30921 research outputs found
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Polycyclic aromatic compounds in Canadian Arctic seabirds: spatiotemporal trends and bioaccumulation patterns
No full textPolycyclic aromatic compounds (PACs) are a complex class of organic contaminants associated with petroleum. Many PACs have been identified as a concern due to their persistence in the environment, their potential to bioaccumulate, and their toxicity to living organisms. In the Canadian Arctic, emissions from natural seeps and increasing industrial activities, particularly shipping and mining, pose significant threats to the region’s vulnerable marine ecosystems. While numerous contaminants have been reported in this region, targeted monitoring of PACs remains limited. Seabirds serve as established bioindicators of marine ecosystem health and are commonly used for environmental monitoring. This thesis presents two complementary studies investigating PAC contamination in Arctic seabirds using gas chromatography-tandem mass spectrometry. The first study was a spatial and temporal analysis of PACs in seabird eggs collected from high Arctic and low Arctic colonies between 1993 and 2024. Higher PAC concentrations were detected in eggs from seabirds breeding in the high Arctic, with considerable interannual variation at both sites and many of the higher PAC concentrations occurring in the past decade. The second study focused on species- and tissue-specific PAC accumulation in three species of Arctic seabirds. Substantial variation in PAC concentrations and chemical profiles was observed between tissue types and among species. This variability reflects species-specific differences in PAC exposure, accumulation, and metabolism, driven by a combination of foraging ecology, breeding phenology, and physiological factors. As activity in the Arctic and interest in Canada’s northern shipping routes continue to grow, the need for monitoring oil and gas related contaminants in the Arctic region is essential to detect emerging trends, identify potential sources and support informed decision-making to ensure the protection of Canada’s Arctic wildlife.October 202
Bridging the gap between genes and fungal natural products: Functional heterologous expression of the genes from the lichen Cladonia uncialis
No full textFungi, with an estimated 5 million species, constitutes the second most diverse kingdom on Earth. However, only about 10% of these species have been identified, highlighting the vast, untapped potential for discovering bioactive natural products. This thesis focuses on two main objectives: (1) exploring the chemical diversity of fungal natural products and (2) heterologous expression of biosynthetic gene clusters (BGCs) from the lichenized fungus Cladonia uncialis.
The first objective involved the isolation, characterization, and bioactivity profiling of secondary metabolites (SMs) from Aspergillus fumigatus and Penicillium sanguifluum. Two compounds were characterized from the A. fumigatus: N-formyl-4-hydroxyphenyl-acetamide (compound 1) and atraric acid (compound 2), with the latter being the first instance of its production from a non-lichenized fungus. In addition, two compounds were identified from P. sanguifluum: dehydrocurvularin (compound 3) and 11-hydroxycurvularin (compound 4).
Despite the identification of over 1,000 SMs, establishing definitive connections between these SMs and their BGCs remains elusive. Our group identified and annotated 48 secondary metabolite BGCs from the fungal partner of C. uncialis. This thesis investigates the heterologous expression of two BGCs from this collection: the orsellinic acid (OA) BGC (cu-nr-pks-5) and the halogenated isocoumarin BGC (cu-pks-4) in A. oryzae NSAR1. The OA gene cluster contains two genes, one encodes for the PKS enzyme and the other for a post-PKS tailoring enzyme, decarboxylase. The heterologous expression of PKSs revealed that A. oryzae can successfully produce de-novo OA from non-lichen fungi (Fusarium spp.), but not from lichen fungus C. uncialis. The expression of the decarboxylase gene demonstrated reversible decarboxylation of OA, marking the first instance of a native lichen gene expression in a heterologous host.
Additionally, halogenated isocoumarin BGC was explored. The core PKS (Cu-A) showed similarity to TerA in Aspergillus terreus, suggesting it catalyzes similar condensation reactions to form 2,3-dihydro-6-hydroxymellein. Unique genes within the cluster, Cu-halo and Cu-OMT, are proposed to catalyze halogenation and O-methylation, respectively, to produce halogenated isocoumarin. The heterologous expression of the cluster, both at the individual gene level and as a complete BGC, resulting in the production of various compounds, confirming its functional activity and potential for novel metabolite synthesis.October 202
Thermal analysis and performance validation for in-vacuum operation of Compton HV-MAPS electron detector for the MOLLER Experiment
No full textThe Measurement Of a Lepton-Lepton Electroweak Reaction (MOLLER) experiment aims
to explore new dynamics beyond the Standard Model. The experiment is placed in Hall A at
the Thomas Jefferson National Accelerator Facility (JLab) in Newport News, Virginia, USA.
