Análisis de metodologías activas

En relación, a los cambios sociales a día de hoy, la educación necesita de un cambio pedagógico centrado en el alumnado. Es por esto mismo, que la implementación de las metodologías activas posibilita a los estudiantes participar activamente en el proceso de enseñanza y aprendizaje. Por esta razón con este estudio tiene como objetivo conocer diferentes tipos de metodologías activas que se pueden aplicar en las aulas y examinar los distintos criterios de los futuros docentes sobre estas. Para ello, se realiza un estudio descriptivo para el que se utiliza como instrumento de recogida de datos un cuestionario anónimo previamente validado, dirigido a futuros docentes. Los resultados muestran que un alto porcentaje de los individuos que componen la muestra son mujeres, y que además hay una gran diferencia de porcentaje entre las metodologías que han experimentado con las metodologías que llevarían a cabo. Como conclusión, cabe destacar que la gran mayoría de los encuestados están a favor de aplicar las metodologías activas para potenciar los procesos de enseñanza de los alumnos.<br /

Heme Oxygenase-1 (HO-1) Expression in Prostate Cancer Cells Modulates the Oxidative Response in Bone Cells.

Prostate cancer (PCa) is a leading cause of death among males. It is currently estimated that inflammatory responses are linked to 15-20% of all deaths from cancer worldwide. PCa is dominated by complications arising from metastasis to the bone where the tumor cells interact with the bone microenvironment impairing the balance between bone formation and degradation. However, the molecular nature of this interaction is not completely understood. Heme oxygenase-1 (HO-1) counteracts oxidative damage and inflammation. Previous studies from our laboratory showed that HO-1 is implicated in PCa, demonstrating that endogenous HO-1 inhibits bone derived-prostate cancer cells proliferation, invasion and migration and decreases tumor growth and angiogenesis in vivo. The aim of this work was to analyze the impact of HO-1 modulated PCa cells on osteoblasts proliferation in vitro and on bone remodeling in vivo. Using a co-culture system of PC3 cells with primary mice osteoblasts (PMOs), we demonstrated that HO-1 pharmacological induction (hemin treatment) abrogated the diminution of PMOs proliferation induced by PCa cells and decreased the expression of osteoclast-modulating factors in osteoblasts. No changes were detected in the expression of genes involved in osteoblasts differentiation. However, co-culture of hemin pre-treated PC3 cells (PC3 Hem) with PMOs provoked an oxidative status and activated FoxO signaling in osteoblasts. The percentage of active osteoblasts positive for HO-1 increased in calvarias explants co-cultured with PC3 Hem cells. Nuclear HO-1 expression was detected in tumors generated by in vivo bone injection of HO-1 stable transfected PC3 (PC3HO-1) cells in the femur of SCID mice. These results suggest that HO-1 has the potential to modify the bone microenvironment impacting on PCa bone metastasis.Fil: Ferrando, María Mercedes Catalina. DTO.DE QUIMICA BIOLOGICA;Fil: Wan, Xinahi.Fil: Meissl, Roberto Jose. Academia Nacional de Medicina de Buenos Aires;Fil: Yang, Yung.Fil: de Siervi, Adriana. Consejo Nacional de Invest.cientif.y Tecnicas. Instituto de Biologia y Medicina Experimental (i);Fil: Navone, Nora.Fil: Vazquez, Elba Susana. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Biologica

Aminopropyltransferases Involved in Polyamine Biosynthesis Localize Preferentially in the Nucleus of Plant Cells

Plant aminopropyltransferases consist of a group of enzymes that transfer aminopropyl groups derived from decarboxylated S-adenosyl-methionine (dcAdoMet or dcSAM) to propylamine acceptors to produce polyamines, ubiquitous metabolites with positive charge at physiological pH. Spermidine synthase (SPDS) uses putrescine as amino acceptor to form spermidine, whereas spermine synthase (SPMS) and thermospermine synthase (TSPMS) use spermidine as acceptor to synthesize the isomers spermine and thermospermine respectively. In previous work it was shown that both SPDS1 and SPDS2 can physically interact with SPMS although no data concerning the subcellular localization was reported. Here we study the subcellular localization of these enzymes and their protein dimer complexes with gateway-based Bimolecular Fluorescence Complementation (BiFC) binary vectors. In addition, we have characterized the molecular weight of the enzyme complexes by gel filtration chromatography with in vitro assembled recombinant enzymes and with endogenous plant protein extracts. Our data suggest that aminopropyltransferases display a dual subcellular localization both in the cytosol and nuclear enriched fractions, and they assemble preferably as dimers. The BiFC transient expression data suggest that aminopropyltransferase heterodimer complexes take place preferentially inside the nucleus

