Rôle des récepteurs aux protéines G (GPR55, GPR91 et GPR99) dans la croissance et le guidage axonal au cours du développement du système visuel.

Lors de l’attribution du prix Nobel de chimie aux docteurs Robert Leftkowitz et Brian Kobika pour leurs travaux essentiels sur les récepteurs couplés à des protéines G (RCPGs), Sven Lindin, membre du comité Nobel, a affirmé que « jusqu'à la moitié » des médicaments « reposent sur une action ciblant les RCPG ». En raison de leurs rôles importants, leurs mécanismes d'activation et l’action de leurs ligands, les RCPG demeurent les cibles potentielles de la majorité des recherches pour le développement de nouveaux médicaments et de leurs applications cliniques. Dans cette optique, nous avons concentré nos recherches à travers cette thèse pour élucider les rôles, les mécanismes d’action et les effets des ligands de trois RCPG : GPR55; GPR91 et GPR99 au cours du développement des axones des cellules ganglionnaires de la rétine (CGRs). Les résultats de nos études confirment l’expression des récepteurs lors du développement embryonnaire, postnatal et adulte des CGRs ainsi qu’au cours de l’établissement de la voie rétinothalamique. In vitro, la modulation pharmacologique et génétique de l’activité de ces RCPGs réorganise la morphologie du cône de croissance des CGRs, celle des neurones corticaux et elle modifie la croissance axonale globale. De plus, les effets de la stimulation avec des ligands des ces trois RCPGs sur le guidage axonal varient d’aucun effet (GPR91 et GPR99) à la répulsion ou l’attraction (GPR55). La voie de signalisation MAPK-ERK1/2 joue un rôle essentiel dans la médiation des effets des ligands de ces récepteurs avec une implication de la voie de RhoA à hautes concentrations pour l’agoniste endogène de GPR55. In vivo, cette recherche démontre également l’implication de GPR55 dans les processus de sélection des cibles thalamiques et de raffinement au cours du développement du système nerveux visuel.

40 20th Century Spanish Sculptresses

This article presents a compilation of female artists who carried out their sculptural work during the twentieth century. With a brief presentation of each of them I want to implement visibility and the importance of incorporating their works to the collective imagery in order to be added to Spanish contemporary arts history. Some of them have public monuments of great popular recognition but their names have not been mentioned yet. Some others have “minor” works but they were relevant teachers to other artists. A few of them have extensive monographs about their life and their works. While others have almost gone unnoticed, but the proof of their professional career’s existence seems fundamental to us and they must be incorporated to history either through text books, university research works, ideally achieving a supported research project, to provide them the visibility their works and their vital trajectories deserve.

El declive de la memoria en "Tu rostro" mañana de Javier Marías: la escritura revivida

Este trabajo tiene como objetivo estudiar los diferentes estados mentales de los personajes de las novelas de Tu rostro mañana, de Javier Marías. Estudiando las reflexiones del narrador sobre J. Deza, Peter Wheeler o Francisco Rico observamos que su decadencia mental se muestra a través de una suerte de ―presciencia‖ o lucidez momentánea que puede servir para mostrar el silencio como única tendencia de todo discurso. Desde el momento en que toda historia de ficción se cimenta sobre un discurso –no importa su cauce de presentación, ni su fuente– este es falsificado por el tiempo, la gente y cualquier otra herramienta que pueda ser utilizada para contar nada. Las conclusiones de este trabajo muestran la quimera que implica tratar de mantener una contención absoluta sobre lo acaecido, pues dicho vacío de narrativas será ocupado por una suplantación que suele ser el reverso más infame de sus actores. Es por ello que el narrador J. Deza sigue conminado a explicar sus historias, incluso allí donde uno diría que ya no puede haber ni palabras suficientes para traducir un hecho en ficción.

Motivation and Vocabulary Breadth in CLIL and EFL Contexts. Different age, Same Time of Exposure

Numerous studies have found a positive connection between learners’ motivation towards foreign language and foreign language achievement. The present study examines the role of motivation in receptive vocabulary breadth (size) of two groups of Spanish learners of different ages, but all with 734 hours of instruction in English as a Foreign Language (EFL): a CLIL (Content and Language Integrated Learning) group in primary education and a non-CLIL (or EFL) group in secondary education. Most students in both groups were found to be highly motivated. The primary CLIL group slightly overcame the secondary non-CLIL group with respect to the mean general motivation but this is a non-significant difference. The secondary group surpass significantly the primary group in receptive vocabulary size. No relationship between the receptive vocabulary knowledge and general motivation is found in the primary CLIL group. On the other hand, a positive significant connection, although a very small one, is identified for the secondary non-CLIL group. We will discuss on the type of test, the age of students and the type of instruction as variables that could be influencing the results.