The measurements are acquired by the scattering of longitudinally polarized electrons off un-
polarized electrons in a liquid hydrogen target. MOLLER will utilize High Voltage-Monolithic
Active Pixel Sensors (HV-MAPS) in the Hall A’s Compton polarimeter to monitor the polariza-
tion of the incoming beam from the Continuous Electron Beam Acceleration Facility (CEBAF).
The HV-MAPS based electron detector contains a quad-planar geometry and each plane incor-
porates three HV-MAPS chips attached. Compton polarimeter utilizes this detector assembly
placed inside the vacuum to detect the compton scattered electrons. The chips generate heat
during operation, and thus require an effective cooling system in vacuum. The temperature
measurement of the HV-MAPS is useful to understand the thermal properties of the pixel de-
tector and cooling needs. The present study reviews the efforts towards the cooling strategies,
structure modification, and thermal simulations to achieve an in-vacuum operation. Further,
the prototyping and successful testing of the electron detector’s cooling system (using a test
version of HV-MAPS chips with equivalent heat load) in a local laboratory was performed, and
computational fluid dynamics studies are compared with the collected data.October 202
Brightly Luminescent Platinum Complexes of N^C-^N Ligands Forming Six-Membered Chelate Rings: Offsetting Deleterious Ring Size Effects Using Site-Selective Benzannulation
No full textBrightly emissive platinum(II) complexes (λemission,max = 607–612 nm) of the type RLPtCl are reported, where RL is a cyclometalated N∧C–∧N-coordinating ligand derived from 1,3-di(2-trifluoromethyl-4-phenanthridinyl)benzene (CF3LH) or 1,3-di(2-tert-butyl-4-phenanthridinyl)benzene (tBuLH). Metathesis of the chlorido ligand can be achieved under mild conditions, enabling isolation of ionic compounds with the formula [CF3LPtL′]PF6 where L′ = pyridine or (4-dimethylamino)pyridine (DMAP), as well as the charge-neutral species tBuLPt(C≡C─C6H4─tBu) (C≡C─C6H4─tBu = 4-tert-butylphenylacetylido). Compared with N∧N∧N-ligated Pt(II) complexes that form 5-membered chelates, these compounds all contain 6-membered rings. Expanding the chelate ring size from 5 to 6 has been previously demonstrated to enhance emission in some N∧N∧N-coordinated Pt(II) species─for example, in complexes of 2,6-di(8-quinolinyl)pyridine vs. those of 2,2′:6′,2″-terpyridine─but in related N∧C–∧N-coordinated species, luminescence quantum yields are significantly lower for the 6-membered chelate ring complexes. Here, we demonstrate that site-selective benzannulation of the quinolinyl side-arms can offset the deleterious effect of changing the chelate ring-size and boost photophysical properties such as the quantum yield. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations suggest that benzannulation counterintuitively destabilizes the emissive triplet states compared to the smaller π-system, with the 'imine-bridged biphenyl' form of the phenanthridinyl arm helping to buffer against larger molecular distortions, enhancing photoluminescence quantum yields up to 0.09 ± 0.02. The spontaneous formation under aerated conditions of a Pt(IV) derivative CF3LPtCl3 is also reported, together with its molecular structure in the solid state
17-beta estradiol in mitochondrial function and neuroprotection in central and peripheral nervous systems: mechanisms and implications
No full textNeurodegenerative diseases, such as Alzheimer's disease (AD) and peripheral neuropathies, are characterized by progressive neuronal damage and dysfunction. Estradiol (E2), a potent estrogen, has been shown to exert neuroprotective effects in both the central nervous system (CNS) and peripheral nervous system (PNS). This thesis investigated the mechanisms underlying E2's neurotrophic and neuroprotective actions in dorsal root ganglion (DRG) neurons and cortical neurons, focusing on mitochondrial function, axonal regeneration, neuroinflammation, and neuronal survival.
E2 enhanced mitochondrial respiration and promoted neurite outgrowth in cultured DRG neurons from the PNS through activation of AMP-activated protein kinase (AMPK) and its downstream effectors, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and activating transcription factor 3 (ATF3), which are proteins involved in mitochondrial biogenesis and axonal regeneration, respectively. I identified Ca²⁺/calmodulin-dependent protein kinase kinase beta (CaMKKβ) pathway as a key upstream regulator of AMPK activation in DRG neurons. In primary cortical neurons of the CNS, E2 countered amyloid-beta (Aβ)-induced toxicity by improving mitochondrial function and suppressing pro-inflammatory NF-κB signaling, underscoring its potential in mitigating AD-related neuronal loss. Notably, pharmacological inhibition of AMPK using Compound C (CC) abolished E2’s protective effects, confirming AMPK’s central role in mediating E2’s actions in cortical neurons.
