Stability of the transthyretin molecule as a key factor in the interaction with a-beta peptide--relevance in Alzheimer's disease

Transthyretin (TTR) protects against A-Beta toxicity by binding the peptide thus inhibiting its aggregation. Previous work showed different TTR mutations interact differently with A-Beta, with increasing affinities correlating with decreasing amyloidogenecity of the TTR mutant; this did not impact on the levels of inhibition of A-Beta aggregation, as assessed by transmission electron microscopy. Our work aimed at probing differences in binding to A-Beta by WT, T119M and L55P TTR using quantitative assays, and at identifying factors affecting this interaction. We addressed the impact of such factors in TTR ability to degrade A-Beta. Using a dot blot approach with the anti-oligomeric antibody A11, we showed that A-Beta formed oligomers transiently, indicating aggregation and fibril formation, whereas in the presence of WT and T119M TTR the oligomers persisted longer, indicative that these variants avoided further aggregation into fibrils. In contrast, L55PTTR was not able to inhibit oligomerization or to prevent evolution to aggregates and fibrils. Furthermore, apoptosis assessment showed WT and T119M TTR were able to protect against A-Beta toxicity. Because the amyloidogenic potential of TTR is inversely correlated with its stability, the use of drugs able to stabilize TTR tetrameric fold could result in increased TTR/ABeta binding. Here we showed that iododiflunisal, 3-dinitrophenol, resveratrol, [2-(3,5-dichlorophenyl)amino] (DCPA) and [4- (3,5-difluorophenyl)] (DFPB) were able to increase TTR binding to A-Beta; however only DCPA and DFPB improved TTR proteolytic activity. Thyroxine, a TTR ligand, did not influence TTR/A-Beta interaction and A-Beta degradation by TTR, whereas RBP, another TTR ligand, not only obstructed the interaction but also inhibited TTR proteolytic activity. Our results showed differences between WT and T119M TTR, and L55PTTR mutant regarding their interaction with A-Beta and prompt the stability of TTR as a key factor in this interaction, which may be relevant in AD pathogenesis and for the design of therapeutic TTR-based therapies

Potential biomass production of a short rotation crop in Portugal

There is a growing consensus that CO2 emissions from burning fossil fuels are altering the global climate. The Portuguese government aims to reduce national CO2 emissions by 8 %, at the levels of 1990, by 2012. The use of short rotation crops (SRC) such as willow and poplar as an energy source that produces very low net CO2 emissions could help meet these targets. In 2008, in the framework of the research project PTDC/AGR-CFL/64500/2006, a SRC crop was established in the Trás-os-Montes Region, Northern Portugal. The SRC was installed in a 4 ha area using willow (local hybrid Salix alba x Salix fragilis and a Swedish Salix. L. clone, Terra Nova), poplar (local Populus nigra and Populus x euroamericana, clone I-214) and ash (Fraxinus angustifolia). The crop was planted by simply pushing cuttings using a double row design with densities ranging from 15000 to 20000 cuttings per hectare for willow and 10000 to 15000 cuttings per hectare for poplar and ash. The cut back was done one growing season after plantation to encourage the development of coppice to produce more shoots. The SRC research trial is in the second year of the first 3-year cutting cycle. At this stage the potential biomass production and carbon storage were assessed. Poplar and willow clones presented higher growth and higher number of shoots per stool than their native counterparts. They also presented higher biomass production and, consequently, higher carbon storage. The potential biomass production ranged from 149.7 kg ha-1 to 1980.0 kg ha-1 for ash and poplar I-214, respectively, and, the carbon storage ranged from 74.9 kg ha-1 to 990.0 kg ha-1 for the same species. Although our results came from a Mediterranean Region they are consistent with the results from other studies in Central Europe.PTDC/AGR-CFL/64500/200

