Phenotype-Based Discovery of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a Novel Regulator of Ocular Angiogenesis

Retinal angiogenesis is tightly regulated to meet oxygenation and nutritional requirements. In diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, uncontrolled angiogenesis can lead to blindness. Our goal is to better understand the molecular processes controlling retinal angiogenesis and discover novel drugs that inhibit retinal neovascularization. Phenotype-based chemical screens were performed using the ChemBridge Diverset^TM library and inhibition of hyaloid vessel angiogenesis in Tg(fli1:EGFP) zebrafish. 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol, (quininib) robustly inhibits developmental angiogenesis at 4–10 μM in zebrafish and significantly inhibits angiogenic tubule formation in HMEC-1 cells, angiogenic sprouting in aortic ring explants, and retinal revascularization in oxygen-induced retinopathy mice. Quininib is well tolerated in zebrafish, human cell lines, and murine eyes. Profiling screens of 153 angiogenic and inflammatory targets revealed that quininib does not directly target VEGF receptors but antagonizes cysteinyl leukotriene receptors 1 and 2 (CysLT_1–2) at micromolar IC₅₀ values. In summary, quininib is a novel anti-angiogenic small-molecule CysLT receptor antagonist. Quininib inhibits angiogenesis in a range of cell and tissue systems, revealing novel physiological roles for CysLT signaling. Quininib has potential as a novel therapeutic agent to treat ocular neovascular pathologies and may complement current anti-VEGF biological agents.

Using genomics for drug discovery in medulloblastoma

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

Prospects and Problems for Religious Education in England, 1967-1970: Curriculum Reform in Political Context

This article provides an historical case study of an abortive attempt to revise policy and legislation relating to Religious Education (RE) in English schools in the late 1960s and early 1970s. Drawing upon published sources, including parliamentary debates, as well as previously unutilised national archival sources from the Department of Education and Science, it comments upon events which have hitherto been omitted from the historiography of RE, but which help to contextualise significant changes in RE theory and practice at that time. Moreover, it demonstrates that the current parlous state of RE in schools is in part the result of latent and longstanding issues and problems, rather than a consequence of present-day government policy alone. Therefore, in reviewing and developing RE policies and practices, all stakeholders are urged to look more closely at both changes and continuities in the subject’s past and the contexts in which they occurred.

Conceptualizing and Researching the Professionalization of Religious Education Teachers: Historical and International Perspectives

Current discussions on Religious Education (RE), both in Germany and England, focus on the quality of teaching and the professionality of teachers, but neglect the historical and institutional process of professionalization upon which conceptions of teaching quality and teacher professionality hinge. This article seeks to provide definitional clarity by differentiating between individual and collective professionalization; exploring teacher professionalization in general and in the special case of RE; and operationalizing the concept of RE teacher professionalization for the purposes of planned historical and international comparative research. A three-fold conceptualization of professionalization is proposed, consisting of the following inter-related levels: (1) initial and continuing professional development; (2) professional self-organization and professional politics; and (3) professional knowledge. The breadth, complexity and significance of the historical and institutional processes associated with the professionalization of RE teachers at each of these levels is described and discussed. It is argued that further historical and international comparative research on these lines would contribute a broader and deeper understanding of the presuppositions of RE teacher professionality beyond current debates.

The Professionalisation of Non-Denominational Religious Education in England: Politics, Organisation and Knowledge

In response to contemporary concerns, and using neglected primary sources, this article explores the professionalisation of teachers of Religious Education (RI/RE) in non-denominational, state-maintained schools in England. It does so from the launch of Religion in Education (1934) and the Institute for Christian Education at Home and Abroad (1935) to the founding of the Religious Education Council of England and Wales (1973) and the British Journal of Religious Education (1978). Professionalisation is defined as a collective historical process in terms of three inter-related concepts: (1) professional self-organisation and professional politics, (2) professional knowledge, and (3) initial and continuing professional development. The article sketches the history of non-denominational religious education prior to the focus period, to contextualise the emergence of the professionalising processes under scrutiny. Professional self-organisation and professional politics are explored by reconstructing the origins and history of the Institute of Christian Education at Home and Abroad, which became the principal body offering professional development provision for RI/RE teachers for some fifty years. Professional knowledge is discussed in relation to the content of Religion in Education which was oriented around Christian Idealism and interdenominational networking. Changes in journal name in the 1960s and 1970s reflected uncertainties about the orientation of the subject and shifts in understanding over the nature and character of professional knowledge. The article also explores a particular case of resistance, in the late 1960s, to the prevailing consensus surrounding the nature and purpose of RI/RE, and the representativeness and authority of the pre-eminent professional body of the time. In conclusion, the article examines some implications which may be drawn from this history for the prospects and problems of the professionalisation of RE today.

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

Kiss of God: Spiritual Death in Jewish Religious History, pt. 2

Discussion of the spiritual face of Judaism in one of its many appearances. Fishbane explores the quest for spiritual perfection in early rabbinic sources and in Jewish philosophy and mysticism. The "kiss of God," a symbol for union with God, and the ritual practices - meditation and performance - connected with it are presented.

Kiss of God: Spiritual Death in Jewish Religious History, pt. 1

Discussion of the spiritual face of Judaism in one of its many appearances. Fishbane explores the quest for spiritual perfection in early rabbinic sources and in Jewish philosophy and mysticism. The "kiss of God," a symbol for union with God, and the ritual practices - meditation and performance - connected with it are presented.

Kiss of God: Spiritual Death in Jewish Religious History, pt. 3

Discussion of the spiritual face of Judaism in one of its many appearances. Fishbane explores the quest for spiritual perfection in early rabbinic sources and in Jewish philosophy and mysticism. The "kiss of God," a symbol for union with God, and the ritual practices - meditation and performance - connected with it are presented.

Reflections on conducting research on the ‘war on terror’: religious identity, subjectivity and emotions

In recent years there has been an increase in literature which has explored the insider/outsider position through ethnic identities. However, there remains a neglect of religious identities, even though it could be argued that religious identities have become increasingly important through being prominent in international issues such as the ‘war on terror’ and the Middle East conflict. Through drawing on the concept of subjectivity, I reflect on research I conducted on the impact of the ‘war on terror’ on British Muslims. I explore the space between the insider/outsider position demonstrating how my various subjectivities – the ‘non-Islamic appearance I’, the ‘Muslim I’, the ‘personal I’, the ‘exploring I’, the ‘Kashmiri I’ or the ‘Pakistani I’, the ‘status I’ and the ‘outsider I’ – assisted in establishing trust, openness and commonality. I conclude by demonstrating how the ‘emotional I’ allowed me to manage my own emotions and participants emotions.

A Mixed Blessing: Market-mediated Religious Authority in Neopaganism

This is a study of the interplay of market-mediated and religious authority in the context of new religious movements. Specifically, we explore the ambivalent relationship followers of Wicca have with the marketplace. Our main argument is that in this context marketplace success can be a source of religious legitimacy and validation. At the same time, however, excessive engagement with the market can act as a powerful delegitimizing mechanism, leading religious leaders to continually monitor their practices. Market success is thus a mixed blessing that can increase religious authority and influence, but is just as likely to decrease authority and credibility. Based on an ethnographic study, we explore the boundary work carried out by religious marketers and consumers in order to establish themselves in a “safety area” where engagement with the market brings its positive effects without causing a loss of credibility.

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.