Clearing the cloudy crystal balls: Hybrid modelling for energy and climate change mitigation scenarios – A case study for Portugal

Dissertação para obtenção do Grau de Doutor em Ambiente

Schistosomiasis mansoni and severe gastrointestinal cytomegalovirus disease in a patient with acquired immunodeficiency syndrome

The behavior of the Schistosoma mansoni infection in patients with AIDS has not been explored. The case of a young woman with schistosomiasis mansoni, AIDS, and cytomegalovirus disease is reported. The authors suggest that the helminth was not a bystander in this case, or rather, by interfering with the host's immune response, it set the stage for the development and/or aggravation of the viral infection.

Predicting the impacts of climate change on the distribution and conservation of endemic forest land snails of Madeira Island

Climate change is emerging as one of the major threats to natural communities of the world’s ecosystems; and biodiversity hotspots, such as Madeira Island, might face a challenging future in the conservation of endangered land snails’ species. With this thesis, progresses have been made in order to properly understand the impact of climate on these vulnerable taxa; and species distribution models coupled with GIS and climate change scenarios have become crucial to understand the relations between species distribution and environmental conditions, identifying threats and determining biodiversity vulnerability. With the use of MaxEnt, important changes in the species suitable areas were obtained. Laurel forest species, highly dependent on precipitation and relative humidity, may face major losses on their future suitable areas, leading to the possible extinction of several endangered species, such as Leiostyla heterodon. Despite the complexity of the biological systems, the intrinsic uncertainty of species distribution models and the lack of information about land snails’ functional traits, this analysis contributed to a pioneer study on the impacts of climate change on endemic species of Madeira Island. The future inclusion of predictions of the effect of climate change on species distribution as part of IUCN assessments could contribute to species prioritizing, promoting specific management actions and maximizing conservation investment.

Dissecting gastrointestinal dysfunction and inflammation in a “pre-motor” rodent model of Parkinson’s disease

Research on Parkinson’s disease (PD) has mainly focused on the degeneration of the dopaminergic neurons of nigro-striatal (NS) pathway; also, post-mortem studies have demonstrated that the noradrenergic and the serotonergic transmitter systems are also affected (Jellinger, 1999). Degeneration of these neuronal cell bodies is generally thought to start prior to the loss of dopaminergic neurons in the NS pathway and precedes the appearance of the motor symptoms that are the “hallmark” of PD. Gastrointestinal (GI) motility is often disturbed in PD, manifesting chiefly as impaired gastric emptying and constipation. These GI dysfunction symptoms may be the result of a loss in noradrenergic and serotonergic innervation. GI deficits were evaluated using an organ bath technique. Groups treated with different combinations of neurotoxins (6-OHDA alone, 6-OHDA + pCA or 6-OHDA + DSP-4) presented significant differences in gut contractility compared to control groups. Since a substantial body of literature suggests the presence of an inflammatory process in parkinsonian state (Whitton, 2007), changes in pro-inflammatory cytokines in the gut were assessed using a cytokine microarray. It has been found in this work that groups with a combined dopaminergic and noradrenergic lesion have a significant increase in both expressions of IL-13 and VEGF. IL-6 also shows a decrease in treatment groups; however this decrease did not reach statistical significance. The therapeutic value of Exendin-4 (EX-4) was evaluated. It has been previously demonstrated that EX-4, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is neuroprotective in rodent models of PD (Harkavyi et al., 2008). In this thesis it has been found that EX-4 was able to reverse a decrease in gut contractility obtained through intracerebral bilateral 6-OHDA injection. Although more studies are required, EX-4 could be used as a possible therapy for the GI symptoms prominent in the early stages of PD.