Função do marketing em instituições de ensino superior

O actual estado do Ensino Superior em Portugal é uma das questões complexas com que se debate a sociedade portuguesa. A problemática do Ensino Superior percorre alguns aspectos fundamentais tais como as constantes mutações do meio envolvente, o decréscimo de candidatos, o acréscimo de concorrência, as restrições financeiras, o desajustamento entre a oferta de formação superior e a procura dessa formação por parte do mercado de trabalho. A orientação para os públicos-alvo, através da oferta de serviços orientados para as necessidades e exigências presentes e futuras dos seus clientes actuais e potenciais, torna-se fundamental para as instituições de Ensino Superior, tal como acontece com a generalidade das actividades económicas e sociais. Assim, a adopção de perspectivas de gestão estratégica enquadradas nas metodologias e técnicas de marketing, permitirá que as instituições se posicionem de forma diferenciada face aos seus públicos-alvo, alcançando níveis acrescidos de competitividade. Neste contexto, o futuro do Ensino Superior em Portugal dependerá enormemente da capacidade das instituições para assumirem estratégias competitivas, detectarem novos segmentos de mercado, procurarem alternativas de financiamento, encontrarem novas formas de relacionamento com o tecido sócio económico, reverem os cursos existentes e/ou criarem novos cursos e promoverem eficazmente os seus serviços, educacionais e outros. Resumidamente, poder-se-á afirmar que as instituições de Ensino Superior necessitam desenvolver soluções organizacionais que lhes possibilitem enfrentar, com sucesso, os desafios com que se confrontam. No presente trabalho são apresentadas as teorias e técnicas de marketing aplicadas ao Ensino Superior, a análise da situação actual do Ensino Superior em Portugal e um estudo sobre as características da escolha dos cursos de 1ª opção por parte dos candidatos ao Ensino Superior que ingressaram, no ano lectivo de 2003/04, na Universidade do Minho, em cursos da área tecnológica e não tecnológica. Por fim, é concretizada a proposta de um modelo de marketing, adequado às condições presentes das instituições de Ensino Superior em Portugal.The present situation of Higher Education in Portugal is one of the complex issues under debate for the Portuguese society. The questions raised pervade some key aspects such as the constant changing in the involving environment, the decreasing applications, the increasing competition among institutions, the financial constraints, the imbalance between the offer of higher education and its demand by the labour market. As the case goes for most of social and economic activity, orientation towards target-publics is of utmost importance for the institutions of Higher Education, by offering their present and potential clients services which aim at meeting their present and future needs and demands. Thus, adopting an approach of strategic management supported by marketing methodologies and techniques will allow institutions to differentiate their positioning towards their target-publics and reach increasing levels of competitiveness. In such a context, the future of Higher Education in Portugal will depend greatly on the capacity of institutions to assume competitive strategies, detect new segments of market, get alternative financing, find new ways of relating with the social and economic sector, revise existing courses and/or design new courses and efficiently promote their educational services and others. In brief, it is possible to say that the institutions of Higher Education need to develop organizational solutions that allow them to cope with their challenges successfully. The present study discusses marketing theories and techniques applied to Higher Education, analyses the present situation of Higher Education in Portugal, and researches into the characteristics of the choice of first option courses by applicants to Higher Education who registered in the University of Minho in 2003/04 in courses of the technological area or other. Finally, a proposal of marketing model adequate to the present conditions of the institutions of Higher Education in Portugal is presented

Perfil volátil de excrementos de veado

Mestrado em Ecologia, Biodiversidade e Gestão de EcossistemasCurrent populations of red deer (Cervus elaphus) in Portugal derive from recent reintroduction processes and natural dispersion movements from Spain. These movements promote the expansion of the species and reproduction among different populations, increasing the need for more sophisticated methodologies able to differentiate populations and determine sex-ratio, two demographic parameters used in the management of populations. Headspace solid phase microextraction and comprehensive two-dimensional chromatography coupled to mass spectrometry for time of flight gas phase mode (HS-SPME/GC×GC– ToFMS) arises as a possible solution to the determination of these parameters. Thus, this work aims to test for differences between red deer populations, using scats from natural fenced red deer populations as a model to distinguish between sexes. The obtained volatiles are an attempt to determine specific sets of compounds or chemical families’ markers for males, females and for each population, targeting the use in wildlife approaches. In fact, results showed that populations and gender successful differentiation was based on a sub-set of probably, diet and chemical communication compounds, respectively. The mechanism underling this differentiation is probably the interaction of genetics and environment leading to changes in animals’ physiology, based in the expressed volatile metabolites detected in the scats. The absence of literature data that relates the tentatively identified compounds (mainly aliphatic ketones and hydrocarbons) to chemical signals between red deer requires future bioassays testing the achieved compounds to predetermined behaviours. It is considered that the results and conclusions of this work may be applied to big scale wild populations, allowing the assessment of ecological parameters that otherwise would be expansive and time consuming.Os recentes programas de reintrodução de veados (Cervus elaphus) e os movimentos naturais de dispersão de indivíduos provenientes de Espanha resumem a história das actuais populações deste mamífero em Portugal. À medida que estas se expandem e que populações com diferentes origens se reproduzem, aumenta a necessidade de metodologias mais sofisticadas capazes de as diferenciar independentemente da origem, e de determinar o rácio sexual, dois parâmetros usados na gestão de populações. A microextracção em fase sólida e em modo espaço de cabeça e cromatografia abrangente bidimensional em fase gasosa acoplada à espectrometria de massa por tempo de voo (HS-SPME/GC×GC– TOFMS) surge como possível solução para a determinação destes parâmetros. Assim, este trabalho tem como objetivos diferenciar populações de veados, usando animais em cativeiro como modelo, bem como efectuar a distinção entre sexos. Os compostos voláteis obtidos são uma tentativa de determinar marcadores (compostos ou famílias químicas) para machos, fêmeas e para cada população, visando o uso na gestão de vida selvagem. De facto, os resultados deste estudo mostram que a diferenciação bem sucedida de populações e sexos foi baseada num sub-conjunto de compostos possivelmente derivados da dieta e comunicação química. O mecanismo que poderá estar na base destas distinções é a interação da genética e de fatores ambientais que conduziram a alterações metabólicas e fisiológicas nos animais, expressas com base nos metabolitos voláteis detetados nos seus excrementos. A ausência de literatura que relacione os compostos identificados (principalmente cetonas e hidrocarbonetos alifáticos) com a comunicação química entre veados leva à necessidade de bioensaios futuros onde se testem os compostos identificados neste estudo e a resposta dos animais. Considera-se que os resultados e conclusões deste trabalho poderão ter uma aplicação ecológica ao nível de populações selvagens de grande escala, permitindo a determinação de parâmetros ecológicos que de outro modo seriam dispendiosos e morosos

