The role of IFNγ in higher brain function: in health and under chronic stress

Tese de Doutoramento em Ciências da Saúde

Development of a novel aptamer-based multi-sensor device for the detection of osteopontin

Doctoral Dissertation for PhD degree in Chemical and Biological Engineering

Development of multifunctional coatings deposited on polymers based sensors for biomedical applications

Tese de Doutoramento (Programa Doutoral em Engenharia de Materiais)

Macroscopic and histopathological study of the placenta: an essential resource in litigation processes

The pathological study of the placenta is of upmost importance in cases of unexplained fetal/perinatal loss and often these carry litigation implications. Integrating pathological findings and the underlying pathophysiological processes, leading to placental lesions, is fundamental for the evaluation of poor fetal and perinatal outcomes and to distinguish from cases of true negligence.

Influence of chitosan coating on protein-based nanohydrogels properties and in vitro gastric digestibility

Chitosan coating was applied in Lactoferrin (Lf)-Glycomacropeptide (GMP) nanohydrogels by layer-by-layer coating process. A volume ratio of 0.1 of Lf-GMP nanohydrogels (0.2 mg.mL-1, at pH 5.0) to chitosan (1 mg.mL-1, at pH 3) demonstrated to be the optimal condition to obtain stable nanohydrogels with size of 230 ± 12 nm, a PdI of 0.22 ± 0.02 and a -potential of 30.0 ± 0.15 mV. Transmission electron microscopy (TEM) images showed that the application of chitosan coating in Lf-GMP did not affect the spherical shape of nanohydrogels and confirmed the low aggregation of nanohydrogels in solution. The analysis of chemical interactions between chitosan and Lf-GMP nanohydrogels were performed by Fourier transform infrared spectroscopy (FTIR) and by circular dichroism (CD) that revealed that a specific chemical interaction occurring between functional groups of protein-based nanohydrogels and active groups of the chitosan was established. The effect of chitosan coating on release mechanisms of Lf-GMP nanohydrogels at acid conditions (pH 2, 37 ºC) was evaluated by the encapsulation of a model compound (caffeine) in these systems. Linear Superposition Model was used to fit the experimental data and revealed that Fick and relaxation mechanisms are involved in caffeine release. It was also observed that the Fick contribution increase with the application of chitosan coating. In vitro gastric digestion was performed with Lf-GMP nanohydrogels and Lf-GMP nanohydrogels with chitosan coating and it was observed that the presence of chitosan improve the stability of Lf and GMP (proteins were hydrolysed at a slower rate and were present in solution by longer time). Native electrophoreses revealed that the nanohydrogels without coating remained intact in solution until 15 min and with chitosan coating remained intact until 60 min, during gastric digestion.

A critical evaluation of methods for the reconstruction of tissue-specific models

Under the framework of constraint based modeling, genome-scale metabolic models (GSMMs) have been used for several tasks, such as metabolic engineering and phenotype prediction. More recently, their application in health related research has spanned drug discovery, biomarker identification and host-pathogen interactions, targeting diseases such as cancer, Alzheimer, obesity or diabetes. In the last years, the development of novel techniques for genome sequencing and other high-throughput methods, together with advances in Bioinformatics, allowed the reconstruction of GSMMs for human cells. Considering the diversity of cell types and tissues present in the human body, it is imperative to develop tissue-specific metabolic models. Methods to automatically generate these models, based on generic human metabolic models and a plethora of omics data, have been proposed. However, their results have not yet been adequately and critically evaluated and compared. This work presents a survey of the most important tissue or cell type specific metabolic model reconstruction methods, which use literature, transcriptomics, proteomics and metabolomics data, together with a global template model. As a case study, we analyzed the consistency between several omics data sources and reconstructed distinct metabolic models of hepatocytes using different methods and data sources as inputs. The results show that omics data sources have a poor overlapping and, in some cases, are even contradictory. Additionally, the hepatocyte metabolic models generated are in many cases not able to perform metabolic functions known to be present in the liver tissue. We conclude that reliable methods for a priori omics data integration are required to support the reconstruction of complex models of human cells.

