p53 Regulates the Formation of Lamellipodia and Circular Dorsal Ruffles Through Caldesmon and PTEN

Vascular smooth muscle cell migration is a significant contributor to many aspects of heart disease, and specifically atherosclerosis. Tissue damage in the arteries can result in the formation of a fatty streak. Smooth muscle cells (SMC) can then migrate to this site to form a fibrous cap, stabilizing the fatty plaque. Since cardiovascular disease is the leading cause of death in developed countries, this function of SMC is an essential area of study. The formation of lamellipodia and circular dorsal ruffles were studied in this project as indicators that cell migration is occurring. The roles of the proteins p53, Rac, caldesmon and PTEN were investigated with regards to these actin-based structures. The tumour suppressor p53 is often reported to cause apoptosis, senescence or cell cycle arrest when stress is placed on a cell, but has recently been shown to regulate cell migration as well. It was determined in this project that p53 could inhibit the formation of both lamellipodia and circular dorsal ruffles. It was also shown that this could occur directly through an inhibition of the GTPase Rac. Previous studies have shown that p53 can upregulate caldesmon, a protein which is known to bind to and stabilize actin filaments while inhibiting Arp2/3-mediated branching. It was confirmed that p53 could upregulate caldesmon, and that caldesmon could inhibit the formation of lamellipodia and circular dorsal ruffles. The phosphorylation of caldesmon by p21-associated kinase (PAK) or extracellular signal-related kinase (Erk) was shown to effectively reverse the ability of caldesmon to inhibit these structures. The role of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was also studied with regards to this signalling pathway. PTEN was shown to inhibit lamellipodia and circular dorsal ruffles through its lipid phosphatase activity. It was concluded that p53 can inhibit the formation of lamellipodia and circular dorsal ruffles in vascular SMC, and that this occurs through Rac, caldesmon and PTEN.

Breaking New Ground: The First Generation of Women to Work as Professional Authors in English Canada (1880-1920)

In the later decades of the nineteenth century and the early decades of the twentieth, large numbers of Canadian women were stepping out of the shadows of private life and into the public world of work and political action. Among them, both a cause and an effect of these sweeping social changes, was the first generation of Canadian women to work as professional authors. Although these women were not unified by ideology, genre, or date of birth, they are studied here as a generation defined by their time and place in history, by their material circumstances, and by their collective accomplishment. Chapters which focus on E. Pauline Johnson (Tekahionwake), the Eaton sisters (Sui Sin Far and Onoto Watanna), Joanna E. Wood, and Sara Jeannette Duncan explore some of the many commonalities and interrelationships among the members of this generation as a whole. This project combines archival research with analytical bibliography in order to clarify and extend our knowledge of Johnson’s and Duncan’s professional lives and publishing histories, and to recover some of Wood’s “lost” stories. This research offers a preliminary sketch of the long tradition of the platform performance (both Native and non-Native) with which Johnson and others engaged. It explores the uniquely innovative ethnographic writings of Johnson, Duncan, and the Eaton sisters, among others, and it explores thematic concerns which relate directly to the experiences of working women. Whether or not I convince other scholars to treat these authors as a generation, with more in common than has previously been supposed, the strong parallels revealed in these pages will help to clarify and contextualize some of their most interesting work.