By using a fusion construct to green fluorescent protein (GFP), the subcellular localization and dynamics of C. albicans Cdc10 in the different morphologies that this fungus is able to adopt was identified. The localization features reached were contrasted and compared with the results obtained from Candida cells directly extracted from an animal infection model under environmental conditions as similar as possible to the physiological conditions encountered by C. albicans during host infection. [Int Microbiol 2004; 7(2):105–112

Increased Protein Stability and Interleukin-2 Production of a LAT(G131D)Variant With Possible Implications for T Cell Anergy

The adaptor LAT plays a crucial role in the transduction of signals coming from the TCR/CD3 complex. Phosphorylation of some of its tyrosines generates recruitment sites for other cytosolic signaling molecules. Tyrosine 132 in human LAT is essential for PLC-gamma activation and calcium influx generation. It has been recently reported that a conserved glycine residue preceding tyrosine 132 decreases its phosphorylation kinetics, which constitutes a mechanism for ligand discrimination. Here we confirm that a LAT mutant in which glycine 131 has been substituted by an aspartate (LAT(G131D)) increases phosphorylation of Tyr132, PLC-gamma activation and calcium influx generation. Interestingly, the LAT(G131D)mutant has a slower protein turnover while being equally sensitive to Fas-mediated protein cleavage by caspases. Moreover, J.CaM2 cells expressing LAT(G131D)secrete greater amounts of interleukin-2 (IL-2) in response to CD3/CD28 engagement. However, despite this increased IL-2 secretion, J.CaM2 cells expressing the LAT(G131D)mutant are more sensitive to inhibition of IL-2 production by pre-treatment with anti-CD3, which points to a possible role of this residue in the generation of anergy. Our results suggest that the increased kinetics of LAT Tyr132 phosphorylation could contribute to the establishment of T cell anergy, and thus constitutes an earliest known intracellular event responsible for the induction of peripheral tolerance

Use of Natural Microtalcs during the Virgin Olive Oil Production Process to Increase Its Content in Antioxidant Compounds

During the olive oil production process, certain olive varieties, such as ‘Hojiblanca’ and ‘Picual’, create pastes from which it is difficult to separate the oil, resulting in low extraction yields. To improve oil extraction, one alternative is the addition of natural microtalcs (NMT). In the present study, a NMT of great purity (CaCO3 concentration less than 6 wt.%) and small average particle size (φ ≤ 2.1 µm) was added in the malaxation stage on an industrial scale at two olive mills. In one of them and using ‘Hojiblanca’ olives, the performance of the high-purity NMT was compared with that of a traditional NMT, while in the other, the effect of its dosage in the quality of ‘Picual’ oils was assessed. The performance of the high-purity NMT was evaluated in terms of industrial oil yield, extractability index, quality parameters and oxidative stability of the resulting oils. The addition of the high-purity NMT not only increased the extraction yields but also improved the quality of the virgin olive oils, especially in relation to antioxidant compounds (tocopherols and phenolic compounds). Increases of 10.4% in phenolic compounds and of 21.5% in the tocopherols were found, thus enhancing the oxidative stability of the oils

Upgrade of a climate service tailored to water reservoirs management

We present the upgrade of a web tool designed to help in the decision making process for water reservoirs management in Spain. The tool, called S-ClimWaRe (Seasonal Climate predictions in support of Water Reservoirs management), covers the extended winter season (from November to March), when the North Atlantic Oscillation (NAO) pattern strongly influences the hydrological interannual variability in South-Western Europe. This climate service is fully user driven, and aims at meeting their requirements incorporating recent scientific progress.The research leading to these results has received funding from the MEDSCOPE project co-funded by the European Commission as part of ERA4CS, an ERA-NET initiated by JPI Climate, grant agreement 690462

A Novel, LAT/Lck Double Deficient T Cell Subline J.CaM1.7 for Combined Analysis of Early TCR Signaling