Caracterização do papel dos genes TYMS e MTR no desenvolvimento de Cancro Colo-Rectal

RESUMO: O cancro colo-rectal (CCR) é um dos cancros que possui maior taxa de mortalidade a nível mundial. Em Portugal esta patologia é responsável pela morte de cerca de 3700 pessoas por ano, sendo que estes números aumentam de ano para ano. Ao longo das últimas décadas o papel das alterações genéticas na etiologia das patologias oncológicas tem vindo a ter cada vez mais um maior destaque. O número de estudos que avaliam a importância de polimorfismos, mutações, alterações na regulação génica e interacções entre genes no desenvolvimento destas patologias tem aumentado exponencialmente. Com o aumento do conhecimento da forma como estas alterações influenciam o desenvolvimento do cancro surgiram os primeiros meios de diagnóstico genético, levando assim a uma alteração da forma como são encarados o diagnóstico e a prevenção destas doenças. No CCR as formas hereditárias com alterações genéticas inequivocamente identificadas representam apenas 5% dos casos. Existem cerca de 25% que representam formas hereditárias para as quais ainda não foram estabelecidos os padrões de alterações genéticas subjacentes. Desta forma, estudos que venham contribuir para um maior conhecimento dos mecanismos moleculares responsáveis pelo aumento da susceptibilidade dos indivíduos para o desenvolvimento de CCR são extremamente importantes. O CCR é uma patologia multifactorial, onde factores genéticos interagem com factores ambientais no surgimento e desenvolvimento da doença. Assim, torna-se essencial integrar o estudo das alterações genéticas no contexto ambiental onde os indivíduos em estudo se encontram. No caso desta patologia um dos principais factores ambientais estudado é a nutrição. Vários estudos têm sido realizados ao longo dos últimos anos de forma a compreender como pode a ingestão dos nutrientes influenciar o desenvolvimento de CCR e de que forma interage com as alterações genéticas individuais. O ciclo do folato é um dos processos metabólicos onde o papel da nutrição em interacção com alterações genéticas mais tem sido estudado nos últimos anos. Deste cruzamento entre o estudo das alterações genéticas e ambientais surge a Nutrigenética. O conjunto de estudos da presente tese tem como objectivo aumentar o conhecimento do papel das alterações em genes do ciclo do folato, em interacção com factores nutricionais e de estilo de vida, não só no desenvolvimento de CCR, mas também de outra patologia do tracto gastrointestinal, a Doença de Crohn (DC), uma doença inflamatória muitas vezes associada como factor de risco para o desenvolvimento de CCR. Este estudo debruçou-se essencialmente no estudo dos genes timidilato sintetase (TYMS) e metionina sintetase (MTR) em populações com CCR e DC, bem como no padrão nutricional destas populações com particular incidência nos nutrientes envolvidos no ciclo do folato (folato, metionina, vitamina B6, vitamina B12). Analisando o conjunto de resultados obtidos para os estudos do CCR podemos concluir que quer a TYMS quer a MTR possuem um papel relevante na susceptibilidade para desenvolver esta patologia, assim como têm destaque no funcionamento do ciclo celular durante o processo oncogénico. Os resultados demonstram que os factores que levam a uma menor disponibilidade de grupos metil no ciclo de folato (baixos níveis de folato, alteração da actividade de MTR, elevada expressão de TYMS) constituem factores de risco, muito provavelmente por contribuírem para uma desregulação dos níveis de metionina disponível para a metilação do DNA da célula. Demonstram ainda que em células tumorais ocorrem alterações na regulação do ciclo do folato de forma a favorecer a síntese de DNA em detrimento da metilação do mesmo, alterando para isso a expressão dos genes de forma a que o fluxo de grupos metil provenientes do folato sejam encaminhados para a enzima TYMS. O polimorfismo de deleção 6pb da TYMS surge como um factor de diagnóstico e de prognóstico de CCR para a população portuguesa. Dos factores nutricionais analisados apenas o folato aparenta ter um papel relevante na modelação do risco de desenvolver CCR. Na doença de Crohn (DC) podemos verificar que a homocisteína e o seu metabolismo poderão contribuir para o aparecimento e desenvolvimento da patologia. O aumento da homocisteína poderá ser o responsável por um aumento da resposta auto-imune do organismo, promovendo o aparecimento da DC. O polimorfismo A2756G MTR desempenha um papel preponderante como factor de diagnóstico da DC, tendo sido associado pela primeira vez a esta patologia. Tem também um papel importante no desenvolvimento da doença, uma vez que está associado a uma idade de diagnóstico mais baixa, sugerindo assim que o desenvolvimento da doença ocorre de forma mais precoce. Concluindo, com este estudo pensamos ter contribuído para um melhor entendimento do papel do ciclo do folato no desenvolvimento de CCR e DC, sendo um ponto de partida para futuras investigações que possam revelar cada vez melhor as complexas interacções metabólicas desta via e a sua influência nas patologias estudadas. Do nosso estudo destacamos a importância de uma análise global das várias etapas do ciclo do folato para que se possa compreender a dinâmica que se estabelece no desenvolvimento destas patologias, podendo diversas alterações, quer a nível genético quer a nível nutricional, exercerem efeitos diferentes consoante o estado dos restantes intervenientes do ciclo do folato. Acreditamos que no futuro este estudo permitirá que o conhecimento do ciclo do folato tenha cada vez mais uma relevância fundamental a nível de diagnóstico e terapêutica destas patologias.