Regeneração do conjunto patrimonial da cidadela de Peniche

Dissertação de Mestrado Integrado em Arquitetura, com a especialização em Arquitetura apresentada na Faculdade de Arquitetura da Universidade de Lisboa para obtenção do grau de Mestre.O presente trabalho partiu do interesse pelo património esquecido, no qual se insere a Fortaleza de São Francisco, em Peniche. Debruçada sobre o mar e de atmosfera singular, ela interpela-nos à descoberta da sua história e das camadas que a constroem. Considerada uma das praças-fortes mais importantes do reino, fez parte do conjunto de defesa costeiro da capital e um dos maiores exemplares de arquitetura militar portuguesa que prevaleceu, não intacta, ao passar do tempo. Dos seus apoios defensivos, pouco ou nada resta. Parte-se da reflexão sobre o seu valor patrimonial, do carácter e da sua essência. Da ligação entre o património e o espaço que o envolve. Do que o lugar quer ser, do que se pode tornar. Estuda-se a sua evolução, como se alterou no tempo e explora-se as valências que contem, a singularidade do lugar. Numa tentativa de reavivar a sua importância, de compreender de que modo se reergue um monumento perdido no tempo, apresenta-se uma proposta que assume a sua regeneração, através da ligação entre as suas pré-existências e a atribuição de uma nova linguagem arquitetónica. Concede-se um novo uso, uma nova vivência, como resposta ponderada às fragilidades do lugar.ABSTRACT: The present work started from the interest in the forgotten heritage, in which the Fortress of San Francisco, in Peniche, is located. Leaning over the sea and with a unique atmosphere, it challenges us to discover its history and the layers that build it. Considered one of the most important strongholds of the kingdom, it was part of the coastal defense complex of the capital and one of the largest examples of portuguese military architecture that prevailed, not intact, over time. Of its defensive supports, little or nothing remains. It starts from the reflection on its patrimonial value, the character and its essence; the link between heritage and the space that surrounds it. What the place wants to be, what it can become. Its evolution is studied, as it has changed over time and explores the valences that it contains, the singularity of the place. In an attempt to revive its importance, to understand how a monument lost in time retains, a proposal that assumes its regeneration, through the link between its pre-existences and the attribution of a new architectural language is presented. A new use, a new experience, is given as a pondered response to the fragility of the place.N/

Infeções fúngicas de origem tropical

Dissertação para obtenção do grau de Mestre no Instituto Universitário Egas MonizA presente monografia representa um estudo bibliográfico efetuado sobre o tema "Infeções Fúngicas Tropicais" onde os principais objetivos passam por identificar e descrever as caraterísticas das infeções estritamente superficiais, cutâneas, subcutâneas, sistémicas ou oportunistas, mencionando sobretudo a sua epidemiologia, manifestações clínicas e diagnóstico. As infeções estritamente superficiais são limitadas à superfície da pele e cabelos; as infeções cutâneas são não só limitadas às camadas queratinizadas da pele como aos folículos pilosos, unhas e membranas mucosas; as infeções subcutâneas são causadas por diversos fungos saprófitas ambientais do solo, madeira ou vegetação em decomposição; e as infeções sistémicas/oportunistas são de emergência médica, apresentando altas taxas de mortalidade, mesmo que aplicada a terapia apropriada mais tardiamente. As infeções causadas por fungos são bastante comuns e apesar de apresentarem, geralmente, uma expressão clínica benigna, causam elevada morbilidade.This monograph represents a bibliographical study on the topic "Tropical Fungal Infections", where the main goals are to identify and describe the characteristics of strictly superficial, cutaneous, subcutaneous, systemic or opportunistic infections, especially mentioning its epidemiology, clinical manifestations and diagnosis. Strictly superficial infections are limited to the surface of the skin and hair; skin infections are not only limited to the keratinized layers of the skin but also to the hair follicles, nails and mucous membranes; the subcutaneous infections are caused by several environmental saprophytic fungus of the soil, wood or decaying vegetation; and systemic/opportunistic infections are of medical emergency, presenting high mortality rates, even if applied to appropriate therapy later. Infections caused by fungus are quite common and although they generally present a benign clinical expression, they cause high morbidity

