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    Effects of mutations in the post-translational modification sites on the trafficking of hyaluronan synthase 2 (HAS2)

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    Vesicular trafficking of hyaluronan synthases (HAS1-3) from endoplasmic reticulum (ER) through Golgi to plasma membrane (PM), and either back to endosomes and lysosomes, or out into extracellular vesicles, is important for their activities. We studied how post-translational modifications affect the trafficking of HAS2 by mutagenesis of the sites of ubiquitination (K190R), phosphorylation (T110A) and O-GlcNAcylation (S221A), using Dendra2- and EGFP-HAS2 transfected into COS1 cells. Confocal microscopy showed HAS2 wild type (wt) and its K190R and S221A mutants in ER, Golgi and extracellular vesicles, while the T110A mutant remained mostly in the ER. HA synthesis was reduced by S221A, while completely blocked by K190R and T110A. Cell-surface biotinylation indicated that T110A was absent from PM, while S221A was close to the level of wt, and K190R was increased in PM. TIRF microscopy analysis gave similar results. Rab10 silencing increased HA secretion by HAS2, likely by inhibiting endocytosis of the enzyme from PM, as reported before for HAS3. Green-to-red photo-conversion of Dendra2-HAS2 constructs suggested slower decay of K190R and S221A than HAS2 wt, while T110A was barely degraded at all. S221D and S221E, the phosphomimetic mutants of this site, decayed faster and blocked hyaluronan synthesis, suggesting alternative O-GlcNAc/-PO4 substitution to regulate the stability of the enzyme. Probing the role of dynamic O-GlcNAcylation at S221 by adding glucosamine increased the half-life of only HAS2 wt. The Dendra2·HAS2 disappearance from Golgi was slower for K190R. Of the two inactive constructs, K190R co-transfected with HAS2 wt suppressed, whereas T110A had no effect on HA synthesis. Interestingly, the HAS2-stimulated shedding of extracellular vesicles was dependent on HAS residence in PM but independent of HA synthesis. The results indicate that post-translational modifications control the trafficking of HAS2, and that trafficking is an integral part of the post-translational regulation of HAS2 activity

    Clinical Relevance and Prognostic Value of Persistently Negative (1,3)-β-D-Glucan in Adults With Candidemia: A 5-year Experience in a Tertiary Hospital

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    Background. The clinical relevance and the potential prognostic role of persistently negative (1,3)-β-D-glucan (BDG) in adults with proven candidemia is unknown. Methods. This retrospective study included all adults diagnosed with candidemia our tertiary university hospital from 2012–2017 who had at least 2 serum BDG determinations throughout the episode of fungemia (Fungitell Assay; positive cut-off ≥80pg/mL). Epidemiology and clinical outcomes were compared between patients with all negative versus any positive BDG tests. Poor clinical outcomes included complications due to candidemia or 30-day all-cause mortality. Results. Overall, 26/148 (17.6%) candidemic adults had persistently negative BDG tests. These patients were less likely to present Candida growth in all 3 sets of blood cultures (15.4% vs 45.1%; P = .005) and had less severe clinical presentations (median Pitt score, 0 [interquartile range {IQR} 0–1] vs 1 [IQR 0–2] in patients with any positive BDG test; P = .039). Although adequate treatment was equally provided to both groups (96.2% in persistently negative group vs 93.4 in positive group; P = .599), the persistently negative group had a higher rate of microbiological clearance in the first follow-up blood cultures (92.3% vs 69.7% in positive group; P = .005), fewer complications due to candidemia (7.7% vs 33.6% in positive group; P = .008), a lower 30-day mortality rate (3.8% vs 23.8% in positive group; P = .004), and a shorter in-hospital stay (34 days [IQR 18–55] vs 51 days [IQR 35–91] in positive group; P = .003). In the multivariate analysis, persistently negative BDG tests were independently associated with better prognoses (odds ratio 0.12, 95% confidence interval 0.03–0.49; P = .003). Conclusions. Candidemic patients with persistently negative BDG tests present a better prognosis than the comparative group, probably due to a lower systemic fungal burden. In this context, the appropriate use of persistently negative BDG results could be an aid to individualize therapeutic management in the near future

    Forgotten before being known. The absence of female writers in textbooks in compulsory education

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    La investigación se centra fundamentalmente en demostrar la necesidad de incluir a las mujeres escritoras en los libros de texto, sus biografías y sus obras, igual que quedan recogidos sus contemporáneos masculinos. Se hace un estudio comparativo del número de hombres escritores frente al número de mujeres que aparecen en los libros de Lengua castellana y Literatura, y se proponen nombres, datos biográficos y textos representativos para la inclusión desde la Edad Media hasta el S. XIX. En este estudio exploratorio y explicativo, se trata de dar respuesta al motivo de la ausencia de dichas mujeres y a la urgencia de su presencia en los libros de Enseñanza Secundaria Obligatoria

    Dimensions of Anger Reactions-Revised: Validation of a brief anger measure in Australia and Spain.

