The role of ADAM10, ADAM17, and Spag6 in humoral immunity and secondary lymphoid tissue architecture

ADAM10, ADAM17, and SPAG6 contribute significantly to humoral immunity and secondary lymphoid tissue architecture. ADAM10 and ADAM17 are two closely related zinc-metalloproteinases. Through cleavage of their ligands CD23 and TNF, respectively, they greatly influence IgE production and secondary lymphoid tissue architecture maintenance. Th1 prone WT strains initially exhibit increased ADAM17 and TNF yet reduced ADAM10 relative to Th2 prone WT strains. In the absence of B cell ADAM10, a compensatory increase in ADAM17 and TNF cleavage is noted only in Th1 prone C57Bl/6, not Th2 prone Balb/c. B cell TNF homeostasis is important for maintaining secondary lymphoid tissue architecture. We show for the first time that excessive B cell TNF production in C57-ADAM10B-/- lymph nodes contributes to loss of B/T segregation, increased HEV number and size, fibrosis, loss of FDC networks, and impaired germinal center formation. Furthermore, B cell ADAM10, which enhances IgE production through CD23 cleavage, is shown to be a marker of Th2 susceptibility. B cell ADAM10 is elevated in Th2 prone mouse strains and allergic patients compared to Th1 prone controls and as B cell ADAM10 level increases, so does IgE production. Lastly, the B cell profile of allergic patients is determined to be B cell ADAM10highADAM17lowTNFlow. Furthermore, the mechanism underlying reduced class-switched antibody production in C57-ADAM10B-/- mice is explored. C57-ADAM10B-/- B cells exhibit a B10, or IL-10 producing, phenotype, which is linked to reduced antibody production. Furthermore, increased Tregs noted in C57-ADAM10B-/- mice contributed to reduced class switched IgE production and disease parameters following a house dust mite airway inflammation challenge. SPAG6, a component of the central apparatus of the “9+2” axoneme, plays a central role in flagellar stability and motility. Immune cells lack cilia, but the immunological synapse is a surrogate cilium as it utilizes the same machinery as ciliogenesis including the nucleation of microtubules at the centrosome. We demonstrate that Spag6 localizes in the centrosome and is critical for centrosome polarization at and actin clearance away from the synapse between CTL and target cells. Furthermore, improper synapse formation and function likely explains reduced CTL function and class-switched antibody production in Spag6KO mice

Structural and mechanistic studies of iron containing proteins

Dissertação apresentada para obtenção do Grau de Doutor em Bioquímica, ramo de Bioquímica-Física, pela Universidade Nova de Lisboa, Faculdade de Ciências e TecnologiaOver the last few decades a large effort has been done in the structural biochemistry field. This effort is based on the study of some proteins, namely metalloproteins, that contain cofactors and/or active sites with metal ions in their constitution. This thesis will focus on different studies performed in metalloproteins that contain non-heme iron centers. An important point is their relation to oxygen and reactive oxygen species. To perform these studies, fast kinetic techniques were used coupled to spectroscopic techniques, such as Electronic Paramagnetic Resonance (EPR), Mössbauer and UVVisible.Fundação para a Ciência e Tecnologia (SFRH/BD/18905/2004

Benefits of maintenance management software: a study on Portuguese market

In a world where maintenance has evolved over the years, it is expected that technological investment will continue to grow and become even more important for the development of maintenance, contributing to the profitability of organisations. This dissertation seeks to identify the benefits obtained by organisations after the implementation of maintenance management software. From an extensive literature review and contacts made with the industry, a set of benefits were included in a questionnaire to Portuguese companies belonging to different sectors, with the purpose of assessing the level of measurement of each benefit and evaluating the acceptance of the project of maintenance management software in organisations. Results demonstrate that many companies confirm the achievement of the benefits suggested in the questionnaire. However, this research has also shown that few organisations evaluate the benefits in such a way that translate the benefits into financial value. The study contributes with findings that are based on empirical research, providing market data that are useful for both vendors of maintenance management software and companies that use or intend to use this type of system.Num mundo em que a manutenção tem evoluído ao longo dos anos, é esperado que o investimento tecnológico continue a crescer e se torne ainda mais importante no desenvolvimento da manutenção, contribuindo para a rentabilidade das organizações. Esta dissertação procura identificar os benefícios obtidos pelas empresas após a implementação de software de gestão de manutenção. A partir de uma extensa revisão de literatura e contatos realizados com a indústria, identificaram-se um conjunto de benefícios que foram incluídos num questionário realizado a empresas Portuguesas de diferentes setores, com o intuito de verificar o nível de medição de cada benefício e avaliar a aceitação do projeto de software de gestão de manutenção nas organizações. Os resultados demonstram que muitas empresas confirmam a obtenção dos benefícios sugeridos no questionário. No entanto, esta investigação revela também que poucas organizações avaliam os benefícios de tal forma que consigam traduzi-los em valor financeiro. O estudo contribui com conclusões que se baseiam em pesquisa empírica, disponibilizando dados de mercado que são úteis tanto para fornecedores de software de gestão de manutenção como para empresas que utilizam ou pretendem vir a utilizar este tipo de sistema