------------ ABSTRACT: Colorectal Cancer (CRC) is one of the cancers that have a higher rate of mortality worldwide. In Portugal this pathology is responsible for the deaths of about 3700 people per year, and these numbers increase each year. Over the past few decades the role of genetic changes in the etiology of oncological pathologies has had an increasingly greater emphasis. The number of studies that evaluate the importance of polymorphisms, mutations, changes in gene regulation and gene interactions in the development of these diseases has increased exponentially. With the increased knowledge of how these changes influence the development of cancer, appeared the first means for genetic diagnostic, leading to a change in the way diagnosis is seen and in the prevention of these diseases. In CRC the hereditary forms with clearly identified genetic changes represent only 5% of cases. There are about 25% representing hereditary forms for which the patterns of genetic changes haven’t been established. In this way, studies that will contribute to a greater understanding of the molecular mechanisms responsible for increased susceptibility of individuals to the CRC development are extremely important. CRC is a multifactorial pathology, where genetic factors interact with environmental factors in the emergence and development of the disease.Thus, it is essential to integrate the study of genetic changes in the environmental context of the individuals under study. In the case of this pathology one of the main environmental factors studied is nutrition. Several studies have been conducted over the past few years in order to understand how the intake of nutrients can influence the development of CRC and how nutrients interact with the individual genetic changes. The folate cycle is one of the metabolic processes where the role of nutrition in interaction with genetic alterations has been studied in recent years. This cross between the study of genetic and environmental changes developed Nutrigenetics. The set of studies of this thesis aims to increase awareness of the role of changes in genes of the folate cycle, in interaction with nutritional factors and lifestyle, not only in the development of CRC, but also of another pathology of the gastrointestinal tract, Crohn's disease (CD), an inflammatory disease often associated as a risk factor for the development of CRC. This study dealt mainly in the study of genes thymidylate synthase (TYMS) and methionine synthase (MTR) in populations with CRC and CD, as well as in the nutritional pattern of these populations with particular focus on nutrients involved in the folate cycle (folate, methionine, vitamin B6, vitamin B12). Analyzing the results obtained for the CRC studies we conclude that either the MTR TYMS have a relevant role in susceptibility to develop this pathology, and have an important role in the functioning of the cell cycle during oncogenesis. The results show that the factors that lead to a lower availability of methyl groups in folate cycle (low levels of folate, change the activity of MTR, high expression of TYMS) constitute risk factors, most likely by contribute to a dysregulation of methionine levels available for DNA methylation of the cell. Our results also demonstrate that in tumor cells occur changes in the regulation of the folate cycle in order to promote the synthesis of DNA, to the detriment of methylation of the same by changing the expression of genes so that the methyl groups from folate are forwarded to the TYMS enzyme reaction. The deletion polymorphism 6bp of TYMS emerges as a diagnostic and prognostic factor of CCR for the Portuguese population. Nutritional factors analyzed only folate appears to have a major role in modulating the risk of developing CCR.In Crohn’s disease (CD) we can check that homocysteine and its metabolism may contribute to the emergence and development of this pathology. Increased homocysteine may be responsible for an increase in the body's autoimmune response, promoting the emergence of CD. The polymorphism A2756G MTR plays a leading role as a factor of diagnosis of DC, having been associated with this pathology for the first time. It also has an important role in the development of the disease, since it is associated with a lower diagnostic age, suggesting that the development of the disease occurs earlier. In conclusion, our study has contributed to a better understanding of the role of folate cycle in the development of CRC and CD, being a starting point for future research that may prove increasingly complex metabolic interactions in this via and its influence on the pathologies studied. In our study we highlight the importance of a comprehensive analysis of the various steps of the folate cycle in order to understand the dynamics that settles in the development of these pathologies, and a number of amendments, whether at the genetic level or at the nutritional level, exercise different effects depending on the stage of the remaining participants in the folate cycle. We believe that in the future this study will allow the knowledge of folate cycle to have increasingly a fundamental relevance at the level of diagnosis and treatment of these diseases.

