Identification and characterization of proteins involved in the cytoskeletal rearrangements caused by bacterial pathogens

Bacterial pathogens have evolved to alter the cytoskeleton of their hosts during their respective infection processes. The extracellular bacterium, enteropathogenic Escherichia coli (EPEC), generates an actin-rich pedestal to “surf” along the host cell surface. In contrast, L. monocytogenes (L. monocytogenes) invades its host and polymerizes actin filaments to generate a comet tail for movement within and among host cells of epithelia. Salmonella enterica serovar Typhimurium (S. Typhimurium) induces actin-rich membrane-ruffles to invade its host cell. These bacteria have evolved to generate their respective actin-rich structures to colonize the intestinal epithelia. To further characterize the actin-rich structures generated by these bacteria, I selected four proteins from a mass spectrometry analysis of EPEC pedestals previously conducted in our laboratory. I found that the known actin-bundling proteins calponin 1 and calponin 2 decorated all the actin-rich structures formed by these three bacteria. Another actin-stabilizing protein transgelin (SM22) also decorated EPEC pedestals and L. monocytogenes comet tails. Moreover, the formation of pedestals and comet tails were dependent on SM22 protein levels. Aside from these three members of the calponin family, I found that a ubiquitin conjugating enzyme Ube2N was enriched at the invasion events and at the plasma membrane-bound comet tails formed by L. monocytogenes. This novel association of Ube2N with actin structures at the plasma membrane led to my discovering that Ube2N binds directly to actin, and that Ube2N function influences actin-based whole cell motility. Another bacterial pathogen, Klebsiella pneumoniae (K. pneumoniae), has been shown by others to alter the host actin cytoskeleton. I have found that the disassembly of the host microtubule networks precedes these actin cytoskeletal alterations in lung epithelial cells, and show that the Klebsiella pneumoniae gene ytfL (Kp ytfL) initiates this microtubule disassembly and that the katanin catalytic subunit A like 1 protein (KATNAL1) as well as the katanin regulatory subunit B1 protein (KATNB1) are activated to cause microtubule severing. Through this, I identified the bacterial initiator and the host cell effector proteins responsible for K. pneumoniae-induced microtubule disassembly. From these, I identified proteins that are novel to the actin structures of EPEC, L. monocytogenes and S. Typhimurium as well as effector proteins that are crucial for the novel host microtubule alterations of K. pneumoniae

Changes in Causes of Death, the Impact on Life Expectancy, and the Risk of Myocardial Infarction Among People Living with and without HIV

Background: Within the context of aging with HIV in the combination antiretroviral therapy (ART) era, the set of four papers that make up this dissertation aimed to: summarize the existing evidence on the risk of myocardial infarction (MI) among people living HIV (PLHIV) (Chapter 2); characterize changes over time in rates and causes of death among HIV-positive and HIV-negative individuals (Chapter 3); assess the impact of the changing causes of death on life expectancy and potential gains in life expectancy over time (Chapter 4); estimate the incidence of MI and its association with HIV infection, ART, and other explanatory variables, among HIV-positive and HIV-negative individuals (Chapter 5).Methods: A systematic review and meta-analysis of MI risk among PLHIV was initially performed. Next, data from the COAST studya linked population-based, retrospective cohort study containing longitudinal data on over half a million HIV-positive and HIV-negative adults in British Columbia (BC)were assessed to investigate several issues pertinent to aging with HIV. With the hope of producing evidence to inform relevant programmatic and clinical guidelines/policies among aging HIV-positive individuals, a series of analyses were performed to examine mortality changes over time, cause-deleted life expectancy, and the risk of MI among HIV-positive compared to HIV-negative individuals. Results: We observed significant declines in mortality and dramatic shifts in the causes of death between 1996 and 2012 among HIV-positive compared to HIV-negative individuals. Although HIV/AIDS continues to account for the greatest burden of mortality among PLHIV, other non-AIDS-defining conditions have become increasingly relevant. Consequently, our results suggest that managing cardiovascular diseases and non-AIDS-defining cancers among PLHIV has the same effect on life expectancy in this population as in HIV-negative individuals. Increasing age, male sex, and HIV infection (including exposure to some ART regimens) were found to be associated with a higher risk of MI.Conclusion: Taken together, our findings highlight the increasing need to concurrently consider multiple factors, including HIV infection itself, other emerging non-HIV-related conditions, exposure to ART, and demographic and clinical risk factors, as part of the effort to address and improve the care of aging HIV-positive individuals

