La cornée humaine, un modèle évitant la transformation tumorale induite par les rayons ultraviolets : étude comparant la fréquence d’induction de dommages à l’ADN, leur l’efficacité de réparation ainsi que la sensibilité à la mort cellulaire induite par les rayons ultraviolets entre la cornée et l’épiderme

Bien qu’ils soient exposés tous deux aux rayons ultraviolets (UVR) solaires, cette exposition génotoxique n’entraîne pas les mêmes conséquences dans l’oeil et la peau. Le rôle des rayons UV dans l’induction et la progression des cancers cutanés est bien démontré. Ces rayons génotoxiques sont absorbés par l’ADN. Ils y induisent ainsi des changements conformationnels pouvant mener à la formation de différents dommages. On retrouve de façon prédominante la liaison de pyrimidines adjacentes en dimères cyclobutyliques de pyrimidines (CPD). Ceux-ci causent les mutations signatures responsables des cancers de la peau induits par les UVR. Cependant, aucune évidence ne démontre l’existence de cancer induit par les UVR dans la cornée. Nous avons donc tenté de découvrir les mécanismes permettant à la cornée d’éviter la transformation tumorale induite par les UVR. L’irradiation d’yeux de lapins aux rayons UVB a permis de prouver la capacité de ces rayons à induire la formation de CPD, et ce, de la cornée jusqu’au cristallin. Par la suite, l’irradiation d’yeux humains aux trois types de rayons UV (UVA, B et C) a permis d’y établir leur patron d’induction de CPD. Nous avons ainsi démontré que l’épithélium cornéen est particulièrement sensible à l’induction de CPD, tous types de rayons UV confondus. Enfin, la comparaison de la quantité de dommages présents dans des échantillons de peaux et de cornées irradiées à la même dose d’UVB a permis de démontrer que l’épithélium cornéen est 3.4 fois plus sensible à l’induction de CPD que l’épiderme. Nous avons par la suite étudié les mécanismes de réponse à ce stress. L’analyse de la viabilité cellulaire à la suite d’irradiations à différentes doses d’UVB a révélé que les cellules de la cornée et de la peau ont la même sensibilité à la mort cellulaire induite par les UVR. Nous avons alors analysé la vitesse de réparation des dommages induits par les UVR. Nos résultats démontrent que les CPD sont réparés 4 fois plus rapidement dans les cellules de la cornée que de la peau. L’analyse des protéines de reconnaissance des dommages a révélé que les cellules de la cornée possèdent plus de protéines DDB2 que les cellules de la peau, et ce, surtout liées à la chromatine. Nous avons alors tenté d’identifier la cause de cette accumulation. Nos analyses révèlent que la cornée possède une moins grande quantité d’ARNm DDB2, mais que la demi-vie de la protéine y est plus longue. Enfin, nos résultats suggèrent que l’accumulation de DDB2 dans les cellules de la cornée est entre autres due à une demi-vie plus longue de la protéine. Cette forte présence de DDB2 dans les cellules de la cornée permettrait un meilleur balayage de l’ADN, faciliterait de ce fait la détection de CPD ainsi que leur réparation et contribuerait donc à la capacité de la cornée à éviter la transformation tumorale induite par les UVR.

New approaches for the diagnosis of human papillomavirus infection:relevance for clinical practice and cancer prevention

Tese de doutoramento, Biologia (Microbiologia), Universidade de Lisboa, Faculdade de Ciências, 2014

New synthetic methodologies for the transformation of biomass derived intermediates to valuable molecules

Tese de doutoramento, Farmácia (Química Farmacêutica e Terapêutica), Universidade de Lisboa, Faculdade de Farmácia, 2014

Questioning the Universality of Institutional Transformation Theories in Spatial Planning: Shopping Mall Developments in Palermo

Theories about institutional transformation in spatial planning, although mainly based on the Anglo-Saxon context, have assumed a dominant role in planning research and theory as means to understand the transformations that have been restructuring planning systems in recent decades in the Western world and beyond. The article, looking at transformations of planning practice through the lenses of the concept of planning cultures, debates the utility of building ‘universal’ theories for spatial planning and advocates for the need for a de-provincialization of planning theories. This is done through a case-study approach applied to the history of the transformation of the retail system in a context characterized by the specificities of the Italian planning context and Southern European cities, namely: the planning processes for, and power relationships underlying, the first shopping malls opened in Palermo, Italy, since 2009 — some decades later than most of Western cities.