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    Objective A validated, brief measure of anger is needed in clinical settings to screen for problematic anger. This study examined the validity of the seven‐item Dimensions of Anger Reactions‐Revised (DAR‐R), including a version for the Spanish population. Method Multiple psychometric instruments administered to 541 (76.6% female) adults in Australia and 1,115 (56.3% female) in Spain were analyzed. Results A two‐factor model (anger response and anger impairment) was confirmed. Concurrent, convergent, and discriminant validity were supported. Anger response items strongly correlated with established measures of anger/aggression State‐Trait Anger Expression Inventory (Aggression Questionnaire), whereas anger impairment items strongly correlated with anxiety Generalized Anxiety Disorder‐7 and depression Patient Health Questionnaire‐9 measures. Internal consistency and test–retest reliability (3 months) were good. Cut‐off scores for problematic anger were established. There were no gender differences in anger in the Spanish sample, but Australian males had higher anger scores than females. Conclusion Results substantiate the utility of the DAR‐R as a concise, clinically informative measure of anger

    Effects of acute ingestion of caffeine on team sports performance: a systematic review and meta-analysis

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    The aim of this investigation was to perform a systematic review and meta-analysis to determine the efficacy of the acute ingestion of caffeine (from 3 to 6 mg/kg) to increase performance on variables related to team sports. A systematic review was performed in scientific databases from January to April 2018. All studies included had cross-over experimental designs comparing caffeine to an identical placebo condition. A meta-analysis was performed using the random effects model and pooled standardized mean differences (Glass’s Δ). Thirty-four studies published between 2001 and 2018 were included in the analysis. The meta-analysis revealed that caffeine increased single (Δ;95% confidence intervals = 0.19;0.14–-0.25; p < 0.01) and repeated jump height (0.29;0.16–0.42;p < 0.01), single (0.16;0.02–0.30; p = 0.03) and repeated sprint velocity (0.14;0.03–0.25; p = 0.02), and reduced the time to complete agility tests (0.41;0.04–0.77; p = 0.03). During team sport matches, caffeine increased total running distance (0.41;0.20–0.62; p < 0.01), distance covered at sprint velocity (0.36;0.12–0.59; p < 0.01) and the number of sprints (0.44;0.18–0.69; p < 0.01). The acute ingestion of a moderate dose of caffeine had a small but significant positive effect on several aspects related to physical performance in team sports

    La webserie en el aula de ELE: una propuesta desde la Interculturalidad

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    La llamada educación intercultural está siendo considerada desde hace años como uno de los enfoques predominantes en numerosas propuestas educativas. Al ser el aula de lengua extranjera un espacio de enseñanza-aprendizaje multicultural, caracterizado por la diversidad, cada vez se hace más necesario el desarrollo de la competencia intercultural si queremos ofrecer una enseñanza de calidad en esta sociedad cada vez más multilingüe y multicultural. La investigación del Marco de Referencia para los Enfoques Plurales de las Lenguas y de las Culturas en Europa (en adelante MAREP 2007) destaca que esta competencia es generalmente relegada, o excluida del currículum de las clases de lengua extranjera, para dar prioridad al desarrollo de la competencia lingüística. A esto se une la falta de capacitación o inadecuada formación de los docentes para el desarrollo de dicha competencia. En el apartado teórico se hará un recorrido por las perspectivas que conducen a la adquisición de la llamada competencia intercultural y los contenidos más importantes que la integran, que posteriormente se llevarán a una propuesta didáctica, destinada a desarrollar la competencia comunicativa intercultural en la enseñanza de ELE.In the last few years intercultural education has been considered as one of the predominant approaches in a large number of educational proposals. A foreign language class being a multicultural teaching-learning space, characterized by its diversity, intercultural proficiency development is each time becoming more necessary if we want to offer quality teaching in this increasingly more multilingual and multicultural society. The research carried out by the Reference Frame for Plural Approaches of Languages and Cultures in Europe (MAREP 2007) highlights that intercultural competency is usually excluded or relegated far from the foreign language curriculum to prioritise the development of linguistic competency. This together with the lack of adequate teacher training does not help the development of this competency. During the theoretical part a route will be made through the perspectives which led to the acquisition of the so-called intercultural competency and its main contents, which will later be put in a didactic proposal, aimed to develop intercultural communicative competence in Spanish teaching

