30921 research outputs found
Sort by
Genetic control of melanin production in the polyextremotolerant fungus Exophiala dermatitidis
Full text linkExophiala dermatitidis is a polymorphic black yeast found in various habitats such as soil, leaf litter and man-made environments including sinks, dishwashers and saunas. E. dermatitidis is also an opportunistic pathogen of humans where it can cause phaeohyphomycosis and skin infections. 1,8-DHN melanin found in E. dermatitidis has been shown to provide various functions that range from protection against cellular damage to conversion of visible UV energy into heat. Although the E. dermatitidis genome sequence has revealed the presence of genes responsible for production of melanin via three different pathways, relatively little is known about the relative contribution of these pathways to melanization. The aim of this study was to address this issue by using an unbiased genetic approach to determine which pathways are essential for melanin production. To this end, albino mutants lacking the ability to produce melanin were obtained using UV irradiation. Based on genome re-sequencing and SNVs analysis, all the albino mutants showed variants in the PKS1 gene including mutations ranging from missense base substitutions to frameshifts and short deletions. When grown on different carbon sources, some albino mutants were able to recover melanin production. Ultimately, comparative transcriptomics was used as a tool to examine differentially expressed genes when the various albino mutants were grown on different carbon sources. Transcriptomics analysis allowed us to investigate the expression of alternative genes/pathways that can promote the recovery of melanin production in the conditional albino mutants.National Science Foundation award number 2434259.February 202
Sébastien Brémond’s Paratexts: Authorship, Genre, and Masculinity
Full text linkIn this article, I argue that Sébastien Brémond (1646?–1705?) used his dedicatory paratexts to create a homosocial bond between the author and libertine members of the French faction at Charles II’s court. Coupled with Brémond’s use of the secret history genre and his North African settings that catered to the “Ottomanphilia” of the court during the 1670s, these paratexts situated Brémond as a court insider close to the king, ascribing him with some of the celebrity inherent in that court, and appealing to a wider audience eager to read about the antics of the libertine circle and the king. Looking at these paratexts as a group shows the translatability of the secret history genre across readerships, across political factions, and through time, while the case of Brémond reveals the ways that changing readerships impacted an author’s control over the meanings of their texts and their own authorial persona
Airway epithelial-derived Semaphorin3E modulates airway hyperresponsiveness, inflammation, and remodeling in acute and chronic models of asthma
No full textAsthma is a heterogeneous inflammatory disorder that affects more than 300 million individuals worldwide. It is clinically characterized by recurrent episodes of airway hyperresponsiveness (AHR), wheezing, and cough. The disease exhibits considerable variability, encompassing distinct phenotypes such as type-2 high (eosinophilic) and type-2 low (neutrophilic) endotypes, which differ in underlying immunological mechanisms and responsiveness to treatment. Although inhaled corticosteroids (ICS) represent the cornerstone of therapy, nearly 10% of patients remain partially or completely resistant, underscoring an urgent need for alternative therapeutic strategies.
Emerging studies have highlighted Semaphorin3E (Sema3E), a secreted neuronal guidance cue, and its receptor plexinD1 as key regulators of airway immunity. Airway epithelial cells (AECs) have been identified as the predominant pulmonary source of Sema3E, with reduced epithelial expression strongly associated with asthma severity and impaired lung function. Our group demonstrated diminished Sema3E expression in both human asthmatic airway tissues and murine models following house dust mite (HDM) exposure. Collectively, these findings suggest that epithelial-derived Sema3E is critical for maintaining airway homeostasis.
We hypothesized that airway epithelial–derived Sema3E regulates key inflammatory and structural features of asthma across distinct models and that its overexpression provides protective effects that may complement corticosteroid therapy. To test this, we used a novel transgenic mouse model with inducible Sema3E expression in AECs and investigated its function in acute and chronic asthma settings, including both type-2 high and type-2 low endotypes. Disease outcomes were evaluated using airway mechanics (AHR), histopathology, and immunological assays.
Our results demonstrated that epithelial Sema3E overexpression significantly reduced AHR, mucus production, airway wall thickening, and subepithelial fibrosis in acute HDM models. These effects correlated with increased expansion of Foxp3⁺ regulatory T (Treg) cells. Mechanistic studies using Treg-specific plexinD1 knockout mice confirmed a direct role for the Sema3E–plexinD1 axis in promoting Treg-mediated immune regulation. Furthermore, in chronic models, global Sema3E deficiency exacerbated pathology, while AEC-specific restoration ameliorated disease features. Importantly, therapeutic comparisons showed that epithelial-derived Sema3E reconstitution achieved effects comparable to dexamethasone.
