Novel functional interaction between the plasma membrane Ca2+ pump 4b and the proapoptotic tumor suppressor Ras-associated factor 1 (RASSF1)

Plasma membrane calmodulin-dependent calcium ATPases (PMCAs) are enzymatic systems implicated in the extrusion of calcium from the cell. We and others have previously identified molecular interactions between the cytoplasmic COOH-terminal end of PMCA and PDZ domain-containing proteins. These interactions suggested a new role for PMCA as a modulator of signal transduction pathways. The existence of other intracellular regions in the PMCA molecule prompted us to investigate the possible participation of other domains in interactions with different partner proteins. A two-hybrid screen of a human fetal heart cDNA library, using the region 652-840 of human PMCA4b (located in the catalytic, second intracellular loop) as bait, revealed a novel interaction between PMCA4b and the tumor suppressor RASSF1, a Ras effector protein involved in H-Ras-mediated apoptosis. Immunofluorescence co-localization, immunoprecipitation, and glutathione S-transferase pull-down experiments performed in mammalian cells provided further confirmation of the physical interaction between the two proteins. The interaction domain has been narrowed down to region 74-123 of RASSF1C (144-193 in RASSF1A) and 652-748 of human PMCA4b. The functionality of this interaction was demonstrated by the inhibition of the epidermal growth factor-dependent activation of the Erk pathway when PMCA4b and RASSF1 were co-expressed. This inhibition was abolished by blocking PMCA/RASSSF1 association with an excess of a green fluorescent protein fusion protein containing the region 50-123 of RASSF1C. This work describes a novel protein-protein interaction involving a domain of PMCA other than the COOH terminus. It suggests a function for PMCA4b as an organizer of macromolecular protein complexes, where PMCA4b could recruit diverse proteins through interaction with different domains. Furthermore, the functional association with RASSF1 indicates a role for PMCA4b in the modulation of Ras-mediated signaling.

Multi-scale dynamics on the Eastern Brazilian margin

Este trabalho combina esforços de simulação numérica e de análise de dados para investigar a dinâmica em diversos compartimentos (oceano aberto, plataforma continental e zona costeira-estuarina) e, em multiplas escalas, na Margem Continental Leste Brasileira (MCLB). A circulação de largo e mesoescala espacial e a propagação da maré barotrópica são investigadas através de uma configuração aninhada do modelo numérico ROMS. O estudo da dinâmica regional da Baía de Camamu (CMB) baseia-se na análise de dados locais. A MCLB, localizada a SW do Atlântico Sul entre 8±S e 20±S, possui plataforma estreita, batimetria complexa, e baixa produtividade primária. A sua dinâmica é influenciada pela divergência da Corrente Sul Equatorial (CSE). As simulações refletem as conexões sazonais e espaciais entre a Corrente do Brasil e a Contra Corrente Norte do Brasil , em conexão com a dinâmica da CSE. As simulações revelam atividades vorticais nas proximidades da costa e interações com a dinâmica costeira, cujos padrões são descritos. A validação do modelo em mesoescala é baseada em cálculos de energia cinética turbulenta e em dados históricos de transporte. A CMB, localizada a 13±400S, abriga uma comunidade piscatória tradicional e extenso de manguezal. Situa-se porém sobre uma bacia sedimentar com grande reservas de óleo e gás, estando em tensão permanente de impacto ambiental. Neste trabalho sumarizamos as condições físicas regionais e investigamos sua dinâmica interna, focando sua variabilidade em amostragens realizadas sob condições de seca (Setembro de 2004) e de chuva (Julho de 2005). Finalmente, o modelo numérico ROMS é forçado com o sinal de maré, empregando-se uma configuração simples (com coeficientes de atrito de fundo constantes e condições hidrográficas homogéneas), com o intuito de avaliar sua resposta e investigar a natureza da propagação da maré barotrópica na MCLB, convergindo na CMB. A análise da resposta do modelo à maré basea-se em séries históricas do nível do mar para a MCLB e dados recentes da CMB.

Governance structures and performance management systems in universities: a comparative study between the UK and Portugal