Creating restoration landscapes: partnerships in large-scale conservation in the UK

It is increasingly recognized that ecological restoration demands conservation action beyond the borders of existing protected areas. This requires the coordination of land uses and management over a larger area, usually with a range of partners, which presents novel institutional challenges for conservation planners. Interviews were undertaken with managers of a purposive sample of large-scale conservation areas in the UK. Interviews were open-ended and analyzed using standard qualitative methods. Results show a wide variety of organizations are involved in large-scale conservation projects, and that partnerships take time to create and demand resilience in the face of different organizational practices, staff turnover, and short-term funding. Successful partnerships with local communities depend on the establishment of trust and the availability of external funds to support conservation land uses. We conclude that there is no single institutional model for large-scale conservation: success depends on finding institutional strategies that secure long-term conservation outcomes, and ensure that conservation gains are not reversed when funding runs out, private owners change priorities, or land changes hands.

Colombia frente a la coyuntura financiera internacional

Las perspectivas de la economía colombiana y en particular su situación fiscal y cambiaria se analizan a la luz de las políticas sugeridas por el Consenso de Washington (ajuste fiscal, privatización y apertura) y las críticas a este enfoque realizadas por el premio Nobel, Joseph Stiglitz. A partir de la experiencia de los países del sudeste asiático y su respuesta exitosa a la crisis financiera internacional, las políticas de austeridad fiscal y apertura a los mercados externos ganan credibilidad ante los organismos financieros internacionales. Sin embargo, los casos de Argentina y Brasil minan las bases de esta confianza. Argentina enfrenta una situación caótica, con una devaluación del 250 porciento y restricciones a las operaciones comerciales. También Brasil presenta un alto riesgo de crisis, a pesar del apoyo recibido por el FMI. Colombia enfrenta una situación crítica que le implica altos esfuerzos fiscales, a pesar de ser un país que siempre ha cumplido con sus obligaciones. Si a los esfuerzos fiscales no los acompaña un crecimiento apreciable de la economía, difícilmente la situación sea sostenible. La interpretación de esta coyuntura es iluminada por la posición de Stiglitz frente a la globalización, quien aboga por un enfoque de mayor contenido social y un crecimiento gradual puesto que se plantea serias dudas sobre la eficiencia de los mercados. En el largo plazo, mayores niveles de exportación e integración regional, y disciplina fiscal son cruciales para encaminar a Colombia en la senda definitiva del desarrollo.

MOLECULAR MASS MANIPULATION ENABLED BY GRAPHENE BASED NANOSTRUCTURES

The surge of interest in graphene, as epitomized by the Nobel Prize in Physics in 2010, is attributed to its extraordinary properties. Graphene is ultrathin, mechanically tough, and has amendable surface chemistry. These features make graphene and graphene based nanostructure an ideal candidate for the use of molecular mass manipulation. The controllable and programmable molecular mass manipulation is crucial in enabling future graphene based applications, however is challenging to achieve. This dissertation studies several aspects in molecular mass manipulation including mass transportation, patterning and storage. For molecular mass transportation, two methods based on carbon nanoscroll are demonstrated to be effective. They are torsional buckling instability assisted transportation and surface energy induced radial shrinkage. To achieve a more controllable transportation, a fundamental law of direction transport of molecular mass by straining basal graphene is studied. For molecular mass patterning, we reveal a barrier effect of line defects in graphene, which can enable molecular confining and patterning in a domain of desirable geometry. Such a strategy makes controllable patterning feasible for various types of molecules. For molecular mass storage, we propose a novel partially hydrogenated bilayer graphene structure which has large capacity for mass uptake. Also the mass release can be achieved by simply stretching the structure. Therefore the mass uptake and release is reversible. This kind of structure is crucial in enabling hydrogen fuel based technology. Lastly, spontaneous nanofluidic channel formation enabled by patterned hydrogenation is studied. This novel strategy enables programmable channel formation with pre-defined complex geometry.

