A novel and efficient approach to new N3-substituted-6,8-diaminopurines

[Excerpt] Purine nucleobases are fundamental biochemicals in living organisms. They have been a valuable inspiration for drug design once they play several key roles in the cell.1 To the best of our knowledge, reported routes to 8-aminopurines are still scarce due to the difficulty in introducing amino groups in this position of the purine ring. Here we report a novel, inexpensive and facile synthetic method to generate N3,N6-disubstituted-6,8-diaminopurines. In our research group, a number of substituted purines have been obtained from a common imidazole precursor, the 5-amino-4-cyanoformimidoyl imidazole 1. Recently, a comprehensive study on the reactivity of imidazoles 1 with nucleophiles under acidic conditions led us to develop experimental methods to incorporate primary amines into the cyanoformimidoyl group.2 (...)

A new and efficient synthesis of benzoimidazopurine derivatives

[Excerpt] Purine nucleobases are essential biomolecules in living organisms. Playing several key roles in the cell, they have been a significant inspiration for drug design.1 Benzimidazole nucleus is an important pharmacophore in the development of molecules with pharmaceutical or biological interest. Benzimidazoles have been reported to display significant pharmacological activities such as antiulcer, antifungal, antiparkinson, anticancer and antibiotic.2 Fused structures incorporating these two scaffolds might be important for medicinal chemistry and, to the best of our knowledge, there are no reports of these systems in the literature. In particular, benzo[4,5]imidazo[2,1]purines seem to be novel and must be important target molecules in the heterocyclic synthesis. (...)

MOEA/VAN: Multiobjective Evolutionary Algorithm based on Vector Angle Neighborhood

Natural selection favors the survival and reproduction of organisms that are best adapted to their environment. Selection mechanism in evolutionary algorithms mimics this process, aiming to create environmental conditions in which artificial organisms could evolve solving the problem at hand. This paper proposes a new selection scheme for evolutionary multiobjective optimization. The similarity measure that defines the concept of the neighborhood is a key feature of the proposed selection. Contrary to commonly used approaches, usually defined on the basis of distances between either individuals or weight vectors, it is suggested to consider the similarity and neighborhood based on the angle between individuals in the objective space. The smaller the angle, the more similar individuals. This notion is exploited during the mating and environmental selections. The convergence is ensured by minimizing distances from individuals to a reference point, whereas the diversity is preserved by maximizing angles between neighboring individuals. Experimental results reveal a highly competitive performance and useful characteristics of the proposed selection. Its strong diversity preserving ability allows to produce a significantly better performance on some problems when compared with stat-of-the-art algorithms.

Exploring female mice interstrain differences relevant for models of depression

Depression is an extremely heterogeneous disorder. Diverse molecular mechanisms have been suggested to underlie its etiology. To understand the molecular mechanisms responsible for this complex disorder, researchers have been using animal models extensively, namely mice from various genetic backgrounds and harboring distinct genetic modifications. The use of numerous mouse models has contributed to enrich our knowledge on depression. However, accumulating data also revealed that the intrinsic characteristics of each mouse strain might influence the experimental outcomes, which may justify some conflicting evidence reported in the literature. To further understand the impact of the genetic background, we performed a multimodal comparative study encompassing the most relevant parameters commonly addressed in depression, in three of the most widely used mouse strains: Balb/c, C57BL/6, and CD-1. Moreover, female mice were selected for this study taken into account the higher prevalence of depression in women and the fewer animal studies using this gender. Our results show that Balb/c mice have a more pronounced anxious-like behavior than CD-1 and C57BL/6 mice, whereas C57BL/6 animals present the strongest depressive-like trait. Furthermore, C57BL/6 mice display the highest rate of proliferating cells and brain-derived neurotrophic factor (Bdnf) expression levels in the hippocampus, while hippocampal dentate granular neurons of Balb/c mice show smaller dendritic lengths and fewer ramifications. Of notice, the expression levels of inducible nitric oxide synthase (iNos) predict 39.5% of the depressive-like behavior index, which suggests a key role of hippocampal iNOS in depression. Overall, this study reveals important interstrain differences in several behavioral dimensions and molecular and cellular parameters that should be considered when preparing and analyzing experiments addressing depression using mouse models. It further contributes to the literature by revealing the predictive value of hippocampal iNos expression levels in depressive-like behavior, irrespectively of the mouse strain.