À semelhança do que aconteceu em muitas instituições públicas, as universidades têm enfrentado pressões crescentes para mudar, tendo de repensar as suas formas de governança e de gestão, dando mais ênfase à implementação de sistemas de gestão do desempenho (SGD). Apesar de existirem vários estudos sobre o desempenho, estes têm ignorado o uso dado à informação recolhida. Além disso, e apesar de terem ocorrido várias reformas na governança destas instituições, existem ainda poucos estudos que relacionam a governança e o desempenho. Assim, esta pesquisa visa explorar a forma como as universidades medem, reportam e gerem o desempenho e como as estruturas de governança se relacionam com estas práticas. Para alcançar o objetivo proposto, um estudo comparativo entre universidades britânicas e portuguesas foi realizado. Os dados foram recolhidos através da utilização de uma metodologia qualitativa, sendo os métodos utilizados a análise documental e entrevistas semi-estruturadas a membros dos órgãos de governo e gestão de cada instituição. A análise dos dados mostrou a inexistência de um sistema completamente integrado de gestão de desempenho (SGD) em ambas as instituições, essencialmente devido à falta de práticas de gestão de desempenho. De facto, apesar de alguns dos entrevistados terem reportado o "uso positivo" de dados sobre o desempenho, alguns relataram o "não uso" desses dados, principalmente em relação ao desempenho individual, e outros o "mau uso" dessa informação, tendo sido reportadas práticas de gaming e deturpação dos resultados. Como forma de ultrapassar alguns destes problemas, verificou-se a co-existência de duas estruturas de governança: uma 'formal', da qual fazem parte todos os órgão de governo, com um valor mais 'simbólico'; e uma estrutura 'paralela', constituída por órgãos mais ágeis, que gerem a universidade no dia a dia. Verificou-se terem sido vários os fatores a afetarem, negativa e positivamente, os SGD em ambas as instituições, tendo sido rotulados de "inibidores" e "determinantes", respetivamente. A pesquisa mostrou que, apesar de as estruturas de governança serem importantes para a implementação e funcionamento de um SGD, há outros fatores que precisam de ser levados em consideração, nomeadamente, o nível de comunicação e o nível de envolvimento dos atores no processo. Estes dois fatores são considerados relevantes para a integração bem sucedida de práticas de medição, reporte e gestão de desempenho. Esta integração, juntamente com outras mudanças que ocorreram em termos de governança, contribuirá certamente para que se passe de um sistema em que se governa o desempenho para um sistema em que se governa para o desempenho.

Between the Bullet and the Hole

Between the Bullet and the Hole is a film centred on the elusive and complex effects of war on women's role in ballistic research and early computing. The film features new and archival high-speed bullet photography, schlieren and electric spark imagery, bullet sound wave imagery, forensic ballistic photography, slide rulers, punch cards, computer diagrams, and a soundtrack by Scanner. Like a frantic animation storyboard, it explores the flickering space between the frames, testing the perceptual mechanics of visual interpolation, the possibility of reading or deciphering the gap between before and after. Interpolation - the main task of the women studying ballistics in WW2 - is the construction or guessing of missing data using only two known data points. The film tries to unpack this gap, open it up to interrogation. It questions how we read, interpolate or construct the gaps between bullet and hole, perpetrator and victim, presence and absence. The project involves exchanges with specialists in this area such as the Cranfield University Forensics department, London-based Forensic Firearms consultancy, the Imperial War Museum, the ENIAC programmers project, the Smithsonian Institute, and Forensic Scientists at Palm Beach County Sheriff's Office (USA). Exhibitions: Solo exhibition at Dallas Contemporary (Texas, Jan-Mar 2016), including newly commissioned lenticular prints and a dual slide projector installation; Group exhibition the Sydney Biennale (Sydney, Mar-June 2016); UK premiere and solo retrospective screening at Whitechapel Gallery (London); forthcoming solo exhibition at Iliya Fridman Gallery (NY, Oct-Dec 2016); Film festivals and screenings: International Film Festival Rotterdam (Jan 2016); Whitechapel Gallery (London Feb 2016); Cornerhouse/Home (Manchester Nov 2016); Public lectures: Whitechapel Gallery with prof. David Alan Grier and Morgan Quaintance; Carriageworks (Sydney) Prof. Douglas Khan; Monash University (Melbourne); Gertrude Space (Melbourne). Reviews and interviews: Artforum, Studio International, Mousse Magazine.

Profiles of ageing in the South of Portugal: education and cognitive functioning in elderly persons living in institutionalized and community contexts

The region of the Algarve shows huge differences between the coastline where population in the urban areas grows, and the inland rural areas, in some cases very isolated, which frequently have high ageing indexes. This general scenario, with an elderly population with very different economic and social conditions, frames the ongoing PhD research designed as a cross-sectional study of an intentional sample of elderly persons. The basic theoretical framework departs from the perspective of developmental psychology of life-span and the model of selection, optimisation and compensation for optimal ageing (Baltes & Baltes, 1990; Freund & Baltes, 2002). The present study is a first step in the analysis of empirical data collected in the PhD sample (N=156; age range 65 to 97 years; M = 80.4 years; SD = 7.2 years). Its purpose is to assess the cognitive functioning of participants, screening for cognitive impairment and examine the relations between the cognitive status of the subjects and a number of selected variables including educational level, age, physical activity and living contexts of the subjects. We accessed the cognitive status of the participants with the Portuguese version of Mini Mental State Examination (MMSE) finding a 10.3% prevalence of positive cases with cognitive impairment. The results also show significant relationships between the cognitive status accessed by the MMSE and educational level, professional qualification, age, living arrangement and activity level of the participants. The relationship verified between educational level and cognitive status of the participants was the largest correlation found in the study with the variability in educational level accounting for 44.8% of the variability in MMSE score. This results points in the same direction of several lines of research that corroborate the strong intercorrelation between education and cognitive functioning in old age.