Analysis of Protein Oxidative Modifications in Follicular Fluid from Fertile Women: Natural Versus Stimulated Cycles

Oxidative stress is associated with obstetric complications during ovarian hyperstimulation in women undergoing in vitro fertilization. The follicular fluid contains high levels of proteins, which are the main targets of free radicals. The aim of this work was to determine specific biomarkers of non-enzymatic oxidative modifications of proteins from follicular fluid in vivo, and the effect of ovarian stimulation with gonadotropins on these biomarkers. For this purpose, 27 fertile women underwent both a natural and a stimulated cycle. The biomarkers, glutamic semialdehyde (GSA), aminoadipic semialdehyde (AASA), N-epsilon-(carboxymethyl)lysine (CML), and N-epsilon-(carboxyethyl)lysine (CEL), were measured by gas-liquid chromatography coupled to mass spectrometry. Results showed that follicular fluid contained products of protein modifications by direct metal-catalyzed oxidation (GSA and AASA), glycoxidation (CML and CEL), and lipoxidation (CML). GSA was the most abundant biomarker (91.5%). The levels of CML amounted to 6% of the total lesions and were higher than AASA (1.3%) and CEL (1.2%). In the natural cycle, CEL was significantly lower (p < 0.05) than in the stimulated cycle, suggesting that natural cycles are more protected against protein glycoxidation. These findings are the basis for further research to elucidate the possible relevance of this follicular biomarker of advanced glycation end product in fertility programs.This research was funded by the Basque Government, Department of Education, Universities and Research (project ref. IT687-13 and predoctoral grant to I.P.) and Department of Economic Development and Competitiveness, SPRI (refs. IG-20130001214 and IG-2014 0000837), University of the Basque Country UPV/EHU (ref. GIU16/62), and Fundacion Jesus Gangoiti (grant to S.M.)

Plan Ceibal e Inclusión Social. Perspectivas interdisciplinarias

El objetivo de este libro es difundir los resultados de tres investigaciones financiadas por el Programa de Proyectos de Investigación Orientados a la Inclusión Social de la Comisión Sectorial de Investigación Científica (CSIC) en el llamado del año 2008 de la Universidad de la República Oriental del Uruguay. Se trata de tres equipos interdisciplinarios cuyas investigaciones abordan la contribución de Plan Ceibal a la inclusión social desde distintos problemas y perspectivas. Se trata de una publicación que es única en cuanto a estas características. Parte de los objetivos de las investigaciones fue su contribución a la inclusión social y la relación con los sujetos vinculados a la temática que es objeto de estudio. Estos elementos se evidencian en las estrategias metodológicas y los procesos de cada una de las investigaciones

Gene Network of Susceptibility to Atypical Femoral Fractures Related to Bisphosphonate Treatment

Atypical femoral fractures (AFF) are rare fragility fractures in the subtrocantheric or diaphysis femoral region associated with long-term bisphosphonate (BP) treatment. The etiology of AFF is still unclear even though a genetic basis is suggested. We performed whole exome sequencing (WES) analysis of 12 patients receiving BPs for at least 5 years who sustained AFFs and 4 controls, also long-term treated with BPs but without any fracture. After filtration and prioritization of rare variants predicted to be damaging and present in genes shared among at least two patients, a total of 272 variants in 132 genes were identified. Twelve of these genes were known to be involved in bone metabolism and/or AFF, highlighting DAAM2 and LRP5, both involved in the Wnt pathway, as the most representative. Afterwards, we intersected all mutated genes with a list of 34 genes obtained from a previous study of three sisters with BP-related AFF, identifying nine genes. One of these (MEX3D) harbored damaging variants in two AFF patients from the present study and one shared among the three sisters. Gene interaction analysis using the AFFNET web suggested a complex network among bone-related genes as well as with other mutated genes. BinGO biological function analysis highlighted cytoskeleton and cilium organization. In conclusion, several genes and their interactions could provide genetic susceptibility to AFF, that along with BPs treatment and in some cases with glucocorticoids may trigger this so feared complication

