Enfoque inductivo frente al enfoque deductivo en la enseñanza de la Fonética Inglesa a alumnos universitarios

El trabajo muestra un análisis contrastivo de los enfoques inductivo y deductivo en la enseñanza de la Fonética Inglesa a alumnos universitarios. Para realizar dicho estudio se ha diseñado un cuestionario que pretende medir conocimientos básicos de Fonética Inglesa. En el trabajo se presentan los resultados obtenidos tras pasar el cuestionario a tres grupos diferentes de estudiantes universitarios de Fonética Inglesa de la Universidad de Sevilla. Se habían seguido distintos enfoques metodológicos en clase para los tres grupos representados en el cuestionario. El primer grupo (grupo A) siguió un enfoque meramente deductivo en el que el profesor aportaba toda la información teórica en clase y la apoyaba posteriormente con supuestos prácticos. El segundo grupo (grupo B) siguió un enfoque inductivo: el profesor partía de los conocimientos previos con ejercicios centrados en distintos aspectos de la pronunciación inglesa desde los que se iban construyendo los conocimientos. El tercer grupo (grupo C) siguió un enfoque híbrido, es decir, se alternaban la exposición de ideas con ejercicios de pronunciación al comienzo del desarrollo de los temas. Los resultados obtenidos demuestran que aquellos alumnos que han seguido un enfoque inductivo (grupo B) en la materia consiguen mejores resultados en conocimientos teóricos, seguido del grupo C. Los peores resultados se consiguieron en el grupo A. El grupo B también muestra los mejores resultados en cuanto a pronunciación, seguido en este caso del grupo A. La principal conclusión que se puede extraer de este estudio es que el enfoque inductivo en la enseñanza de la Fonética y Fonología Inglesa consigue mejorar los niveles de aprendizaje tanto a nivel teórico como a nivel práctico

Finezas de Jesús Sacramentado para con los hombres, e ingratitudes de los hombres para con Jesús Sacramentado

Copia digital : Junta de Castilla y León. Consejería de Cultura y Turismo, 201

Neuronal accumulation of unrepaired DNA in a novel specific chromatin domain: structural, molecular and transcriptional characterization

There is growing evidence that defective DNA repair in neurons with accumulation of DNA lesions and loss of genome integrity underlies aging and many neurodegenerative disorders. An important challenge is to understand how neurons can tolerate the accumulation of persistent DNA lesions without triggering the apoptotic pathway. Here we study the impact of the accumulation of unrepaired DNA on the chromatin architecture, kinetics of the DNA damage response and transcriptional activity in rat sensory ganglion neurons exposed to 1-to-3 doses of ionizing radiation (IR). In particular, we have characterized the structural, molecular and transcriptional compartmentalization of unrepaired DNA in persistent DNA damaged foci (PDDF). IR induced the formation of numerous transient foci, which repaired DNA within the 24 h post-IR, and a 1-to-3 PDDF. The latter concentrate DNA damage signaling and repair factors, including ?H2AX, pATM, WRAP53 and 53BP1. The number and size of PDDF was dependent on the doses of IR administered. The proportion of neurons carrying PDDF decreased over time of post-IR, indicating that a slow DNA repair occurs in some foci. The fine structure of PDDF consisted of a loose network of unfolded 30 nm chromatin fiber intermediates, which may provide a structural scaffold accessible for DNA repair factors. Furthermore, the transcription assay demonstrated that PDDF are transcriptionally silent, although transcription occurred in flanking euchromatin. Therefore, the expression of ?H2AX can be used as a reliable marker of gene silencing in DNA damaged neurons. Moreover, PDDF were located in repressive nuclear environments, preferentially in the perinucleolar domain where they were frequently associated with Cajal bodies or heterochromatin clumps forming a structural triad. We propose that the sequestration of unrepaired DNA in discrete PDDF and the transcriptional silencing can be essential to preserve genome stability and prevent the synthesis of aberrant mRNA and protein products encoded by damaged genes

Nucleolar disruption and cajal body disassembly are nuclear hallmarks of DNA damage-induced neurodegeneration in purkinje cells

