Participación del tráfico y la distribución de proteínas en la polaridad y el desarrollo de procesos neuronales. Protein sorting and trafficking participation in neuronal processes polarity and development.

El estudio del tráfico intracelular en neuronas ha despertado gran interés en los últimos años, debido a que un gran número de enfermedades neurodegenerativas y neuropsiquiátricas parecen tener origen en en el transporte defectuoso de proteínas en estos tipos celulares. Mediante el uso de técnicas de biología celular y molecular, fuimos capaces de describir una de las vías que regula la fisión de las vesículas que llevan su cargo desde la última cisterna del Aparato de Golgi hacia la superficie celular en células epiteliales no polarizadas. Uno de los componentes clave de esa vía resultó ser la Proteina Kinasa D1 (PKD1), cuya actividad en el Aparato de Golgi es esencial para un normal transporte intracelular. Sorprendentemente, observamos que la PKD1 en neuronas con polaridad establecida no regula la fisión en el Golgi, pero si estaría involucrada en la selectividad y distribución (sorting) de vesículas cuyo cargo debe ser específicamente dirigido a las membranas dendríticas. El bloqueo de la actividad de la PKD1 no solamente cambia el destino final de estos cargos, que son enviados de esta forma a la membrana terminal del axón, sino que también es capaz de inducir defectos en el desarrollo y crecimiento de los procesos dendríticos a largo plazo. En este proyecto estudiaremos de que manera influye la perturbación del sorting, en ausencia de PKD1 activa y de otros componentes que la regulan, en la distribución de receptores de factores neurotróficos y de neurotransmisores glutamatérgicos, y cómo estos cambios en su distribución afectan el número, tamaño, y funcionalidad de los procesos neuronales (axones y dendritas). Estos resultados contribuirán a adquirir mayores conocimientos de los mecanismos dependientes del transporte y sorting de proteínas de membrana que participan en la regulación del crecimiento neuronal, los cuales a su vez aportarán información valiosa en la comprensión de un gran número de enfermedades neurológicas. The study of intracellular trafficking in neurons has arisen a great deal of interest in the last years, since a great number of neurodegenerative and neuropsychiatric disorders seem to be originated in abnormal protein transport in these type of cells. Using cell and molecular biology methodologies, we have been capable of describe one of the pathways that regulate the fission of vesicles that carry their cargo from the last Golgi Apparatus cisternae to the cell surface in non-polarized epithelial cells. One of the key components in this pathway is the Protein Kinase D1 (PKD1), whose activity in the Golgi Apparatus is essential for a normal intracelular transport. Surprisingly, we have observed that PKD1 does not regulate fission in neurons with established polarity, but it would be involved in vesicles' sorting at Golgi, particularly of those that carry specific dendritic cargo. Blocking PKD1 activity changes the final destination of these cargoes, which is now sent to the axons' terminal membranes, and also produces late dendritic development and growing defects. In this project we will study how sorting perturbation in absence of PKD1 and its regulators activities influences selectivity and distribution of neurotrophic and neurotransmitter receptors, and how these sorting changes affect number, size and functionality of neuronal processes (axons and dendrites). These results will help to acquire greater knowledge about transport and sorting mechanisms of neuronal growth regulatory membrane proteins. In addition, these studies will contribute with new valuable information necessary to understand numerous neurological diseases.

Employment and public capital in spain

This paper analyses the e¤ects on employment of increasing the stock of public capital. To this end, we derive a wage equation so that wages are endogenized. This allows us to show that, by means of a higher elasticity of labour demand with respect to wages, a rise in public capital increases employment. The estimation of a structural model for the Spanish private sector tests and con…rms empirically this relationship. The results show that an increase in public capital has a significant and positive direct influence on employment, and indirect e¤ects derived from lower wages and higher economic growth. Finally, we undertake a simulation exercise to assess the long run efects on employment and economic growth of increasing public capital.

Barriers to innovation and public policy in Catalonia

The present paper analyses the link between firms’ decisions to innovate and the barriers that prevent them from being innovative. The aim is twofold. First, it analyses three groups of barriers to innovation: the cost of innovation projects, lack of knowledge and market conditions. Second, it presents the main steps taken by Catalan Government to promote the creation of new firms and to reduce barriers to innovation. The data set used is based on the 2004 official innovation survey of Catalonia which was taken from the Spanish CIS-4 sample. This sample includes individual information on 2,954 Catalan firms in manufacturing industries and knowledge-intensive services (KIS). The empirical analysis reveals pronounced differences regarding a firm’s propensity to innovate and its perception of barriers. Moreover, the results show that cost and knowledge barriers seem to be the most important and that there are substantial sectoral differences in the way that firms react to barriers. The results of this paper have important implications for the design of future public policy to promote entrepreneurship and innovation together.

Strategy for personal and public involvement in Health and Social Care research

This report outlines the strategic need for, and benefits of, personal and public involvement to all levels of Health and Social Care Research and Development Division activity.

Strategy for personal and public involvement in Health and Social Care research

This report outlines the strategic need for, and benefits of,�personal and public involvement�to all levels of Health and Social Care Research�&�Development Division activity.