Synergy of combined Doxycycline/TUDCA treatment in lowering Transthyretin deposition and associated biomarkers: studies in FAP mouse models

Familial Amyloidotic Polyneuropathy (FAP) is a disorder characterized by the extracellular deposition of fibrillar Transthyretin (TTR) amyloid, with a special involvement of the peripheral nerve. We had previously shown that doxycycline administered for 3 months at 40 mg/Kg/ml in the drinking water, was capable of removing TTR amyloid deposits present in stomachs of old TTR-V30M transgenic mice; the removal was accompanied by a decrease in extracellular matrix remodeling proteins that accompany fibrillar deposition, but not of non-fibrillar TTR deposition and/or markers associated with pre-fibrillar deposits. On the other hand, Tauroursodeoxycholic acid (TUDCA), a biliary acid, administrated to the same mouse model was shown to be effective at lowering deposited non-fibrillar TTR, as well as the levels of markers associated with pre-fibrillar TTR, but only at young ages

The role of social organisations in the promotion of recreation and tourism activities for people with special needs

Although leisure and tourism are recognised as rights for all people, many people with special needs (PwSN) still have very limited opportunities for participating in these activities. Social organisations (SO) are potential mediators between the tourism industry and this market, especially for reducing barriers to participation. However, there is a lack of research on the role these organisations perform as facilitators of access to leisure and tourism. This paper aims to identify the difficulties faced and strategies adopted by SO when developing recreation and tourism activities, as well as the benefits of these activities for PwSN. A qualitative approach was adopted, namely semi-structured interviews with representatives of Portuguese SO working with PwSN. The findings highlight that Portuguese SO have had a dynamic and proactive behaviour in the development of recreation and tourism activities, contributing to increased access of PwSN to tourism activities, especially for people belonging to socially and economically disadvantaged groups. However, the results also show that SO face several constraints, specifically financial constraints, lack of specialised human resources and the lack of suitable tourism supply (e.g. accommodation, transportation) for this market. The paper ends with strategies that these organisations may adopt to cope with these constraints.This research was funded by the project ACTION – Accessible Tourism: Co-Creation of Tourism Experiences Through Web-Based Intelligent Systems, funded by FEDER, through COMPETE2020 – Programa Operacional Competitividade e Internacionalização (POCI-01-0145-FEDER-030376), and by national funds (OE), through FCT/MCTES (PTDC/EGE-OGE/30376/2017publishe

Differentiation and coordination within a composite training policy providing efficient support namely to isolated museum professionals

In Portugal, namely in municipal museums, the reduced percentage of museum professionals that have a stable administrative position imposes a high degree of polyvalence allowing them to coordinate, often by themselves, the quotidian activities at the museum(s) they run

Uso de parásitos como marcadores biológicos en la identificación de stocks de sable negro, Aphanopus carbo Lowe, 1839 (Osteichthyes: Trichiuridae) en aguas portuguesas

