Estudos sobre a organização genômica, evolução e expressão de microRNAs

Os microRNAs (miRNAs) são pequenos RNAs não codificadores de proteínas presentes na maioria dos eucariotos. Esses RNAs regulam a expressão gênica em nível pós-transcricional através do silenciamento de mRNAs-alvo que possuem sítios complementares às suas sequências, atuando em praticamente todos os processos celulares. Embora a estrutura e função dos miRNAs estejam bem caracterizadas, aspectos relacionados à sua organização genômica, evolução e atuação em doenças são tópicos que apresentam enormes lacunas. Nesta tese, utilizamos abordagens computacionais para investigar estes temas em três trabalhos. No primeiro, processamos e integramos um vasto volume de dados publicamente disponíveis referentes aos miRNAs e genes codificadores de proteínas para cinco espécies de vertebrados. Com isso, construimos uma ferramenta web que permite a fácil inspeção da organização genômica dos miRNAs em regiões inter e intragênicas, o acesso a dados de expressão de miRNAs e de genes codificadores de proteínas (classificados em genes hospedeiros e não hospedeiros de miRNAs), além de outras informações pertinentes. Verificamos que a ferramenta tem sido amplamente utilizada pela comunidade científica e acreditamos que ela possa facilitar a geração de hipóteses associadas à regulação dos miRNAs, principalmente quando estão inseridos em genes hospedeiros. No segundo estudo, buscamos compreender como o contexto genômico e a origem evolutiva dos genes hospedeiros influenciam a expressão e evolução dos miRNAs humanos. Nossos achados mostraram que os miRNAs intragênicos surgem preferencialmente em genes antigos (origem anterior à divergência de vertebrados). Observamos que os miRNAs inseridos em genes antigos têm maior abrangência de expressão do que os inseridos em genes novos. Surpreendentemente, miRNAs jovens localizados em genes antigos são expressos em um maior número de tecidos do que os intergênicos de mesma idade, sugerindo uma vantagem adaptativa inicial que pode estar relacionada com o controle da expressão dos genes hospedeiros, e como consequência, expondo-os a contextos celulares e conjuntos de alvos diversos. Na evolução a longo prazo, vimos que genes antigos conferem maior restrição nos padrões de expressão (menor divergência de expressão) para miRNAs intragênicos, quando comparados aos intergênicos. Também mostramos possíveis associações funcionais relacionadas ao contexto genômico, tais como o enriquecimento da expressão de miRNAs intergênicos em testículo e dos intragênicos em tecidos neurais. Propomos que o contexto genômico e a idade dos genes hospedeiros são fatores-chave para a evolução e expressão dos miRNAs. Por fim, buscamos estabelecer associações entre a expressão diferencial de miRNAs e a quimioresistência em câncer colorretal utilizando linhagens celulares sensíveis e resistentes às drogas 5-Fluoruracil e Oxaliplatina. Dentre os miRNAs identificados, o miR-342 apresentou níveis elevados de expressão nas linhagens sensíveis à Oxaliplatina. Com base na análise dos alvos preditos, detectamos uma significativa associação de miR-342 com a apoptose. A superexpressão de miR-342 na linhagem resistente SW620 evidenciou alterações na expressão de genes da via apoptótica, notavelmente a diminuição da expressão do fator de crescimento PDGFB, um alvo predito possivelmente sujeito à regulação direta pelo miR-342.

On the forecast accuracy and consistency of exchange rate expectations: The Spanish PwC Survey.

We examine the predictive ability and consistency properties of exchange rate expectations for the dollar/euro using a survey conducted in Spain by PwC among a panel of experts and entrepreneurs. Our results suggest that the PwC panel have some forecasting ability for time horizons from 3 to 9 months, although only for the 3-month ahead expectations we obtain marginal evidence of unbiasedness and efficiency in the forecasts. As for the consistency properties of the exchange rate expectations formation process, we find that survey participants form stabilising expectations in the short-run and destabilising expectations in the long- run and that the expectation formation process is closer to fundamentalists than chartists.

A Review on Repeated Games and Reputations with Incomplete Information

In this project we review the effects of reputation within the context of game theory. This is done through a study of two key papers. First, we examine a paper from Fudenberg and Levine: Reputation and Equilibrium Selection in Games with a Patient Player (1989). We add to this a review Gossner’s Simple Bounds on the Value of a Reputation (2011). We look specifically at scenarios in which a long-run player faces a series of short-run opponents, and how the former may develop a reputation. In turn, we show how reputation leads directly to both lower and upper bounds on the long-run player’s payoffs.