Critical Community Engaged Scholarship — with Liz Jackson

The Community Engaged Scholarship Institute, situated at the University of Guelph, brings together community and campus skills and resources in order to advance community-identified research goals. This episode describes various projects, such as the Community Engaged Teaching and Learning (CETL) Program, the Research Shop, and the Guelph Lab. Am and Liz discuss the role of the Institute and how community engaged research can be used to provide a foundation for policy development and in widening imaginations and creating possibilities on the ground. Liz also describes her life trajectory that brought her to this work and led her to Critical Community Engaged Scholarship

Remembering BC’s 1983 Solidarity Uprising — with David Spaner

In 1983, the province of British Columbia saw the rise of a social movement like no other since — uniting activists, community organizations and trade unionists in protest. This time on Below the Radar, host Am Johal speaks to David Spaner, an author, cultural critic, and organizer who has written a compelling history of the Solidarity resistance movement. Released in December of 2021 by Ronsdale Press, Solidarity: Canada\u27s Unknown Revolution of 1983 is David’s chronicling of the organizing efforts by the Solidarity movement and its ongoing implications for worker justice in BC. He and Am go behind the scenes of the book, as David recalls experiences from being on the ground as a reporter and activist during that time

Research Meets Policy: Getting the Media Involved

This explainer document is the fourth in a four part series based on Research Meets Policy at SFU 2021 - a virtual summer institute hosted by the SFU Knowledge Mobilization Hub.The media is an effective channel for reaching policy makers, as it is a proven way to gain the interest and attention of voters on a particular topic, or as another way to attract the attention of policy makers directly. When short on time, many policy makers rely on trusted voices on Twitter or other media outlets for quick takes on pressing issues. In this explainer, we share how you can get started engaging the media for communicating to policy makers

Research Meets Policy: Introducing Research Communication

This explainer document is the first in a four part series based on Research Meets Policy at SFU 2021 - a virtual summer institute hosted by the SFU Knowledge Mobilization Hub.In this explainer, we provide an overview to orient you to research communication in a policy setting. The main goal of research in the policy landscape is to support evidence-informed policy development, that is, to contribute to well-informed decisions to make positive social, economic, and environmental impacts

Examining Eating: Bridging the Gap Between ‘Lab Eating’ and ‘Free-Living Eating’

Food consumption and its physiological, psychological, and social antecedents and outcomes have received considerable attention in research across many disciplines, including consumer research. Although researchers use various methods to examine food decision-making, many insights generated stem from observing eating choices in tightly controlled lab settings. Although much insight can be gained through such studies (or “lab eating”), it is apparent that many factors differ between such settings and everyday consumption (or “free-living eating”). This article highlights key differences between “lab eating” and “free-living eating,” discusses ways in which such differences matter, and provides recommendations for researchers regarding how and when to narrow the gap between them, including by enriching lab studies in ways inspired by free-living eating. Besides suggesting how researchers can conduct studies offering a deeper understanding of eating patterns, we also highlight practical implications for improving food consumption for consumers, marketers, and policymakers

Suboptimal Nonmedical Qualities of Primary Care Linked with Care Avoidance Among People Who Use Drugs in a Canadian Setting Amid an Integrated Health Care Reform

Background: People who use unregulated drugs (PWUD) often face significant barriers to—and thereby avoid seeking—health care. In Vancouver, Canada, a neighborhood-wide health care system reform began in 2016 to improve health care delivery and quality. In the wake of this reform, we sought to determine the prevalence of health care avoidance and its association with emergency department use among PWUD in this setting and examine patient-reported nonmedical qualities of health care (“responsiveness”). Methods: The study derived data from two prospective cohort studies of community-recruited PWUD in Vancouver in 2017–18. Responsiveness was ascertained by the World Health Organizations’ standardized measurements and we evaluated seven domains of responsiveness (dignity, autonomy, communication, confidentiality, prompt attention, choice of provider, and quality of basic amenities). The study used Pearson chi-squared test to examine differences in responsiveness between those who did and did not avoid care. The study team used multivariable logistic regression to determine the relationship between care avoidance due to past mistreatment and emergency department use, adjusting for potential confounders. Results: Among 889 participants, 520 (58.5%) were male, 204 (22.9%) reported avoiding health care, most commonly for chronic pain (47.4%). Overall, 6.6% to 36.2% reported suboptimal levels (i.e., not always meeting the expected quality) across all seven measured domain of responsiveness. Proportions reporting suboptimal qualities were significantly higher among those who avoided care than those who did not across all domains, including care as soon as wanted (51.0% vs. 31.8%), listened to carefully (44.1% vs. 20.4%), and involved in health care decision making (27.9% vs. 12.7%) (all p<0.05). In multivariable analyses, avoidance of health care was independently associated with self-reported emergency department use (adjusted odds ratio=1.49; 95% confidence interval:1.01–2.19). Conclusion: We found that almost a quarter of our sample of PWUD avoided seeking health care due to past mistreatment, and all seven measured domains of responsiveness were suboptimal and linked with avoidance. Individuals who reported avoidance of health care were significantly more likely to report emergency department use. Multi-level interventions are needed to remedy the suboptimal qualities of health care and thereby reduce care avoidance

