Modulation of microRNA editing, expression and processing by ADAR2 deaminase in glioblastoma.

Background: ADAR enzymes convert adenosines to inosines within double-stranded RNAs, including microRNA (miRNA) precursors, with important consequences on miRNA retargeting and expression. ADAR2 activity is impaired in glioblastoma and its rescue has anti-tumoral effects. However, how ADAR2 activity may impact the miRNome and the progression of glioblastoma is not known. Results: By integrating deep-sequencing and array approaches with bioinformatics analyses and molecular studies, we show that ADAR2 is essential to edit a small number of mature miRNAs and to significantly modulate the expression of about 90 miRNAs in glioblastoma cells. Specifically, the rescue of ADAR2 activity in cancer cells recovers the edited miRNA population lost in glioblastoma cell lines and tissues, and rebalances expression of onco-miRNAs and tumor suppressor miRNAs to the levels observed in normal human brain. We report that the major effect of ADAR2 is to reduce the expression of a large number of miRNAs, most of which act as onco-miRNAs. ADAR2 can edit miR-222/221 and miR-21 precursors and decrease the expression of the corresponding mature onco-miRNAs in vivo and in vitro, with important effects on cell proliferation and migration. Conclusions: Our findings disclose an additional layer of complexity in miRNome regulation and provide information to better understand the impact of ADAR2 editing enzyme in glioblastoma. We propose that ADAR2 is a key factor for maintaining edited-miRNA population and balancing the expression of several essential miRNAs involved in cancer

Particle learning for Bayesian non-parametric Markov Switching Stochastic Volatility model

This paper designs a Particle Learning (PL) algorithm for estimation of Bayesian nonparametric Stochastic Volatility (SV) models for financial data. The performance of this particle method is then compared with the standard Markov Chain Monte Carlo (MCMC) methods for non-parametric SV models. PL performs as well as MCMC, and at the same time allows for on-line type inference. The posterior distributions are updated as new data is observed, which is prohibitively costly using MCMC. Further, a new non-parametric SV model is proposed that incorporates Markov switching jumps.The proposed model is estimated by using PL and tested on simulated data. Finally, the performance of the two non-parametric SV models, with and without Markov switching, is compared by using real financial time series. The results show that including a Markov switching specification provides higher predictive power in the tails of the distribution.Virbickaite, A. and Ausín, C.M. are grateful for the financial support from MEC grant ECO2011-25706. Galeano, P. acknowledges financial support from MEC grant ECO2012- 3844

Strenuous exercise worse than sedentarism?

Schnohr et al. (1) reported a U-shaped association between all-cause mortality and exercise dose in a Danish cohort. Jogging 1 to 2.4 h/week was associated with the lowest mortality, whereas jogging >3 times/week was no better than being inactive and was worse than light jogging (adjusted hazard ratio [HR]: 9.08; 95% confidence interval [CI]: 1.87 to 44.01). Furthermore, older (61.3 16.2 years) sedentary nonjoggers with cardiovascular disease (CVD) risk factors...

The Era of Smartphones: Back to Our Biological Makeup?

Physical inactivity is a major modifiable cardiovascular risk factor that has become a growing health problem in the 21st century: 83% of adolescents aged 13-15 years and approximately 1/3 of adults worldwide are inactive, that is, not meeting the minimum international physical activity (PA) recommendations (=150 minutes/week of moderate to vigorous PA) [1, 2]. Thus, the PA levels of the general population, especially of individuals at cardiovascular risk, should be routinely assessed by health care professionals, as it has been recently recommended by the American Heart Association [3]. To this end, accelerometers (usually attached to an elastic belt around the waist) allow objective quantification of PA by providing continuous recordings. At least 3 to 5 days of accelerometer monitoring (including weekend days) are required to determine habitual PA, and it is generally accepted that the device should be worn for =10 hours/day [4]. For this reason, the simple and inexpensive method of PA questionnaires is more widely used and generally better accepted. Unfortunately, the validity of self-reported PA is questionable..

