ROLE OF MICRORNA LET-7 IN PANCREATIC BETA CELLS

MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression at transcriptional or post-transcriptional level. Let-7 family is among the first identified human miRNAs and regulates multiple cellular processes including glucose metabolism in multiple organs. It has been reported that overexpression of let-7 resulted in insulin resistance and impaired glucose tolerance through repressing insulin signaling pathway in both muscle and liver. However, the role and mechanism underlying let-7 function in pancreatic beta-cells have yet to be elucidated. Let-7 family contains nine members, which poses a significant challenge in complete deletion of this miRNA family. To study the function of let-7 and to overcome the functional redundancies of various let-7 members in pancreatic beta-cells, the highly expressed let-7a and let-7b were blocked simultaneously using short tandem target mimic (STTM) approach developed in our laboratory. Introducing STTM-let7 into beta-cells markedly increased the expression of Caspase 3, a direct target of let-7, confirming a sufficient functional knockdown of let-7a/b by STTM-let7. STTM-let7 enhanced apoptotic cell death induced by cytokine, indicating that let-7a/b is able to protect from apoptosis through attenuating Caspase 3 expression in pancreatic beta-cells. In contrast to the previous observation that let-7 silencing increases insulin signaling in muscle and liver, inhibition of let-7 with STTM-let7 significantly repressed glucose-stimulated insulin signaling in pancreatic beta-cells, leading to impaired insulin secretion and reduced beta-cell proliferation. Taken together, an appropriate level of let-7 is essential in maintaining beta-cell function and viability. Dysregulation of let-7 may contribute to the pathogenesis of type 2 diabetes.

THE CELEBRITY BURDEN: CELEBRITY CAMPAIGNS IN THE PURSUIT OF HUMANITARIANISM

Celebrity participation in humanitarianism and politics has received a lot of attention in recent times. Though many researchers have sought to explain the reasons underlying this phenomenon, there appears to be little information as to the efficacy of these celebrity efforts. The present research thus undertakes an analysis of the celebrity's participation through a study on the effectiveness of the celebrity-led campaign. To achieve this, I conduct a discourse and visual analysis of media publications surrounding two celebrity-led campaigns. The research leans heavy on theories underlining the celebrity mechanism and Street et al's framework on celebrity participation in politics. The study confirms Street et al's argument that performance, legitimacy and organization are central to the success of the celebrity-led campaign. For campaigns aimed at initiating policy change, I propose an additional category of stakeholders' response which provides a means of evaluating efficacy. My findings show that organization, legitimization, stakeholders' response and performance are highly dependent on the actions of the lead celebrity, making these celebrities active agents in the production of discourse on the "third world". As celebrities engage in humanitarian work, they take up positions as representatives of the aid recipient. The result is the dispossession and silencing of the aid recipient. Out of my discussion of these practices evolves the concept of the celebrity burden.