Autophagy, an intracellular degradation, and recycling process is essential in maintaining cellular homeostasis. Dysregulated autophagy is linked to the pathogenesis of various diseases, including inflammatory bowel disease (IBD) which consists of Crohn’s disease and ulcerative colitis. In IBD, enterochromaffin cell numbers and one of its main product serotonin (5-hydroxytryptamine; 5-HT) levels are elevated. Previously, we had shown that tryptophan hydroxylase 1 deficient (Tph1-/-) mice, with reduced gut 5-HT had decreased severity of colitis. Here, we showed that gut 5-HT plays a vital role in modulating autophagy and thus regulating gut microbial composition and susceptibility to intestinal inflammation. Tph1-/- mice, had upregulated colonic autophagy via the mammalian target of rapamycin pathway (mTOR), and decreased colitis severity. Tph1-/- mice after 5-HT replenishment, and serotonin reuptake transporter deficient (SERT-/-) mice, which have increased 5-HT levels, showed converse results. Deletion of intestinal epithelial cell-specific autophagy gene, Atg7, in Tph1-/- mice (DKO mice) abolished the protective effect of Tph1 deficiency in colitis, decreased the production of antimicrobial peptide, β-defensin 1 and promoted colitogenic microbiota. Furthermore, using cecal microbial transplantation, we found that the colitic microbiota of the DKO mice contributed to the increased severity of colitis. Supporting this pathway's translational importance, we uncovered that 5-HT treatment of peripheral blood mononuclear cells from both healthy volunteers and patients with Crohn’s disease inhibited autophagy via the mTOR pathway. Our results in this thesis emphasize the role of 5-HT-autophagymicrobiota axis in intestinal inflammation. Moreover, these findings suggest 5-HT as a novel therapeutic target in intestinal inflammatory disorders such as IBD that exhibit dysregulated autophagy. / Thesis / Doctor of Philosophy (PhD) / Approximately 0.7% of Canadians are currently affected with inflammatory bowel disease (IBD). The gut hormone serotonin, which regulates many normal functions, is elevated in gut inflammation. Reduced serotonin levels decrease the severity of inflammation. IBD pathology has been linked to a unique cell self-eating process called autophagy. Using cell lines, mice, and samples from IBD patients, we assessed the interactions between serotonin signaling and autophagy during gut inflammation. I found that an increase in serotonin levels enhances the severity of gut inflammation by inhibiting autophagy. We also established the connection between serotonin and autophagy in the intestinal epithelial cells, and how this modulates epithelial cell function. Furthermore, we demonstrated the establishment of an altered gut microbiota upon disruption of the serotonin-autophagy axis in the epithelial cells, which subsequently influenced gut inflammation severity. Thus, we identified one of the key triggers related to the pathogenesis and severity of IBD.

The Conservative government applied restrictive immigration policies on people from the Indian sub-continent (Pakistan, India and Bangladesh) on a large scale during the 1980s for reasons which have been depicted as economic, political, and nationalistic. The Conservative party under Thatcher made immigration control one of its main themes in the 1979 Conservative Manifesto. This thesis looks at the repercussions of Thatcher's immigration policy for people from the Indian sub-continent living in Glasgow. Drawing on a wealth of primary sources, the thesis will argue that Thatcher's immigration policy amounted to discrimination as Indian sub-continent nationals, especially males, suffered unfairly when the policy was implemented. Evidence of this unfairness was implicit in: the various rules and laws which contained elements of discrimination; and evidence from the organisation network in Glasgow which revealed that they had to deal with extra work and with more contentious cases during the 1980s. The impact on individuals was most strongly exemplified by a survey and by individual case studies which revealed problems such as provocative questioning, application of stringent criteria to satisfy the authorities, and the break-up and separation of families who were prevented from being reunited, in some cases even temporarily, by the actions of the authorities. The fact is that no account was taken of the clinical characteristics of the Indian sub-continent which clashed in particular with the primary purpose rule which the authorities applied rigorously. While it is acknowledged that other groups of blacks and coloured immigrants also suffered from the Conservative immigration regime, it will be noted that the impact was most severe on immigrants from the Indian sub-continent. The tough policy on immigration only served to encourage more clandestine means of entry into the United Kingdom, and this gave the government a further pretext to impose more controls on immigration from the Indian sub continent. It has to be emphasised that the extent of the restrictive immigration control regime will be measured not simply in terms of numbers allowed entry but also the procedures used such as the type of questions asked, interviewing techniques and manners, and various provisions made in legislative acts which served against potential immigrants from the Indian sub-continent.

The motivation for this research is based on the very serious problem – local identity loss of village extensions in the Chinese ordinary villages. During the new development of Chinese ordinary villages, international concrete blocks and multi-storey apartments, which have been mass-produced in urban areas, are simply copied into rural areas replacing the local distinctive built environment. The author of this thesis set out to rethink the design principles of new urbanism in a way which can help create an urban/village extension of a town or a village to respect local identity or local context. Therefore, the research question is that ‘Can the design principles of new urbanism promote local identity or harmony with local context for urban/village extension? By reviewing the primary theories and ideas, the literature review draws upon primary sources of new urbanism including introduction and design principles which underlies a fundamental theoretical framework of design principles of new urbanism, and the overall view of the practice. Once the framework of design principles of new urbanism have been established in this research, it is essential to test it through case studies. The purpose of case studies is to identify if the design principles of new urbanism can promote local identity or harmony with local context in practice. Two UK cases, Poundbury and Upton were selected and analysed. During case studies, the interview plays an important role in modifying the design principles of new urbanism which direct the analysis of the physical environments of Poundbury and Upton. The initial outcomes are expected to confirm that the design principles of new urbanism could promote local identity or harmony with local context based on the case study findings. In order to further investigate these outcomes, factual information was collected through questionnaires administered face-to-face and on-the-spot to the residents of Poundbury and Upton. The findings of the questionnaire provided strong investigated evidence along with the initial outcomes addressed by literature review and the case studies. Finally, it can be concluded that the design principles of new urbanism are appropriate to promote local identity or harmony with local context for creating an urban/village extension. Keywords: urban/village extension, design principles of new urbanism, local identity, harmony with local context.