Índice Digital Regional 2014

O objetivo subjacente a toda a investigação que deu origem ao Índice Digital Regional (IDR), inserida num projeto de doutoramento, ia no sentido da “compreensão da realidade da Sociedade da Informação nas sete regiões NUTs II portuguesas, comparando-as e contrastando-as”. À semelhança do que acontece em grande parte dos indicadores de desenvolvimento, em que as assimetrias regionais são uma evidência verificada há várias décadas, importava perceber até que ponto o desenvolvimento da Sociedade da Informação em Portugal está a ser desencadeado sem ter ou não em atenção os valores da equidade, da coesão nacional e da solidariedade regional. Este artigo analisa os resultados do IDR recalculado com os dados estatísticos mais recentes.

Aromatic amines sources, environmental impact and remediation

Aromatic amines are widely used industrial chemicals as their major sources in the environment include several chemical industry sectors such as oil refining, synthetic polymers, dyes, adhesives, rubbers, perfume, pharmaceuticals, pesticides and explosives. They result also from diesel exhaust, combustion of wood chips and rubber and tobacco smoke. Some types of aromatic amines are generated during cooking, special grilled meat and fish, as well. The intensive use and production of these compounds explains its occurrence in the environment such as in air, water and soil, thereby creating a potential for human exposure. Since aromatic amines are potential carcinogenic and toxic agents, they constitute an important class of environmental pollutants of enormous concern, which efficient removal is a crucial task for researchers, so several methods have been investigated and applied. In this chapter the types and general properties of aromatic amine compounds are reviewed. As aromatic amines are continuously entering the environment from various sources and have been designated as high priority pollutants, their presence in the environment must be monitored at concentration levels lower than 30 mg L1, compatible with the limits allowed by the regulations. Consequently, most relevant analytical methods to detect the aromatic amines composition in environmental matrices, and for monitoring their degradation, are essential and will be presented. Those include Spectroscopy, namely UV/visible and Fourier Transform Infrared Spectroscopy (FTIR); Chromatography, in particular Thin Layer (TLC), High Performance Liquid (HPLC) and Gas chromatography (GC); Capillary electrophoresis (CE); Mass spectrometry (MS) and combination of different methods including GC-MS, HPLC-MS and CE-MS. Choosing the best methods depend on their availability, costs, detection limit and sample concentration, which sometimes need to be concentrate or pretreated. However, combined methods may give more complete results based on the complementary information. The environmental impact, toxicity and carcinogenicity of many aromatic amines have been reported and are emphasized in this chapter too. Lately, the conventional aromatic amines degradation and the alternative biodegradation processes are highlighted. Parameters affecting biodegradation, role of different electron acceptors in aerobic and anaerobic biodegradation and kinetics are discussed. Conventional processes including extraction, adsorption onto activated carbon, chemical oxidation, advanced oxidation, electrochemical techniques and irradiation suffer from drawbacks including high costs, formation of hazardous by-products and low efficiency. Biological processes, taking advantage of the naturally processes occurring in environment, have been developed and tested, proved as an economic, energy efficient and environmentally feasible alternative. Aerobic biodegradation is one of the most promising techniques for aromatic amines remediation, but has the drawback of aromatic amines autooxidation once they are exposed to oxygen, instead of their degradation. Higher costs, especially due to power consumption for aeration, can also limit its application. Anaerobic degradation technology is the novel path for treatment of a wide variety of aromatic amines, including industrial wastewater, and will be discussed. However, some are difficult to degrade under anaerobic conditions and, thus, other electron acceptors such as nitrate, iron, sulphate, manganese and carbonate have, alternatively, been tested.

Effects of fermentation residues on the melt processability and thermomechanical degradation of PHBV produced from cheese whey using mixed microbial cultures

"Available online 28 March 2016"

