Structural view on 60S ribosome biogenesis

Eukaryotic ribosomes undergo a complex maturation process through which the ribosomal RNA (rRNA) must bind to ribosomal proteins (r-proteins) and fold into its native state. This requires numerous auxiliary factors responsible of rRNA processing, remodeling, intracellular transport and quality control checkpoints. Impairments in the process of ribosome production can lead to different diseases known as ribosomopathies. However, little is known about which defects in the ribosome biogenesis pathway can escape all quality checkpoints and what targets these faulty ribosomes and their putative products for degradation. The first part of this thesis constitutes a first attempt to address these questions, focusing on a specific impairment of the 60S biogenesis pathway that leads to the production of structurally deficient 80S ribosomes. Here, using cryo-EM and biochemical analysis, it is shown that large structural defects in the ribosome may bypass all quality control mechanisms in the nucleus, but are recognized in the cytoplasm after faulty ribosomes engage in translation. Then, the resulting proteins are targeted for degradation by the ribosome quality-control complex (RQC) after subunit splitting is carried out. The second part of this thesis focuses on a nucleoplasmic step of 60S ribosome biogenesis in which both the Rix1 complex and the dynein related AAA+ ATPase Rea1 bind to maturing pre-60S particles. Rea1 is required for the ATP-dependent dissociation of the assembly factor Rsa4 and may be involved in rearranging the Central Protuberance (CP). Several cryo-electron microscopy (cryo-EM) structures of native pre-60S particles bound to the Rix1-Rea1 machinery are presented in this thesis. Overall, the Rix1-Rea1 particle is similar to the earlier intermediate, the socalled Arx1 particle. However, a 180° rotation of the CP required to reach the final conformation of the 60S, has already happened in the Rix1-Rea1 state, constituting the largest remodeling step at the end of the maturation pathway. By performing cryo-EM analysis on two similar particles that were mutated on either Rix1 or Rea1 and by comparing the structures of the Arx1 and Rix1-Rea1 particles, a mechanistic model for the transition between the two intermediates is provided

The geography of innovation: the effects of university research

Applied studies on the relationship between geography and technological innovation for United States, Germany, France and Italy have shown the positive effects that academic research exerts on the innovative output of firms at a spatial level. The purpose of this paper is to look for new evidence on the possible effects of the university research for the case of Spain. To do so, within the framework of a Griliches-Jaffe knowledge production function, and using panel data and count models, the relationship between innovative inputs and patents, in the case of the Spanish regions is explored.geography of innovation, patents, r&d

New Revelations about Unemployment Persistence in Spain

This paper aims to re-examine the persistence of unemployment in Spain. For this purpose, we use time series and cross-section analysis. From a time series viewpoint we disaggregate unemployment by regions, and use unit root tests, AR coefficients and fractional differencing parameters as indicators of persistence. For the cross-section approach, we first estimate mean regressions of regional unemployment rates. Then, using a panel of 114 periods and 50 provinces, we estimate pooled, fixed and random effects models. Finally, following some recent developments, we implement several panel data unit root tests. Previous studies had already shown the strong persistence of Spanish unemployment. Our disaggregated analysis extends that finding to reveal that the persistence is greater in the most industrialised regions. The results also suggest that a structural break took place in 1994, implying a decline in the unemployment persistence since then.

Measuring empathy feelings in football through media value

This paper applies media value appraisals to measure the degree of identification that players and teams inspire in football supporters. Using a large data set of media value scores in season 2014/15, we rank the most popular football players and clubs worldwide; as well as the teams' managers with the greatest media value exposure. Then, building upon individual ratings, we determine the hierarchy of the "Big Five" European domestic leagues, according to their comparative media value status.En este artículo se emplean indicadores de valor mediático en el fútbol para estimar el grado de identificación que jugadores y clubs inspiran entre los aficionados. A partir de amplias bases de datos del valor mediático en la temporada 2014/15, se elaboran los rankings mundiales de jugadores y clubs, así como el ranking de los entrenadores con mayor visibilidad en los medios. Además, agregando registros individuales, puede determinarse la jerarquía de estatus mediático de las cinco grandes ligas domésticas de Europa

Uncharged tRNA Activates GCN2 by Displacing the Protein Kinase Moiety from a Bipartite tRNA-Binding Domain