Functional characterization of a GGPPS variant indentified in atypical femoral fracture patients and delineation of the role of GGPPS in bone-relevant cell types

Atypical femoral fractures (AFFs) are a rare but potentially devastating event, often but not always linked to bisphosphonate (BP) therapy. The pathogenic mechanisms underlying AFFs remain obscure, and there are no tests available that might assist in identifying those at high risk of AFF. We previously used exome sequencing to explore the genetic background of three sisters with AFFs and three additional unrelated AFF cases, all previously treated with BPs. We detected 37 rare mutations (in 34 genes) shared by the three sisters. Notably, we found a p.Asp188Tyr mutation in the enzyme geranylgeranyl pyrophosphate synthase, a component of the mevalonate pathway, which is critical to osteoclast function and is inhibited by N-BPs. In addition, the CYP1A1 gene, responsible for the hydroxylation of 17β-estradiol, estrone, and vitamin D, was also mutated in all three sisters and one unrelated patient. Here we present a detailed list of the variants found and report functional analyses of the GGPS1 p.Asp188Tyr mutation, which showed a severe reduction in enzyme activity together with oligomerization defects. Unlike BP treatment, this genetic mutation will affect all cells in the carriers. RNAi knockdown of GGPS1 in osteoblasts produced a strong mineralization reduction and a reduced expression of osteocalcin, osterix, and RANKL, whereas in osteoclasts, it led to a lower resorption activity. Taken together, the impact of the mutated GGPPS and the relevance of the downstream effects in bone cells make it a strong candidate for AFF susceptibility. We speculate that other genes such as CYP1A1 might be involved in AFF pathogenesis, which remains to be functionally proved. The identification of the genetic background for AFFs provides new insights for future development of novel risk assessment tools. © 2018 American Society for Bone and Mineral Research

GGPS1 Mutation and Atypical Femoral Fractures with Bisphosphonates

Atypical femoral fractures have been associated with long-term bisphosphonate treatment.1,2 However, the underlying mechanisms remain obscure. We studied three sisters who had atypical femoral fractures after receiving various oral bisphosphonates for 6 years. Two of the sisters had a single fracture (at the ages of 64 and 73 years), and one had bilateral fractures (one at the age of 60 years and the other at the age of 61 years). Given the low incidence of atypical femoral fractures in the general population (5.9 per 10,000 person-years),3 we hypothesized that these sisters might have an underlying genetic background that contributed to these fractures

Phenotypic characterization of X-linked hypophosphatemia in pediatric Spanish population

BACKGROUND: X-linked hypophosphatemia (XLH) is a hereditary rare disease caused by loss-of-function mutations in PHEX gene leading tohypophosphatemia and high renal loss of phosphate. Rickets and growth retardation are the major manifestations of XLH in children, but there is a broad phenotypic variability. Few publications have reported large series of patients. Current data on the clinical spectrum of the disease, the correlation with the underlying gene mutations, and the long-term outcome of patients on conventional treatment are needed, particularly because of the recent availability of new specific medications to treat XLH. RESULTS: The RenalTube database was used to retrospectively analyze 48 Spanish patients (15 men) from 39 different families, ranging from 3months to 8years and 2months of age at the time of diagnosis (median age of 2.0years), and with XLH confirmed by genetic analysis. Bone deformities, radiological signs of active rickets and growth retardation were the most common findings at diagnosis. Mean (±SEM) height was - 1.89±0.19 SDS and 55% (22/40) of patients had height SDS below-2. All cases had hypophosphatemia, serum phosphate being - 2.81±0.11 SDS. Clinical manifestations and severity of the disease were similar in both genders. No genotype-phenotype correlation was found. Conventional treatment did not attenuate growth retardation after a median follow up of 7.42years (IQR=11.26; n=26 patients) and failed to normalize serum concentrations of phosphate. Eleven patients had mild hyperparathyroidism and 8 patients nephrocalcinosis. CONCLUSIONS: This study shows that growth retardation and rickets were the most prevalent clinical manifestations at diagnosis in a large series of Spanish pediatric patients with XLH confirmed by mutations in the PHEX gene. Traditional treatment with phosphate and vitamin D supplements did not improve height or corrected hypophosphatemia and was associated with a risk of hyperparathyroidism and nephrocalcinosis. The severity of the disease was similar in males and females