We studied the use of parasites as biological tags for discriminating fish stocks of Aphanopus carbo (Osteichthyes: Trichiuridae) from Portugal (Sesimbra on the mainland, Madeira and the Azores). Sixteen different metazoan parasites were found (14 from Madeira, 9 from Sesimbra and 7 from the Azores). Some parasites occurred only in fish from Madeira. The prevalence and mean intensity of the infection was recorded for each parasite and locality, and their values were statistically compared between the three sampling localities and related to host length classes. The differences between some of these parameters were statistically significant among the three localities or between two of them. It is suggested that 6 parasites (Tentacularia coryphaenae, Sphyriocephalus tergestinus, Campbelliella heteropoeciloacantha, Anisakis spp., Bolbosoma vasculosum and unidentified Acanthocephala larvae) can be used as biological tags to discriminate Portuguese stocks of Aphanopus carbo.Se estudió el uso de parásitos como marcadores biológicos para discriminar los stocks de Aphanopus carbo (Osteichthyes, Trichiuridae) de Portugal (Sesimbra en el continente, Madeira y Azores Islas). Dieciséis parásitos metazoarios fueron encontrados (14 en Madeira, 9 en Sesimbra y 7 en Azores). Algunos parásitos se presentaron sólo en Madeira. La prevalencia y la intensidad media de las infecciones fueron calculadas para cada parásito y cada región, y sus valores fueron comparados estadísticamente entre los tres lugares de muestreo, y relacionados con la talla del huésped. Se encontraron diferencias estadísticamente significativas entre algunos de estos parámetros de las tres regiones o entre dos de ellas. Se sugiere que 6 parásitos (Tentacularia coryphaenae, Sphyriocephalus tergestinus, Campbelliella heteropoeciloacantha, Anisakis spp., Bolbosoma vasculosum y larvas no identificadas de Acanthocephala) pueden ser usados como marcadores biológicos para discriminación de stocks de Aphanopus carbo de Portugal

Estudo em Ruditapes decussatus (Linnaeus, 1758) em cenários de alterações climáticas, relação entre disponibilidade de alimento e temperatura

O crescimento populacional tem vindo a aumentar exponencialmente, e com ele uma maior pressão sobre os stocks naturais, que estão cada vez mais sobre explorados e fragilizados. Esta detioração ambiental tem sido intensificada fortemente pela poluição e efeitos das alterações climáticas, efeitos como o aumento da temperatura da água do mar e disponibilidade de alimento. Os stocks naturais marinhos, estão especialmente suscetíveis a estas alterações, sendo os organismos sésseis e com menor capacidade de movimento os mais afetados, como é o caso da amêijoa Ruditapes decussatus, que tem em Portugal uma enorme importância comercial. Vários estudos foram desenvolvidos com estes organismos em relação ao seu comportamento e relação com alterações no meio. Este trabalho visa complementar esta informação avaliando a forma como dois destes fatores, a temperatura e disponibilidade de alimento em conjunto vão afetar as amêijoas desta espécie. Para este trabalho, as amêijoas foram divididas em seis tratamentos em que dois deles receberam alimento total, dois metade dessa quantidade e os últimos dois permaneceram em jejum, três destes tratamentos (um de cada dieta) foram então expostos a stresse por aumento de temperatura e os outros três mantidos à mesma temperatura. De forma a pudermos atingir os nossos objetivos, foram efetuadas cinco amostragens, nas quais foram retirados seis exemplares de cada tanque: três para análise da resposta imune e análise histologia e outros três para análises de biomarcadores de stresse oxidativo. Os diferentes efeitos da interação destes dois agentes ambientais na sobrevivência e respostas bioquímicas das amêijoas R. decussatus são apresentados e discutidos em detalhe na presente tese. Em resumo, as amêijoas dos tratamentos que sofreram choque térmico apresentaram maior mortalidade, bem como uma maior debilidade do sistema imunitário e maior efeito do stresse oxidativo. A dieta desempenhou um papel crucial na capacidade imunitária e de sobrevivência das amêijoas, sendo notória a diminuição de capacidade de resposta ao choque térmico, nas amêijoas que não receberam alimento total. No entanto as amêijoas que não receberam alimento apresentaram menor mortalidade do que as que tiveram acesso a metade do alimento o que comprova a capacidade destes organismos de resistir a stress ambiental durante curtos períodos (uma semana) recorrendo ao fecho das valvas