MarinEye - A tool for marine monitoring

This work presents an autonomous system for marine integrated physical-chemical and biological monitoring – the MarinEye system. It comprises a set of sensors providing diverse and relevant information for oceanic environment characterization and marine biology studies. It is constituted by a physicalchemical water properties sensor suite, a water filtration and sampling system for DNA collection, a plankton imaging system and biomass assessment acoustic system. The MarinEye system has onboard computational and logging capabilities allowing it either for autonomous operation or for integration in other marine observing systems (such as Observatories or robotic vehicles. It was designed in order to collect integrated multi-trophic monitoring data. The validation in operational environment on 3 marine observatories: RAIA, BerlengasWatch and Cascais on the coast of Portugal is also discussed.info:eu-repo/semantics/publishedVersio

Structural and biophysical insights into the mode of covalent binding of rationally designed potent BMX inhibitors.

The bone marrow tyrosine kinase in chromosome X (BMX) is pursued as a drug target because of its role in various pathophysiological processes. We designed BMX covalent inhibitors with single-digit nanomolar potency with unexploited topological pharmacophore patterns. Importantly, we reveal the first X-ray crystal structure of covalently inhibited BMX at Cys496, which displays key interactions with Lys445, responsible for hampering ATP catalysis and the DFG-out-like motif, typical of an inactive conformation. Molecular dynamic simulations also showed this interaction for two ligand/BMX complexes. Kinome selectivity profiling showed that the most potent compound is the strongest binder, displays intracellular target engagement in BMX-transfected cells with two-digit nanomolar inhibitory potency, and leads to BMX degradation PC3 in cells. The new inhibitors displayed anti-proliferative effects in androgen-receptor positive prostate cancer cells that where further increased when combined with known inhibitors of related signaling pathways, such as PI3K, AKT and Androgen Receptor. We expect these findings to guide development of new selective BMX therapeutic approaches

A guerra sertaneja do Contestado

Formato: Documentário – Duração: 29 minutos – Ano: 2004Entrevista com o professor Paulo Pinheiro Machado, autor da tese de doutorado “Um estudo sobre as origens sociais e a formação política das lideranças sertanejas do Contestado, 1912-1916”

Evaluating the Potential of the Defatted By-Product of Aurantiochytrium sp. Industrial Cultivation as a Functional Food

While Aurantiochytrium sp. is an increasingly popular source of polyunsaturated fatty acids (PUFAs), its extraction generates high amounts of waste, including the spent, defatted residue. The composition and bioactivities of this by-product could prove to be a major part of the sustainable valorisation of this organism within the framework of a circular economy. In this study, the defatted biomass of commercial Aurantiochytrium sp. was nutritionally characterised, and its amino acid profile was detailed. Additionally, the antioxidant and prebiotic potentials of an enzymatically digested sample of defatted Aurantiochytrium sp. were evaluated under a set of miniaturised in vitro assays. The nutritional profile of the spent Aurantiochytrium biomass revealed a protein and dietary-fibre rich product, with values reaching 26.7% and 31.0% for each, respectively. It also held high concentrations of glutamic and aspartic acid, as well as a favourable lysine/arginine ratio of 3.73. The digested samples demonstrated significant Weissela cibaria and Bifidobacterium bifidum growth-enhancing potential. Residual ferric reducing antioxidant power (FRAP) activity was likely attributed to antioxidant amino acids or peptides. The study demonstrated that some of the nutritional and functional potential that reside in the defatted Aurantiochytrium sp. waste encourages additional studies and the development of food supplements employing this resource’s by-products under a biorefinery framework

Rationally Designed Potent BMX Inhibitors Reveals Mode of Covalent Binding at the Atomic Level

BMX is pursued as a drug target because of its role in various pathophysiological processes. We designed BMX covalent inhibitors with single-digit nanomolar potency with unexploited topological pharmacophore patterns. Importantly, we reveal the first X-ray crystal structure of covalently inhibited BMX at Cys496, which displays key interactions with Lys445, responsible for hampering ATP catalysis and the DFG-out-like motif, typical of an inactive conformation. Molecular dynamic simulations also showed this interaction for two ligand/BMX complexes. Kinome selectivity profiling showed that the most potent compound JS25 is the strongest binder and displays intracellular target engagement in BMX-transfected cells with two-digit nanomolar inhibitory potency. The new inhibitors displayed anti-proliferative effects in androgen-receptor positive prostate cancer cells that where further increased when combined with known inhibitors of related signaling pathways, such as PI3K, AKT and Androgen Receptor. We expect these findings to guide development of new selective BMX therapeutic approaches.</p

Whey Protein Isolate-Supplemented Beverage, Fermented by Lactobacillus casei BL23 and Propionibacterium freudenreichii 138, in the Prevention of Mucositis in Mice

Mucositis is a clinically important gastrointestinal inflammatory infirmity, generated by antineoplastic drugs cytotoxic effects. The inflammatory process caused by this disease frequently leads to derangements in the alimentary tract and great malaise for the patient. Novel strategies are necessary for its prevention or treatment, as currently available treatments of mucositis have several limitations in relieving its symptoms. In this context, several research groups have investigated the use of probiotic bacteria, and in particular dairy bacterial strains. Compelling evidences reveal that milk fermented by certain probiotic bacteria has the capacity to ameliorate intestinal inflammatory disorders. In addition, innovative probiotic delivery strategies, based on probiotics incorporation into protective matrices, such as whey proteins, were able to increase the therapeutic effect of probiotic strains by providing extra protection for bacteria against environmental stresses. Therefore, in this study, we evaluated the role of the whey protein isolate (WPI), when added to skim milk fermented by Lactobacillus casei BL23 (L. casei BL23) or by Propionibacterium freudenreichii CIRM-BIA138 (P. freudenreichii 138), as a protective matrix against in vitro stress challenges. In addition, we investigated the therapeutic effect of these fermented beverages in a murine model of mucositis induced by 5-Fluorouracil (5-FU). Our results demonstrated that milk supplementation with 30% (w/v) of WPI increases the survival rate of both strains when challenged with acid, bile salts, high temperature and cold storage stresses, compared to fermented skim milk without the addition of WPI. Moreover, treatment with the probiotic beverages prevented weight loss and intestinal damages in mice receiving 5-FU. We conclude that the presence of WPI maximizes the anti-inflammatory effects of L. casei BL23, but not for P. freudenreichii 138, suggesting that whey protein enhancement of probiotic activity might be strain-dependent

MarinEye – A tool for marine monitoring

This work presents an autonomous system for marine integrated physical-chemical and biological monitoring – the MarinEye system. It comprises a set of sensors providing diverse and relevant information for oceanic environment characterization and marine biology studies. It is constituted by a physical-chemical water properties sensor suite, a water filtration and sampling system for DNA collection, a plankton imaging system and biomass assessment acoustic system. The MarinEye system has onboard computational and logging capabilities allowing it either for autonomous operation or for integration in other marine observing systems (such as Observatories or robotic vehicles. It was designed in order to collect integrated multi-trophic monitoring data. The validation in operational environment on 3 marine observatories: RAIA, BerlengasWatch and Cascais on the coast of Portugal is also discussed.info:eu-repo/semantics/publishedVersio