Transportes e sustentabilidade económica, social, territorial e ambiental : o caso português no contexto da UE

Mestrado em Economia Internacional e Estudos EuropeusNuma economia cada vez mais global e integrada, o estudo da evolução dos transportes e as suas implicações económicas não podem ser negligenciados. O sector dos transportes deveria funcionar como recurso fundamental para que a UE alcançasse a sua pretensão de economia dinâmica e de coesão social no seu território. No presente trabalho de investigação faz-se a revisão da literatura teórica e empírica relacionada com o impacto económico dos investimentos em infra-estruturas de transportes, procu-rando analisar o efeito do sector na produtividade nacional, no comércio internacional, no emprego ou no produto. Recorrendo aos principais indicadores económicos, caracte-riza-se o sector e analisa-se a sua evolução, não só a nível nacional, como a nível comu-nitário, tendo como enquadramento PCT e as necessidades assistidas pela implementa-ção da RTE-T. Os últimos dois PET são examinados por forma a compreender qual o impacto das alterações do paradigma político em questões estruturantes como a dos transportes.In an economy increasingly global and integrated the study of transport evo-lution and their economic implications cannot be overlooked. The transport sector should act as a key resource for the European Union (EU) in order to reach its pretense of dynamic economy and social cohesion within its territory. This research work review the theoretical and empirical literature related to the economic impact of investment in transport infrastructure, assessing the effect of the sector in national productivity, inter-national trade, employment or product. Drawing on key economic indicators, the sector evolution is characterized and analyzed, not only at national level, but also at Commu-nity level, taking as a framework the Common Transport Policy and the needs assisted by the implementation of the trans-European network for Transport. The last two strate-gic plans of transport are examined in order to understand the impact of changes in the political paradigm in structuring issues such as transport

Factores de risco associados á transmissão de diarreia em crianças dos 6 meses aos 7 anos no bairro do Xipamanine

As diarreias continuam a ser em Moçambique e em muitos paises em desenvolvimento um dos problemas de Saúde pública mais importantes. São doenças transmissiveis não preveniveis por vacina eque ocorrem com frequencia de forma isolada ou associada à malnutrição e malaria causando elevadas taxas de mortalidade nos países em desenvolvimento. Para cada caso foi escolhido um controle constituido por indivíduos do mesmo sexo e idade que o casos, e residentes na mesma area, sem historia de dejecções liquidas nos ultimos 60 dias anteriores á data de recolha de dados. A área de estudo foi o Bairro do Xipamanine. Motivou a escolha desta zona o facto de este bairro ter durante anos consecutivos registado o maior número de casos das diarreias ocorridas na Cidade de Maputo. De acordo com dados da Direcção de Saude da Cidade do Maputo, em 1996, por exemplo, registaram-se 34.095 casos de diarrea nesta zona, dos quais 25.406 (75%) em crianças do 0-14 anos

Prevalence of sexually transmitted infections in women attending antenatal care in Tete province, Mozambique

