There are four mammalian SSB proteins (SSB-1 to -4), and these are characterized by a C-terminal SOCS box and central SPRY domain. The C-terminal SOCS box was first observed in proteins that were found to act as Suppressors of Cytokine Signalling and function by virtue of their SH2 domain. Other families containing the SOCS box motif were defined by the domains N-terminal to this, such as the ASBs (Ankyrin repeats), WSBs (WD40 repeats) and of course the SSBs (SPRY domains). This thesis describes a very broad investigation of the SSBs, a protein family about which very little was known. To begin with, functional investigation into the evolution of this family and analysis of murine SSB expression patterns was performed. This highlighted that the family was highly conserved and had differential expression in the mouse, suggestive of important, unique functional roles for the individual family members. The majority of work in the thesis then proceeds in three directions; (i) analysis of the SSB proteins in vivo, with genetic deletion of SSB-2 in the mouse, (ii) biochemically, with analysis of SSB binding partners, and (iii) structurally, with functional analysis of the structure of SSB-2.

In the 1960s, Irene Spry served as the Federated Women's Institutes of Canada (FWIC) representative to the Associated Country Women of the World (ACWW). In 1967 she accepted an offer to be the ACWW deputy president, a post that she held until the mid-1970s. During this time, the ACWW and its member societies engaged in international development efforts around the world. This was a critical moment in the history of international development. The Canadian movement for development was propelled by domestic and global politics, as well as a changing society that embraced a sense of global citizenship. Arising out of this context and armoured with her own socialist politics, Spry carefully navigated the development efforts of the ACWW. These efforts straddled grassroots ideals and mainstream pressures from the United Nations (UN). As a women's Non-Governmental Organization (NGO), the ACWW was part of the initial force behind the global shift in the approach to development referred to as Women in Development (WID). Contemporary research, however, suggests that WID has not succeeded in addressing the concerns of women in "developing" countries. As a case study, this paper examines some of the historical roots of WID and identifies the historical continuities that persist in today's development discourse. Analyzing Spry's documents from the Library and Archives Canada through the lens of feminist postcolonial theory reveals the dominance of Eurocentric ideologies within the development practices of the ACWW. The impetus to reach out to help people in developing countries became socially and politically part of the Canadian identity and, as Spry's navigation through the discourses of the international agencies and ACWW members reveal, such sentiments of international benevolence were inherently neo-colonial. In much the same way that Himani Bannerji suggests that subjects are "invented," women involved in this movement intersected discourses of modernity and "race" with essentializing notions of gender, which contributed to a standardized practice of development. This case study ultimately demonstrates that good intentions were not enough to decolonize western women's efforts to "develop" parts of Africa in the late 1960s and early 1970s.

In the 1960s, Irene Spry served as the Federated Women's Institutes of Canada (FWIC) representative to the Associated Country Women of the World (ACWW). In 1967 she accepted an offer to be the ACWW deputy president, a post that she held until the mid-1970s. During this time, the ACWW and its member societies engaged in international development efforts around the world. This was a critical moment in the history of international development. The Canadian movement for development was propelled by domestic and global politics, as well as a changing society that embraced a sense of global citizenship. Arising out of this context and armoured with her own socialist politics, Spry carefully navigated the development efforts of the ACWW. These efforts straddled grassroots ideals and mainstream pressures from the United Nations (UN). As a women's Non-Governmental Organization (NGO), the ACWW was part of the initial force behind the global shift in the approach to development referred to as Women in Development (WID). Contemporary research, however, suggests that WID has not succeeded in addressing the concerns of women in "developing" countries. As a case study, this paper examines some of the historical roots of WID and identifies the historical continuities that persist in today's development discourse. Analyzing Spry's documents from the Library and Archives Canada through the lens of feminist postcolonial theory reveals the dominance of Eurocentric ideologies within the development practices of the ACWW. The impetus to reach out to help people in developing countries became socially and politically part of the Canadian identity and, as Spry's navigation through the discourses of the international agencies and ACWW members reveal, such sentiments of international benevolence were inherently neo-colonial. In much the same way that Himani Bannerji suggests that subjects are "invented," women involved in this movement intersected discourses of modernity and "race" with essentializing notions of gender, which contributed to a standardized practice of development. This case study ultimately demonstrates that good intentions were not enough to decolonize western women's efforts to "develop" parts of Africa in the late 1960s and early 1970s.