Collectively, these findings highlight E2’s neurotrophic and neuroprotective effects in both peripheral and central neurons, with AMPK emerging as a critical mediator. Additionally, they underscore the therapeutic potential of targeting mitochondrial health and inflammatory pathways, alongside AMPK, in neurodegenerative disorders. Future research directions include in vivo validation, investigation of sex-specific responses, and development of safer estrogen-based alternatives, such as selective estrogen receptor modulators (SERMs) to fully harness estradiol's multifaceted neuroprotective roles in both CNS and PNS disorders.Alzheimer’s Society of Manitoba
McCrorie-West Family Fellowship
University of Manitoba Graduate Fellowship
Stephanson, Eirikur & Thorbjorg ScholarshipOctober 202
Comparison of short vs conventional networks to alleviate food insecurity through supply chain resilience.
No full textThis study presents a pioneering quantitative comparison of the resilience and performance of short and long supply chains in the face of disruptions. The case study on raspberry production is conducted to perform this analysis. Through a comprehensive simulation framework, we analyze and compare a localized supply chain in the Northwest Territories of Canada against a long-distance supply chain importing raspberries from Mexico. This research makes a unique contribution to the field by quantitatively evaluating the performance and resilience of both short and long supply chains. Through a disruption history encompassing 54 varied scenarios, this study enables a clear, data-driven judgment of the two supply chain networks. This approach moves beyond the traditional reliance on qualitative and theoretical advantages, offering an empirical basis to compare their efficiency and robustness under disruptive conditions. The findings reveal significant insights into the costs, efficiency, and robustness of both supply chain models. The model developed here applies seven different network compositions for short and long supply networks to the 54 disruption scenarios, picking the optimal network overall in each scenario, leading to an average 5.2 percent increase in resilience, all while reducing costs by $4500. Importantly, the methodology and framework developed in this study are not confined to raspberry production; they hold potential for broader application across various supply networks. This aspect is particularly valuable for entrepreneurs and businesses in evaluating the feasibility and resilience of new ventures. Moreover, our findings offer actionable insights for governmental bodies, like the Government of Canada, in strategizing to incentivize local production. This approach could be a crucial step towards ensuring national food security and stabilizing food prices across the country, thereby having significant implications for policy-making and economic planning.October 202
Towards a peaceable process: Canadian theatre directing after 2014
No full textThe role of the director in Anglophone Canadian theatre has undergone a transformation. Beginning around 2014, this shift saw the hierarchical model of the position come into question from multiple sources resulting in the development of a suite of new methodologies and creative collaborators that are actively shifting the role of the director into a malleable process structure accountable to both the artistic ensemble and the audience. This new liminal reality reflects a more peaceable sensibility. This study begins with an exploration of the development of professional Anglophone direction in Canada, linking back to the European tradition with a focus on the rise of the professional director, the birth of the Stratford Festival, and the impact of Tyrone Guthrie on the profession. The next six chapters each represent one methodology or position that is functioning to dismantle or re-shape the previously idealized model of the hierarchical director. The first of these chapters, Chapter 4, focuses on decolonization and Indigenization within the process of theatrical direction. Chapter 5 charts significant milestones in antiracist practices in professional directing in Canada. Chapter 6 chronicles the emergence of cultural consultants as new collaborators within the field of professional theatre. Chapter 7 is an inquiry into accessibility practices that inform professional directorial processes while highlighting disability justice frameworks and the social model of disability. Chapter 8 is dedicated to presenting how trauma informed practice/care is changing the way directors are interacting within rehearsal halls and auditions. Lastly, Chapter 9 provides an overview and outline of the profession of intimacy direction and reflects on how this new position alters the role of the director. The conclusion offers examples of how public calls for change within the culture of professional theatre in Canada have reshaped how directors are working. It proposes the new term “peaceable direction” (a liminal process structure that values flexibility over hierarchy) as a container for all these changes, calls attention to two new collaborative artistic positions, and posits that previously marginalized equity-based artistic practices have become part of mainstream directorial process since 2014.October 202
How systemic racism results in poorer outcomes for First Nations, and what First Nations are doing about it: the example of kidney health
No full textBackground: End-stage kidney disease continues to disproportionally impact the lives of First Nations peoples. Systemic racism is a key determinant, and manifests as differential access to determinants of health (housing, employment, access to care) and differential care. This paper discusses how different models of primary healthcare operating in rural and remote Manitoba communities results in different outcomes for patients identified as being at risk of kidney disease.
Methods: This study is a partnership between researchers from the First Nations Health and Social Secretariat of Manitoba and the University of Manitoba. We used health administrative data held at the Manitoba Centre for Health Policy for the period of 2006-2019, linked to the Manitoba First Nations Research File to identify First Nations. We compared rates of laboratory follow-up tests, nephrology consults, PHC visits, and hospitalizations between different models of care using a negative binomial regression model adjusted for age, sex, eGFR heat-map category, urine ACR heat-map category, and Elixhauser comorbidity index.