2,3-Diphosphoglycerate and the Protective Effect of Pyruvate Kinase Deficiency against Malaria Infection—Exploring the Role of the Red Blood Cell Membrane

Malaria remains a major world public health problem, contributing to poverty and inequality. It is urgent to find new efficacious tools with few adverse effects. Malaria has selected red blood cell (RBC) alterations linked to resistance against infection, and understanding the protective mechanisms involved may be useful for developing host-directed tools to control Plasmodium infection. Pyruvate kinase deficiency has been associated with resistance to malaria. Pyruvate kinase-deficient RBCs display an increased concentration of 2,3-diphosphoglycerate (2,3-DPG).We recently showed that 2,3-DPG impacts in vitro intraerythrocytic parasite growth, induces a shift of the metabolic profile of infected cells (iRBCs), making it closer to that of noninfected ones (niRBCs), and decreases the number of parasite progenies that invade new RBCs. As an increase of 2,3-DPG content may also have an adverse effect on RBC membrane and, consequently, on the parasite invasion, in this study, we explored modifications of the RBC morphology, biomechanical properties, and RBC membrane on Plasmodium falciparum in vitro cultures treated with 2,3-DPG, using atomic force microscopy (AFM)-based force spectroscopy and other experimental approaches. The presence of infection by P. falciparum significantly increased the rigidity of parasitized cells and influenced the morphology of RBCs, as parasitized cells showed a decrease of the area-to-volume ratio. The extracellular addition of 2,3-DPG also slightly affected the stiffness of niRBCs, making it more similar to that of infected cells. It also changed the niRBC height, making the cells appear more elongated. Moreover, 2,3-DPG treatment influenced the cell surface charge, becoming more negative in treated RBCs than in untreated ones. The results indicate that treatment with 2,3-DPG has only a mild effect on RBCs in comparison with the effect of the presence of the parasite on the host cell. 2,3-DPG is an endogenous host metabolite, which may, in the future, originate a new antimalarial tool with few adverse effects on noninfected cells.publishersversionpublishe

Genetic diversity and biogeographical patterns of Caulerpa prolifera across the Mediterranean and Mediterranean/Atlantic transition zone

© 2015, Springer-Verlag Berlin Heidelberg. Knowledge of spatial patterns of genetic differentiation between populations is key to understanding processes in evolutionary history of biological species. Caulerpa is a genus of marine green algae, which has attracted much public attention, mainly because of the impacts of invasive species in the Mediterranean. However, very little is known about the ecological and evolutionary history of the Mediterranean native Caulerpa prolifera, a species which is currently found at sites distributed worldwide. C. prolifera provides a good model to explore the patterns of genetic diversity at different scales across the Mediterranean and Atlantic area. This study aims to investigate the biogeographical patterns of diversity and differentiation of C. prolifera in the Mediterranean, with special focus on the Mediterranean/Atlantic transition zone. We used two nuclear (ITS rDNA and the hypervariable microsatellite locus CaPr_J2) and one chloroplast (tufA) DNA markers on samples of C. prolifera from its entire range. Analyses of 51 sequences of the cpDNA tufA of C. prolifera, 87 ITS2 sequences and genotypes of 788 ramets of C. prolifera for the locus CaPr_J2 revealed three different biogeographical areas: West Atlantic, East Atlantic and a larger area representing the Mediterranean, the Mediterranean/Atlantic transition zone and a Pacific site (Bali). It was found out that the Mediterranean/Atlantic transition zone is a biogeographical boundary for C. prolifera. A lack of connectivity was revealed between Atlantic and Mediterranean types, and identical sequences found in the Mediterranean and Indo-Pacific suggest either recent gene flow along the Red Sea connection or a possible ancient Indo-Pacific origin.Financial support for this study was provided by several research projects: CAULERPA_GENETICS (PTDC/MAR/70921/2006) by FCT (Portuguese Science Foundation) co-funded by FEDER and a postdoctoral fellowship (SFRH/BPD/17206/2004) from FCT, Portugal, co-funded by FSE, both to EVA, EXCL/AAG-GLO/0661/2012 to ES, CAULEXPAN (Spanish Ministry of Education, REN2002-00701) to NM, MedVeg (EU contract no. Q5RS-2001-02456), PRADERAS by the Foundation BBVA (Banco Bilbao Vizcaya Argentaria) to CDPeer Reviewe