In conclusion, this thesis establishes airway epithelial-derived Sema3E as a central regulator of airway immunity and remodeling. Collectively, these findings provide mechanistic and therapeutic evidence positioning Sema3E as a promising steroid-sparing immunomodulator with translational potential for asthma.February 202
The effect of nitrogen management on dual-purpose intermediate wheatgrass (Thinopyrum intermedium) stands in western Canada
Full text linkIntermediate wheatgrass (IWG, Thinopyrum intermedium (Host) Barkworth & D. R. Dewey) is being bred for perennial grain production. This thesis investigated the dual-purpose use for grain and stockpiled forage production of IWG. The first experiment consisted of four treatments tested for up to three production years at four locations in Manitoba and Saskatchewan. The objective was to determine the effect of nitrogen (N) fertility on IWG grain production and fall stockpiled biomass yield (FSB) and chemical composition. Treatments were an unfertilized IWG control (NOFERT); IWG with 50 kg N ha-1 post grain harvest (FERT); an IWG-aliske clover (Trifolium hybridum L.) intercrop (INTER); and a stockpile forage control (FORCON) consisting of tall fescue (Schedonorus arundinaceus Schreb.) /alfalfa (Medicago sativa L.) /cicer milkvetch (Astragalus cicer L.). Nitrogen fertilization increased grain yield by 199.1 kg ha-1 compared with the grain yield of the NOFERT treatment in the third production year. On a dry matter (DM) basis, the FSB of the FERT treatment produced a chemical composition which had total digestible nutrient, neutral detergent fibre and acid detergent fibre concentrations that were better than that of the NOFERT treatment in 2 of 5 site-years. The second experiment consisted of four treatments at Carman, Manitoba, Canada. The objective was to determine the effect of timing of N fertility application on grain production, FSB and chemical composition. Treatments included: unfertilized IWG control (NOFERT); IWG with 50 kg N ha-1 post grain harvest (FALL) or spring (SPRING) and IWG with 35 kg N ha-1 post grain harvest and 15 kg N ha-1 the subsequent spring (SPLIT). Reported on a DM basis, the SPRING treatment produced biomass at grain harvest yield which was significantly lower than that of the NOFERT treatment. Total aboveground shoot biomass yield produced by the NOFERT treatment was significantly greater than that in the FALL treatment by 2000 kg DM ha-1, and 3000 kg DM ha-1 more than that in the SPRING treatment. Both experiments at all sites encountered moisture limitations during the 2020 and 2021 growing seasons. Low moisture levels likely suppressed vegetative and reproductive development leading to minimal, significant treatment differences. Timing of fertility changed within plant biomass allocations but did not influence grain production. These results indicate that stand age and fertility can influence grain production and biomass yield, however, stand age and fertility responses are mediated by growing conditions.February 202
Examining the transcriptome of a copper-tolerant Pseudomonas aeruginosa sink drain isolate for the role of pH on the antimicrobial actions of copper
No full textThe copper tolerance of Pseudomonas aeruginosa in sink-drain environments, frequently linked to the genomic island 7 (GI-7), presents a challenge to the antimicrobial effectiveness of copper. While copper plumbing materials are regaining popularity in water systems due to their antimicrobial properties, copper’s mode of action is complex, as increasing copper concentrations (>0.5 mg/mL Cu²⁺) also acidify the surrounding environment. Understanding the genetic and environmental factors underlying copper tolerance, including the role of pH, is essential to closing this knowledge gap. In this study, the transcriptomic responses and copper survival of P. aeruginosa strains PAO1, PA-8 (a French sink-drain isolate harboring GI-7 element), and PA-8 ΔGI-7 (PA-8 lacking GI-7) were compared. Survival was assessed following 72-hour incubations of all 3 strains in sterile water with and without 600 µg/L copper sulfate (CuSO₄). The transcriptomes of all 3 mid-log strains were analyzed after exposure to either 2 mg/mL CuSO₄ or an acidified medium of pH 5.5. The overarching hypotheses of this study are that GI-7 confers enhanced copper tolerance relative to PAO1, and that acid stress genes overlap with copper-induced responses at high copper concentrations.
After 72 hours, PAO1 exhibited early copper susceptibility at 18 hrs, with no viable cells recovered following plating, whereas both PA-8 and PA-8 ΔGI-7 survived copper exposure up to 15 days. Transcriptomic analyses revealed that Cu²⁺ exposure induced a 2-4 fold greater number of differentially expressed genes (DEGs) than acid stress alone across all strains, where overlaps in copper tolerance and uptake systems as well as general and acid stress-associated genes were identified under both stress exposure conditions. PA-8 showed the most significant Cu²⁺-induced response, whereas PA-8 ΔGI-7 exhibited fewer Cu²⁺-responsive DEGs and slightly greater acid-induced response. Although deletion of GI-7 reduced the Cu²⁺-induced transcriptional response, PA-8 ΔGI-7 demonstrated copper survival, it also suggests that GI-7 alone does not fully account for copper tolerance in PA-8.
