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Evidence points to that the prevalence of teenage pregnancies is higher within refugee camps than elsewhere. Yet little research attention has been given the subject of teenage pregnancy within refugee situations where the numbers are steadily increasing, an area that therefore needs to be explored further. This thesis is based on a qualitative field study conducted within two Burundian refugee camps in Tanzania, Nduta and Kanembwa. Semi structured interviews were conducted with both teen mothers and Non Governmental Organizations (NGOs) and Bloc leader with knowledge in the area in order to investigate the reasons for and implications of teenage pregnancy within a refugee setting. The research question is why the prevalence of teenage pregnancy is higher within a refugee context. And what can be done to empower young mothers with the knowledge and skills to protect themselves and to successfully claim their reproductive and sexual rights? The findings of the study points to that similar factors contributing to teenage pregnancy such as education, culture, poverty and unstable family relations are also applicable in a refugee situation. Conditions within refugee camps are however more extreme and the prevalence are therefore higher than in other settings. Taking a Liberal feminist standpoint based on the ideas of Amartyra Sen (1999) it is argued that the empowerment of women’s free agency and wellbeing is the key to a decline in fertility rate amongst teen mothers in refugee camps. Thus it follows that if women are to successfully claim their sexual and reproductive rights more efforts needs to be made in promoting the inclusion of women into educational and vocational activities.

Cyclic AMP (cAMP) is a second messenger that translates extracellular signals into tightly regulated biological responses. The cAMP binding domain (CBD) is a conserved regulatory switch that binds to cAMP and allosterically controls multiple cellular functions. All CBDs share a common architecture comprised of α- and β-subdomains. cAMP binds to the phosphate binding cassette (PBC) nested within the β-subdomain. In mammals the main cAMP receptors are protein kinase A (PKA), guanine exchange factors (EPAC) and ion channel proteins, including both the hyperpolarization-activated cyclic nucleotide-dependent channels (HCN channels) and the cyclic nucleotide-gated channels (CNG channels). Impaired activities of these proteins are associated with diabetes, cardiovascular diseases, cancer and Alzheimer's disease. Therefore, these proteins represent promising therapeutical targets. However, the mechanism of their cAMP-dependent allosteric control is not completely understood. In the present thesis we have studied the allosteric mechanism of activation in PKA and EPAC using an NMR-based approach and we have proposed a model explaining how cAMP allosterically controls the activity of PKA and EPAC. Binding of cAMP to the Regulatory (R) subunit of PKA facilitates the release of the Catalytic (C) subunit. According to our model, binding of cAMP triggers long range perturbations that propagate from the PBC to the R:C interface through both direct and indirect pathways. The indirect pathway involves two key relay sites located at the C-terminus of β2 (1163) and at the N-terminus of β3 (D170). D170 functions as an electrostatic switch that mediates the communication between the PBC and the helical subdomain, whereas 1163 controls the global unfolding. Hence, removal of cAMP uncouples the α- and β-subdomains by breaking the circuitry of cooperative interactions radiating from the PBC. The proposed model was further validated by the cAMP agonist Sp-cAMPS and the cAMP antagonist Rp-cAMPS. It was observed that Rp-cAMPS, in which the equatorial exocylic oxygen is replaced by sulphur, does not activate a necessary indirect allosteric pathway, while its diastereoisomer (Sp-cAMPS) with opposite phosphorus chirality behaves similarly to cAMP activating all allosteric pathways. Our data also showed that the cAMP-antagonist stabilizes a ternary inhibitory complex between the effector ligand and both the regulatory and the catalytic subunits of PKA. At this point it is still not understood how the proposed model of cAMP allostery is conserved in other cAMP binding proteins such as EPAC. EPAC is a multidomain guanine nucleotide exchange factor specific for small GTP-binding proteins and is directly activated by cAMP. We have probed how cAMP docks into the EPAC1 CBD and how its signal allosterically propagates from the cAMP binding site to the helical subdomain, which mediates the inhibitory interactions between the regulatory and catalytic regions of EPAC. Our comparative NMR investigation of cAMP signalling in PKA and EPAC revealed key functionally significant differences between these two systems that will facilitate the design of EPAC-selective therapeutics. / Thesis / Doctor of Philosophy (PhD)