Principais fatores motivacionais na compra de livros de ficção

O presente projeto de Mestrado assenta no estudo dos principais fatores motivacionais na compra de livros de ficção, aprofundando a dicotomia uso próprio versus oferta, englobando duas perspetivas complementares: a sustentação bibliográfica e uma pesquisa quantitativa que foi concretizada através da distribuição de um inquérito por questionário, em formato digital, que permitiu obter 487 respostas válidas e completas. Os dados obtidos foram tratados no SPSS (Statistical Package for the Social Sciences), utilizando análises descritivas, que foram complementadas com técnicas de inferência estatística. Os resultados permitiram concluir que, apesar de homens e mulheres oferecerem um número idêntico de livros, as mulheres compram e leem mais. Além disso, cerca de um terço dos livros comprados destina-se a oferta. Ficou ainda provado que a interação com os autores nas redes sociais apresenta uma associação positiva com a importância atribuida a esse fator na hora de comprar o(s) livro(s). As mulheres são mais sensíveis às “Políticas de Marketing” (Atendimento Personalizado; Facilidade de Pagamento; Local com Cartão de Fidelização; Preços e Descontos; Elevada quantidade de livros), enquanto critérios de seleção do local de compra. Importa referir que a compra é concretizada de forma menos impulsiva quando o livro é para oferta. Os atributos da capa mais relevantes no processo de decisão de compra são o “Título” e a “Sinopse”. Contudo, os diferentes fatores da capa estudados não apresentam diferenças significativas na compra para uso próprio comparativamente à oferta, no que respeita à sua importância. “Autores com prémios literários” e “Nobel” e “Ser uma novidade” (livro) são outros fatores (não da capa) que apresentam diferenças significativas favoráveis à compra para oferta. Por outro lado, “Recomendação de Amigos e Familiares” e “Presença/Ligação/Interação com o Autor nas redes sociais” são mais favoráveis à compra para uso próprio. As conclusões são relevantes para enquadrar as preferências dos consumidores, possibilitando aos profissionais do marketing algumas referências para definir estratégias que respondam às suas necessidades e ambições. Além disso, ao explorar a dimensão dos submercados (Uso próprio versus Oferta), será possível ir ao encontro das exigências dos compradores, tornando a subjetividade da aquisição/utilização numa ferramenta eficaz da própria idealização e personalização dos livros, permitindo conceber e implementar ideias empreendedoras que visem estimular a compra e, consequentemente, melhorar os hábitos de leitura de todos os portugueses.

Más piedad que improperios: un informe pericial del Dr. Egas Moniz sobre homosexualidad

A principios del siglo XX, Egas Moniz, insigne neurólogo y Premio Nobel portugués, emitió un informe pericial sobre homosexualidad para un caso de anulación matrimonial que constituye un material de gran valor como ejemplo de aplicación efectiva del conocimiento sexológico disponible en la época. En este mismo periodo la flamante legislación republicana estableció la anulación del matrimonio contemplando causas de carácter médico y se tipificaron penalmente las relaciones entre personas del mismo sexo, o contra natura. En su informe, Egas Moniz interpretó desde las categorías sexológicas de la época distintos elementos de la vida del sujeto estudiado, ilustrando la interacción entre estas categorías y las formas cambiantes que adoptó la homosexualidad (o las personas homosexuales) de la época.

STRUCTURE AND FUNCTION OF THE GROUP III CHAPERONINS, A UNIQUE CLADE OF PROTEIN FOLDING NANOMACHINES

The survival and descent of cells is universally dependent on maintaining their proteins in a properly folded condition. It is widely accepted that the information for the folding of the nascent polypeptide chain into a native protein is encrypted in the amino acid sequence, and the Nobel Laureate Christian Anfinsen was the first to demonstrate that a protein could spontaneously refold after complete unfolding. However, it became clear that the observed folding rates for many proteins were much slower than rates estimated in vivo. This led to the recognition of required protein-protein interactions that promote proper folding. A unique group of proteins, the molecular chaperones, are responsible for maintaining protein homeostasis during normal growth as well as stress conditions. Chaperonins (CPNs) are ubiquitous and essential chaperones. They form ATP-dependent, hollow complexes that encapsulate polypeptides in two back-to-back stacked multisubunit rings, facilitating protein folding through highly cooperative allosteric articulation. CPNs are usually classified into Group I and Group II. Here, I report the characterization of a novel CPN belonging to a third Group, recently discovered in bacteria. Group III CPNs have close phylogenetic association to the Group II CPNs found in Archaea and Eukarya, and may be a relic of the Last Common Ancestor of the CPN family. The gene encoding the Group III CPN from Carboxydothermus hydrogenoformans and Candidatus Desulforudis audaxviator was cloned in E. coli and overexpressed in order to both characterize the protein and to demonstrate its ability to function as an ATPase chaperone. The opening and closing cycle of the Chy chaperonin was examined via site-directed mutations affecting the ATP binding site at R155. To relate the mutational analysis to the structure of the CPN, the crystal structure of both the AMP-PNP (an ATP analogue) and ADP bound forms were obtained in collaboration with Sun-Shin Cha in Seoul, South Korea. The ADP and ATP binding site substitutions resulted in frozen forms of the structures in open and closed conformations. From this, mutants were designed to validate hypotheses regarding key ATP interacting sites as well as important stabilizing interactions, and to observe the physical properties of the resulting complexes by calorimetry.

Shortcuts to adiabaticity in the double well

123 p.