Efeito do composto 2,3-difosfoglicerato (2,3-DPG) no desenvolvimento do parasita Plasmodium falciparum – análise transcriptómica

Plasmodium falciparum é um parasita transmitido pelos mosquitos do género Anopheles, responsável por causar a forma mais grave da malária humana. O aparecimento de resistências aos antimaláricos e aos inseticidas, aliado aos fracos recursos financeiros dos países de baixa renda nas áreas endémicas, contribuem para que os grandes desafios do combate à malária sejam a sua prevenção e tratamento. No entanto, apesar da malária continuar a causar milhões de infeções e milhares de mortes todos os anos, tem vindo a selecionar polimorfismos genéticos dos eritrócitos, como a deficiência em piruvato cinase, que se revelam como protetores contra a doença e contribuem para uma maior sobrevivência do hospedeiro humano. O composto 2,3-DPG poderá vir a ser um agente terapêutico promissor, capaz de mimetizar a deficiência em piruvato cinase e, sendo endógeno, com uma toxicidade menor para o doente. Além disso, resultados prévios apontam para um efeito do composto no crescimento do parasita. É, assim, de enorme importância compreender o efeito da adição de 2,3-DPG no desenvolvimento parasitário através da análise da maturação parasitária e da resposta transcriptómica do parasita. A maturação parasitária em culturas in vitro de P. falciparum tratadas e não tratadas com 2,3-DPG foi monitorizada através de citometria de fluxo, ao longo do ciclo eritrocitário completo, até à sua lise. Posteriormente foi analisada a expressão génica através da sequenciação de bibliotecas de cDNA de parasitas tratados e não tratados com o composto no estadio de trofozoíto usando a tecnologia de sequenciação por nanoporos. O composto 2,3-DPG parece influenciar a maturação do parasita, bem como a sua progenia, com a diminuição na produção de merozoítos, o que leva a menores densidades parasitárias em culturas in vitro. O estudo da resposta transcricional mostrou o efeito que o composto 2,3- DPG tem na resposta da célula parasitária para a sua sobrevivência num ambiente hostil. A análise trascriptómica realizada sugere que a resposta ao composto pode envolver vários processos biológicos (proteção contra o stress celular, regulação do crescimento e desenvolvimento do parasita, perda de patogenicidade e virulência, entre outros). Os resultados obtidos no presente trabalho suportam o estudo mais aprofundado da deficiência em piruvato cinase, em especial o efeito de 2,3-DPG, que poderá contribuir para o aparecimento de novos agentes antimaláricos.Plasmodium falciparum is a parasite transmitted by mosquitoes of the genus Anopheles, responsible for the most severe form of human malaria. The emergence of resistance to antimalarials and insecticides and very limited resources of poor countries in endemic areas, contribute to the major challenges in the fight against malaria being its prevention and treatment. Malaria continues to cause millions of infections and thousands of deaths every year, however, erythrocyte genetic polymorphisms, such as pyruvate kinase deficiency, have been selected because they confer some protection against the disease, contributing to a greater survival of the human host. The compound 2,3-DPG may prove to be a promising therapeutic agent, capable of mimicking the deficiency in pyruvate kinase, and being endogenous with less toxicity for the patient. Furthermore, previous results point to an effect of 2,3-DPG on parasite development. It is, therefore, of great importance to understand the effect of the addition of 2,3-DPG on the parasite development through the analysis of the parasite maturation and the parasite transcriptomic response. In the present study, parasite maturation was monitored by flow cytometry, throughout the complete erythrocyte cycle. Gene expression at the trophozoite stage was analyzed by sequencing of cDNA libraries in P. falciparum in vitro cultures treated and not treated with 2,3-DPG using nanopore sequencing technology. Addition of 2,3-DPG seems to influence the maturation of the parasite, as well as its progeny, with a decrease in the merozoites production, which leads to lower parasite densities in the treated cultures. Furthermore, the study of the transcriptional response has shown the effect that 2,3-DPG has on the parasite cell response regarding its survival in a hostile environment. Transcriptomic analysis suggests that this response may involve several biological processes (protection against cell stress, regulation of parasite growth and development, loss of pathogenicity and virulence, and others). The results obtained in the present work support a furtherstudy of pyruvate kinase deficiency, in particular, the effect of 2,3-DPG, which may contribute to the emergence of new antimalarial agents