A Conversation About Urban Choreography — with Justine A. Chambers, Alana Gerecke & Annabel Vaughan

This episode of Below the Radar is a special live event recording from “A Conversation About Urban Choreography,” presented in-person at SFU’s Vancouver campus on November 9, 2021. Taking gesture as a point of entry, Justine A. Chambers and Alana Gerecke extend their collaborative exploration of the everyday choreographies that are built into an urban experience. Combining artistic and academic research, they index the various bodily orientations cultivated by the built and social structures that shape everyday spaces. By tracking an archive of everyday gestures that are prompted by various components of built and social space, they insist on the lasting and vital information contained within those specific organizations of moving bodies. They emphasize the significance of embodied knowledge—even, or especially, as it lives in invisibilized daily gestures.  In this discussion, Chambers and Gerecke are joined by architect Annabel Vaughan. Together, the panelists explore the accumulation of living archival gestures generated by the interactions between moving bodies and built space, an evolving assembly of lost gestures. This public conversation was presented with the aim of sharing evolving research by inviting those present to engage in a consideration of the embodied details of urban circulation

Paleoecological Investigation of Vegetation, Climate and Fire History in, and Adjacent to, Kootenay National Park, Southeastern British Columbia, Canada

Paleoecological investigation of two montane lakes in the Kootenay region of southeast British Columbia, Canada, reveal changes in vegetation in response to climate and fire throughout the Holocene. Pollen, charcoal, and lake sediment carbon accumulation rate analyses show seven distinct zones at Marion Lake, presently in the subalpine Engelmann Spruce-Subalpine Fir (ESSF) biogeoclimatic (BEC) zone of Kootenay Valley, British Columbia. Comparison of these records to nearby Dog Lake of Kootenay National Park of Canada in the Montane Spruce (MS) BEC zone of Kootenay Valley, British Columbia reveals unique responses of ecosystems in topographically complex regions. The two most dramatic shifts in vegetation at Marion Lake occur firstly in the early Holocene/late Pleistocene in ML Zone 3 (11,010–10,180 cal. yr. B.P.) possibly reflecting Younger Dryas Chronozone cooling followed by early Holocene xerothermic warming noted by the increased presence of the dry adapted conifer, Douglas-fir (Pseudotsuga menziesii) and increasing fire frequency. The second most prominent change occurred at the transition from ML Zone 5 through 6a (∼2,500 cal. yr. B.P.). This zone transitions from a warmer to a cooler/wetter climate as indicated by the increase in western hemlock (Tsuga heterophylla) and subsequent drop in fire frequency. The overall cooling trend and reduction in fire frequency appears to have occurred ∼700 years later than at Dog Lake (∼43 km to the south and 80 m lower in elevation), resulting in a closed montane spruce forest, whereas Marion Lake developed into a subalpine ecosystem. The temporal and ecological differences between the two study sites likely reflects the particular climate threshold needed to move these ecosystems from developed forests to subalpine conditions, as well as local site climate and fire conditions. These paleoecological records indicate future warming may result in the MS transitioning into an Interior Douglas Fir (IDF) dominated landscape, while the ESSF may become more forested, similar to the modern MS, or develop into a grassland-like landscape dependent on fire frequency. These results indicate that climate and disturbance over a regional area can dictate very different localized vegetative states. Local management implications of these dynamic landscapes will need to understand how ecosystems respond to climate and disturbance at the local or ecosystem/habitat scale