30921 research outputs found
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Aubigny’s Métis and French-Canadian founding families based on its Catholic registries
Full text linkThis thesis is a microhistory focusing on the families found in the registries of the French-Canadian parish of Aubigny in Manitoba; where they came from and what could be understood of the kinship ties evident in the data. It distinguishes categories of settlers including Métis families and francophone families from the United States and Quebec and relies on family reconstitution methods to better make use of the primary source. The registries show how kinship is an aid to settlement and persistence, how marriages create new ties in the community, and how godparenting roles reveal both matrilineal kinship and the presence or absence of rapport between families in the established categories. In addition, use of various databases and newspaper archives trace an outline of families’ political involvement, previous employment, and immigration routes. This work renders a high-definition picture of a very small community, serving to complement or contrast the beginnings of other rural parishes.February 202
Characterization of V3 interneuron firing patterns during rhythmic locomotor-like ventral root activity
Full text linkV3 interneurons (INs) are a genetically defined population of glutamatergic spinal neurons implicated in regulating the robustness of locomotion. Previous studies using computational modeling have postulated that V3 INs play a critical role in maintaining robust, coordinated alternation during rhythmic motor output. However, to date, no studies have directly recorded from identified V3 INs during rhythmic locomotor-like activity in the mammalian spinal cord. Therefore, the purpose of this study is to characterize the intrinsic electrophysiological properties and activity patterns of V3 INs during rhythmic motor activity using whole-cell patch-clamp (WCPC) recordings in Sim1Cre/TdTomato P1–P5 mouse spinal cord preparations. Electrophysiological recordings were preformed prior to and during pharmacologically induced tonic and rhythmic locomotor like ventral root (VR) activity via perfusion of serotonin (5-HT) and N-methyl-D-aspartate (NMDA). Analysis to date indicate that most V3 INs are quiescent at baseline, although some demonstrate spontaneous activity. Variable responses were recorded from V3 INs during drug evoked tonic VR activity. Specifically, following 5-HT and NMDA application and the emergence of tonic VR activity, most V3 INs recorded to date displayed an increase in excitability. This was characterized by a depolarized resting membrane potential and an increased firing rate correlating with the onset of tonic activity in VR recordings. Conversely, some V3 INs demonstrated decreased activity during drug evoked tonic VR activity, suggesting functional diversity within the recorded V3 INs. Similarly, V3 INs recorded during rhythmic VR activity also appeared to be tonic. However, due to our limited sample size, future research should aim to examine a larger sample and record V3s in a wider range of spinal segments to determine whether the observed pattern of firing during drug evoked locomotor activity is a more widespread phenomena/characteristic. These findings will provide critical insights into the cellular mechanisms and contributions of V3 INs to the generation and modulation of spinal locomotor circuits.February 202
Designing cell and protein-based DON biosensors for use in investigating DON-biotransforming microbes
Full text linkFusarium head blight (FHB) poses a major threat to small-grain cereals, reducing yield, quality,
and contaminating grains with the mycotoxin deoxynivalenol (DON). Once contaminated, it is
difficult and costly to remove DON from grains. New rapid and low-cost assays for detecting the
presence of DON are needed in order to screen for novel DON biotransforming microbial strains.
This thesis develops and evaluates two novel biosensors for detecting DON: a cell-based
Escherichia coli biosensor with a GFP reporter and a protein-based sensor engineered from
Fusarium graminearum acetyltransferase TRI101.
The Horizon Discovery E. coli Promoter Collection was screened using fluorescence-activated
cell-sorting, followed by sequencing and fluorescence plate assays for DON-responsive strains.
Strain rmf (ribosome modulation factor) exhibited a reproducible increase in fluorescence (~1.3
1.4× increase) when incubated in the presence of DON. Re-engineering this strain with the
brighter GFP variant mClover3 improved peak ON/OFF fluorescence ratio to ~1.6-1.7. A
medium-throughput fluorescence assay was developed and tested on 142 cultured soil microbial
strains.
Molecular dynamics (MD) simulations were performed to analyze the behaviour of TRI101 in its
apo form as well as with a DON ligand. Computational analysis of TRI101 was used to
determine the best residue fluorophore conjugation sites to produce a modified TRI101 that
could report the presence of DON in a solution. Amino acid residues G421 and A218 were
identified as the best candidates and a TRI101-G421C was designed and expressed
recombinantly in E. coli. When conjugated to TRI101-G421C, 7-diethylamino-3-(4′
maleimidylphenyl)-4-methylcoumarin (CPM) produced a detectable response to DON in
fluorescence assay with a decrease of 8-9% in emission intensity at the emission maximum
wavelength (480 nm).
