The contemporary emergence of payday lending as a major source of high-cost short-term credit for credit-constrained populations has prompted debates among government officials, business representatives, advocacy groups and academics over how best to regulate the industry. Such debates typically focus on the prevailing lending practices and interest charges in the industry. While critics associate these with usury, supporters of payday lenders defend them as appropriately priced responses to market demand. This dissertation seeks to contextualize, and contribute to a deeper understanding of, the terms of these debates through an exploration of the recently concluded political exercise in Canada where responsibility for the governance of payday lending has been shifted from the federal government, with its criminal law power over usury, to provincial governments with their various regulatory powers over licensing and consumer protection. The dissertation begins with the observation that there are competing moral discourses about money and interest simultaneously embedded in the financial policy-making process in Canada, a fact that has complicated regulatory efforts aimed at payday lending. While these efforts have largely been informed by varying assessments of the transparency and competiveness of the payday lending market, this dissertation contends that a conceptually more useful way of understanding this market is to study the organizational and marketing strategies employed by payday lenders to indentify and retain a stable customer base, and the reciprocal moves on the part of customers to improve upon their terms of trade. In detailing the political process which culminated in a new regulatory regime for payday lending, this dissertation draws on the “regulation through networks” literature to help explain its progress. A major contribution this dissertation makes to this explanatory approach is in its emphasis on the dual legitimation imperatives with which the network actors had to contend as they negotiated their way to a consensus on a politically acceptable regulatory structure for payday lending. This consensus has proved to be politically vulnerable because of the continuing normative conflicts embedded in official financial policy discourse, and inter alia, in the legitimation imperatives which have permeated the policy-making process.

The trophoblast transcription factor glial cell missing-1 (GCM1) regulates asymmetric division of placental cytotrophoblast to form the differentiated syncytiotrophoblast. Reduced GCM1 expression is a key feature of the hypertensive disorder preeclampsia. In-silico techniques identified a novel calcium-dependent transcriptional repressor – DREAM as a regulatory candidate for GCM1. The overall objective of this thesis was to determine if DREAM regulates GCM1 expression and therefore villous trophoblast turnover. siRNA-mediated DREAM silencing in both BeWo cells and floating villous explants significantly upregulated GCM1 causing reduced cytotrophoblast proliferation. Calcium-dependency was demonstrated in both BeWo cells and floating villous explants by contrasting the effects of ionomycin and nimodipine. A direct interaction between DREAM and the GCM1 promoter was demonstrated using EMSA and ChIP assay. DREAM is a negative upstream regulator of GCM1 expression in human placenta that participates in calcium-dependent trophoblast differentiation.

The mechanisms that regulate the activity of the neuron specific K+Cl- cotransporter (KCC2) remain poorly understood, despite the critical importance of this transporter in inhibitory synaptic transmission and plasticity. In this thesis I made three novel discoveries which reveal the cellular and molecular mechanisms of KCC2 regulation. First, I assayed the K+Cl- cotransport function of KCC2 under isotonic conditions and determined the molecular domain of the cotransporter required for constitutive Cl- transport in hippocampal neurons (Acton et al 2012). Specifically, I identified the 15 amino acid domain of the C-terminus in neurons that is responsible for the ability of KCC2 to cotransport K+Cl- under basal isotonic conditions, allowing it to remain constitutively active to create the steep Cl- gradient across the neuronal membrane required for synaptic inhibition. Secondly, I investigated a novel KCC2-interacting protein named Neto2 and determined its effect on the postsynaptic action of GABA (Ivakine et al 2013). I have found that Neto2, which is also an auxiliary protein of kainate-type ionotropic receptors, can also regulate the activity of the KCC2. Neto2 is required for neurons to maintain low [Cl-]i and strong synaptic inhibition. Third, I examined the functional relevance of the KCC2:Neto2:KAR multiprotein complex and found that this complex regulates the surface level membrane expression pattern of KCC2 and the stability of the cotransporter in the membrane. Moreover, I have provided the first evidence that the interactions of KCC2:Neto2:GluK2 regulate KCC2 via a PKC-mediated phosphorylation of the cotransporter. Taken together, these results resolve three novel mechanisms of KCC2 regulation: the identity of the key C-terminal domain of KCC2 required for isotonic transport, the functional significance of the KCC2:Neto2 interaction, and the mechanism by which the KCC2:Neto2:KAR complex regulates KCC2 expression and mobility in the neuronal membrane.