To promote their desired national identity, the North Macedonian government funded the Skopje 2014 Project––an initiative including abundant statues, architectural façades, and other structures that depict Ancient Macedon as North Macedonia’s heritage. This project received copious amounts of criticism on two central fronts: first, that its allusions to Ancient Macedon are a false depiction of history; second, that its aesthetic is tacky. While valid arguments are made on each of these fronts, I argue that the latter complicates the former when analyzed in the context of North Macedonia’s precarity. In this analysis, I employ the work of Judith Butler and Liron Lavi as a theoretical backdrop to interrogate the nature of North Macedonia’s precarity. Analyzing political negotiations between North Macedonia and Greece surrounding Skopje 2014, I introduce the term persistent infelicity––a type of precarity in which the validity of an identity performance is made inaccessible for a given entity. Further, the commodification of the Ancient Macedon narrative has transformed North Macedonia’s identity performance from an iterative production to an instantaneous transaction, limiting North Macedonia’s opportunity to challenge its infelicitous state. However, I assert that the aesthetic of Skopje 2014 creates space for subversion even considering these limitations. Expanding upon the work of Susan Sontag, I identify Skopje 2014’s aesthetic as camp and delineate its function in the project as one of subversive compliance. Camp as a rhetorical tool allows North Macedonia to perform a bifurcated identity—one identity that is insincere yet appeases its international audience and another that is more authentic yet controversial directed toward an intra-national audience. While this has modestly empowering implications for Skopje 2014, this analysis concludes that the identity performance of North Macedonia has been propelled into the realm of simulacra—a realm ultimately and perilously untethered to the “real”––and prompts further consideration for other precarious nations whose identities may be fated to persistent infelicity.

The purpose of this study was to evaluate some of the achievements of the camp in furthering the social development of the campers as a means of directing future procedures used in the camp.

Vitamin D plays a vital role in modulating both innate and adaptive immune systems. Therefore, vitamin D deficiency has been associated with higher levels of autoimmune response and increased susceptibility to infections. CYP27B1 encodes a member of the cytochrome P450 superfamily of enzymes. It is instrumental in the conversion of circulating vitamin D (calcifediol) to active vitamin D (calcitriol). This is a crucial step for macrophages to express Cathelicidin Anti-microbial Peptide (CAMP), an anti-bacterial factor released during the immune response. Our recent study indicated that Crohn's disease (CD)-associated pathogen known as Mycobacterium avium paratuberculosis (MAP) decreases vitamin D activation in macrophages, thereby impeding cathelicidin production and MAP infection clearance. The mechanism by which MAP infection exerts these effects on the vitamin D metabolic axis remains elusive. In this study, we found that MAP infection interferes with vitamin D activation inside THP-1 macrophages by reducing levels of CYP27B1 and vitamin D receptor (VDR) gene expression via interaction with the TLR2-dependent p38/MAPK pathway. MAP infection exerts its effects in a time-dependent manner, with the maximal inhibition observed at 24 hours post-infection. We also demonstrated the necessity to have toll-like receptor 2 (TLR2) for MAP infection to influence CYP27B1 and CAMP expression, as TLR2 gene knockdown resulted in an average increase of 7.78±0.88 and 13.90±3.5 folds in their expression, respectively. MAP infection also clearly decreased the levels of p38 phosphorylation and showed dependency on the p38/MAPK pathway to influence the expression of CYP27B1, VDR, and CAMP which was evident by the average fold increase of 1.93±0.28, 1.86±0.27, and 6.34±0.51 in their expression, respectively, following p38 antagonism. Finally, we showed that calcitriol treatment, and p38/MAPK blockade reduce cellular oxidative stress and inflammatory markers in Caco-2 monolayers following macrophage-mediated MAP infection. In conclusion, this study characterized the primary mechanism by which MAP infection leads to diminished levels of active vitamin D and cathelicidin in CD patients, which may explain the exacerbated vitamin D deficiency state in these cases.

Thesis (M.S.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / 2999-01-01