Fulminant gastrointestinal hemorrhage due to Strongyloides stercoralis hyperinfection in an AIDS patient

Strongyloides stercoralis is an endemic nematode to tropical and subtropical regions of the globe. The parasite is capable of autoinfection, which is limited by an intact immune response. In immunocompromised hosts, hyperinfection and dissemination can occur and have a high index of mortality. A hyperinfection syndrome with dissemination is frequently associated with corticosteroid administration and other conditions (malignancies and organ transplantation). Interestingly, although strongyloidiasis is common among AIDS patients in endemic areas, the hyperinfection syndrome is rarely noted. We report here on a rare manifestation of fulminant gastrointestinal hemorrhage due to hyperinfection of strongyloidiasis in a female drug-abusing, alcoholic HIV/AIDS patient.

How can packaging change children's eating habits from un-healthy food towards healthier options?

Field Lab: Children consumer behaviour

The effects of glutamine-supplemented diet on the intestinal mucosa of the malnourished growing rat

Glutamine is the most abundant amino acid in the blood and plays a key role in the response of the small intestine to systemic injuries. Mucosal atrophy is an important phenomenon that occurs in some types of clinical injury, such as states of severe undernutrition. Glutamine has been shown to exert powerful trophic effects on the gastrointestinal mucosa after small bowel resection or transplant, radiation injury, surgical trauma, ischemic injury and administration of cytotoxic drugs. Since no study has been performed on the malnourished animal, we examined whether glutamine exerts a trophic effect on the intestinal mucosa of the malnourished growing rat. Thirty-five growing female rats (aged 21 days) were divided into 4 groups: control - chow diet; malnutrition diet; malnutrition+chow diet; and malnutrition+glutamine-enriched chow diet (2%). For the first 15 days of the experiment, animals in the test groups received a malnutrition diet, which was a lactose-enriched diet designed to induce diarrhea and malnutrition. For the next 15 days, these animals received either the lactose-enriched diet, a regular chow diet or a glutamine-enriched chow diet. After 30 days, the animals were weighed, sacrificed, and a section of the jejunum was taken and prepared for histological examination. All the animals had similar weights on day 1 of experiment, and feeding with the lactose-enriched diet promoted a significant decrease in body weight in comparison to the control group. Feeding with both experimental chow-based diets promoted significant body weight gains, although the glutamine-enriched diet was more effective. RESULTS: The morphological and morphometric analyses demonstrated that small intestinal villous height was significantly decreased in the malnourished group, and this change was partially corrected by the two types of chow-based diet. Crypt depth was significantly increased by malnutrition, and this parameter was partially corrected by the two types of chow-based diet. The glutamine-enriched diet resulted in the greatest reduction of crypt depth, and this reduction was also statistically significant when compared with control animals. CONCLUSIONS: Enteral glutamine has some positive effects on body weight gain and trophism of the jejunal mucosa in the malnourished growing rat.