The chronic food deficit of early modern Portugal : curse or myth?

Two historiographical currents have debated whether early modern Portugal was cursed by an excessive dependence on foreign food imports as a result of being unable to feed its population, or not. In this short paper, the first long-run systematic quantitative study of this question, we show that the former view is a myth and therefore could not be a curse. Throughout the entire period, a certain amount of grain was in fact imported but cereal purchases abroad never represented more than a diminutive percentage of total food consumption. More importantly, the country carried out a diversified trade in foodstuffs which was seldom seriously out of balance. Portuguese agriculture showed itself consistently capable of specializing in different foodstuffs for export. It was thus not hopelessly inefficient and succeeded reasonably well in meeting the basic nutritional needs of the population.

The European Citizens‘ Initiative – Chances, Constraints and Limits. IHS Political Science Series No. 134, April 2013

In order to celebrate the 20th anniversary of the establishment of European Union citizenship under the Maastricht Treaty in 1993, the year 2013 has been designated by the European Commission as the ‘European Year of Citizens’. The European Citizen’s Initiative (ECI) – labelled by the Commission as a ‘direct gateway through which citizens can make their voices heard in Brussels’ - may emerge in the European awareness as a new appealing platform for policy-shaping and communication. The ECI, through its transnational vox civilis character, figures among the most important novelties in the Lisbon Treaty and in the long run may facilitate and accelerate the bottom-up building of a European demos. The question is, however, whether the mechanism of pan-European signature collection is strong enough to face the democratic challenges present in the EU, especially during the ongoing financial crisis.

Exports and Capacity Constraints: A smooth transition regression model for six euro-area countries. CEPS Working Document No. 395/May 2014

The significant gains in export market shares made in a number of vulnerable euro-area crisis countries have not been accompanied by an appropriate improvement in price competitiveness. This paper argues that, under certain conditions, firms consider export activity as a substitute for serving domestic demand. The strength of the link between domestic demand and exports is dependent on capacity constraints. Our econometric model for six euro-area countries suggests domestic demand pressure and capacity-constraint restrictions as additional variables of a properly specified export equation. As an innovation to the literature, we assess the empirical significance through the logistic and the exponential variant of the non-linear smooth transition regression model. We find that domestic demand developments are relevant for the short-run dynamics of exports in particular during more extreme stages of the business cycle. A strong substitutive relationship between domestic and foreign sales can most clearly be found for Spain, Portugal and Italy, providing evidence of the importance of sunk costs and hysteresis in international trade.

Migration and asylum: The movement of people in the Mediterranean Region - Future scenarios and the EU response. Jean Monnet Occasional Paper No. 11/2014

Introduction. In recent years, the global discussion on migration and asylum has evolved from polarization of perspectives and mistrust, to improving partnerships and fostering cooperation between countries and regions. The paradigm has shifted from control and security exclusively to an increased awareness of the ramifications of migration in development and labour markets, the increasing demographic gap1 and the dangers of exclusion faced by migrant workers (regular or irregular). Eastern Europe will suffer the biggest population decline in the coming years, and Nigeria’s population will reach one billion by 2100. In Europe, the work replacement ratio will be two pensioners for one active worker. It has become clear that these facts cannot be ignored and that there is a need for greater convergence of policies (migration/mobility, fundamental rights, and economic growth), with a migrant-centred approach.2. The assumption that Europe will remain a geopolitical and economic hub that attracts immigrants at all skill levels might not hold water in the long run. The evolving demographic and economic changes have made it evident that the competitiveness of the EU (Europe 2020 Strategy) is also at stake, particularly if an adaptable workforce with the necessary skills is not secured in view of shortfalls in skill levels and because of serious labour mismatches. Therefore, it is the right moment to develop more strategic and long-term migration policies that take into account the evolving position of Europe and its neighbours in the world. By the same token, labour market strategies that meet needs and promote integration of regular migrants are still a pending task for the Member States (MS) in terms of the free movement of people, but also in relation with neighbouring and partner countries.