Metodologias para a qualificação de águas minerais naturais e águas de nascente

Dissertação de mestrado em Ordenamento e Valorização de Recursos Geológicos

Bacterial cellulose-lactoferrin as an antimicrobial edible packaging

Bacterial cellulose (BC) films from two distinct sources (obtained by static culture with Gluconacetobacter xylinus ATCC 53582 (BC1) and from a commercial source (BC2)) were modified by bovine lactoferrin (bLF) adsorption. The functionalized films (BC+bLF) were assessed as edible antimicrobial packaging, for use in direct contact with highly perishable foods, specifically fresh sausage as a model of meat products. BC+bLF films and sausage casings were characterized regarding their water vapour permeability (WVP), mechanical properties, and bactericidal efficiency against two food pathogens, Escherichia coli and Staphylococcus aureus. Considering their edibility, an in vitro gastrointestinal tract model was used to study the changes occurring in the BC films during passage through the gastrointestinal tract. Moreover, the cytotoxicity of the BC films against 3T3 mouse embryo fibroblasts was evaluated. BC1 and BC2 showed equivalent density, WVP and maximum tensile strength. The percentage of bactericidal efficiency of BC1 and BC2 with adsorbed bLF (BC1+bLF and BC2+bLF, respectively) in the standalone films and in inoculated fresh sausages, was similar against E. coli (mean reduction 69 % in the films per se versus 94 % in the sausages) and S. aureus (mean reduction 97 % in the films per se versus 36 % in the case sausages). Moreover, the BC1+bLF and BC2+bLF films significantly hindered the specific growth rate of both bacteria. Finally, no relevant cytotoxicity against 3T3 fibroblasts was found for the films before and after the simulated digestion. BC films with adsorbed bLF may constitute an approach in the development of bio-based edible antimicrobial packaging systems.

Production of whey protein-based aggregates under ohmic heating

Formation of whey protein isolate protein aggregates under the influence of moderate electric fields upon ohmic heating (OH) has been monitored through evaluation of molecular protein unfolding, loss of its solubility, and aggregation. To shed more light on the microstructure of the protein aggregates produced by OH, samples were assayed by transmission electron microscopy (TEM). Results show that during early steps of an OH thermal treatment, aggregation of whey proteins can be reduced with a concomitant reduction of the heating chargeby reducing the come-up time (CUT) needed to reach a target temperatureand increase of the electric field applied (from 6 to 12 V cm1). Exposure of reactive free thiol groups involved in molecular unfolding of -lactoglobulin (-lg) can be reduced from 10 to 20 %, when a CUT of 10 s is combined with an electric field of 12 V cm1. Kinetic and multivariate analysis evidenced that the presence of an electric field during heating contributes to a change in the amplitude of aggregation, as well as in the shape of the produced aggregates. TEM discloses the appearance of small fibrillar aggregates upon the influence of OH, which have recognized potential in the functionalization of food protein networks. This study demonstrated that OH technology can be used to tailor denaturation and aggregation behavior of whey proteins due to the presence of a constant electric field together with the ability to provide a very fast heating, thus overcoming heat transfer limitations that naturally occur during conventional thermal treatments.

The state of art of biological processes in paternal care

This review of the state of art aimed to present the most recent data on neuronal, neurochemical, hormonal and genetic bases of paternal care using MEDLINE and PsycInfo databases (1970-2013). An integrated model of biological substrates that assist men in the transition to fatherhood is presented. Guided by a genetic background, hypothalamic-midbrain-limbic-paralimbic-cortical circuits were found to be activated in fathers when infant stimuli are presented. A set of specifi c neuropeptides and steroid hormones are produced and seem to be related to brain activation, potentiating the paternal phenotype. Together, genetic, brain and hormonal processes suggest the existence of biological bases of paternal care in humans, activated and enhanced by infant stimuli and responsive to variations in the father-infant relationship.

Quantifying the legacy of the Chinese Neolithic on the maternal genetic heritage of Taiwan and Island Southeast Asia

There has been a long-standing debate concerning the extent to which the spread of Neolithic ceramics and Malay-Polynesian languages in Island Southeast Asia (ISEA) were coupled to an agriculturally driven demic dispersal out of Taiwan 4000 years ago (4 ka). We previously addressed this question using founder analysis of mitochondrial DNA (mtDNA) control-region sequences to identify major lineage clusters most likely to have dispersed from Taiwan into ISEA, proposing that the dispersal had a relatively minor impact on the extant genetic structure of ISEA, and that the role of agriculture in the expansion of the Austronesian languages was therefore likely to have been correspondingly minor. Here we test these conclusions by sequencing whole mtDNAs from across Taiwan and ISEA, using their higher chronological precision to resolve the overall proportion that participated in the "out-of-Taiwan" mid-Holocene dispersal as opposed to earlier, postglacial expansions in the Early Holocene. We show that, in total, about 20 % of mtDNA lineages in the modern ISEA pool result from the "out-of-Taiwan" dispersal, with most of the remainder signifying earlier processes, mainly due to sea-level rises after the Last Glacial Maximum. Notably, we show that every one of these founder clusters previously entered Taiwan from China, 6-7 ka, where rice-farming originated, and remained distinct from the indigenous Taiwanese population until after the subsequent dispersal into ISEA.