Beyond human and intellectual capital: Profiling the value of knowledge, skills and experience

The concept of human capital is associated mainly with the Nobel Laureate Gary Becker and, in his usage, has a clear conceptual basis as investment in the costs of formal education. By contrast, this paper suggests that ‘intellectual capital’ is a re-branding of knowledge, skills and experience rather than re-conceptualisation of resource based learning. Becker also chose not to include informal knowledge, skills or experience within his concept of human capital, which remains limited by its constrained premises. This paper submits that both human capital and intellectual capital advocates fail to identify or measure the tacit knowledge and implicit learning which increasingly is recognised as a key to the competitive advantage of organisations. It first focuses on the conceptual basis of claims made for human capital and intellectual capital, outlines limits in their methodology, and contrasts these with insights from theories of tacit knowledge and implicit learning and the central role within them of informal or non-formal skill acquisition. It develops and illustrates instances of interfacing tacit and explicit knowledge before introducing a methodology for profiling the acquisition of knowledge, ability and skills. It does so by introducing the concepts of non-formal learningfrom- work (LfW) and informal learning-from-life (LfL), with evidence from a four country EU case study commissioned within the lifelong learning remit of the Lisbon Agenda.

Lectura y bibliotecas en la obra de José Saramago

[Español] Este ensayo presenta una revisión sobre los temas lectura y bibliotecas en la obra literaria del escritor José Saramago, premio Nobél de Literatura 1998. Reviste importancia en el sentido de que aunque son variados los temas de tipo social que trata la obra saramaguiana, hasta ahora no se habían analizado ni la lectura ni las bibliotecas. Nos daremos cuenta que Saramago fue un usuario asiduo de las bibliotecas desde el inicio de su formación como escritor hasta llegar a conformar una biblioteca personal importante que compartió con el público investigador. También promovió el hábito de la lectura a través de su participación en ferias del libro y siendo parte de organizaciones como las fundaciones “José Saramago” y “Alonso Quijano”. [Inglés] This essay presents a review on the issues of reading and libraries in the literary work of the writer José Saramago, Nobel laureate of literature in 1998. It highlights importance in the sense that although the social issues in the Saramaguian work are varied, as of today reading and libraries had not been analysed in his work. We will be aware that Saramago was a regular user of libraries since the beginning of his formation as a writer until he built an important personal library that he shared with the research public. In addition he promoted the reading habit through his participation in book fairs, and being part of fundations such as “José Saramago” and “Alonso Quijano.”

Using induced pluripotent stem cells to investigate the mechanistic link between Gaucher disease and Parkinson related synucleinopathies

Dissertação de Mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015

Uma "Viagem ao Algarve" a duas vozes

Depois de ler o livro de Diego Mesa, vêm à memória desta cronista uns versos de Camões: «Transforma-se o amador na cousa amada/ por virtude do muito imaginar». Ao ler o livro de José Saramago, Viagem a Portugal (1981), o mesmo terá acontecido a Diego Mesa, escritor natural de Ayamonte e grande apaixonado pelo nosso país, que mantém um blogue intitulado http://aulajosesaramago. wordpress.com, onde divulga o trabalho que se vai fazendo em prol da disseminação da obra do Nobel da Literatura português, que o inspirou a refazer os seus passos. Escrito na terceira pessoa, Saramago designa a personagem que percorre o país de lés a lés como «o viajante». E este viajante vai ser, para Diego Mesa, «o outro viajante», já que, assumindo uma personagem equivalente, adota um estilo e retórica reconhecíveis para o leitor. Tomando como ponto de partida o último capítulo, «De Algarve e sol, pão seco e pão mole», que ocupa 18 páginas na edição da Viagem a Portugal, do Círculo de Leitores, e fazendo dele o seu guia de viagem, um novo viajante percorre esta terra, de uma ponta a outra, de carro e de comboio, revisitando os lugares ali mencionados. Naturalmente que, passados mais de 30 anos desde a 1ª edição daquela obra, muitas coisas se alteraram e é bom saber que, na sua maioria, para melhor. Os passos citados de José Saramago aparecem em itálico no texto de Diego Mesa, que muito bem os enquadra. Não se pense, porém, que este novo viajante apenas repete o que o outro visitou. É verdade que o usa como guia, mas também faz dele a sua inspiração para novos percursos, como a visita mais demorada a Portimão ou a viagem de comboio entre Vila Real de Santo António e Lagos. Além disso, a Viagem ao Algarve tem algumas breves (e úteis) notas de rodapé e, no final, uma boa bibliografia que poderá ajudar o leitor interessado em aprofundar mais o assunto. Para que fique perfeito, só falta que a próxima edição tenha uma boa revisão de texto. Precisando de selecionar alguns excertos para aqui constarem, deixou-se esta cronista levar pelo seu interesse especial por ruínas e museus, apresentando dois apontamentos sobre estes tipos de espaços.