Overall, these findings indicate that copper induces broader transcriptional stress responses than acid alone and identified key genes involved in copper and acid stress, providing a foundation for elucidating mechanisms underlying copper tolerance and susceptibility in P. aeruginosa.February 202
The bovine victims of the Rwandan, Tibetan, and North American genocides
Full text linkThis thesis examines three instances of mass bovine deaths that occurred alongside genocides targeting human groups. The events studied include the slaughter of Tutsi cattle during the Rwandan genocide, the mass death of yaks during the collectivization of Tibetan nomads, and the extensive hunting of buffalo (American bison) during the genocide against Indigenous Peoples of North America. The study’s analysis utilizes the framework of anti-representationalism, a major pathway to achieving an ontological turn. The research indicates that these bovine animals serve various roles within the communities of genocide victims. They are more than just private property or natural resources; they function as key components of collectivity and as non-human social members. Each case study exemplifies a different aspect of the anti-representationalism paradigm, including things’ agency, human-environment integration, and practice-generated ontologies. This study focuses on anti-anthropocentric perspectives and questions the Cartesian body-mind dualism, as well as the naturalist view that divides culture from nature. The analysis of the three case studies shows that non-human entities’ agency, the environment’s affordances, and the interactions between humans and non-humans can significantly influence human perceptions and behaviour, particularly in how collective categories, such as “people,” are defined and understood. A deeper discussion based on the case comparison reveals that drawing an ontological line around the concept of persons is similar to defining ethnic identity, as both processes involve selecting specific indicators that highlight shared characteristics. This conclusion indicates that the Western collective categories rooted in naturalism may not be applicable to many non-Western societies, where people might choose attributes shared by both humans and non-humans as indicators for defining their collectives. In the context of genocide studies, this suggests that “genos” (collectivity) can have various implications and is not necessarily exclusive to humankind. Therefore, critical reflection on the naturalist bias in Western concepts of collectivity can be a vital strategy for decolonizing genocide studies.February 202
Becoming with/in culturally disruptive pedagogies: teaching science in a pluralistic society
Full text linkEquity and diversity goals in Manitoba education curriculum documents (Manitoba Education and Training, 2000) are not reflected in existing Manitoba science curricula (Kim & Dionne, 2014) and may or may not be realized in science classroom practices. Science education is complicit in reproducing inequities by devaluing certain knowledge systems, reinforcing gender and sexual norms, and privileging Whiteness (Battiste, 2013; Gunckel, 2019a; Ridgeway, 2019). This study aimed to disrupt the privileging of Western Science knowledges, stereotypically masculine norms and binaries, and Whiteness embedded in school science. Through intersectional lenses of Two-Eyed Seeing, queer pedagogy and critical race theory, this critical autoethnography explored how culturally disruptive pedagogy (CDP) could inform my becoming as a middle years science educator working to enact more socially just conceptualizations of science. Following mixed and matched coding of gathered field texts (e.g., teacher journal reflections), secondary reflective vignettes were generated to create anonymized composite narratives. The findings captured moments of arising tension, disruption, self-realization and pedagogical innovation, demonstrating that these CDP tenets may form a useful framework for teachers. Disrupting existing teaching beliefs is possible; grappling with tensions is essential to the fraught process of becoming as a justice-oriented science educator. Field text analysis generated emerging themes specific to each tenet—potentially useful insights for other educators in their own contexts. This study contributes to emerging scholarly work relating to CDP in science education while responding to calls from scholars to consider the role of racially marginalized settlers in addressing reconciliation, examine racial injustices embedded in science, and explore the potential afforded through queering science.February 202
Beyond the diagnosis: women’s experiences of cardiotoxicity secondary to cancer treatment
Full text linkBackground: While chemotherapy can be a life-saving measure for women with cancer, it can also cause serious side effects. Cardiotoxicity, a decline in cardiac function in the form of heart failure, is a rare adverse effect linked to specific anti-neoplastic therapies. A dual diagnosis of cancer and cardiotoxicity (heart failure) has serious implications for women who are living with two potentially life-threatening conditions. There is little research pertaining to the health needs of these women and the impacts they face in their daily lives.
Purpose: The goals of this study were to 1) explore women’s embodied experiences of developing cardiotoxicity related to anti-neoplastic therapy and 2) provide examples of how living with a dual diagnosis impacted their ability to participate in their daily social worlds.