Tratamento de hemangioma gigante com interferon alfa: relato de dois casos Treatment of giant hemangioma with interferon-alpha: report of two cases

O objetivo do trabalho é descrever o uso de interferon alfa no tratamento de pacientes com hemangioma gigante. Os autores relatam e analisam dois casos de hemangioma gigante em tratamento com interferon alfa. IBS, 3 anos, em acompanhamento no Ambulatório de Hematologia desde um ano de idade com quadro de lesão angiomatosa em praticamente toda hemiface direita, acompanhada de sangramentos gengivais importantes. Após a realização de exames complementares (Angiorressonância magnética) e feito o diagnóstico de hemangioma gigante em face, foi iniciado tratamento com prednisona e, posteriormente, associação com interferon alfa e observada importante melhora do quadro, resultando na diminuição dos episódios de sangramento e no tamanho do tumor. C.N.P., 12 anos, apresentando nódulo em região lateral de joelho esquerdo há 2 anos, com aumento progressivo do tamanho e dor local. Fez uso de prednisona e, sem melhora do quadro, introduzido interferon alfa com regressão importante do tamanho do tumor. O tratamento com interferon alfa deve ser considerado no tratamento de hemangiomas, pois apresenta bons resultados em relação à diminuição do tamanho do tumor e, conseqüentemente, reduz as intercorrências clínicas associadas à sua presença, principalmente os sangramentos.<br>The aim of this study is to describe the treatment using interferon-alpha of giant hemangiomas in children. The authors report two cases of children presenting with giant hemangiomas treated using interferon-alpha and analyze the results. IBS, 3 years-old, has been followed up in Famema Hemathology Service since she was 1 year-old with a tumor on the face and persistent bleeding. After clinical and radiologic evaluations and suggested the diagnosis of giant hemangioma, she started treatment with interferon-alpha. A great clinical improvement was observed a reducing of the number of episodes of bleedings and a decrease in of the tumor size. CNP, 12 years-old, came to this service in the last year presenting with a small painful tumor on the left knee. She had already tried a treatment with Prednisone with no improvement. Treatment with interferon-alpha was initiated with a significant decrease in its size. The use of interferon-alpha should be considered in the treatment of giant hemangioma due to its favorable results related to a reduction in the tumor size and the episodes of bleeding

2,3-Diphosphoglycerate and the Protective Effect of Pyruvate Kinase Deficiency against Malaria Infection—Exploring the Role of the Red Blood Cell Membrane

