Browsing by Author "Yates, Robin Michael"

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    Engineering Integrity: Using text-matching software in a graduate level engineering course
    (2019-04-18) Crossman, Katie; Paul, Robyn; Behjat, Laleh; Trifkovic, Milana; Fear, Elise C.; Eaton, Sarah Elaine; Yates, Robin Michael
    Academic misconduct is an unfortunate reality for many post-secondary level educators across disciplines; however, there is currently a paucity of Canadian research on Academic Integrity (Eaton, 2018). This study describes an inter-disciplinary project to investigate the potential for text-matching software to prevent and avoid plagiarism by graduate level engineering students. Conceptual/Theoretical Framework: Our study was informed by the potential for text-matching software to help students understand and avoid plagiarism (Zaza & McKenzie, 2018) and faculty identify instances of plagiarism in an engineering course (Cooper & Bullard, 2014). Although text-matching software has been commercially available since the 1990s, its acceptance within academic contexts is uneven. Reasons for this are manifold, but the most commonly expressed concerns are about a) the punitive nature of the software use; b) the potential for it to be used as a tool for cheating students to “beat the system”, and c) privacy concerns (Savage, 2004). Methodology / Approach: In this project, approved by the institutional REB, assignments submitted in a graduate-level engineering communication course were analyzed using text-matching software, Ithenticate. The first phase of the study involved collecting baseline data from students enrolled in a graduate-level Engineering course (N=132). As per REB protocol, individual results were not shared with the professor or teaching assistants and sharing of aggregated results is not permitted until after February 15, 2019. In our presentation, we share baseline results, as well as outcomes of the second phase of the research, in which the research associate revealed the deception, explained the study, and solicited consent from students to have their next assignment harvested and analyzed. The research associate also introduced the software and provided a workshop on academic integrity including strategies for avoiding plagiarism, such as paraphrasing. Subsequent to these workshops, assignments written by consenting participants were analyzed with Ithenticate to determine whether a reduction in textual similarity occurred. Results / Findings: The results of this study indicate that text-matching software can be useful to students and educators to prevent and identify academic misconduct. This study will add to the growing body of empirical research about academic integrity in Canada and in particular, in engineering contexts.
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    Entamoeba histolytica-Induced Caspase-4 Activation Regulates IL-1β Secretion Through Caspase-1
    (2018-04-27) Quach, Jeanie; Chadee, Kris C.; McCafferty, Donna-Marie; Yates, Robin Michael
    Entamoeba histolytica (Eh) is the causative agent of amebiasis, one of the top four parasitic causes of mortality worldwide. In 90% of infected individuals, Eh harmlessly colonizes the large intestine and results in a non-invasive and asymptomatic infection. In the remaining 10% of infected individuals, the parasite breaches the intestinal barrier causing amebic colitis and in rare cases, it can cause extra-intestinal lesions, mainly liver abscesses. During invasion, Eh encounter macrophages in the lamina propria and this intricate host-parasite interaction is critical in eliciting a tissue damaging raging pro-inflammatory response. When Eh binds macrophages via the Gal-lectin, surface EhCP-A5 ligates α5β1 integrin to activate caspase-1 in a complex known as the NLRP3 inflammasome. In this study, we investigated the parasite requirements underlying macrophage caspase-4 and -1 activation and the role caspase-4 play in augmenting pro-inflammatory cytokine responses. Surprisingly, caspase-4 activation was similar to caspase-1 requiring live Eh attachment via the Gal-lectin, EhCP-A5 and cellular stresses such as K+ efflux and ROS. However, unlike caspase-1, caspase-4 activation was independent of ASC and NLRP3. Using CRISPR/Cas9 gene editing of caspase-4 and caspase-1 in human macrophages, we determined that caspase-1 and bioactive IL-1β release was highly dependent on caspase-4 activation in response to Eh. Formaldehyde cross-linking to stabilize protein-protein interactions in transfected COS-7 cells stimulated with Eh revealed that caspase-4 specifically interacted with caspase-1 in a protein complex that enhanced the cleavage of caspase-1 CARD domains to augment IL-1β release. The mouse ortholog caspase-11, displayed similar requirements for its activation, however, it was not involved in regulating caspase-1 activation in the same way as caspase-4. These findings reveal a novel role for human caspase-4 as a critical sensor molecule to amplify downstream pro-inflammatory responses when macrophage encounters live Eh.
