Browsing by Issue Date, starting with "2021-11-09"
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- Impact of Peripheral Inflammation on the Susceptibility to Neurodegenerative DiseasesPublication . Vale, Ana Margarida Gonçalves Candeias do; Bernardino, Liliana Inácio; Cristóvão, Ana ClaraLipopolysaccharide (LPS) is an inflammatory agent widely used to induce peripheral inflammatory responses in animal models. When administered at low concentrations and over a short time interval, it has the ability to induce neuroprotection in animal models of Alzheimer’s Disease and stroke. This neuroprotective effect is due to the activation of the peripheral immune system and subsequently activation and induction of innate immune memory in microglial cells. Thus, the main objective of this work was to understand the effects of LPS and histamine, a biogenic amine also involved in peripheral inflammatory reactions, in the ability to induce innate immune memory and, consequently, to promote neuroprotection of dopaminergic neurons in an animal model of Parkinson’s Disease (PD). For this, C57BL/6J mice were subjected to intraperitoneal administration with LPS or histamine and, after 3 weeks, were exposed to intrastriatal injury with 6-hydroxydopamine (6-OHDA) to mimetize PD. The inflammatory response was evaluated by the expression of proinflammatory cytokines (TNF-a and IL-1ß) and anti-inflammatory cytokines (IL-10) in the blood, and by the expression of the ionised calcium binding adapter molecule 1 (Iba-1), a cell marker of microglia and macrophage cells, in the brain. To evaluate dopaminergic survival and motor behavior, immunohistochemistry for tyrosine hydroxylase (TH) and apomorphine test were use, respectively. The results suggest that LPS and histamine induce activation of the peripheral inflammatory response with consequent activation of microglia, triggering innate immune memory. In the long term, it is verified that these inflammatory stimuli protect dopaminergic neurons in a PD model, as well as motor recovery, resulting in a new mechanism of prevention and cellular and functional improvement of PD.
- A Design Study of a Low-Cost Heterogeneous Parallel ComputerPublication . Barata, Jorge M M; Silva, André; Garcês, Raúl L. M.A design study of a low-cost heterogeneous parallel computer based on already existing hardware is presented. The UNIX operating system is used together with PVM for message passing control. The parallel machine is constructed using existing Intel PC's and Alpha workstation platforms. The new techniques and algorithms are successfully applied to the grid generation problem based on the solution of partial differential equations with control of the boundary point distribution. Two different programming models were used. One uses decomposition of the domain into as many parts as there are processors, and revealed high reductions on the total turnaround time, although load balancing was a major problem. The other programming model has the possibility of changing the position of the points of the interface between each sub-grid, and allows reductions of the total turnaround time up to 1.6 times for the case of 3 processors, while the quality characteristics of the final grid are maintained. The communication times were reduced up to 7.5% of the total turnaround times, but the recursive nature of the numerical iterative process of the grid generation method causes a substantial increase in the number of iterations, reducing the parallel machine performance.
- José de Urcullu, mediador cultural ibéricoPublication . Cao Míguez, Ana BelénLa reconstrucción de las relaciones interculturales ibéricas a lo largo de la historia debe contemplar a los agentes de mediación que, como el liberal español José de Urcullu (fallecido en 1852), conforman los “ninguéns” o “quase-alguéns” (Magalhães, 2007) empeñados en promover tal comunicación entre culturas y literaturas, incluyendo la establecida por la vía de la traducción. Pese a su relevancia e interés como mediador, y pese al capital sociocultural y político que llegó a acumular este exiliado español afincado en Oporto, resulta la de Urcullu una figura desconocida, o al menos insuficientemente conocida en la actualidad. A intentar rescatarlo de ese olvido que lo hace hoy invisible se destinará el presente trabajo. Para ello, se señalarán algunas actividades en las que Urcullu estuvo implicado como mediador intercultural ibérico y, tratando de indagar cuáles fueron sus motivaciones, se intentará reconstituir su itinerario biográfico, dándose a conocer los resultados de una investigación inédita en torno a este polifacético autor y (auto)traductor.
- Efeito do silenciamento do gene STEAP1 em células LNCaP submetidas ao tratamento com cabazitaxel ou enzalutamidaPublication . Nascimento, Daniel Soares Corrêa do; Baptista, Cláudio Jorge Maia; Rocha, Sandra Catarina MoreiraO cancro de próstata (CaP) é o segundo com maior incidência no homem. As terapias farmacológicas mais utilizadas são as antineoplásicas (docetaxel ou cabazitaxel) e antiandrogénicas (enzalutamida ou apalutamida). Atualmente, investigam-se novos biomarcadores preditivos para deteção precoce, desenvolvimento de terapias combinadas e avaliação da resposta a terapia. Alguns desses potenciais biomarcadores encontram-se sobreexpressos no CaP, como por exemplo, a proteína Six Transmembrane Epitelial Antigen of the Prostate 1 (STEAP1), que é expressa nas células epiteliais e vários estudos indicam que a sobreexpressão da STEAP1 está associada à progressão do CaP. O objetivo deste trabalho foi avaliar se as células tumorais se tornam mais sensíveis ao tratamento com cabazitaxel ou enzalutamida, quando associado ao silenciamento do gene STEAP1, assim como avaliar se a sobreexpressão da STEAP1 pode ser utilizada como biomarcador preditivo na resposta ao tratamento. Foi realizada a transfecção das LNCaP com um siRNA específico para o gene STEAP1, e como controlo as células foram transfectadas com um siRNA contendo uma sequência aleatória. Seguidamente, as células foram tratadas com cabazitaxel ou enzalutamida de forma a avaliar a influência da expressão da STEAP1 na viabilidade celular, proliferação celular, apoptose celular, migração e invasão celular. Os resultados demostraram que o silenciamento reduziu significativamente em 47% a viabilidade no grupo STEAP1 siRNA. entretanto, o tratamento com cabazitaxel reverte a diminuição da viabilidade. Constatamos que o grupo STEAP1+CBZ, apresentavam menor expressão de p-c-myc. Assim, estes resultados preliminares podem indicar que a STEAP1 pode influenciar na resposta ao tratamento do CaP com cabazitaxel ou enzalutamida.