Assessing Crosstalk Between Calcium and cAMP in Pancreatic Alpha Cells

Blood glucose levels are regulated by the interactions between insulin and glucagon. Pancreatic alpha cells release glucagon in response to a drop in blood sugar. Pancreatic alpha cells appear to be regulated through multiple signaling pathways. One potential method of regulation occurs from α-MSH or epinephrine stimulated production of the intracellular messenger cyclic AMP. Exocytosis of dense core vesicles containing glucagon ultimately requires an increase in cytosolic calcium. This study focused on the link between cyclic AMP and calcium in pancreatic alpha cells which allows alpha cell regulation. Interactions between calcium and cyclic AMP in pancreatic alpha cells consists of PKA-dependant and PKA-independent pathways. The results indicate cyclic AMP pathways control L-type voltage-gated calcium channels and also increase cytoplasmic calcium from intracellular stores. Store release appears to be through IP3 mediated pathways and not through the ryanodine-sensitive receptor

Uncovering the Podocyte Foot Process Proteome

Podocytes are highly specialized epithelial cells of the kidney glomerulus. Podocytes’ long protrusions, called foot processes, connect to each other at specialized junctions called slit diaphragms (SD), which are essential for the filtration function of the glomerulus. Glomerular breakdown primarily due to podocyte integrity loss is the most common clinical observation in kidney disease. Due in part to the inaccessibility of the SD to conventional biochemical methods, only a small number of proteins are known to localize to the SD. We hypothesize that unidentified components of the slit diaphragm are integral to podocyte integrity and kidney function. Proximity-Dependent Biotin Identification (BioID) was used to determine proteins associated with endogenous podocin/NPHS2, a well-documented SD protein. We identified an Immunoglobulin-like domain-containing receptor 2 (Ildr2) and a Formin-binding protein 1-like (Fnbp1l) as two novel proteins of the podocyte foot process. Recent data from sc-RNAseq databases suggest that Ildr2 is expressed in human podocytes, localizes in the SD, and plays a crucial role in podocyte integrity. Ongoing work aims to test the importance of these factors in vertebrate kidney function. By investigating the cellular role of SD proteins such as Ildr2 and Fnbp1l, we can better understand the causes of renal disease at the molecular level.Bachelor of Scienc

Rare Case of Pediatric Post-transplant Lymphoproliferative Disorder Presenting with Pleural Masses Complicated by Pleural Effusions

Post-transplant lymphoproliferative disorder is a complication in organ transplant recipients characterized by uncontrolled proliferation of B-lymphocytes, occurring in 6% of pediatric patients, with risk factors including primary Epstein-Barr virus infection, intensity of immunosuppression, and cytomegalovirus infection. The clinical symptoms are often nonspecific, and it is associated with a high mortality rate if left untreated. We describe a rare case of post-transplant lymphoproliferative disorder who presented with pleural-based masses resulting in pleural effusions

The United Nations and the Question of Palestine: A Study in International Legal Subalternity

As one of the longest running disputes on the United Nations agenda, the conventional wisdom holds that the UN’s position on the question of Palestine offers the only normative basis of a just and lasting peace between Israelis and Palestinians grounded in international law. Contrary to this position, this dissertation argues that there has been a continuing though vacillating gulf between the requirements of international law and the position of the UN, which has inevitably frustrated rather than facilitated the search for a just and lasting peace. To this end, the research examines a number of areas in which the UN has assumed a leading role in the question of Palestine since 1947. It critically explores the tensions that exist between the positions adopted by the Organization on the one hand, and various requirements of prevailing international law on the other. If the UN has failed to respect the normative framework of international law in its management of the question of Palestine, what forms has this taken? How long has it persisted? What are the implications, not only on the Palestinian people – whose contemporary leadership has long had faith in the UN as the forum within which their international legal entitlements must be pressed – but also on the Organization itself? By addressing these questions, the research critically interrogates the received wisdom regarding the UN’s fealty to the international rule of law, in favour of what more accurately might be described as an international rule by law. It demonstrates that through the actions of the Organization, Palestine and its people have been committed to a state of what the author calls International Legal Subalternity, according to which the promise of justice through international law has been repeatedly proffered under a cloak of political legitimacy furnished by the international community, but its realization interminably withheld.Social Sciences and Humanities Research Council of Canad

Comparison of Two Lipid Emulsions on the Incidence of Parenteral Nutrition Associated Cholestasis in Neonates

OBJECTIVE: Lipid emulsion contributes to parenteral nutrition associated cholestasis (PNAC). For decades, soybean oil-based intravenous lipid emulsion (SO-ILE) was the predominant product. Recently, a multicomponent lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil and fish oil (SMOF-ILE) has been used off-label in neonatal care. This study evaluates the incidence of PNAC in neonates who received SMOF-ILE or SO-ILE. METHODS: This was a retrospective review of neonates who received SMOF-ILE or SO-ILE for at least 14 days. Patients receiving SMOF-ILE were matched based on gestational age (GA) and birth weight to a historical cohort receiving SO-ILE. The primary outcomes were the incidences of PNAC among all patients and patients without intestinal failure. The secondary outcomes were clinical outcomes and incidence of PNAC stratified by GA. Clinical outcomes included liver function tests, growth parameters, and development of retinopathy of prematurity and intraventricular hemorrhage. RESULTS: Forty-three neonates who received SMOF-ILE were matched to 43 neonates who received SOILE. There were no significant differences in baseline characteristics. The incidence of PNAC in the total population was 12% in the SMOF-ILE cohort and 23% in the SO-ILE cohort (p = 0.26). The lipid dosage of SMOF-ILE was significantly higher at time of peak direct serum bilirubin concentration compared with SO-ILE cohort (p = 0.05). Clinically significant differences were noted in laboratory endpoints in several subgroups. CONCLUSIONS: There was no significant difference in the incidence of PNAC among neonates in a SMOFILE cohort compared with a historical SO-ILE cohort