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    Identification and Characterization of Moesin-, PIP2-mediated Solid Particle Phagocytosis
    (2018-08-09) Tu, Zhongyuan; Shi, Yan; Yates, Robin Michael; Amrein, Matthias; Prenner, Elmar J.; Botelho, Roberto
    Phagocytosis is the defining feature of professional phagocytes of the innate immune system. This function is typically carried out by phagocytic receptors on the cell surface. These receptors can mediate binding and engulfment of solid particles. However, these phagocytic receptors have evolved very recently in history comparing to phagocytosis as a conserved cellular function. This suggests a primordial form of phagocytosis might exist. Years ago, our laboratory uncovered an expected phagocytic mechanism that solid particle can bind to membrane lipids on phagocytes to trigger lipid sorting. Consequently, this can lead to phagocytosis akin to FcγR-based phagocytosis regarding its dependence on Immunoreceptor Tyrosine-based Activation Motif (ITAM), Src-family kinases, Syk, and phosphoinositide 3-kinase (PI3K). Based on these findings, we proposed a hypothetical mechanism for solid particle phagocytosis termed “Signaling Equivalent Platform” (SEP). In short, membrane engagement with solid structures, either via ligand/receptor binding or merely being stabilized by an approaching solid surface will lead to a shared downstream pathway with the same dependence on ITAM and Syk. Both modes of phagocytosis are equivalent for its activation by solid structures. However, the identity of the ITAM-containing molecule and the exact involvement of lipid during solid particle phagocytosis under SEP is still unclear. This thesis serves to strengthen the idea of SEP by identifying the ITAM-containing molecule and further characterizing the involvement of the ITAM-containing molecule and lipids during solid particle phagocytosis. We used a generic ITAM sequence as a probe and identified moesin as the ITAM-containing molecule from the mouse genome. We further demonstrated that a solid structure binding to the cell surface leads to autonomous accumulation of phosphatidylinositol 4, 5-bisphosphate (PIP2) to the site of contact, which attracts moesin, a conserved structural linker, to the plasma membrane. Moreover, Moesin, via its ITAM, is sufficient to activate phagocytic programming including Syk and downstream signaling that is virtually identical to that initiated by Fcγ receptors. Bioinformatic analysis suggested that this moesin-mediated signaling predates modern Fcγ and immune receptors. This thesis, therefore, reveals an evolutionarily conserved moesin-, PIP2-mediated signaling platform for the evolutionarily conserved phagocytosis that provides essential components for modern ITAM-based signaling cascades.
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    Subversion of dendritic cell immunity to Cryptococcus gattii by a novel phagosomal F-actin cage structure
    (2020-04-28) Jamil, Khusraw; Mody, Christopher Hugh; Ganguly, Anutosh; Amrein, Matthias W.; Yates, Robin Michael; Yong, Voon Wee
    The highly virulent fungus, Cryptococcus gattii, emerged as a novel respiratory pathogen on Vancouver Island (British Columbia, Canada) nearly two decades ago and has spread to the surrounding regions encompassing the Pacific Northwest of United States, where there is an ongoing outbreak. C. gattii is a major cause of life-threatening cryptococcosis in immunocompetent individuals and has a mortality rate of up to 33%. Host immune response is a key determining factor for the development of cryptococcal disease. It is now recognized that evasion of host immune recognition is a hallmark of C. gattii pathogenesis, but the mechanism of immune evasion remains unclear. There is increasing evidence that C. gattii subverts dendritic cell (DC) activation to evade the protective T helper cell-mediated immunity. This thesis demonstrates that primary human DC can phagocytose C. gattii yeasts but trafficking to the late phagolysosome is blocked by retention of a filamentous actin (F-actin) cage on the phagosomes. Structural studies by super resolution microscopy revealed a novel, highly branched F-actin cage that physically interfered with lysosomal fusion. C. gattii F-actin cage promoted immune evasion by silencing the canonical RelA signaling of the NF-κB pathway required for DC costimulation and T cell activation. Disruption of the F- actin cage through targeted inhibition or by TNF-α signaling reprogrammed quiescent DC to immunocompetent antigen-presenting cells (APCs). Furthermore, the presence of phagosomal F-actin cage corresponded with the presence of C. gattii polysaccharide capsule. Acapsular mutant strains did not retain phagosomal F-actin and were remarkable at inducing DC activation and T cell proliferation. Collectively, our results have uncovered a unique mechanism of DC immune subversion by intracellular pathogens such as hypervirulent C. gattii. Manipulations of this mechanism can potentially inform novel therapeutic interventions against C. gattii.