O ensino da matemática e a avaliação externa de escolas: um estudo com professores do 1.º e 2.º ciclos

Os processos e práticas de educação e formação portugueses estão cada vez mais integrados em agendas globalmente estruturadas, cujo eixo de influência se situa no quadro comum das políticas da União Europeia e de organismos transnacionais como a OCDE (Pacheco, 2009). A avaliação tem vindo a assumir, nas últimas décadas, um papel central, extrapolando a sua importância para além do campo da educação (Afonso, 2010). O destaque atribuído à avaliação das escolas decorre de duas tendências que marcam a generalidade dos países europeus: a descentralização de meios e a definição de objetivos nacionais e de patamares de resultados escolares (Eurydice, 2011). Utilizando a análise político-económica da globalização na educação e fazendo também uma abordagem crítica às políticas de partilha (Takayama, 2013), pretendese analisar a mediação das pressões das políticas curriculares de homogeneização e estandardização dos resultados (Afonso, 2012; Santiago, Donaldson, Looney & Nusche, 2012) e a sua influência nos professores de Matemática. O presente estudo quantitativo envolve a realização de um inquérito por questionário aos professores do 1.º e 2.º ciclos de Matemática do Ensino Básico, onde se averigua de que forma o modelo de avaliação externa de escolas, implementado em Portugal desde 2006, tem colaborado para a elaboração de consequências concretas nos standards de avaliação, e na preponderância dos testes sumativos na disciplina de Matemática, considerando as mudanças curriculares e pedagógicas.

Mangrove sedimentary characteristics and implications for crab Ucides cordatus (Crustacea, Decapoda, Ucididae) distribution in an estuarine area of the Amazonian region

At the coastal zone sediments, water and organisms interact intensely. At equatorial tidal-dominated coast mangroves are abundant. These areas are well-known for their ecological importance. Considering the mangroves of Atlantic South America, the mangrove crab, Ucides cordatus has ecological and economic prominence. High densities of this crab are found on the Amazon coast. This study investigates the sediment distribution of the Bragança mangrove area (Amazon coast, Brazil) and its correlations with vegetation and mangrove crab distribution. Sediments of 47 sites, as well as crabs from sites with different sediment and vegetation, were sampled. Results show that surface sediment of the area is mainly composed by silt (59%), with 21% sand and 20% clay. Variations in sorting and skewness are the product of local variations in clay and sand content. The vegetation type was significantly correlated to mangrove crab characteristics, abundance and weight/size. Sediment characteristics are also substantially different according to the vegetation type. Areas where Avicennia germinans prevails have more sand and clay than areas of Rizophora mangle, in which silt is dominant and crabs were significantly heavier. The present results have showed that the distribution of sediments, crabs and vegetation at mangrove areas are strongly correlated. Thus, they should be studied in conjunction.

Expressão e caracterização de uma lectina recombinante de interesse biomédico

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Engenharia Clínica)

Chemical composition of phytoplankton from the estuaries of Eastern Amazonia

Phytoplankton is important bioindicator of chemical and biological modifications of natural ecosystems. The objective of this study was to determine the total chemical composition of the phytoplankton of the Pará and Mocajuba estuaries on the eastern coast of the Amazon region in the Brazilian state of Pará. The chemical composition of the surface water, bottom sediments (total sample and bioavailable fraction), and the phytoplankton were determined by inductively coupled plasma optical emission spectrometry. Phytoplankton contained high concentrations of Ca, P, Mn, Fe, Zn, Al, Ba, and Pb. The phytoplankton of the Mocajuba estuary is rich in Fe (2,967-84,750 µg g-1), while those from the Pará is rich in Al (1,216-15,389 µgg-1), probably reflecting divergent anthropogenic inputs. Both samples indicated a high bioconcentration factor derived from both the water and the bioavailable fraction, reflecting the efficiency of these organisms in the concentration of metals.