Transformation or bureaucratisation?: the changing role of community representation in local strategic partnerships in England

The debate about the need to build social capital and to engage local communities in public policy has become a central issue in many advanced liberal societies and developing countries. In many countries new forms of governance have emerged out of a growing realisation that representative democracy by itself is no longer sufficient. One of the most significant public policy trends in the UK has been the involvement of community organisations and their members in the delivery of national policy, mediated through local systems of governance and management. One such policy area is urban regeneration. Central government now requires local authorities in England to set up Local Strategic Partnerships (LSPs) to bring together stakeholders who can prepare Community Strategies and deliver social and economic programmes which target areas of deprivation. This paper reviews the key institutional processes which must be addressed, such as representation, accountability and transformation.

The challenge and response to global tourism in the post-modern era: the commodification, reconfiguration and mutual transformation of Habana Vieja, Cuba

There is a growing literature on the symbolic and cultural meanings of tourism and the ways in which cities are increasingly competing for tourists through the promotion of cultural assets and different forms of spectacle in the `tourist bubble'. To date, research on the role and impact of tourism in cities has largely been confined to those in Western, post-industrial economies. This paper examines the growth of cultural tourism in the central area of Havana, Cuba, and explores the range of unique, devolved, state-owned enterprises that are attempting to use tourism as a funding mechanism to achieve improvements in the social and cultural fabric of the city for the benefit of residents. The paper concludes with an assessment of the implications of this example for our understanding of how the pressures for restructuring and commodification can be moderated at the city level. Copyright 2008 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

The transformation of landscape as as aesthetic idear

The present study seeks to thoroughly investigate and delineate the concept alongside the transformation of landscape as an aesthetic idea. On the one side it runs that nature perceived as landscape remains nothing else but granted, evident or 'natural'. On yet another side, and to some fairly significant extend, this thesis identifies landscape as a sheer idea and concept that is shaped and (re-)mediated in an ongoing process. The thesis examines the role of the observer and brings into agreement that every landscape is a produce of creative mental processes. In brief outline, this approach provides a framework for identifying landscape as being inextricably linked with media from the very beginning of their social and cultural inception. As glowing examples for the paradigmatic shift of the classical subjective vision model culminating in the emergence of a new prototype, the camera obscura, together with the panorama, fortify the prevailing argument that the mode of human sense perception is organised and determined by earlier acquainted recognitions. In this matter, as each and every medium strive after accomplishment, then this accomplishment is substantially determined by overwhelming historic, as well as thriving cultural circumstances. In conclusive terms, this study seeks to show how landscape counts as content of a representation, while simultaneously being a very own medium that specifically carries social, geological as well as historic knowledge. In fact, modern vision shall therefore never be bound to any single format or process, rather it will have to always undergo procedures aiming at reshaping the perceivable. Landscape is playing out its major characteristic, specifically that of being, in essence, a purely intellectual, virtual and synthetic product

Post-Transcriptional Regulation of BCL2 mRNA by the RNA-Binding Protein ZFP36L1 in Malignant B Cells

The human ZFP36 zinc finger protein family consists of ZFP36, ZFP36L1, and ZFP36L2. These proteins regulate various cellular processes, including cell apoptosis, by binding to adenine uridine rich elements in the 3′ untranslated regions of sets of target mRNAs to promote their degradation. The pro-apoptotic and other functions of ZFP36 family members have been implicated in the pathogenesis of lymphoid malignancies. To identify candidate mRNAs that are targeted in the pro-apoptotic response by ZFP36L1, we reverse-engineered a gene regulatory network for all three ZFP36 family members using the ‘maximum information coefficient’ (MIC) for target gene inference on a large microarray gene expression dataset representing cells of diverse histological origin. Of the three inferred ZFP36L1 mRNA targets that were identified, we focussed on experimental validation of mRNA for the pro-survival protein, BCL2, as a target for ZFP36L1. RNA electrophoretic mobility shift assay experiments revealed that ZFP36L1 interacted with the BCL2 adenine uridine rich element. In murine BCL1 leukemia cells stably transduced with a ZFP36L1 ShRNA lentiviral construct, BCL2 mRNA degradation was significantly delayed compared to control lentiviral expressing cells and ZFP36L1 knockdown in different cell types (BCL1, ACHN, Ramos), resulted in increased levels of BCL2 mRNA levels compared to control cells. 3′ untranslated region luciferase reporter assays in HEK293T cells showed that wild type but not zinc finger mutant ZFP36L1 protein was able to downregulate a BCL2 construct containing the BCL2 adenine uridine rich element and removal of the adenine uridine rich core from the BCL2 3′ untranslated region in the reporter construct significantly reduced the ability of ZFP36L1 to mediate this effect. Taken together, our data are consistent with ZFP36L1 interacting with and mediating degradation of BCL2 mRNA as an important target through which ZFP36L1 mediates its pro-apoptotic effects in malignant B-cells.