Malaria remains a major world public health problem, contributing to poverty and inequality. It is urgent to find new efficacious tools with few adverse effects. Malaria has selected red blood cell (RBC) alterations linked to resistance against infection, and understanding the protective mechanisms involved may be useful for developing host-directed tools to control Plasmodium infection. Pyruvate kinase deficiency has been associated with resistance to malaria. Pyruvate kinase-deficient RBCs display an increased concentration of 2,3-diphosphoglycerate (2,3-DPG). We recently showed that 2,3-DPG impacts in vitro intraerythrocytic parasite growth, induces a shift of the metabolic profile of infected cells (iRBCs), making it closer to that of noninfected ones (niRBCs), and decreases the number of parasite progenies that invade new RBCs. As an increase of 2,3-DPG content may also have an adverse effect on RBC membrane and, consequently, on the parasite invasion, in this study, we explored modifications of the RBC morphology, biomechanical properties, and RBC membrane on Plasmodium falciparum in vitro cultures treated with 2,3-DPG, using atomic force microscopy (AFM)-based force spectroscopy and other experimental approaches. The presence of infection by P. falciparum significantly increased the rigidity of parasitized cells and influenced the morphology of RBCs, as parasitized cells showed a decrease of the area-to-volume ratio. The extracellular addition of 2,3-DPG also slightly affected the stiffness of niRBCs, making it more similar to that of infected cells. It also changed the niRBC height, making the cells appear more elongated. Moreover, 2,3-DPG treatment influenced the cell surface charge, becoming more negative in treated RBCs than in untreated ones. The results indicate that treatment with 2,3-DPG has only a mild effect on RBCs in comparison with the effect of the presence of the parasite on the host cell. 2,3-DPG is an endogenous host metabolite, which may, in the future, originate a new antimalarial tool with few adverse effects on noninfected cells

Gene pool and connectivity patterns of Pinna nobilis in the Balearic Islands (Spain, Western Mediterranean Sea): Implications for its conservation through restocking

Pinna nobilis is an endemic bivalve of the Mediterranean Sea, and a vulnerable species registered as endangered and protected under the European Council Directive 92/43/EEC and Barcelona Convention. In early autumn 2016, a mass mortality event impacted P. nobilis populations in the south-western Mediterranean Sea, including the Balearic Islands. At the time of this study, P. nobilis still maintained high population densities along the Balearic coasts (Western Mediterranean). This study evaluated the connectivity of P. nobilis post-larvae and adults in seagrass habitats around the Balearic Islands and identified its source and sink populations. These objectives were reached through a multidisciplinary approach including population genetics (10 microsatellites) and hydrodynamic modelling. High genetic diversity was found and significant genetic differentiation (inferred by fixation index F-ST) was detected between post-larvae samples, but not between adult populations. Significant genic and genotypic differentiation was recorded for adults and post-larvae. This pattern was confirmed by correspondence analysis using allele frequencies. The genetic connectivity pattern was consistent with marine currents and dispersal models. This work not only improves knowledge of the P. nobilis gene pool in south-west Mediterranean populations and their connectivity patterns, but is also crucial to help evaluate the possibility of recovery from source populations and the possibility of restocking programmes, as well as provide a solid base to establish effective marine reserve networks.Spanish National project EstresX [CTM2012-32603]Fundacao para a Ciencia e Tecnologia (FCT, Portugal) programme [UID/Multi/04326/2013]JAE-DOC fellowship (CSIC, Spain)FCT Investigator Programme-Career Development [IF/00998/2014]JAE pre-DOC fellowshi

Synthetic Red Blood Cell-Specific Glycolytic Intermediate 2,3-Diphosphoglycerate (2,3-DPG) Inhibits Plasmodium falciparum Development In Vitro

Mechanisms of malaria parasite interaction with its host red blood cell may provide potential targets for new antimalarial approaches. Pyruvate kinase deficiency has been associated with resistance to malaria in both experimental models and population studies. Two of the major pyruvate kinase deficient-cell disorders are the decrease in ATP and the increase in 2,3-biphosphoglycerate (2,3-BPG) concentration. High levels of this metabolite, only present in mammalian red blood cell, has an inhibitory effect on glycolysis and we hypothesized that its accumulation may also be harmful to the parasite and be involved in the mechanism of protection provided by that enzymopathy. We examined the effect of a synthetic form, 2,3-DPG, on the Plasmodium falciparum intraerythrocytic developmental cycle in vitro. Results showed an impairment of parasite growth with a direct effect on parasite maturation as significant lower progeny emerged from parasites that were submitted to 2,3-DPG. Further, adding the compound to the culture medium did not result in any effect on the host cell, but instead the metabolic profile of an infected cell became closer to that of a non-infected cell.publishersversionpublishe