Objective. To determine the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and syphilis in pregnant women. Methods. A cross-sectional study was conducted among women attending antenatal care clinics (ANCs). Blood samples were tested for syphilis using the rapid plasma reagin (RPR) and treponemal haemagglutination (TPHA) tests; CT and NG were diagnosed using a manual polymerase chain reaction assay on first-void urine samples. A socio-demographic questionnaire was completed. Results were compared with previous published data on sexually transmitted infection (STI) prevalence in Mozambique. Results. Blood and urine samples were collected from 1119 and 835 women, respectively. The prevalence of CT was 4.1%, and that of NG 2.5%. The RPR test was positive in 5.2% of the women, and 7.1% had a positive TPHA test. Active syphilis was found in 4.7%. In univariate analysis, CT was associated with having had any level of education (p25. Multivariate analysis did not show any significant association. In comparison with published data from 1993, a decline was observed for CT (p<0.05), NG and syphilis (p<0.001). Conclusions. Compared with available data, a decline of STI prevalence was observed in our setting. This might be the result of community-based education programmes focusing on changes to sexual behaviour, as well as the widespread use of the syndromic approach to managing STIs and the expansion of syphilis screening in primary health care settings. However, STI rates are still high, and the problem needs more concrete and sustained efforts for its control

Bacterial vaginosis, alterations in vaginal flora and HIV genital shedding among HIV-1-infected women in Mozambique

Objectives. We investigated whether abnormal vaginal flora, including bacterial vaginosis (BV), are associated with detection of cervical HIV-1 RNA among HIV-infected women in Mozambique. Methods. We obtained clinical data and vaginal specimens from HIV-infected women registering for their first visit at one of two HIV care clinics in Mozambique. We compared women with detectable cervical HIV viral load (&ge;40 copies/ml) with women with undetectable cervical HIV. Results. We enrolled 106 women. Women with abnormal vaginal flora (intermediate Nugent scores, 4 - 6) were more likely to have detectable cervical HIV RNA than women with normal vaginal flora (adjusted odds ratio 7.2 (95% confidence interval 1.8 - 29.1), adjusted for CD4 count). Women with BV had a non-significantly higher likelihood of detectable cervical HIV than women with normal flora. Conclusions. Abnormal vaginal flora were significantly associated with cervical HIV expression. Further research is needed to confirm this relationship

Retinopexia com "buckle" escleral e crioterapia guiada por ultrassom: relato de caso

If the ocular media are clear, indirect binocular ophthalmoscopy allows retinal detachment and retinal tear identification and treatment under direct visualization. However, if opacities are present preventing direct fundus examination, ultrasonography becomes the most important tool for evaluating the posterior segment. In addition, ultrasonography can be useful in retinal tear treatment by guiding cryotherapy. In this article we describe a rhegmatogenous retinal detachment treatment technique applied to a patient with corneal opacity. Cryopexy and circumferential and radial buckle positioning were guided by ultrasonography, resulting in retinal attachment during the 6-month follow-up period.Quando os meios oculares são transparentes, oftalmoscopia binocular indireta permite a identificação de descolamento de retina e roturas, bem como seu tratamento sob visibilização direta. Porém, em olhos que apresentam opacidades de meios impedindo o exame oftalmoscópico, a ultrassonografia constitui o exame mais importante do segmento posterior do olho. Além disso, o tratamento de roturas retinianas também pode ser auxiliado pelo uso desse equipamento, orientando a crioterapia. Neste trabalho será apresentada técnica de tratamento de descolamento de retina regmatogênico, no qual a criopexia e o posicionamento dos "buckles" episclerais circunferencial e radial foram guiados pelo ultrassom em paciente com leucoma corneano. O tratamento resultou em aplicação retiniana durante o seguimento em seis meses

Prevalence of sexually transmitted infections in women attending antenatal care in Tete province, Mozambique

Objective. To determine the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and syphilis in pregnant women. Methods. A cross-sectional study was conducted among women attending antenatal care clinics (ANCs). Blood samples were tested for syphilis using the rapid plasma reagin (RPR) and treponemal haemagglutination (TPHA) tests; CT and NG were diagnosed using a manual polymerase chain reaction assay on first-void urine samples. A socio-demographic questionnaire was completed. Results were compared with previous published data on sexually transmitted infection (STI) prevalence in Mozambique. Results. Blood and urine samples were collected from 1 119 and 835 women, respectively. The prevalence of CT was 4.1%, and that of NG 2.5%. The RPR test was positive in 5.2% of the women, and 7.1% had a positive TPHA test. Active syphilis was found in 4.7%. In univariate analysis, CT was associated with having had any level of education (