De la política del sujeto al sujeto político

This article approaches the traditional conceptions about the political subject in order to widen them through a characterization of a dialectical game between the public and the private dimensions in which he acts.The notion resulting from this discussion is confronted with the context of the Colombian conflict. It is assumed, from this perspective, that the Political Subject is not a finished subject, but it is a subject in permanent construction, who is constantly looking for strategies and mechanisms to improve and transform his own reality. Accordingly, the ducational process (both formal and non-formal) may potentiate the subject's structuring.En este artículo se abordan las concepciones tradicionales del sujeto político para ampliarlas a través de una caracterización del juego dialéctico entre las dimensiones pública y privada en las que se desenvuelve, la noción emanada de esta discusión es confrontada con algunas condiciones del conflicto colombiano. Interpelando así la noción tradicional de sujeto político; asumiéndolo de manera compleja, como un sujeto en constante construcción a partir de estrategias y mecanismos que le permitan disponerse a la realidad, y mejorar y transformar la suya propia. En este sentido, se valora el proceso educativo (formal y no formal) que pueda potenciar la formación de dicho sujeto hacia la emancipación

Adeno-associated viral vector-mediated human vascular endothelial growth factor gene transfer stimulates angiogenesis and wound healing in the genetically diabetic mouse

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Regular physical activity: A little is good, but is it good enough?

Ekelund et al. (1) nicely showed that physical inactivity causes an approximate twofold increase in the numbers of deaths compared with those attributable to obesity [BMI (in kg/m2) .30] in a Euro- pean cohort (n 1/4 334,161) that was followed up to 12.4 y on average. Physical activity (PA) levels were estimated by using a standardized questionnaire or in-person interviews and were found to be inversely associated with all-cause mortality at all levels of BMI and waist circumference. Another important finding from their study is that substantial survival benefits may be achieved by fairly small amounts of moderate-intensity PA: that is, ;20 min/d of brisk walking, which is below the current PA recommendations of !30 min/d on most, if not all, days of the week (or !150 min/wk). These important findings in Caucasians are in line with those recently reported in an Asiatic cohort, in whom 15 min/d or 90 min/wk of moderate-intensity PA was associated with lower all-cause mor- tality, even for persons at risk of cardiovascular diseas

Azelastine potentiates antiasthmatic dexamethasone effect on a murine asthma model

Glucocorticoids are among the most effective drugs to treat asthma. However, thesevere adverse effects associated generate the need for its therapeutic optimization. Conversely, though histamine is undoubtedly related to asthma development, there is a lack of efficacy of antihistamines in controlling its symptoms, which prevents their clinical application. We have reported that antihistamines potentiate glucocorticoids? responses in vitro and recent observations have indicated that the coadministration of an antihistamine and a synthetic glucocorticoid has synergistic effects on a murine model of allergic rhinitis. Here, the aim of this work is to establish if this therapeutic combination could be beneficial in a murine model of asthma. We used an allergen‐induced model of asthma (employing ovalbumin) to evaluate the effectsof the synthetic glucocorticoid dexamethasone combined with the antihistamineazelastine. Our results indicate that the cotreatment with azelastine and a suboptimal dose of dexamethasone can improve allergic lung inflammation as shown by a decrease in eosinophils in bronchoalveolar lavage, fewer peribronchial and perivascular infiltrates, and mucin‐producing cells. In addition, serum levels of allergen‐specific IgE and IgG1 were also reduced, as well as the expression of lung inflammatory‐related genes IL‐4, IL‐5, Muc5AC, and Arginase I. The potentiation of dexamethasone effects by azelastine could allow to reduce the effective glucocorticoid dose needed to achieve a therapeutic effect. These findings provide first new insights into the potential benefits of glucocorticoids and antihistamines combination for the treatment of asthma and grants further research to evaluate this approach in other related inflammatory conditions.Fil: Zappia, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Soto, Ariadna Soledad. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Granja Galeano, Gina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Fenoy, Ignacio Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; ArgentinaFil: Fernandez, Natalia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fitzsimons, Carlos P.. University of Amsterdam; Países BajosFil: Goldman, Alejandra. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monczor, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentin

Determinación del consumo de ramio (Bohemeria nivea, Gaud) planta entera cortada a tres edades, por cerdos durante el levante y el desarrollo, en combinación con dos niveles de maíz molido.

Maíz-Zea may