Method: This descriptive qualitative study completed one-on-one semi structured interviews with women (n=7) who received a diagnosis of cardiotoxicity after receiving anti-neoplastic therapy for cancer treatment. The criteria for determining cardiotoxicity (or cancer therapy related cardiac dysfunction) was a left ventricular ejection fraction of absolute value less than 53% or a drop of 10% from baseline. Analysis was completed using Braun and Clark’s (2006) six phases of Thematic Analysis. This study drew from theoretical frameworks focused on the sociology of the body, specifically embodiment theories highlighting how women’s bodies are impacted during illness.
Findings: Women in this study were found to experience embodied trauma through feelings of self-blame, distrust, lack of being monitored and no end in sight to their cardiac issues stemming from cardiotoxicity due to anti-neoplastic therapy. The women in this study also encountered alterations to their daily social worlds with their diagnosis of cardiotoxicity including their roles within the family, careers and maintaining friendships.
Conclusion: This study highlights the importance of trauma informed, person-centred, embodied care for this cohort of women by all levels of healthcare providers. It also uncovers the need for long-term access to psychosocial services and improved secondary screening so that women who are at high risk of developing cardiotoxicity secondary to their cancer treatments do not get lost in the medical system after their cancer treatment.Foundation of Registered Nurses of Manitoba (FRNM) Inc. Graduate Award, Irene E. Norwich Foundation Scholarship, Graduate Nursing Students Association (GNSA) Award, Manitoba Centre for Nursing Health Research (MCNHR) Graduate Student Research Grant, Women’s Health Research Foundation of Canada Graduate Scholarship, and finally the Manitoba Training Program Fellowship Award for Health Services ResearchFebruary 202
Genetic diversity of Candida albicans and Nakaseomyces glabratus across geographic scales and within-host populations
Full text linkCandida albicans and Nakaseomyces glabratus are major opportunistic fungal pathogens, yet both present persistent challenges in the clear delineation of clades. This thesis used whole-genome sequencing (WGS) and comparative genomics to clarify species-level diversity, refine clade designations, and assess genetic variation from global to within-host scales. Analysis of 1,178 global C. albicans isolates revealed six previously unrecognized clades using phased genomes and a standardized clustering framework. Clade distributions differed across continents and isolation sources, although sampling biases limited clear ecological interpretation. Genomic features - including heterozygosity, mating-type locus genotype, aneuploidy, copy number variation, and the potential for RNA interference - varied among isolates but showed limited clade specificity. Intra-host sampling suggested largely clonal colonization, with occasional multi-clade carriage. For N. glabratus, population analysis of 548 isolates from 12 countries showed strong concordance between WGS- and MLST-based clustering. A unified nomenclature linking 27 WGS-defined clusters with dominant MLST sequence types is proposed. Admixture analysis identified 65 isolates with mixed ancestries, indicating both historical and ongoing recombination. Aneuploidy occurred in ~4% of isolates, most frequently involving chromosome E, which harbours the ERG11 gene whose protein product is a key azole target. Intra-host comparisons of rectal and vaginal isolates from recurrent vulvovaginal candidiasis cases demonstrated high genomic similarity across body sites, limited genetic variation, and minimal phenotypic divergence, consistent with frequent migration and recent shared ancestry. Together, these studies provide a standardized framework for defining clades and population structure in C. albicans and N. glabratus. They highlight major geographic and ecological gaps in current isolate collections and underscore the need for more comprehensive sampling to accurately assess global and within-host fungal diversity.University of Manitoba
MITACS Globalink Research award
Genetics Society of America Presidential Membership AwardFebruary 202
Aging together: a two-generational living solution focused on aging in place
Full text linkBy 2060, one in three Germans will be over 60 years old; this aging population presents a housing challenge today (Centre for Public Impact, 2018). In Bad Kreuznach, where 23.4% of the population is already over 65 and 43.8% of households are single-person, it is necessary to reconsider traditional housing models that do not support the desire of older adults to age in place while maintaining their independence. This practicum investigates how interior design strategies can enable two-generation households to support aging in place within the German cultural context that prioritizes autonomy and independence.
Unlike the permanent three-generation co-residence model common in other cultures, this project proposes a “living together but apart” living solution (Isengard & Szydlik, 2012), featuring separate dwelling units for each generation within a common building. The design solution balances three interconnected principles, namely, accessibility, privacy, and connection.
The project delivers a multi-unit intergenerational residential building (MUIRB) design situated in Bad Kreuznach, Germany, to demonstrate how thoughtful interior design can foster voluntary intergenerational interaction and informal caregiving without sacrificing individual autonomy. This context-specific solution offers transferable design principles applicable to similar aging demographic contexts across Germany and Western Europe.The Ageless Living Collaborative Scholarship - Value of 5000 USDFebruary 202