Browsing by Author "Silva, Isabel"
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- Calcium signaling and the novel anti-proliferative effect of the UTP-sensitive P2Y11 receptor in rat cardiac myofibroblastsPublication . Certal, Mariana; Vinhas, Adriana; Pinheiro, Ana Rita; Ferreirinha, Fátima; Barros-Barbosa, Aurora Raquel; Silva, Isabel; Costa, Maria Adelina; Correia-de-Sá, PauloDuring myocardial ischemia and reperfusion both purines and pyrimidines are released into the extracellular milieu, thus creating a signaling wave that propagates to neighboring cells via membrane-bound P2 purinoceptors activation. Cardiac fibroblasts (CF) are important players in heart remodeling, electrophysiological changes and hemodynamic alterations following myocardial infarction. Here, we investigated the role UTP on calcium signaling and proliferation of CF cultured from ventricles of adult rats. Co-expression of discoidin domain receptor 2 and -smooth muscle actin indicate that cultured CF are activated myofibroblasts. Intracellular calcium ([Ca2+]i) signals were monitored in cells loaded with Fluo-4 NW. CF proliferation was evaluated by the MTT assay. UTP and the selective P2Y4 agonist, MRS4062, caused a fast desensitizing [Ca2+]i rise originated from thapsigargin-sensitive internal stores, which partially declined to a plateau providing the existence of Ca2+ in the extracellular fluid. The biphasic [Ca2+]i response to UTP was attenuated respectively by P2Y4 blockers, like reactive blue-2 and suramin, and by the P2Y11 antagonist, NF340. UTP and the P2Y2 receptor agonist MRS2768 increased, whereas the selective P2Y11 agonist NF546 decreased, CF growth; MRS4062 was ineffective. Blockage of the P2Y11receptor or its coupling to adenylate cyclase boosted UTP-induced CF proliferation. Confocal microscopy and Western blot analysis confirmed the presence of P2Y2, P2Y4 and P2Y11 receptors. Data indicate that besides P2Y4 and P2Y2 receptors which are responsible for UTP-induced [Ca2+]i transients and growth of CF, respectively, synchronous activation of the previously unrecognized P2Y11 receptor may represent an important target for anti-fibrotic intervention in cardiac remodeling.
- Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent ratsPublication . Nasuti, Cinzia; Carloni, Manuel; Fedeli, Donatella; Gabbianelli, Rosita; Di Stefano, Antonio; Cerasa, Laura Serafina; Silva, Isabel; Domingues, Valentina F.; Ciccocioppo, RobertoPesticide exposure during brain development could represent an important risk factor for the onset of neurodegenerative diseases. Previous studies investigated the effect of permethrin (PERM) administered at 34 mg/kg, a dose close to the no observable adverse effect level (NOAEL) from post natal day (PND) 6 to PND 21 in rats. Despite the PERM dose did not elicited overt signs of toxicity (i.e. normal body weight gain curve), it was able to induce striatal neurodegeneration (dopamine and Nurr1 reduction, and lipid peroxidation increase). The present study was designed to characterize the cognitive deficits in the current animal model. When during late adulthood PERM treated rats were tested for spatial working memory performances in a T-maze-rewarded alternation task they took longer to choose for the correct arm in comparison to age matched controls. No differences between groups were found in anxiety-like state, locomotor activity, feeding behavior and spatial orientation task. Our findings showing a selective effect of PERM treatment on the T-maze task point to an involvement of frontal cortico-striatal circuitry rather than to a role for the hippocampus. The predominant disturbances concern the dopamine (DA) depletion in the striatum and, the serotonin (5-HT) and noradrenaline (NE) unbalance together with a hypometabolic state in the medial prefrontal cortex area. In the hippocampus, an increase of NE and a decrease of DA were observed in PERM treated rats as compared to controls. The concentration of the most representative marker for pyrethroid exposure (3-phenoxybenzoic acid) measured in the urine of rodents 12 h after the last treatment was 41.50 µ/L and it was completely eliminated after 96 h.
- Estimação nos modelos bivariados de médias móveis de valor inteiroPublication . Torres, Cristina; Silva, Eduarda; Silva, IsabelNas últimas décadas, o estudo das séries temporais de contagem univariadas tem sido objecto de interesse crescente na literatura. Uma das classes de modelos mais populares é a dos modelos auto-regressivos e médias móveis de valor inteiro não-negativo, INARMA, obtida através da substituição da multiplicação por um operador aleatório, chamado thinning, nos modelos ARMA convencionais. Os modelos INAR para séries de contagem univariadas têm sido amplamente estudados na literatura no que diz respeito quer às suas propriedades probabilísticas quer à inferência estatística. Por outro lado, a classe alargada de modelos de médias móveis para séries de valor inteiro, INMA, em que as operações thinning em instantes diferentes são dependentes entre si, não tem sido objecto de tanta atenção. De facto os modelos INMA não são Markovianos pelo que a inferência estatística apresenta dificuldades adicionais. Actualmente o interesse na análise de séries temporais de contagem centra-se em modelos e métodos para séries multivariadas. Neste trabalho, consideram-se os modelos INMA bivariados propostos por Torres et al. (2012). Nesta classe alargada de modelos bivariados INMA, a estrutura de dependência entre as duas séries temporais é introduzia pela dependência entre os dois processos de chegada enquanto que a dependência em cada série é definida pela dependência de operações thinning em instantes diferentes. Consideram-se estimadores baseados em momentos: método dos momentos (MM), método dos momentos generalizados (GMM) e método dos momentos eficiente (EMM), assim como estimadores baseados na função geradora de probabilidades.
- Inference for bivariate integer-valued moving average models based on binomial thinning operationPublication . Silva, Isabel; Eduarda Silva, Maria; Torres, CristinaTime series of (small) counts are common in practice and appear in a wide variety of fields. In the last three decades, several mod-els that explicitly account for the discreteness of the data have been proposed in the literature. However, for multivariate time series of counts several difficulties arise and the literature is not so detailed. This work considers Bivariate INteger-valued Moving Average, BINMA, models based on the binomial thinning operation. The main probabilistic and statistical properties of BINMA models are studied. Two parametric cases are analysed, one with the cross-correlation generated through a Bivariate Poisson innovation process and another with a Bivariate Negative Binomial innovation process. Moreover, parameter estimation is carried out by the Generalized Method of Moments. The performance of the model is illustrated with synthetic data as well as with real datasets.