    The Influence of the Menstrual Cycle on Muscle Strength and Power Performance

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    This study aimed to investigate the fluctuations of muscle performance in the Smith machine half-squat exercise during three different phases of the menstrual cycle. Thirteen resistance-trained and umenorrheic women volunteered to participate in the study (58.6 ± 7.8 kg, 31.1 ± 5.5 years). In a pre-experimental test, the half-squat onerepetition maximum (1RM) was measured. Body mass, tympanic temperature and urine concentration of the luteinizing hormone were estimated daily for ~30 days to determine the early follicular phase (EFP), the late follicular phase (LFP), and the mid-luteal phase (MLP) of the menstrual cycle. On the second day of each phase, performance of the Smith machine half-squats was assessed using 20, 40, 60 and 80% of one repetition maximum (1RM). In each load, force, velocity, and power output were measured during the concentric phase of the exercise by means of a rotatory encoder. The data were analyzed using one-way repeated measures ANOVA coupled with magnitude-based inferences. Overall, force, velocity and power output were very similar in all menstrual cycle phases with unclear differences in most of the pairwise comparisons and effect sizes >0.2. The results of this investigation suggest that eumenorrheic females have similar muscle strength and power performance in the Smith machine half-squat exercise during the EFP, LFP, and MLP phases of the menstrual cycl

    Eficacia de la recuperación activa en medio acuático para la fatiga post-partido en futbolistas aficionados. Diseño cruzado aleatorizado

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    Resumen Introducción: la fatiga generada en fútbol, fenómeno multifactorial, puede influir negativamente en la progresión y rendimiento de los jugadores, e incluso aumentar el riesgo de lesión. Es necesario disponer de estrategias de recuperación adecuadas. La bibliografía no llega a clarificar del todo cual es la más efectiva, incluso, alguna de las empleadas en el ámbito del deporte presenta una mínima base científica, como es el caso de la recuperación en medio acuático. Métodos: se realizó un estudio cruzado aleatorizado con 15 jugadores de fútbol aficionados. Las mediciones fueron realizadas 48 horas antes del partido para obtener unos valores basales, inmediatamente tras el partido y 24 horas después de la estrategia de recuperación. Todos los jugadores recibieron las 3 estrategias de recuperación en 3 semanas de competición distintas: recuperación activa en medio acuático, en seco y recuperación pasiva. La fatiga se monitorizó mediante las variables del salto vertical CMJ (“countermovement jump”) y la fatiga subjetiva percibida mediante el RPE. Resultados: las tres estrategias ocasionaron una mejora similar de las variables del salto CMJ pero sin alcanzar los valores basales. La recuperación en medio acuático presenta mejores resultados en la percepción subjetiva de la fatiga a pesar de no encontrar una correlación adecuada con los valores del salto vertical. Conclusiones: a pesar de obtener mejoras en las variables por parte de las tres recuperaciones, no son del todo determinantes. Son necesarios futuros estudios con un mayor control y seguimiento de los múltiples factores que influyan en dicha fatiga

    Relato de integridad y corrupción

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    El objeto de estas páginas es examinar lo que llamaremos el discurso de integridad en algunos de los títulos rodados durante el mandato de Mariano Rajoy que han reflejado el tema de la corrupción en las pantallas. En concreto, se analizan dos películas, ambas premiadas con el Goya en alguna de las categorías de guion. La primera, El hombre de las mil caras (2016), está escrita por Alberto Rodríguez y Rafael Cobos (también creadores de La peste) a partir de un libro, Paesa, el espía de las mil caras, de Manuel Cerdán. La trama trata del agente secreto Francisco Paesa y del exdirector general de la Guardia Civil, Luis Roldán. La segunda, El Reino (2018), está escrita por Rodrigo Sorogoyen e Isabel Peña y es una indagación sobre los últimos casos de corrupción en España

    Towards Neuro-Inspired Electronic Oscillators Based on The Dynamical Relaying Mechanism

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    Electronic oscillators are used for the generation of both continuous and discrete signals, playing a fundamental role in today’s electronics. In both contexts, these systems require stringent performances such as spectral purity, low phase noise, frequency and temperature stability. In state of the art oscillators the preservation of some of these aspects is jeopardized by specific critical issues, e.g., the sensitivity to load capacitance or the component aging over time. This leaves room for the search of new technologies for their realization. On the other hand, in the last decade electronics has been influenced by a growing number of neuro-inspired mechanisms, which allowed for alternative techniques aimed at solving some classical critical issues. In this paper we present an exploratory study for the development of electronic oscillators based on the neuro-inspired mechanism dynamical relaying, which relies on a structure composed of three delay coupled units (as neurons or even neuron populations) able to resonate and self-organise to generate and maintain a given rhythm with great reliability over a considerable parameter range, showing robustness to noise. We used the recent leaky integrated and fire with latency (LIFL) as neuron model. We have initially developed the mathematical model of the neuro-inspired oscillator, and implemented it using Matlab®; then, we have realized the schematic of such system in PSpice®. Finally, the model has been validated to verify whether it observes the fundamental properties of the dynamical relaying mechanisms described in computational neuroscience studies, and if the circuit implementation presents the same behaviour of the mathematical model. Validation results suggest that the dynamical relaying mechanism can be proficuously taken in consideration as alternative strategy for the design of electronic oscillators.Financial support by the Spanish Ministry of Economy and Competitiveness (PTA-2015- 10395-I

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