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This thesis examines the extent to which equal opportunity legislation has enabled employment policies that aid the development, progression and promotion among public sector employees, specifically those of Afro Caribbean origin, employed during the period between 1988 and 2004. As context, the first part of the thesis presents an historical background of the black presence in the UK and the hostility they experienced through racial discrimination. It considers how governments, politicians and social scientists viewed the social exclusion and disadvantage of ethnic minorities generally and their treatment in the labour market in particular. It also discusses relevant legislation, policies and practices that were developed to address racial discrimination. Drawing on methodologies used in research of similar nature and reviewing literature and research studies, a methodology was chosen that was appropriate for the study and a combination of quantitative and qualitative methods is used. The quantitative data presented in Chapters 7-8 is derived from responses to a questionnaire survey, supplemented by more detailed qualitative responses derived from face to face interviews with employees from participating organisations. Other methods are used only to a very limited extent to supplement the data derived from the questionnaires and interviews. Chapter 9 contains data collected from a separate exercise of a shortened questionnaire on diversity only, consisting of staff from one government department and focus groups from two business streams. The second part of the thesis presents the chosen methodology and analyses evidence collected between 1999 and 2004. Survey data, in depth one-to-one interviews and group interviews show that although progress has been made in combating racial discrimination, the policy of positive action is not a routine tool of organisational policy. An examination of employment practices and processes in the relevant organisations indicates that there exists a combination of organisational, group (subculture) and individual constraints on ethrýc minorities to rise to their full potential. The theoretical view argues that there has been a retreat from progressive equal opportunity policies in employment and this owes much to the policies of the government of the day and organisational procedures. These assumptions have been borne out empirically.

This thesis explores competing meanings of being a woman in Dakar, Senegal. Above all, it is concerned with the relationship between livelihoods – how ordinary Dakarois make ends meet – and women’s gendered identities. It explores the full spectrum of Dakar women’s economic activities, all the while keeping the definition of what, precisely, qualifies as ‘economic’ or as ‘work’ as open as possible. Distancing itself from approaches that privilege the sexual aspects of gender, this thesis asks what kinds of gendered economic identities emerge in the context of the various roles and relationships that constitute women’s everyday lives. What do women do that enables people in this society to get by and to secure their day-­‐to-­‐day needs? How are these activities experienced, and what kind of values are they imbued with? Based on three years’ fieldwork in low-­‐income neighbourhoods across the Dakar region, the thesis advances an ethnographic analysis of women’s roles as wives and girlfriends, sisters and sisters-­‐in-­‐law, daughters, mothers and grandmothers, and members of extended family and community networks. It explores women’s activities as dependents, consumers, providers and informal-­‐sector workers. Together, the chapters shed light on the complexities and contradictions involved in being a woman in this particular part of the world. Building on the ethnographic findings, this thesis argues that it is possible to identify two distinct, even competing conceptions of being a woman in Dakar. One of these can be framed in terms of ‘materialism’, the other around the emic concept of ‘mothering work’. Dakar women, this thesis suggests, draw on both in order to create, defend and challenge the meaning and the value of their everyday experiences.

The introduction of the Social Inclusion Partnership (SIP) programme in Scotland in 1999 emerged as part of policy commitment to achieving social inclusion. The significance of this policy context to the SIP programming came through the move within urban policy programmes from focusing solely on tackling urban deprivation to also target resources towards rural and coalfield areas and socially excluded groups. With this change in approach came an explicit commitment to tackling the social exclusion experienced by young people at both the neighbourhood and local authority levels. Within this policy context, this study set out to compare the approach adopted by one thematic SIP (the Big Step) and one area-based SIP (Drumchapel SIP) to promoting social inclusion for young people. Using a care study methodology, data was collected using a combination of interviews with SIP stakeholders, young people and a range of external ‘experts’, supported by analysis of SIP documents and observation of SIP meetings and other formal events. Three key themes frame the focus of this study. First, an investigation of the theoretical and policy influences steering the approach taken within the case study SIPs to achieve social inclusion for young people illustrates a clear theoretical and policy framework driving the work of the SIPs influenced by concerns to achieve social inclusion by promoting a mixture of rights and responsibilities for excluded groups. The result is an explicit programme of work to promote social integration through active participation in society and the economy. Alongside this, however, emerges an implicit concern with managing the individual and social costs of young people’s exclusion from labour market and other socially acceptable activities in order to reduce the problems associated with young people. Second, the practice of the case study SIPs was compared across three key areas: the working practices of the SIPs in responding to the agenda on ‘strategic working’; the views of respondents on the relative value of working in partnership; and the involvement of young people within the decision-making structures of the SIPs. Clear distinctions in the practices of the case study SIPs were identified. This provided an opportunity to reflect on the relative contribution made by area-based and thematic SIPs to the promotion of social inclusion for young people, and from this to review the wider applicability of the findings from the case study SIPs as the third theme of the study. Extrapolating trends emerging from the case study SIPs, the study concludes that both types of SIP contribute towards promoting the social inclusion of young people, with area-based SIPs addressing the social exclusion of young people within the wider community context and thematic SIPs foregrounding the interests of young people.

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