Influence of river ecological condition on changes in physico-chemical water parameters along rivers

Dissertação de mestrado em Ecology

RNA-seq analysis of the Quercus suber root response to drought

Dissertação de mestrado em Plant Molecular Biology, Biotechnology and Bioentrepreneurship

Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems

A therapeutic deep eutectic system (THEDES) is here defined as a deep eutectic solvent (DES) having an active pharmaceutical ingredient (API) as one of the components. In this work, THEDESs are proposed as enhanced transporters and delivery vehicles for bioactive molecules. THEDESs based on choline chloride (ChCl) or menthol conjugated with three different APIs, namely acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA), were synthesized and characterized for thermal behaviour, structural features, dissolution rate and antibacterial activity. Differential scanning calorimetry and polarized optical microscopy showed that ChCl:PA (1:1), ChCl:AA (1:1), menthol:AA (3:1), menthol:BA (3:1), menthol:PA (2:1) and menthol:PA (3:1) were liquid at room temperature. Dissolution studies in PBS led to increased dissolution rates for the APIs when in the form of THEDES, compared to the API alone. The increase in dissolution rate was particularly noticeable for menthol-based THEDES. Antibacterial activity was assessed using both Gram-positive and Gram-negative model organisms. The results show that all the THEDESs retain the antibacterial activity of the API. Overall, our results highlight the great potential of THEDES as dissolution enhancers in the development of novel and more effective drug delivery systems.

Nanotechnological approaches using curcumin and Withania somnifera: neuroprotection and antimicrobial activities

Tese de Doutoramento em Biologia de Plantas

Hydrocarbonoclastic bacteria: from bioremediation to bioenergy feedstock

Tese de Doutoramento em Engenharia Química e Biológica.

Development of computational and experimental methods for biomass composition and evaluation of its impact in genome-scale models prediction

The use of genome-scale metabolic models has been rapidly increasing in fields such as metabolic engineering. An important part of a metabolic model is the biomass equation since this reaction will ultimately determine the predictive capacity of the model in terms of essentiality and flux distributions. Thus, in order to obtain a reliable metabolic model the biomass precursors and their coefficients must be as precise as possible. Ideally, determination of the biomass composition would be performed experimentally, but when no experimental data are available this is established by approximation to closely related organisms. Computational methods however, can extract some information from the genome such as amino acid and nucleotide compositions. The main objectives of this study were to compare the biomass composition of several organisms and to evaluate how biomass precursor coefficients affected the predictability of several genome-scale metabolic models by comparing predictions with experimental data in literature. For that, the biomass macromolecular composition was experimentally determined and the amino acid composition was both experimentally and computationally estimated for several organisms. Sensitivity analysis studies were also performed with the Escherichia coli iAF1260 metabolic model concerning specific growth rates and flux distributions. The results obtained suggest that the macromolecular composition is conserved among related organisms. Contrasting, experimental data for amino acid composition seem to have no similarities for related organisms. It was also observed that the impact of macromolecular composition on specific growth rates and flux distributions is larger than the impact of amino acid composition, even when data from closely related organisms are used.

Current Challenges in Modeling Cellular Metabolism

Mathematical and computational models play an essential role in understanding the cellular metabolism. They are used as platforms to integrate current knowledge on a biological system and to systematically test and predict the effect of manipulations to such systems. The recent advances in genome sequencing techniques have facilitated the reconstruction of genome-scale metabolic networks for a wide variety of organisms from microbes to human cells. These models have been successfully used in multiple biotechnological applications. Despite these advancements, modeling cellular metabolism still presents many challenges. The aim of this Research Topic is not only to expose and consolidate the state-of-the-art in metabolic modeling approaches, but also to push this frontier beyond the current edge through the introduction of innovative solutions. The articles presented in this e-book address some of the main challenges in the field, including the integration of different modeling formalisms, the integration of heterogeneous data sources into metabolic models, explicit representation of other biological processes during phenotype simulation, and standardization efforts in the representation of metabolic models and simulation results.