Regulatory interactions between the metabolic sensors SIRT1 and AMPK in modulating PPARα linked functions, in obesity-dependent type 2 diabetes mellitus

Tese de doutoramento, Ciências Biomédicas (Ciências Funcionais), Universidade de Lisboa, Faculdade de Medicina, 2014

Labour and the free churches 1918-1939: radicalism, righteousness and religion

It is a commonplace that the labour movement was somehow nurtured within the witness for liberty of the Free Churches. Exploring this at a range of levels - including organisation, rhetoric, policies, electoral politics and people - this book demonstrates the extent to which this remained a reality into the inter-war years. The distinctive religious setting in which it emerged indeed helps to explain the differences between Labour and more Marxist counterparts on the Continent. It is shown here that this setting continued to influence Labour approaches towards welfare, nationalisation and industrial relations between the wars. In the process Labour also adopted some of the righteousness of tone of the Free Churches. This setting was, however, changing. Dropping their traditional suspicion of the State, Nonconformists instead increasingly invested it with religious values, turning it through its growing welfare functions into the provider of practical Christianity. This nationalisation of religion continues to shape British attitudes to the welfare state as well as imposing narrowly utilitarian and material tests of relevance upon the churches and other social institutions. The elevation of the State was not, however, intended as an end in itself. What mattered were the social and individual outcomes. Socialism, for those Free Churchmen and women who helped to shape Labour in the early twentieth century, was about improving society as much as systems.

Rethinking crises and the accretion of executive power: the “War on Terror” and conditionality evidence from seven political systems

External shocks to democratic systems are likely to threaten the stability of relations between the executive and the representative assembly. This article investigates the impact of the so-called “war on terror” on executive-assembly relations in comparative perspective. We analyze data from seven countries, which varied in terms of form of government, level of democracy, culture, social structure, and geographic location, to evaluate its effects. We find that whereas in some systems the “war on terror” altered the balance of power between the executive and the assembly, in other cases the extant balance of power was preserved. We postulate various conditions under which the constitutionally sanctioned balance of power is most likely to be preserved in times of crisis.

Morality and politics: the free churches and the Labour Party between the wars

The inter-war period saw the decline of the Liberal party, the traditional political ally of the free churches, and the rise of the Labour party. This article traces the responses of the free churches to these developments. The relationship of the free churches with the Labour party in this period is examined at three different levels; that of the free church leadership, that of the chapels and the ordinary people in the pews and that of the nonconformists who became active in the Labour party. Whilst attitudes towards the Labour party changed within free church institutions during the inter-war years they did not become important supporters of the party, or greatly influence it. The number and proportion of individual nonconformists who were active and influential in the party in this period was however considerable. In the process not only did Labour M.P.s become the main carriers of the nonconformist conscience on issues such as drink and gambling. They also made a distinctive and important contribution to the development and ideals of the Labour party.

Be careful what you wish for: the legal parameters of EU withdrawal

Easiness with which the political circles talk about withdrawal from the European Union is rather surprising and proves that the legal parameters of an EU exit are not treated seriously enough. In theoretical terms Article 50 TEU allows for a unilateral exit as well as for a consensual divorce. Arguably, the first is an interesting abstract proposition, which, however, in practical terms seems to be an unworkable solution. Hence, the only realistic option is a proper divorce based on a withdrawal agreement. As per Article 50 TEU, it would be negotiated by the European Union with a departing country and should cover the terms of withdrawal and “take account of future relations” between the EU and the divorcee. It is submitted that in order to avoid a legal vacuum, this agreement should not only “take account of future relations” but actually deal with them thoroughly. This will make the negotiations difficult and, most likely, time consuming. One also has to envisage a scenario whereby a country leaving the European Union would join EFTA and become a EFTA-EU Member State of the European Economic Area. Should that happen the scope of a EU withdrawal agreement would be limited to the terms of exit, while future relations between the divorcee and the European Union would be mainly covered by the EEA Agreement. This chapter unlocks the mechanics of Article 50 TEU and the withdrawal procedure it provides for. It covers the issues that should be attended to by the negotiators and provides an overview of dossiers that are likely be covered in a withdrawal agreement.

Blacklisting and its legacy in the UK construction industry: employment relations in the aftermath of exposure of the Consulting Association

This paper explores responses to the exposure of blacklisting in the UK construction industry in the period following the closure of the Consulting Association (CA) in 2009. It asks whether employer collusion to blacklist in this way has been terminated and concludes that it is now largely of historical interest although other forms of anti-union activity continue. It highlights particularly the historic and continuing importance of ‘double breasting’ and reports on divergent employer paths in the aftermath of the exposure and subsequent closure of the activities of the CA.