Generalized Dasymetric Mapping Algorithm for Accessing Land-Use Change

Contém resumo

A wave of change: Labor market and social security impacts of the EU refugee inflow

The recent massive inflow of refugees to the European Union (EU) raises a number of unanswered questions on the economic impact of this phenomenon. To examine these questions, we constructed an overlapping-generations model that describes the evolution of the skill premium and of the welfare benefit level in relevant European countries, in the aftermath of an inflow of asylum-seekers. In our simulation, relative wages of skilled workers increase between 8% and 11% in the period of the inflow; their subsequent time path is dependent on the initial skill premium. The entry of migrants creates a fiscal surplus of about 8%, which can finance higher welfare benefits in the subsequent periods. These effects are weaker in a scenario where refugees do not fully integrate into the labor market.

Empowerment and intentions to resist future change: the moderating effect organization-based self-esteem

Nowadays, organizations face a constant need for adaptability, increasing the importance of change management. Our study focuses of how empowering leadership influences intentions to resist future changes, mediated by the effects of psychological and structural empowerment. From the responses of the two questionnaires (N1=230; Ntf=113), we found that empowering leadership fosters psychological and structural empowerment. Structural empowerment was the main driver in reducing intentions to resist future change when an employee has high organization-based self-esteem. Our findings add to the literature by examining how we can anticipate and manage change under an empowering context, building on social exchange and uncertainty reduction theories

Contributions towards smart cities : exploring block level census data for the characterization of change in Lisbon

The interest in using information to improve the quality of living in large urban areas and its governance efficiency has been around for decades. Nevertheless, the improvements in Information and Communications Technology has sparked a new dynamic in academic research, usually under the umbrella term of Smart Cities. This concept of Smart City can probably be translated, in a simplified version, into cities that are lived, managed and developed in an information-saturated environment. While it makes perfect sense and we can easily foresee the benefits of such a concept, presently there are still several significant challenges that need to be tackled before we can materialize this vision. In this work we aim at providing a small contribution in this direction, which maximizes the relevancy of the available information resources. One of the most detailed and geographically relevant information resource available, for the study of cities, is the census, more specifically the data available at block level (Subsecção Estatística). In this work, we use Self-Organizing Maps (SOM) and the variant Geo-SOM to explore the block level data from the Portuguese census of Lisbon city, for the years of 2001 and 2011. We focus on gauging change, proposing ways that allow the comparison of the two time periods, which have two different underlying geographical bases. We proceed with the analysis of the data using different SOM variants, aiming at producing a two-fold portrait: one, of the evolution of Lisbon during the first decade of the XXI century, another, of how the census dataset and SOM’s can be used to produce an informational framework for the study of cities.

Sustainable mortars with incorporation of microencapsulated phase change materials

The construction industry is responsible for high energy and raw materials consumption. Thus, it is important to minimize the high energy consumption by taking advantage of renewable energy sources and reusing industrial waste, decreasing the extraction of natural materials. The mortars with incorporation of phase change materials (PCM) have the ability to regulate the temperature inside buildings, contributing to the thermal comfort and reduction of the use of heating and cooling equipment, using only the energy supplied by the sun. The simultaneous incorporation of PCM and fly ash (FA) can reduce the energy consumption and the amount of materials landfilled. However, the addition of these materials in mortars modifies its characteristics. The main purpose of this study was the production and characterization in the fresh and hardened state of mortars with incorporation of different contents of PCM and FA. The binders studied were aerial lime, hydraulic lime, gypsum and cement. The proportion of PCM studied was 0%, 20%, 40% and 60% of the mass of the sand. The content of fly ash added to the mortars was 0%, 20%, 40% and 60% of the mass of the binder. It was possible to observe that the incorporation of PCM and fly ash in mortars caused differences in properties such as workability, microstructure, water absorption, compressive strength, flexural strength and adhesion.

Assessing the feasibility of impregnating phase change materials in lightweight aggregate for development of thermal energy storage systems

This paper assesses the feasibility of impregnation/encasement of phase change materials (PCMs) in lightweight aggregates (LWAs). An impregnation process was adopted to carry out the encasement study of two different PCMs in four different LWAs. The leakage of the impregnated/encased PCMs was studied when they were submitted to freeze/thawing and oven drying tests, separately. The results confirmed that, the impregnation/encasement method is effective with respect to the large thermal energy storage density, and can be suitable for applications were PCMs cannot be incorporated directly such as asphalt road pavements.