Intracellular signaling through the T cell receptor (TCR) is essential for T cell development and function. Proper TCR signaling requires the sequential activities of Lck and ZAP-70 kinases, which result in the phosphorylation of tyrosine residues located in the CD3 ITAMs and the LAT adaptor, respectively. LAT, linker for the activation of T cells, is a transmembrane adaptor protein that acts as a scaffold coupling the early signals coming from the TCR with downstream signaling pathways leading to cellular responses. The leukemic T cell line Jurkat and its derivative mutants J.CaM1.6 (Lck deficient) and J.CaM2 (LAT deficient) have been widely used to study the first signaling events upon TCR triggering. In this work, we describe the loss of LAT adaptor expression found in a subline of J.CaM1.6 cells and analyze cis-elements responsible for the LAT expression defect. This new cell subline, which we have called J.CaM1.7, can re-express LAT adaptor after Protein Kinase C (PKC) activation, which suggests that activation-induced LAT expression is not affected in this new cell subline. Contrary to J.CaM1.6 cells, re-expression of Lck in J.CaM1.7 cells was not sufficient to recover TCR-associated signals, and both LAT and Lck had to be introduced to recover activatory intracellular signals triggered after CD3 crosslinking. Overall, our work shows that the new LAT negative J.CaM1.7 cell subline could represent a new model to study the functions of the tyrosine kinase Lck and the LAT adaptor in TCR signaling, and their mutual interaction, which seems to constitute an essential early signaling event associated with the TCR/CD3 complex.This research was funded by Consejeria de Salud de Andalucia, Junta de Andalucia (grant PI-0055-2017 to E.A.), and Fundacion Biomedica Cadiz Proyectos INIBICA 2019 (grant LI19/I14NCO15 to E.A. and M.M.A.-E.)

Predicción de los comportamientos positivos en educación física: una perspectiva desde la Teoría de la autodeterminación

El presente estudio analiza los antecedentes motivacionales que pueden incidir en la realización de comportamientos positivos en las clases de educación física. La muestra está formada por 1692 alumnos con edades comprendidas entre los 12 y los 16 años (M = 13.34; DT = .76), pertenecientes a 99 clases de 32 centros educativos públicos. Se somete a verificación un modelo completo de regresión estructural que, teniendo en cuenta la naturaleza multinivel de los datos, refleja cómo la percepción de apoyo a las necesidades psicológicas básicas predice el tipo de motivación a través de la satisfacción de las necesidades psicológicas básicas, y cómo el tipo de motivación actúa como predictor de los comportamientos positivos. Los resultados destacan los procesos motivacionales como elementos claves para el desarrollo de comportamientos adaptativos en el contexto de la educación física

Filaggrin and cytokines in respiratory samples of preterm infants at risk for respiratory viral infection

Respiratory viral infections (RVIs) are frequent in preterm infants possibly inducing long-term impact on respiratory morbidity. Immune response and respiratory barriers are key defense elements against viral insults in premature infants admitted to Neonatal Intensive Care Units (NICUs). Our main goals were to describe the local immune response in respiratory secretions of preterm infants with RVIs during NICU admission and to evaluate the expression and synthesis of lung barrier regulators, both in respiratory samples and in vitro models. Samples from preterm infants that went on to develop RVIs had lower filaggrin gene and protein levels at a cellular level were compared to never-infected neonates (controls). Filaggrin, MIP-1α/CCL3 and MCP-1 levels were higher in pre-infection supernatants compared to controls. Filaggrin, HIF-1α, VEGF, RANTES/CCL5, IL-17A, IL-1β, MIP-1α and MIP-1β/CCL5 levels were higher during and after infection. ROC curve and logistic regression analysis shows that these molecules could be used as infection risk biomarkers. Small airway epithelial cells stimulated by poly:IC presented reduced filaggrin gene expression and increased levels in supernatant. We conclude that filaggrin gene and protein dysregulation is a risk factor of RVI in newborns admitted at the NICU.This study has been partially supported by ISCIII – Instituto de Salud Carlos III, FIS (Fondo de Investigación Sanitaria—Spanish Health Research Fund) grants FI19/00067, PI18/00167, PI21/00896, PI18CIII/00009 and FEDER funds (Fondo Europeo de Desarrollo Regional); Sociedad Española de Alergología e Inmunología Clínica (SEAIC)Beca19A04_Valverde; Alfonso X El Sabio University Grant: VIII Convocatoria Santander-UAX; CIBER de Enfermedades Respiratorias (CIBERES), a Carlos III Institute of Health Initiative.S