Any changes? The future agenda of Sweden's security policy. OSW Commentary No. 126, 28.01.2014

Sweden’s annual security and defence conference, which this year focused on the future of the country’s security policy, was held in Sälen on 12-14 January. It was attended by almost all the leaders of Sweden’s ruling and opposition parties. The discussions have revealed whether and how the mindset of the Swedish elite has changed following the heated debates on defence issues in 2013. The opposition parties (Social Democrats, the Green Party, and the Left Party), which are likely to form a coalition government after the election to the Swedish parliament in September 2014, were given the opportunity to present their own priorities. The discussions have brought to the surface conflicting perceptions within the political elite concerning the threats and challenges to Swedish security, and divergent positions on the future direction of the country’s security and defence policy. It is highly likely that, due to a coalition compromise, the current course of Sweden’s security policy (namely, a policy of non-alignment along with close co-operation with NATO) will be maintained following the parliamentary election, albeit with new “leftist” influences (a greater involvement in the United Nations). Big changes that could lead to a significant strengthening of Sweden’s defence capabilities, or a decision on NATO membership, are not likely. Paradoxically, polls suggest that in the long run a more radical change in Stockholm’s security policy may be shaped by a gradual, bottom-up evolution of public opinion on the issue.

Is Independence Possible in an Interdependent World? Scotland vs. the UK's Participation in the European Economy. Bruges European Economic Policy (BEEP) Briefing 30/2013

Many commentators have criticised the strategy used to finance regional governments such as the Scottish Parliament – both the block grant system and the limited amount of fiscal autonomy devised in the Scotland Act of 2012. This lecture sets out to identify what level of autonomy or independence would best suit a regional economy in a currency union, and also the institutional changes needed to sustain those arrangements. Our argument is developed along three lines. First, we set out the advantages of a fiscal federalism framework and the institutions needed to support it, but which the Euro-zone currently lacks. The second is to elaborate a model of fiscal federalism where comprehensive powers of taxation and spending are devolved (an independent Scotland and the UK remain constituent members of the EU and European economy). Third, we evaluate the main arguments for the breakup of nations or economic unions with Scotland and the UK as leading examples. We note that greater autonomy may not result in increases in long run economic growth rate, but it does imply that enhancing the fiscal competence and responsibility of regional governments would result in productivity gains and hence higher levels of GDP per head. That means the population is permanently richer than before, even if ultimately their incomes continue to grow at the same rate. It turns out that these improvements can be achieved through devolved tax powers, but not through devolved spending powers or shared taxes.

Designing a Genuine EMU: Which "Unions" for EU and Eurozone? Bruges European Economic Policy (BEEP) Briefing 34/2014

The initial ‘framing’ (in the summer of 2012) of the ‘genuine EMU’ for the wider public suggested to design an entire series of ‘unions’. So many ‘unions’ are neither necessary nor desirable – only some are and their design matters. The paper critically discusses first the negative fall-out of the crisis for EMU, and subsequently assesses the fiscal and the banking unions as accomplished so far, without going into highly specific technical details. The assessment is moderately positive, although there is ample scope for further improvement and a risk for short-term turbulence once the ECB has finished its tests and reviews. What about the parade of other ’unions’ such as economic union, social union and political union? The macro-economic imbalances procedure (MIP) and possibly the ESRB have overcome the pre-crisis disregard of macro competitiveness. The three components of ‘economic union’ (single market, economic policy coordination and budgetary disciplines) have all been strengthened. The last two ‘unions’, on the other hand, would imply a fundamental change in the conferral of powers to the EU/ Eurozone, with drastic and possibly very serious long-run implications, including a break-up of the Union, if such proposals would be pushed through. The cure is worse than the disease. Whereas social union is perhaps easier to dismiss as a ‘misfit’ in the EU, the recent popularity of suggesting a ‘political union’ is seen as worrisome. Probably, nobody knows what a ‘political union’ is, or, at best, it is a highly elastic notion: it might be thought necessary for reasons of domestic economic reforms in EU countries, for a larger common budget, for some EU tax power, for (greater) risk pooling, for ‘symmetric’ macro-economic adjustment and for some ultimate control of the ECB in times of crisis. Taking each one of these arguments separately, a range of more typical EU solutions might be found without suggesting a ‘political union’. Just as ‘fiscal capacity’ was long an all-or-nothing taboo for shifting bank resolution to the EU level, now solved with a modest common Fund and carefully confined but centralised powers, the author suggests that other carefully targeted responses can be designed for the various aspects where seen as indispensable, including the political say of a lender-of-last-resort function of the ECB. Hence, neither a social nor a political union worthy of the name ought to be pursued. Yet, political legitimacy matters, both with national parliaments and the grassroots. National parliaments will have to play a larger role.