In the 1960s, Irene Spry served as the Federated Women's Institutes of Canada (FWIC) representative to the Associated Country Women of the World (ACWW). In 1967 she accepted an offer to be the ACWW deputy president, a post that she held until the mid-1970s. During this time, the ACWW and its member societies engaged in international development efforts around the world. This was a critical moment in the history of international development. The Canadian movement for development was propelled by domestic and global politics, as well as a changing society that embraced a sense of global citizenship. Arising out of this context and armoured with her own socialist politics, Spry carefully navigated the development efforts of the ACWW. These efforts straddled grassroots ideals and mainstream pressures from the United Nations (UN). As a women's Non-Governmental Organization (NGO), the ACWW was part of the initial force behind the global shift in the approach to development referred to as Women in Development (WID). Contemporary research, however, suggests that WID has not succeeded in addressing the concerns of women in "developing" countries. As a case study, this paper examines some of the historical roots of WID and identifies the historical continuities that persist in today's development discourse. Analyzing Spry's documents from the Library and Archives Canada through the lens of feminist postcolonial theory reveals the dominance of Eurocentric ideologies within the development practices of the ACWW. The impetus to reach out to help people in developing countries became socially and politically part of the Canadian identity and, as Spry's navigation through the discourses of the international agencies and ACWW members reveal, such sentiments of international benevolence were inherently neo-colonial. In much the same way that Himani Bannerji suggests that subjects are "invented," women involved in this movement intersected discourses of modernity and "race" with essentializing notions of gender, which contributed to a standardized practice of development. This case study ultimately demonstrates that good intentions were not enough to decolonize western women's efforts to "develop" parts of Africa in the late 1960s and early 1970s. / Arts, Faculty of / History, Department of / Graduate

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The present thesis project focused on the preclinical study of Neurotensin receptor 1 (Ntsr1), Endoglin/CD105 (Eng), Glypican 6 (Gpc6) and Sprouty homolog 4 (Spry4) as potential markers or molecular targets for future therapeutic interventions of gastrointestinal stromal tumors (GIST). Ntsr1 expression was characterized was reported in a paper that I co-authored entitled “Neurotensin receptor 1 is expressed in gastrointestinal stromal tumors but not in interstitial cells of Cajal.” by Gromova et al. PLOS ONE, 2009. As radio-labeled NTSR1 ligand analogues have already been reported for whole-body imaging and therapeutic interventions, prompting us to investigate NTSR1 as a target for in vivo imaging of GIST.Next, expression of Eng was characterized in the KitK641E murine GIST model, human GIST, GIST882 and BaF3 cells. This study has been reported in “Endoglin/CD105 is expressed in KIT positive cells in the gut and gastrointestinal stromal tumors” by Gromova et al. JCMM, 2011, a paper I co-authored. As result, an American start-up approached us to assess their proprietary compound targeting ENG on GIST882 cells. However, concerns were raised about possible non-selective action and the project was stalled by the company.Subsequently, GIST tissue microarrays were examined by immunohistochemistry using the sole commercially available GPC6 antibody. No statistical correlation could be found between GPC6-ir and GIST clinic-pathological features and concerns were raised about the reliability of the GPC6 antibody used. Ultimately, Spry4 was investigated in the last part of my thesis. In vitro, we have demonstrated that Spry4 is specifically upregulated by the ERK pathway in GIST882 cells. In vivo, Spry4 deficient mice showed an ICC hyperplasia in antrum and colon, using a new ICC quantification method developed in the lab, which was reminiscent of the oncogenic GIST murine model KitK641E. Similarities between Spry4 KO and KitK641E heterozygous animals were even further emphasized by functional studies, as both genotypes showed a delay in transit time. This study lead to the publication “Hyperplasia of interstitial cells of Cajal in Sprouty homolog 4 deficient mice” by Thys et al. 2015, PLOS ONE. / Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) / info:eu-repo/semantics/nonPublished

This study examines some of the ways in which Second World War veterans helped shape Canadian society in the years after 1945 by using the life experience of one of their number, Major-General Daniel Charles Spry, as an interpretive model. Just over one million Canadian men and women re-entered civil life after their wartime military service. Representing approximately 35 per cent of Canada’s adult male population aged 25 to 49 in 1951, and found in nearly every facet of Canadian life, Second World War veterans possessed social importance that extended far beyond their experience of the Veterans Charter. Using Dan Spry’s documented thoughts and actions in war and peace, this study argues that a number of these individuals learned lessons regarding leadership, character, citizenship, and internationalism during their wartime military service and – finding them useful – applied such lessons to various aspects of their lives after the war’s end. In so doing, Second World War veterans helped to influence the character of postwar Canada’s institutions, workplaces, and the lives of many Canadians by providing societal leadership, moulding children’s character, developing future citizens, and trying to build a better world. Appreciating their varied contributions provides new insight into both veterans’ attitudes and the sort of place that Canada was after the guns fell silent in 1945.