The Purkinje cell (PC) degeneration (pcd) phenotype results from mutation in nna1 gene and is associated with the degeneration and death of PCs during the postnatal life. Although the pcd mutation is a model of the ataxic mouse, it shares clinical and pathological characteristics of inherited human spinocerebellar ataxias. PC degeneration in pcd mice provides a useful neuronal system to study nuclear mechanisms involved in DNA damage-dependent neurodegeneration, particularly the contribution of nucleoli and Cajal bodies (CBs). Both nuclear structures are engaged in housekeeping functions for neuronal survival, the biogenesis of ribosomes and the maturation of snRNPs and snoRNPs required for pre-mRNA and pre-rRNA processing, respectively. In this study, we use ultrastructural analysis, in situ transcription assay and molecular markers for DNA damage, nucleoli and CB components to demonstrate that PC degeneration involves the progressive accumulation of nuclear DNA damage associated with disruption of nucleoli and CBs, disassembly of polyribosomes into monoribosomes, ribophagy and shut down of nucleolar and extranucleolar transcription. Microarray analysis reveals that four genes encoding repressors of nucleolar rRNA synthesis (p53, Rb, PTEN and SNF2) are upregulated in the cerebellum of pcd mice. Collectively, these data support that nucleolar and CB alterations are hallmarks of DNA damage-induced neurodegeneration.ACKNOWLEDGMENTS: The authors wish to thank Raquel García-Ceballos and Saray Pereda for technical assistance. This work was supported by the following grants: Dirección General de Investigación (BFU2008- 00175); Instituto de Salud Carlos III (CIBERNED, CB06/05/ 0037), Ministerio de Ciencia y Tecnología (BFU2010-18284), Ministerio de Sanidad, Política Social e Igualdad (Plan Nacional Sobre Drogas), Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV, FMV/UC09-02), Junta de Castilla y León, Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León and Fundación Memoria D. Samuel Solórzano-Barruso, all of them from Spain

Persistent accumulation of unrepaired DNA damage in rat cortical neurons: nuclear organization and ChIP-seq analysis of damaged DNA

Neurons are highly vulnerable to DNA damage induced by genotoxic agents such as topoisomerase activity, oxidative stress, ionizing radiation (IR) and chemotherapeutic drugs. To avert the detrimental effects of DNA lesions in genome stability, transcription and apoptosis, neurons activate robust DNA repair mechanisms. However, defective DNA repair with accumulation of unrepaired DNA are at the basis of brain ageing and several neurodegenerative diseases. Understanding the mechanisms by which neurons tolerate DNA damage accumulation as well as defining the genomic regions that are more vulnerable to DNA damage or refractory to DNA repair and therefore constitute potential targets in neurodegenerative diseases are essential issues in the field. In this work we investigated the nuclear topography and organization together with the genome-wide distribution of unrepaired DNA in rat cortical neurons 15 days upon IR. About 5% of non-irradiated and 55% of irradiated cells accumulate unrepaired DNA within persistent DNA damage foci (PDDF) of chromatin. These PDDF are featured by persistent activation of DNA damage/repair signaling, lack of transcription and localization in repressive nuclear microenvironments. Interestingly, the chromatin insulator CTCF is concentrated at the PDDF boundaries, likely contributing to isolate unrepaired DNA from intact transcriptionally active chromatin. By confining damaged DNA, PDDF would help preserving genomic integrity and preventing the production of aberrant proteins encoded by damaged genes.ChIP-seq analysis of genome-wide ?H2AX distribution revealed a number of genomic regions enriched in ?H2AX signal in IR-treated cortical neurons. Some of these regions are in close proximity to genes encoding essential proteins for neuronal functions and human neurodegenerative disorders such as epm2a (Lafora disease), serpini1 (familial encephalopathy with neuroserpin inclusion bodies) and il1rpl1 (mental retardation, X-linked 21). Persistent ?H2AX signal close to those regions suggests that nearby genes could be either more vulnerable to DNA damage or more refractory to DNA repair.This work was supported by the following grants: “Dirección General de Investigación” (BFU2014–54754-P) and “Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas” (CIBERNED; CB06/05/0037) Spain

Effect of VDR gene polymorphisms on osteocalcin secretion in calcitriol-stimulated human osteoblasts

Effect of VDR gene polymorphisms on osteocalcin secretion in calcitriol-stimulated human osteoblasts.BackgroundThe impact of vitamin D receptor (VDR) gene polymorphisms in bone metabolism remains controversial. Some authors have found a beneficial effect of some VDR gene polymorphisms, while others found no differences, or even a lower bone mass in subjects with the same type of polymorphisms. The aim of this study was to assess if the VDR gene polymorphisms could have an effect on the calcitriol-stimulated osteocalcin in human osteoblasts.MethodsOsteoblasts were obtained from human femoral necks replaced because of osteoarthritis. Bones were cut into pieces of 1 to 2mm and placed in a nylon mesh. After the migration of osteoblasts, the pieces were collected and cultured with different concentrations of calcitriol (10−8, 10−9, and 10−10 mol/L). After 48 hours of incubation with calcitriol, the osteocalcin secreted into the medium (corrected by either total proteins or total DNA content) was measured. The DNA was extracted from the osteoblasts, amplified by polymerase chain reaction (PCR), and analyzed for target sequences sites of the BsmI, ApaI, TaqI, and FokI restriction enzymes.ResultsThe response observed in osteocalcin secretion in the bb or TT genotypes doubled the response observed in the BB or tt genotypes (calcitriol 10−8 and 10−9 mol/L). A slight trend was also observed with the aa genotype. Men showed higher levels of osteocalcin secretion than women. Age did not show any influence in osteocalcin secretion.ConclusionVDR alleles and gender demonstrated an effect on the osteocalcin secretion. BB or tt genotypes, and also the “A” allele, showed the lowest calcitriol-stimulated osteocalcin secretion

