Using genomics for drug discovery in medulloblastoma

Tese de doutoramento, Medicina (Neurocirurgia), Universidade de Lisboa, Faculdade de Medicina, 2014

Implementing self-regulated strategy development for teaching argumentative writing : a multidimensional approach

Tese de doutoramento, Psicologia (Psicologia da Educação), Universidade de Lisboa, Faculdade de Psicologia, Universidade de Coimbra, Faculdade de Psicologia e de Ciências da Educação, 2015

Translating proteomics into environmental health : biomarkers discovery for tobacco smoke-induced biological damage

Tese de doutoramento, Biologia (Biologia Molecular), Universidade de Lisboa, Faculdade de Ciências, 2015

Medicinal chemistry approaches to malaria drug discovery

Tese de doutoramento, Farmácia (Química Farmacêutica e Terapêutica), Universidade de Lisboa, Faculdade de Farmácia, 2016

The Edinburgh Critical Edition of the Selected Writing of Andrew Lang, volume 2

This is the first critical edition of the works of Andrew Lang (1844-1912), the Scottish writer whose enormous output spanned the whole range of late nineteenth-century intellectual culture. Neglected since his death, partly because of the diversity of his interests and the volume of his writing, his cultural centrality and the interdisciplinary nature of his work make him a vital figure for contemporary scholars. This volume covers his work on literary criticism, history and biography.

Discipline-specific writing for business students: Research, practice and pedagogy

In the past few years strong arguments have been made for locating academic writing in higher education within the students’ disciplinary contexts in the belief that a full understanding of the role and dynamic of writing can only be achieved if it is examined as a social practice in its context of production. This chapter reports on a study that examined the conceptualisations of writing for business by a group of undergraduate and postgraduate lecturers and students at the business school of a British university. Based on a critical analysis of the literature reviewed for the study, and the data collected, the chapter contributes to existing writing pedagogy with a number of research-informed transformative pedagogical applications for teaching discipline-specific writing for business. Such applications which combine context-oriented practices (e.g. raising awareness of the role of disciplinary values in shaping writing) and text-oriented activities (e.g. discipline-specific referencing) aim at influencing the pedagogic agenda for teaching writing in higher education. The chapter concludes with questions for reflection and discussion that provide an opportunity for readers to reflect upon their own teaching environment.

Voices in search of a reader: the polyphonic writing of António Lobo Antunes

This paper aims at analysing the writing of the Portuguese author António Lobo Antunes, considered one of the major writers in European Literature with 26 books published, by focusing on the strategies deployed in his texts of creating micro-narratives within the main frame, and conveying the elements of individual and collective memory, past and present, the self and the others, using various voices and silences. Lobo Antunes incorporates in his writing his background as a psychiatrist at a Mental Hospital in Lisbon, until 1985 (when he decided to commit exclusively to writing), his experience as a doctor in the Portuguese Colonial War battlefield, but also the daily routines of the pre and post 25th of April 1974 (Portuguese Revolution) with subtle and ironic details of the life of the middle and upper class of Lisbon‘s society: from the traumas of the war to the simple story of the janitor, or the couple who struggles to keep their marriage functional, everything serves as material to develop and interweave a complex plot, that a lot of readers find too enwrapped and difficult to follow through. Some excerpts taken from his first three novels and books of Chronicles and his later novel – Ontem não te Vi em Babilónia (2006) – will be put forward to exemplify the complexity of the writing and the main difficulties of the reader, lost in a multitude of narrators‘ voices. Recently, Lobo Antunes has commented on his work stating: What I write can be read in the darkness. This paper aims at throwing some light by unfolding some of the strategies employed to defy new borders in the process of reading.

Writing and living on the stage of history

This article studies the intercultural trajectory of a Portuguese female aristocrat of the eighteenth to nineteenth centuries. Her trajectory of intercultural transition from a Portuguese provincial lady into an independent owner of a sugar mill in tropical Bahia is documented through family letters, which provide a polyphonic representation of a movement of personal, family, and social transculturation over almost two decades. Maria Bárbara began her journey between cultures as a simple spectator-reader, progressively becoming a commentator-actor-protagonist-author in society, in politics, and in history. These letters function as a translation that is sometimes consecutive, other times simultaneous, of the events lived and witnessed. This concept of intercultural translation is based on the theories of Boaventura de Sousa Santos (2006, 2008), who argues that cultural differences imply that any comparison has to be made using procedures of proportion and correspondence which, taken as a whole, constitute the work of translation itself. These procedures construct approximations of the known to the unknown, of the strange to the familiar, of the ‘other’ to the ‘self’, categories which are always unstable. Likewise, this essay explores the unstable contexts of its object of study, with the purpose of understanding different rationalities and worldviews.

Contribution to drug discovery and development for tauopathies using yeast as a model

This work aimed to contribute to drug discovery and development (DDD) for tauopathies, while expanding our knowledge on this group of neurodegenerative disorders, including Alzheimer’s disease (AD). Using yeast, a recognized model for neurodegeneration studies, useful models were produced for the study of tau interaction with beta-amyloid (Aβ), both AD hallmark proteins. The characterization of these models suggests that these proteins co-localize and that Aβ1-42, which is toxic to yeast, is involved in tau40 phosphorylation (Ser396/404) via the GSK-3β yeast orthologue, whereas tau seems to facilitate Aβ1-42 oligomerization. The mapping of tau’s interactome in yeast, achieved with a tau toxicity enhancer screen using the yeast deletion collection, provided a novel framework, composed of 31 genes, to identify new mechanisms associated with tau pathology, as well as to identify new drug targets or biomarkers. This genomic screen also allowed to select the yeast strain mir1Δ-tau40 for development of a new GPSD2TM drug discovery screening system. A library of unique 138 marine bacteria extracts, obtained from the Mid-Atlantic Ridge hydrothermal vents, was screened with mir1Δ-tau40. Three extracts were identified as suppressors of tau toxicity and constitute good starting points for DDD programs. mir1Δ strain was sensitive to tau toxicity, relating tau pathology with mitochondrial function. SLC25A3, the human homologue of MIR1, codes for the mitochondrial phosphate carrier protein (PiC). Resorting to iRNA, SLC25A3 expression was silenced in human neuroglioma cells, as a first step towards the engineering of a neural model for replicating the results obtained in yeast. This model is essential to understand the mechanisms of tau toxicity at the mitochondrial level and to validate PiC as a relevant drug target. The set of DDD tools here presented will foster the development of innovative and efficacious therapies, urgently needed to cope with tau-related disorders of high human and social-economic impact.