Technical inefficiency and public capital in US States: A stochastic frontier approach

This paper estimates a translog stochastic frontier production function in the analysis of all 48 contiguous U.S. states in the period 1970-1983, to attempt to measure and explain changes in technical efficiency. The model allows technical inefficiency to vary over time, and inefficiency effects to be a function of a set of explanatory variables in which the level and composition of public capital plays an important role. Results indicated that U.S. state inefficiency levels were significantly and positively correlated with the ratio of public capital to private capital. The proportion of public capital devoted to highways is negatively correlated with technical inefficiency, suggesting that not only the level but also the composition of public capital influenced state efficiency.

Abatacept improves health-related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis.

OBJECTIVE: To assess health-related quality of life (HRQOL) in abatacept-treated children/adolescents with juvenile idiopathic arthritis (JIA). METHODS: In this phase III, double-blind, placebo-controlled trial, subjects with active polyarticular course JIA and an inadequate response/intolerance to ≥1 disease-modifying antirheumatic drug (including biologics) received abatacept 10 mg/kg plus methotrexate (MTX) during the 4-month open-label period (period A). Subjects achieving the American College of Rheumatology Pediatric 30 criteria for improvement (defined "responders") were randomized to abatacept or placebo (plus MTX) in the 6-month double-blind withdrawal period (period B). HRQOL assessments included 15 Child Health Questionnaire (CHQ) health concepts plus the physical (PhS) and psychosocial summary scores (PsS), pain (100-mm visual analog scale), the Children's Sleep Habits Questionnaire, and a daily activity participation questionnaire. RESULTS: A total of 190 subjects from period A and 122 from period B were eligible for analysis. In period A, there were substantial improvements across all of the CHQ domains (greatest improvement was in pain/discomfort) and the PhS (8.3 units) and PsS (4.3 units) with abatacept. At the end of period B, abatacept-treated subjects had greater improvements versus placebo in all domains (except behavior) and both summary scores. Similar improvement patterns were seen with pain and sleep. For participation in daily activities, an additional 2.6 school days/month and 2.3 parents' usual activity days/month were gained in period A responders with abatacept, and further gains were made in period B (1.9 versus 0.9 [P = 0.033] and 0.2 versus -1.3 [P = 0.109] school days/month and parents' usual activity days/month, respectively, in abatacept- versus placebo-treated subjects). CONCLUSION: Improvements in HRQOL were observed with abatacept, providing real-life tangible benefits to children with JIA and their parents/caregivers.

Co-evolution of Policy Sectors: Health Care and Public Health in five Countries

Cette thèse analyse la co-évolution de deux secteurs dans la politique de la santé: santé publique (public health) et soins aux malades (health care). En d'autres termes, la relation entre les dimensions curative et préventive de la politique de la santé et leur développement dans la durée. Une telle recherche est nécessaire car les problèmes de la santé sont complexes et ont besoin de solutions coordonnées. De plus, les dépenses de la santé ont augmenté sans arrt durant les dernières décennies. Un moyen de réduire une future augmentation des dépenses pourrait consister en davantage d'investissement dans des mesures préventives. En relation avec cette idée, ma recherche analyse les politiques de la santé publique et les soins aux malades de cinq pays: Allemagne, Angleterre, Australie, Etats-Unis et Suisse. En m'appuyant sur la littérature secondaire, des statistiques descriptives et des entretiens avec des experts et des politiciens, j'analyse la relation entre les deux secteurs depuis la fin du dix-neuvième siècle. En particulier, je me focalise sur la relation des deux champs sur trois niveaux: institutions, acteurs et politiques. Mes résultats montrent les similitudes et les différences d'évolution entre les cinq pays. D'un c^oté, lorsque la profession médicale est politiquement active et que le pays consiste en une fédération centralisée ou en un gouvernement unitaire, les deux secteurs sont intégrés au niveau institutionnel, ralliant les professions et groupes d'intérêt des deux secteurs la cause commune dans une activité politique. Par contre, dans tous les pays, les deux secteurs ont co-évolué vers une complémentarité malgré de la politisation des professions et la centralisation du gouvernement. Ces résultats sont intéressants pour la science politique en général car ils soulignent l'importance des professions pour le développement institutionnel et proposent un cadre pour l'analyse de la co-évolution des politiques publiques en général. -- This Ph.D. thesis analyzes the co-evolution of the health care and the public health sectors. In other words, the relation between preventive and curative health policy and its evolution over time. Such research is necessary, because current health problems are complex and might need coordinated solutions. What is more, health expenditures have increased continuously in the last decades. One way to slow down further increase in health spending could be to invest more in preventative health policies. Therefore, I am connecting individual health care and public health into a common analysis, taking Australia, Germany, Switzerland, the UK and the U.S. as examples. Based on secondary literature, descriptive statistics and interviews with experts and policymakers, I am analyzing how the two sectors' relations co-evolved between the late nineteenth and the early twenty-first century. Specifically, I am researching how health care and public health were related on the levels of institutions, actors and policies. My results show that there are differences and similarities in the co-evolution of policy sectors between these countries. On the one hand, when the medical profession was politically active and the country a centralized federation or a unitary state, there was institutional integration and common political advocacy of the sectors' interest groups and professions. On the other hand, in all countries, both sectors co-evolved towards complementarity, irrespectively of the politicization of professions and centralization of government. These findings are interesting for the political science literature at large, because they underline the importance of professions for institutional development and propose an analytical framework for analyzing the co-evolution of policy sectors in general.