Protein kinase GCN2 regulates translation in amino acid–starved cells by phosphorylating eIF2. GCN2 contains a regulatory domain related to histidyl-tRNA synthetase (HisRS) postulated to bind multiple deacylated tRNAs as a general sensor of starvation. In accordance with this model, GCN2 bound several deacylated tRNAs with similar affinities, and aminoacylation of tRNAPhe weakened its interaction with GCN2. Unexpectedly, the C-terminal ribosome binding segment of GCN2 (C-term) was required in addition to the HisRS domain for strong tRNA binding. A combined HisRS+C-term segment bound to the isolated protein kinase (PK) domain in vitro, and tRNA impeded this interaction. An activating mutation (GCN2c-E803V) that weakens PK–C-term association greatly enhanced tRNA binding by GCN2. These results provide strong evidence that tRNA stimulates the GCN2 kinase moiety by preventing an inhibitory interaction with the bipartite tRNA binding domain

Economic evaluation of football players through media value

This paper describes an approach based on media value to evaluate sport talent. We then apply this methodology to estimate the theoretical value of transfer fees for professional football players. First, we compute the individual index of media value and e xpressed it with respect to the average of the top 2,500 players included in our data set of more than 5,000 individuals. The media value score is the factor by which the number of news of a player multiplies the news articles of the normal (average) playe r in our sample. Based on individual appraisals, we then work out the media value rank of football teams and leagues. To calculate the theoretical value of football players, we estimate regression models using as dependent variable the transfer fees actu ally paid. Our analyses allow us to conclude that, in determining the theoretical transfer fee of a player, it is necessary to consider a few variables, among which the media value status plays a major role. Other explanatory variables to explain the trans fer fees are: contract duration, economic status of the hiring team, number of years of experience (quadratic form), player's age at the end of the contract, and media value share of the player within his team

How the UEFA Financial Fair Play regulations affect football clubs’ priorities and leagues’ competitive balance?

Institutional and legal reforms applied in the context of sports competitions often provoke structural changes that can be empirically investigated. Using a data set of 560 observations (20 teams per season, from 2009/10 to 2015/16, of teams playing in the Premier League, La Liga, Serie A and Ligue 1), this paper examines how the UEFA Financial Fair Play (FFP) regulations may have altered the football clubs’ decisions concerning their sport and financial priorities. Moreover, based on a simple theoretical description, the paper shows that the increasing financial stability promoted by the FFP rules might actually imply – as an undesired side effect – a declined competitive balance affecting the European football leagues. Finally, the paper discusses some policy issues and recommendations

The determinants of University patenting: do incentives matter?

In recent years various studies have examined the factors that may explain academic patents. Existing analyses have also underlined the substantial differences to be found in European countries in the institutional framework that defines property rights for academic patents. The objective of this study is to contribute to the empirical literature on the factors explaining academic patents and to determine whether the incentives that universities offer researchers contribute towards explaining the differences in academic patenting activity. The results of the econometric analysis for the Spanish universities point towards the conclusion that the principal factor determining the patents is funding of R&D while royalty incentives to researchers do not appear to be significant

Free Entrance and Social Welfare. Explaining the Causes of Excessive Entry Bias

The economic theory has proved that free entry is not always advantageous from a social welfare point of view. Fro instance, a number of inefficiencies can arise from free entry in the presence of fixed set-up costs. Then, an excessive number of firms can usually be settled in homogeneous produc markets within an imperfect competition framework. The economic forces underlying the entry biases are somewhat obscure yet. This paper claims that capacity constraints and diseconomies of scale ought to be driving the discussion of this issue. The characteristics of the cost function, rather than other features, play the major role and should attract the attention of the future research effort. The paper develops an example with which to illustrate the discussion.

Pay and Performance in the Spanish Soccer League: Who Gets the Expected Monopsony Rents?

In the labour markets that gather few companies to compete for many workers, the economic theory predicts the existence of monopsony rents. It should also be the case of the Spanish soccer industry. However, the clubs of this league do not profit from the expected rents. The purpose of this paper is to explain such a contradictory evidence. Spanish soccer labour market is characterised by the presence of some outstanding workers (soccer superstars). It means that the winner-take-all hypothesis holds when analysing the soccer industry. This idea states that being slightly better than the other workers generates large earnings differentials (escalating earnings of league superstars). This paper considers the soccer industry as a dual labour market. One segment of this market could certainly be characterised by the traditional analysis of monopsony, in which a little number of clubs are willing to hire many potential candidates. The opposite occurs when studying the case of the superstar players. A number of entities (not just Spanish clubs) would fiercely compete for hiring those few superstars, who accumulate market power. The paper suggests that the monopsony rents that the clubs were to obtain from most of the soccer players, would eventually revert to the superstars, who enjoy strong bargaining power. In order to empirically test this idea, the paper analyses the data of the Spanish professional soccer league, for the season 2001/02. The analysis pays especial attention to the economic impact associated to each particular player, as far as it may help to explain the large wage differentials that could not be explained due to performance differentials.