Sociological Knowledge and Transformation at ‘Diversity University’, UK

This chapter is based on a case study of one UK university sociology department and shows how sociology knowledge can transform the lives of ‘non-traditional’ students. The research from which the case is drawn focused on four departments teaching sociology-related subjects in universities positioned differently in UK league tables. It explored the question of the relationship between university reputation, pedagogic quality and curriculum knowledge, challenging taken-for-granted judgements about ‘quality’ and in conceptualising ‘just’ university pedagogy by taking Basil Bernstein’s ideas about how ‘powerful’ knowledge is distributed in society to illuminate pedagogy and curriculum. The project took the view that ‘power’ lies in the acquisition of specific (inter)disciplinary knowledges which allows the formation of disciplinary identities by way of developing the means to think about and act in the world in specific ways. We chose to focus on sociology because (1) university sociology is taken up by all socio-economic classes in the UK and is increasingly taught in courses in which the discipline is applied to practice; (2) it is a discipline that historically pursues social and moral ambition which assists exploration of the contribution of pedagogic quality to individuals and society beyond economic goals; (3) the researchers teach and research sociology or sociology of education - an understanding of the subjects under discussion is essential to make judgements about quality. ‘Diversity’ was one of four case study universities. It ranks low in university league tables; is located in a large, multi-cultural English inner city; and, its students are likely to come from lower socio-economic and/or ethnic minority groups, as well as being the first in their families to attend university. To make a case for transformative teaching at Diversity, the chapter draws on longitudinal interviews with students, interviews with tutors, curriculum documents, recordings of teaching, examples of student work, and a survey. It establishes what we can learn from the case of sociology at Diversity, arguing that equality, quality and transformation for individuals and society are served by a university curriculum which is research led and challenging combined with pedagogical practices which give access to difficult-to-acquire and powerful knowledge.

Welcome to the new world disorder: conflict and transformation in Ian McEwan’s saturday

Ian McEwan‘s novel Saturday deals with the complex issues of conflict and transformation in the age of terrorism. The plot presents one internal dilemma and several interpersonal altercations that occur within a mere twenty-four hours: a) Perowne (the protagonist) vs. himself, in face of his ambivalent thoughts regarding British military participation in the war in the Middle East; b) The protagonist vs. Baxter, a ruffian from East End, in the context of a car accident; c) Perowne vs. a fellow anaesthetist, Jay Strauss, during a squash game; d) Perowne‘s daughter, Daisy vs. her grandfather, John Grammaticus, both poets and rivals; e) Perowne‘s family vs. Baxter, who intrudes the protagonist‘s house. In this paper, I exemplify, analyse and discuss how: a) Understanding the causes of what we call evil constitutes an important step towards mutual understanding; b) Both science and arts (which Perowne considers, at first, irrelevant) are important elements in the process of transformation; c) Both personal and interpersonal conflicts are intrinsic to human nature — but they also propitiate healthy changes in behaviour and opinion, through reflection. In order to do so, I resort to Saturday, and to the work of several specialists in the field of conflict management.

Reallocation of resources between the tradable and non-tradable sector in Portugal: Assessing the degree of structural transformation in the Portuguese economy

Portugal implemented a large number of structural reforms in the recent years, which are expected to enhance the allocation of resources in the economy, namely from the non-tradable to tradable sector. We argue that the methodology to identify the tradable sector used by some international institutions is outdated and may hamper an accurate assessment of the progress achieved so far. Based on an enhanced methodology to identify the tradable sector, we are able to provide a more accurate, clearer picture of the recent structural developments of the Portuguese economy.