Thesis (M.S.)--University of Hawaii at Manoa, 2006. / Includes bibliographical references (leaves 83-86). / x, 86 leaves, bound ill. 29 cm

Identification and characterization of regions influencing the precise spatial and temporal expression of genes is critical to our understanding of gene regulatory networks. Connecting transcription factors to the cis-regulatory elements that they bind and regulate remains a challenging problem in computational biology. The rapid accumulation of whole genome sequences and genome-wide expression data, and advances in alignment algorithms and motif-finding methods, provide opportunities to tackle the important task of dissecting how genes are regulated. Genes exhibiting similar expression profiles are often regulated by common transcription factors. We developed a method for identifying statistically over-represented regulatory motifs in the promoters of co-expressed genes using weight matrix models representing the specificity of known factors. Application of our methods to yeast fermenting in grape must revealed elements that play important roles in utilizing carbon sources. Extension of the method to metazoan genomes via incorporation of comparative sequence analysis facilitated identification of functionally relevant binding sites for sets of tissue-specific genes, and for genes showing similar expression in large-scale expression profiling studies. Further extensions address alternative promoters for human genes and coordinated binding of multiple transcription factors to cis-regulatory modules. Sequence conservation reveals segments of genes of potential interest, but the degree of sequence divergence among human genes and their orthologous sequences varies widely. Genes with a small number of well-distinguished, highly conserved non-coding elements proximal to the transcription start site may be well-suited for targeted laboratory promoter characterization studies. We developed a “regulatory resolution” score to prioritize lists of genes for laboratory gene regulation studies based on the conservation profile of their promoters. Additionally, genome-wide comparisons of vertebrate genomes have revealed surprisingly large numbers of highly conserved non-coding elements (HCNEs) that cluster nearby to genes associated with transcription and development. To further our understanding of the genomic organization of regulatory regions, we developed methods to identify HCNEs in insects. We find that HCNEs in insects have similar function and organization as their vertebrate counterparts. Our data suggests that microsynteny in insects has been retained to keep large arrays of HCNEs intact, forming genomic regulatory blocks that surround the key developmental genes they regulate.

NKT cells are a population of T cells that have a broad range of regulatory effects on the immune system. Somewhat paradoxically, they can both suppress and potentiate cell-mediated immune responses; for example, while they can suppress some autoimmune diseases, they can also promote potent tumour rejection. There is accumulating evidence to suggest that this functional dichotomy can be explained by the existence of functionally distinct NKT cell subsets, which can differentially regulate the behaviour of other immune cells and drive remarkably different outcomes in disease settings. / Studies in vivo and in vitro have demonstrated remarkable functional diversity between NKT cell subsets of different phenotypes, and deriving from different tissues. This thesis examined functional differences between NKT cell subsets in the context of type 1 diabetes in NOD mice, identified a phenotypically and developmentally distinct IL-17 producing NKT cell subset, and investigated the functional effects of thymic NKT cells on the development and maintenance of conventional T cells and thymic stromal cells. The data presented in this thesis adds to the accumulating evidence that NKT cells are a functionally heterogeneous population, and reiterates the important point that subsets of NKT cells should be studied separately in order to properly understand the biological function of this important regulatory T cell population, and to maximise their clinical potential.

Thesis (Ph. D.)--University of Adelaide, Dept. of Biochemistry, 1987. / Includes bibliographical references.

Thesis (M.S.) -- Worcester Polytechnic Institute. / Keywords: gene function and regulation; splicing; apobec3; genetics. Includes bibliographical references (p. 55-58).

Universiẗat, Diss., 2007--Giessen.

Thesis (Ph. D.)--University of Hong Kong, 2007. / Also available in print.