RET is a transmembrane receptor that is implicated in a variety of processes such as cell proliferation, differentiation, migration, survival, and death. One of the proteins that is activated downstream of RET is the guanine nucleotide exchange factor (GEF), BetaPIX. BetaPIX removes GDP bound to inactive Cdc42/Rac, freeing a space for GTP-binding and transformation of Cdc42/Rac to the active GTPase state. BetaPIX is vital in cytoskeletal rearrangements and the regulation of focal adhesion complex assembly and disassembly. Although our lab has previously shown that RET and BetaPIX do not directly interact, the mechanism through which BetaPIX is activated downstream of RET is not yet known. In the current study, we confirmed that RET activation mediates BetaPIX phosphorylation. We showed that mutations in the SH3 and Dbl-homology domains of BetaPIX result in slower rates and in some cases impairment of wound healing and cell migration downstream of RET, indicating a role for BetaPIX in RET-mediated cell migration. In contrast, we have shown that GTPase mutants of Cdc42 and Rac were not sufficient to impair wound healing, but did result in less cell migration. This suggests that similar, yet distinct roles exist for Cdc42 and Rac in the regulation of cytoskeletal dynamics. We have shown that SH3 and Dbl-homology domain mutations in BetaPIX result in changes in cell morphology, suggesting a role of BetaPIX in the development of cell extensions downstream of RET. Alternatively, we have shown that GTPase mutants of Cdc42 or Rac alone do not induce cell morphology changes, further emphasizing the similar, yet distinct roles for Cdc42 and Rac in RET-mediated cell migration. Lastly, we have shown that BetaPIX is re-localized from the focal adhesion to the cytoplasm upon RET activation, suggesting that following focal adhesion complex formation, BetaPIX may be recycled. / Thesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2009-09-23 13:05:57.86

Recently, a chronic idiopathic disease of the esophagus has emerged, which is now known as eosinophilic esophagitis (EoE). Incomplete knowledge regarding the pathogenesis of EoE has limited treatment options. EoE is known to be a Th2-type immune-mediated disorder. Based on previous studies in both patients and experimental models, it is possible that an abnormal reaction to antigen mediates the pathophysiology of EoE. In this thesis, symptoms and signs unique to EoE were identified by an age-matched, case-controlled study of 326 patients with EoE and gastroesophageal reflux disease. The molecular mechanisms involved in antigen detection in the esophagus, in relation to EoE were then investigated. Esophageal epithelial cells were found, for the first time, to be capable of acting as non-professional antigen presenting cells, with the ability to engulf, process and present antigen on MHC class II to T helper lymphocytes. Antigen presentation by esophageal epithelial cells was induced by interferon-γ, which is increased in biopsies from patients with EoE. Next, it was discovered that esophageal epithelial cell lines expressed functional toll-like receptor (TLR) 2 and TLR3, but in esophageal mucosal biopsies only infiltrating immune cells (including eosinophils) expressed TLR2 and TLR3. Finally, the potential involvement of IgE in the pathogenesis of esophageal inflammation was investigated. IgE in the esophagus was found to be present on mast cells, which are increased in density in the esophageal mucosae of patients with EoE and especially those with a history of atopy. Mechanisms of antigen detection may mediate the pathophysiology of EoE in the esophagus through antigen presentation by epithelial cells, detection by TLRs on immune cells and detection through IgE on mucosal mast cells. Together, these findings demonstrate that mechanisms of antigen detection may actually contribute to the pathophysiology of EoE. Through increased understanding of the mechanisms of EoE, the results of this thesis may contribute to future therapy. / Thesis (Ph.D, Anatomy & Cell Biology) -- Queen's University, 2011-06-27 14:07:03.348

Venturia inaequalis (Cke.) Wint. is the incitant of apple scab, a disease of great economic importance throughout the world. This pathogen, in the early stages of infection, is confined to the area between the cuticle and the epidermis of the host and thrives there in intimate contact with these layers. This rather peculiar growth habit seems to indicate that lipids might have an important role in determining the host specificity and the pathogenicity of V. inaequalis. [...]

Cercospora beticola Sacc. is a necrogenic pathogene which produces brown small nearly circular spots on the foliage of table beets, sugar beets, mangolds and Swiss chard. On beet leaves the spots have a reddish-purple border, while on mangolds there is usually a pale green border around each spot. The center of the spot is grayish due to long septate conidia produced on conidiophores which come out through the stomata.

The so-called age of antibiotics is generally considered to be of recent origin but the foundation of its beginning goes back to the last century. The phenomenon of antibiosis, the production by one organism of a specific chemical substance or substances which have an injurious effect upon another organism, was noticed by many of the early microbiologists. Although Tyndall, Pasteur, and DeBary worked in different fields of biology, each mentioned this phenomenon of antibiosis in his writings.

Red clover (Trifolium pratense L.) is one of the most important and most widely grown cultivated legumes in Canada. The early flowering varieties are the most popular in the clover growing areas of Quebec, Ontario and the Maritime provinces because they are able to make a rapid recovery after the first cutting. Red clover is subject to numerous diseases and insects, some of which cause severe injury to the plant, while others inhibit plant growth and thus reduce the yield or quality of the bay.

Wheat, an important food crop of the world, suffers from a number of diseases which cause a heavy loss to the growers every year. Stem rust (Puccinia graminis tritici Eriks. and Henn.) is one of these serious diseases and it often occurs in an epiphytotic form. It is a common observation that some wheat varieties are very susceptible to a particular rust race and are sometimes completely destroyed while other varieties prove to be resistant. The knowledge of these facts led plant pathologists to realise the importance of resistant varieties and to study the nature of resistance to this disease.

Disease resistance in a plant is a manifestation of a complex phenomenon which involves among other things, the inherent and acquired physiologic properties of not only the host but also those of the pathogen influenced by ever-changing conditions of both the macro- and micro-environment.

The study of various aspects of the wilt diseases of plants which are caused by fungi inhabiting the vascular systems of the host plants has engaged the attention of a number of research workers for over half a century. Various theories have been proposed to explain the wilt symptoms in several species of plants, yet none can be considered to fully explain how the fungus in the vascular elements causes the plant to become diseased and die. The wilt disease caused by Fusarium oxysporum f. lycopersici (Sacc.) Snyder & Hansen is specific to the tomato, Lycopersicon app.

Autoradiograms of plants which had one of their leaves (presentation leaf) photosynthesizing in C14O2 show high concentration of radioactivity in the growing point and roots and low concentration in leaves below the presentation leaf. Infection on two of these lower leaves increases the concentration of radioactivity in them, especially around lesions, but has no marked and consistent effect on the concentration in other organs. Infection on the presentation leaf reduces photosynthesis and export of C14 to other parts. Heat girdling of petioles of healthy and infected leaves show that in both cases, C14 export takes place through phloem and its import through xylem. Radioactivity in detached leaves exposed to C14O2 , either in light or in darkness, is uniformly distributed in healthy leaves, but accumulates around lesions in diseased ones. Starch has similar distribution. Pathological increase in transpiration and metabolic activity are probably responsible for the altered cl4 distribution in diseased leaves.