Impact of dynamical regionalization on precipitation biases and teleconnections over West Africa

West African societies are highly dependent on the West African Monsoon (WAM). Thus, a correct representation of the WAM in climate models is of paramount importance. In this article, the ability of 8 CMIP5 historical General Circulation Models (GCMs) and 4 CORDEX-Africa Regional Climate Models (RCMs) to characterize the WAM dynamics and variability is assessed for the period July-August-September 1979-2004. Simulations are compared with observations. Uncertainties in RCM performance and lateral boundary conditions are assessed individually. Results show that both GCMs and RCMs have trouble to simulate the northward migration of the Intertropical Convergence Zone in boreal summer. The greatest bias improvements are obtained after regionalization of the most inaccurate GCM simulations. To assess WAM variability, a Maximum Covariance Analysis is performed between Sea Surface Temperature and precipitation anomalies in observations, GCM and RCM simulations. The assessed variability patterns are: El Nio-Southern Oscillation (ENSO); the eastern Mediterranean (MED); and the Atlantic Equatorial Mode (EM). Evidence is given that regionalization of the ENSO-WAM teleconnection does not provide any added value. Unlike GCMs, RCMs are unable to precisely represent the ENSO impact on air subsidence over West Africa. Contrastingly, the simulation of the MED-WAM teleconnection is improved after regionalization. Humidity advection and convergence over the Sahel area are better simulated by RCMs. Finally, no robust conclusions can be determined for the EM-WAM teleconnection, which cannot be isolated for the 1979-2004 period. The novel results in this article will help to select the most appropriate RCM simulations to study WAM teleconnections

Contribution of genetic and epigenetic mechanisms to Wnt pathway activity in prevalent skeletal disorders

Producción CientíficaWe reported previously that the expression of Wnt-related genes is lower in osteoporotic hip fractures than in 26 osteoarthritis. We aimed to confirm those results by analyzing β-catenin levels and explored potential genetic 27 and epigenetic mechanisms involved. 28 β-Catenin gene expression and nuclear levelswere analyzed by real time PCR and confocal immunofluorescence. 29 Increased nuclear β-catenin was found in osteoblasts isolated from patients with osteoarthritis (99 ± 4 30 units vs. 76 ± 12, p = 0.01, n = 10), without differences in gene transcription, which is consistent with 31 a post-translational down-regulation of β-catenin and decreased Wnt pathway activity. 32 Twenty four single nucleotide polymorphisms (SNPs) of genes showing differential expression between fractures 33 and osteoarthritis (WNT4, WNT10A, WNT16 and SFRP1) were analyzed in DNA isolated from blood of 853 pa- 34 tients. The genotypic frequencies were similar in both groups of patients, with no significant differences. 35 Methylation ofWnt pathway genes was analyzed in bone tissue samples (15 with fractures and 15 with osteo- 36 arthritis) by interrogating a CpG-based methylation array. Six genes showed significant methylation differences 37 between both groups of patients: FZD10, TBL1X, CSNK1E, WNT8A, CSNK1A1L and SFRP4. The DNA demethylating 38 agent 5-deoxycytidine up-regulated 8 genes, including FZD10, in an osteoblast-like cell line, whereas it down- 39 regulated other 16 genes. 40 In conclusion,Wnt activity is reduced in patientswith hip fractures, in comparisonwith thosewith osteoarthritis. 41 It does not appear to be related to differences in the allele frequencies of the Wnt genes studied. On the other 42 hand, methylation differences between both groups could contribute to explain the differences inWnt activit

Scans per day as predictors of optimal glycemic control in people with type 1 diabetes mellitus using flash glucose monitoring: What number of scans per day should raise a red flag?

Aims: This study aimed to determine the minimum frequency of flash glucose monitoring (FGM) scans necessary for optimal glycemic control in patients with type 1 diabetes (T1D). Methods: Data were collected from 692 patients (47.5% female, with a median age of 47.4 years) who used FGM systems daily and recorded their clinical variables and device data. Results: Logistic regression models showed that performing more than 12 scans per day was associated with improved T1D control (OR = 4.22, p < 0.001) and a reduction in HbA1c (7.6 vs 7.0%, 60–53 mmol/mol p < 0.001). However, those performing less than 6 scans showed no improvement in HbA1c (7.9 vs 7.8%, 63–61 mmol/mol p = 0.514). Thirteen daily scans were determined as the optimal cutoff point for predicting optimal glycemic control using a maximally selected rank algorithm. Significant reductions were observed in mean glucose (< 0.001), coefficient of variation (< 0.001), HbA1c (< 0.001), and an increase in TIR (< 0.001) in patients who performed more than 12 daily scans. Conclusions: The results suggest that a higher frequency of daily scans by T1D patients using FGM systems leads to improved chronic glycemic control. The minimum recommended frequency for optimal control is 13 scans per day, and more than 6 daily scans are needed to improve HbA1