Effects of Economic Factors on Adoption of Robotics and Consequences of Automation for Productivity Growth of Dairy Farms. Factor Markets Working Paper No. 32, December 2012

In the long term, productivity and especially productivity growth are necessary conditions for the survival of a farm. This paper focuses on the technology choice of a dairy farm, i.e. the choice between a conventional and an automatic milking system. Its aim is to reveal the extent to which economic rationality explains investing in new technology. The adoption of robotics is further linked to farm productivity to show how capital-intensive technology has affected the overall productivity of milk production. The empirical analysis applies a probit model and an extended Cobb-Douglas-type production function to a Finnish farm-level dataset for the years 2000–10. The results show that very few economic factors on a dairy farm or in its economic environment can be identified to affect the switch to automatic milking. Existing machinery capital and investment allowances are among the significant factors. The results also indicate that the probability of investing in robotics responds elastically to a change in investment aids: an increase of 1% in aid would generate an increase of 2% in the probability of investing. Despite the presence of non-economic incentives, the switch to robotic milking is proven to promote productivity development on dairy farms. No productivity growth is observed on farms that keep conventional milking systems, whereas farms with robotic milking have a growth rate of 8.1% per year. The mean rate for farms that switch to robotic milking is 7.0% per year. The results show great progress in productivity growth, with the average of the sector at around 2% per year during the past two decades. In conclusion, investments in new technology as well as investment aids to boost investments are needed in low-productivity areas where investments in new technology still have great potential to increase productivity, and thus profitability and competitiveness, in the long run.

The Determinants of Country Risk in Eastern European Countries. Evidence from Sovereign Bond Spreads. Bruges European Economic Research (BEER) Papers 8/November 2006

The paper studies country risk in two Central and Eastern European countries - Bulgaria and Poland. The long run relationship between the yield differential (spread) of Eastern European national bonds (denominated in US dollars) over a US Treasury bond on one the hand and the country’s fundamentals as well as an US interest rate on the other hand, is examined. The cointegrated VAR model is used. First, the yield differentials are analyzed on a country by country basis to extract stochastic trends which are common for all bonds in a given country. Thereafter, the risk is disentangled into country and higher level risk. This paper is among the first ones which use time series data to study the evidence from sovereign bond spreads in Eastern Europe.

Investment behaviour of EU arable crop farms in selected EU countries and the impact of policy reforms. Factor Markets Working Document No. 42, May 2013

This deliverable provides a comparative analysis, among selected EU member states, of the investment demand of a sample of specialised field crop farms for farm buildings, machinery and equipment as determined by different types and levels of Common Agricultural Policy support. It allows for the existence of uncertainty in the price of output farmers receive and for both long- and short-run determinants of investment levels, as well as for the presence of irregularities in the cost adjustment function due to the existence of threshold-type behaviours. The empirical estimation reveals that three investment regimes are consistently identified in Germany and Hungary, across asset and support types, and in France for machinery and equipment. More traditional disinvestment-investment type behaviours characterise investment in farm building in France and the UK, across support types, and Italy for both asset classes under coupled payments. The long-run dynamic adjustment of capital stocks is consistently and significantly estimated to be towards a – mostly non-stationary – lower level of capitalisation of the farm analysed. By contrast, the expected largely positive short-run effects of an increase in output prices are often not significant. The effect of CAP support on both types of investment is positive, although seldom significant, while the proxy for uncertainty employed fails to be significant yet, in most cases, has the expected effect of reducing the investment levels.

Current Account ‘Core-Periphery Dualism’ in the EMU. CEPS Working Document No. 406/March 2015

Current account dispersion within EU member states has been increasing since the 1990s. Interestingly, the persistent deficits in many peripheral countries have not been accompanied by a significant growth process that is able to stimulate a long-run rebalancing, as neoclassical theory predicts. To shed light on the issue this paper investigates the determinants of eurozone current account imbalances, focusing on the role played by financial integration. The analysis considers two samples of 22 OECD and 15 EU countries; three time horizons corresponding to various steps in European integration; different control variables; and several panel econometric methods. The results suggest that within the OECD and EU groups, financial integration helped to explain CA deterioration in the peripheral countries, especially in the post-EMU period. The business cycle seems to have played a growing role over time, whereas the role of competiveness seems to have diminished.

Comparing fiscal multipliers across models and countries in Europe. National Bank of Belgium Working Paper No. 278, March 2015

This paper employs fifteen dynamic macroeconomic models maintained within the European System of Central Banks to assess the size of fiscal multipliers in European countries. Using a set of common simulations, we consider transitory and permanent shocks to government expenditures and different taxes. We investigate how the baseline multipliers change when monetary policy is transitorily constrained by the zero nominal interest rate bound, certain crisis-related structural features of the economy such as the share of liquidity-constrained households change, and the endogenous fiscal rule that ensures fiscal sustainability in the long run is specified in terms of labour income taxes instead of lump-sum taxes.