Pregnancy-specific glycoprotein function, conservation and receptor investigation

Pregnancy-specific glycoproteins (PSGs) are highly glycosylated secreted proteins encoded by multi-gene families in some placental mammals. They are carcinoembryonic antigen (CEA) family and immunoglobulin (Ig) superfamily members. PSGs are immunomodulatory, and have been demonstrated to possess antiplatelet and pro-angiogenic properties. Low serum levels of these proteins have been correlated with adverse pregnancy outcomes. Objectives: Main research goals of this thesis were: 1). To attempt to replicate previously reported cytokine responses to PSG-treatment of immune cells and subsequently to investigate functionally important amino acids within PSG1. 2). To determine whether candidate receptor, integrin αvβ3, was a binding partner for PSG1 and to investigate whether PSG1 possessed functionality in a leukocyte-endothelial interaction assay. 3). To determine whether proteins generated from recently identified putative PSG genes in the horse shared functional properties with PSGs from other species. Outcomes: 1). Sequential domain deletion of PSG1 as well as mutation of conserved residues within the PSG1 Ndomain did not affect PSG1-induced TGF-β1. The investigated response was subsequently found to be the result of latent TGF-β1 contaminating the recombinant protein. Protein further purified by SEC to remove this showed no induction of TGF-β1. The most N-terminal glycosylation site was demonstrated to have an important role in PSG N domain secretion. PSG1 attenuated LPS-induced IL-6 and TNF-α. Investigations into signalling underpinning this proved inconclusive. 2). Integrin αvβ3 was identified as a novel PSG1 receptor mediating an as yet unknown function. Preliminary investigations into a role for PSGs as inhibitors of leukocyte endothelial interactions showed no effect by PSG1. 3). Horse PSG protein, CEACAM49, was shown to be similarly contaminated by latent TGF-β1 particle and once removed did not demonstrate TGF-β1 release. Interestingly horse PSG did show anti-platelet properties through inhibition of the plateletfibrinogen interaction as previously published for mouse and human PSGs.

The protection and security of vulnerable populations in complex emergencies using the Dadaab refugee camps in the north eastern province of Kenya as a case study

The past two decades has seen a dramatic upheaval in the international world order: the end of the Cold War, the 9/11 attacks and the subsequent 'War on Terror', increased Jihadist activities, the accelerated pace of globalization, climate change and the 2008 global financial crisis have contributed to fear, uncertainty, poverty, conflict, massive displacements of populations of asylum seekers and refugees globally and a proliferation of Protracted Refugee Situations (PRS), defined as situations in which refugees have been in exile 'for 5 years or more after their initial displacement, without immediate prospects for implementation of durable solutions. In the past two decades there has been a huge proliferation of these with more than 7.2 million refugees now trapped in these PRS, with a further 16 million internally displaced persons (IDPs) trapped in camps within their own countries. The Dadaab refugee complex in Kenya, which of as March 2012, holds over 463,000 refugees, is the most significant and extreme example in recent times of a PRS. It was established in 1991 following the collapse of the Somali Government of Dictator Siad Barre, and the disintegration of Somalia into the chaos that still exists today. PRS such as Dadaab raise particular issues about humanitarianism in terms of aid, protection, security, human rights and the actions (or inaction) of the various stakeholders on an international, national and local level. This thesis investigates these issues by the use of a case study methodology on Dadaab as a PRS, framed in the context of humanitarianism and in particular the issues that arise in terms of how the international community, the UN system and individual states provide assistance and protection to vulnerable populations. Although the refugee camps have been in existence (as of 2012) for over 20 years, there has never been such a detailed study of Dadaab (or any other PRS) undertaken to date and would be of interest to academics in the areas of international relations, refugee/migration studies and global Governance as well as practitioners in both humanitarian response and development

The importance of interaction strength for food web dynamics and ecosystem functioning

Global biodiversity is eroding at an alarming rate, through a combination of anthropogenic disturbance and environmental change. Ecological communities are bewildering in their complexity. Experimental ecologists strive to understand the mechanisms that drive the stability and structure of these complex communities in a bid to inform nature conservation and management. Two fields of research have had high profile success at developing theories related to these stabilising structures and testing them through controlled experimentation. Biodiversity-ecosystem functioning (BEF) research has explored the likely consequences of biodiversity loss on the functioning of natural systems and the provision of important ecosystem services. Empirical tests of BEF theory often consist of simplified laboratory and field experiments, carried out on subsets of ecological communities. Such experiments often overlook key information relating to patterns of interactions, important relationships, and fundamental ecosystem properties. The study of multi-species predator-prey interactions has also contributed much to our understanding of how complex systems are structured, particularly through the importance of indirect effects and predator suppression of prey populations. A growing number of studies describe these complex interactions in detailed food webs, which encompass all the interactions in a community. This has led to recent calls for an integration of BEF research with the comprehensive study of food web properties and patterns, to help elucidate the mechanisms that allow complex communities to persist in nature. This thesis adopts such an approach, through experimentation at Lough Hyne marine reserve, in southwest Ireland. Complex communities were allowed to develop naturally in exclusion cages, with only the diversity of top trophic levels controlled. Species removals were carried out and the resulting changes to predator-prey interactions, ecosystem functioning, food web properties, and stability were studied in detail. The findings of these experiments contribute greatly to our understanding of the stability and structure of complex natural communities.

Not thinking straight? A critical discourse analysis of the 2006 Irish High Court ruling in Zappone and Gilligan v. Revenue Commissioners and Attorney General

The recognition and protection of constitutional rights is a fundamental precept. In Ireland, the right to marry is provided for in the equality provisions of Article 40 of the Irish Constitution (1937). However, lesbians and gay men are denied the right to marry in Ireland. The ‘last word’ on this issue came into being in the High Court in 2006, when Katherine Zappone and Ann Louise Gilligan sought, but failed, to have their Canadian marriage recognised in Ireland. My thesis centres on this constitutional court ruling. So as to contextualise the pursuit of marriage equality in Ireland, I provide details of the Irish trajectory vis-à-vis relationship and family recognition for same-sex couples. In Chapter One, I discuss the methodological orientation of my research, which derives from a critical perspective. Chapter Two denotes my theorisation of the principle of equality and the concept of difference. In Chapter Three, I discuss the history of the institution of marriage in the West with its legislative underpinning. Marriage also has a constitutional underpinning in Ireland, which derives from Article 41 of our Constitution. In Chapter Four, I discuss ways in which marriage and family were conceptualised in Ireland, by looking at historical controversies surrounding the legalisation of contraception and divorce. Chapter Five denotes a Critical Discourse Analysis of the High Court ruling in Zappone and Gilligan. In Chapter Six, I critique text from three genres of discourse, i.e. ‘Letters to the Editor’ regarding same-sex marriage in Ireland, communication from legislators vis-à-vis the 2004 legislative impediment to same-sex marriage in Ireland, and parliamentary debates surrounding the 2010 enactment of civil partnership legislation in Ireland. I conclude my research by reflecting on my methodological and theoretical considerations with a view to answering my research questions. Author’s Update: Following the outcome of the 2015 constitutional referendum vis-à-vis Article 41, marriage equality has been realised in Ireland.