Results: We identified 12,613 First Nations people with chronic kidney disease (CKD) during the study period. First Nations individuals with CKD who reside in communities served by Nursing Stations (most remote communities) when supplemented by additional Indigenous programs were consistently more likely to receive follow-up serum creatinine (OR 1.37, 95% CI: 1.30-1.45, p<0.001), urine ACR (OR 1.22, 95% CI: 1.16-1.28, p<0.001), serum potassium (OR 1.40, 95% CI: 1.32-1.49, p<0.001) than individuals who lived in communities served by Nursing Stations alone, Health Centres, Health Offices, or Off Reserve.
Conclusions: Our results show that addressing the rise in premature mortality experienced by First Nations from kidney diseases require greater investments in First Nations-centric primary healthcare, that is locally managed. Additionally, off-reserve primary healthcare services must be alerted to their need to better address the needs of First Nations at risk of CKD, with more consistent follow up, referrals, and in providing culturally safe care. Finally, First Nations-led research in kidney health and primary healthcare is leading to significant improvements in outcomes, and needs to be better supported and resourced, and imbedded in a context of greater investments to improve access to all determinants of health and counter systemic racism
Using Drosophila melanogaster to determine the phenotypic spectrum of pathogenic KAT6A and KAT6B variants
No full textOver 700 patients with KAT6 syndromes, caused by heterozygous pathogenic variants in KAT6A and KAT6B (KAT6A/B), have been reported. Shared clinical features include intellectual disability, feeding difficulties, characteristic facial features and cardiac anomalies. Individuals with KAT6B syndromes also present with skeletal and genital features. KAT6A/B encode paralogous lysine acetyltransferases, which play an important role in development. Most KAT6A/B variants are de novo, with some reports of inherited variants. Truncating variants are typically classified as pathogenic and are thought to lead to loss-of-function (LoF) and haploinsufficiency. By contrast, most missense variants are classified as variants of uncertain significance, and the underlying disease mechanism is poorly understood. The aim of this study was to use the GAL4/UAS system in Drosophila melanogaster to characterize variant impact to better understand the phenotypic spectrum of KAT6 syndromes. Variants were overexpressed ubiquitously, in cells that express the fly ortholog, enok, and in the developing wing. Phenotypes (i.e., lethality, wing morphology) were assessed. Functional results were compared against clinical severity and the location of the variant in the gene/protein structures. Overexpression of most KAT6A/B truncating variants and KAT6B missense variants leads to LoF in the fly models. By contrast, KAT6A missense variants exhibit gain-of-function (GoF) activity. GoF effects are also observed in the KAT6A p.R1129* variant and the KAT6B p.E1022*, p.K1258Gfs*13 and p.E1681K variants. The p.R1129* and p.K1258Gfs*13 variants, both located at the start of the final exon, are associated with the most severe clinical phenotypes, while the remaining variants are linked to mild to moderate phenotypes. Functional characterization of KAT6A/B variants in flies demonstrates distinct mechanisms of pathogenicity and clinical outcomes, which emphasizes the importance of variant-specific effects in disease expression. This knowledge contributes to a deeper understanding of KAT6 syndromes.October 202
Civil-military coordination in responding to nature-triggered disasters: understanding the challenges and opportunities of the Canadian emergency response structure
No full textThis study explores the challenges and opportunities associated with engaging the military in domestic nature-triggered disasters within Canada’s evolving federal and provincial emergency management framework. As climate change intensifies the scale and frequency of emergencies, the Canadian Armed Forces (CAF) has become increasingly involved in domestic responses—despite operating within a governance structure that prioritizes provincial autonomy and civilian-led coordination. Using a qualitative case study approach, this research draws on inputs from 26 Key Informant interviews, a multi-stakeholder focus group session, and a comprehensive literature review to examine how institutional structures, interagency coordination, and stakeholder perspectives influence military involvement in disaster scenarios.
The findings reveal that, although the CAF offers critical operational capabilities—such as logistics and rapid air deployment—its integration into domestic response systems remains are challenged by procedural ambiguity, organizational culture gaps, and varying levels of operational and institutional preparedness across civilian agencies, particularly in areas of training, equipment, and interagency coordination readiness. The research identifies strategic risks in Canada’s overall disaster response capacity, including unsustainable reliance on military support, delays in mobilization, and insufficient investment in local disaster infrastructure. Through comparative analysis with selected countries, namely the United States (US) and New Zealand, the study highlights how clear mandates, joint training, and intermediate response bodies can improve coordination and efficiency. The thesis calls for a nationally coherent framework that clarifies the CAF’s support role, strengthens civilian capacity, and ensures balanced disaster governance in Canada.October 202