Together, these results show that an E. coli rmf promoter-based biosensor can inexpensively
detect DON in liquid samples with relatively high detection sensitivity. A TRI101-based
biosensor demonstrated functionality in detecting DON however assay signal contrast and
production of recombinant TRI101 remain as limiting factors. Improvements to TRI101 yield,
testing A218C and other TRI101 mutants for improved performance, as well as further
enhancing the sensitivity and assay signal contrast for both biosensor designs should be the focus
of future research.Engineering Research Council of Canada (NSERC) Discovery Grants programFebruary 202
Acrylamide formation in wholewheat bread: quantitation using LC-MS approaches and understanding the effect of mitigation strategies
No full textSince the detection of acrylamide in foods, there has been growing interest in developing reliable, validated methods to quantify its concentration in staples such as bread, particularly in Canada. Processing factors like high temperature, low moisture, and long cooking times favor acrylamide formation, yet its quantitation is challenging due to the molecule’s small size, high polarity, and matrix effects that can exaggerate or underestimate concentrations. Thus, the development of validated methods and mitigation strategies are needed to accurately assess acrylamide formation during processing. In the first study, 40 diverse Canadian Western Red Spring Wheat cultivars were used to prepare wholewheat breads for acrylamide quantitation and bread quality analysis. The highest level observed was in the crust of Lillian (2021; 145.74 ng g−1), while the lowest was found in the crumb of Napayo (2020; 20.07 ng g−1). The second study tested fermentation time, baking regimen, steam injection, and L-asparaginase treatments (250, 500, 750 µg kg−1). Crust and crumb were analyzed for acrylamide, and the bread quality was evaluated by Volscan profiler, colorimeter, and an AACC scoring method. Baking loaves at a lower temperature for a longer time was the most ideal baking regimen for minimizing acrylamide formation in the bread samples. Additionally, 500 µg kg−1 enzyme was most effective at reducing acrylamide concentrations in bread samples. Furthermore, a short fermentation time (1.5 hr) significantly reduced (p< 0.0001) the acrylamide concentrations formed during baking. Conversely, a longer fermentation time and a shorter baking time at high temperature increased acrylamide the most across all treatments. Subsequent studies should focus on scaling findings to an industrial level to explore the feasibility of scaling up the various mitigation techniques. Overall, this research provides insights into strategies to mitigate acrylamide in bread production.February 202
The effects of nitrogen availability on plant species in the boreal tundra ecotone
Full text linkIn high latitude biomes, increasing temperatures due to climate change are predicted to increase nutrient availability. Given the boreal region is dominated by plant and fungal species that are adapted to surviving in low nutrient soil, an increase in nutrients like nitrogen may cause a variety of responses in mycorrhizae fungi and their host plants. I found that several plant species responded to three years of 10 – 100 kg ha-1 nitrogen addition by changing their leaf N isotope ratios, morphology and physiology. However, these changes showed no obvious correspondence with mycorrhizal status. Although ectomycorrhizal fungi slow down the mineralization rates of nitrogen, and help to immobilize nitrogen, both ectomycorrhizal host plants, Picea glauca (Moench) Voss, and Dryas integrifolia Vahl, increased in total chlorophyll ∂15N while lowering the C:N ratio within their tissue due to fertilizer. The ericoid host plants (Ledum decumbens (Aiton) Lodd. ex. Steud, Vaccinium uliginosum L., and Empetrum nigrum L.) all responded differently from one another and did not respond to nitrogen unlike the ectomycorrhizal host plants. These results suggest that mycorrhizal types do not predict how boreal plant species will take up and utilize inorganic nitrogen. In some regions, climate change has resulted in boreal forests range expanding northwards, especially with a northward shift of coniferous trees. Northward range expansion for conifers on the tundra may involve the establishment and expansion of tree islands: clusters of conifers that create microhabitats on their leeward side. While we predicted these microhabitats would benefit conifer establishment and survival, we did not find this. After planting P. glauca and Pinus banksiana Lamb, seed around tree islands near Churchill, Manitoba, I found higher germination further away from the tree islands and on the windward side.February 202
Investigating ubiquitin dynamics and its impact on chromosome instability and colorectal cancer pathogenesis
No full textColorectal cancer (CRC) is the second leading cause of cancer-related mortality in Canada. These statistics underscore the need to develop more effective therapies, which requires a deeper understanding of CRC pathogenesis. Chromosome instability (CIN) is characterized by an increased rate of chromosome gains and losses and occurs in approximately 85% of CRC cases. However, the aberrant genes driving CIN (i.e., CIN genes) are largely unknown. Emerging data suggest ubiquitin homeostasis is crucial for maintaining chromosome stability, and ubiquitylation and deubiquitylation genes undergo copy number losses in CRC. Thus, I hypothesized that diminished expression of ubiquitylation and deubiquitylation genes induce CIN and cellular transformation, promoting CRC development. This thesis utilized an established research pipeline coupling gene silencing with quantitative imaging microscopy (QuantIM) to investigate 581 ubiquitylation and 94 deubiquitylation genes for impacts on CIN across three karyotypically stable cell lines (HCT116, 1CT and hTERT) (Chapter 4). This screen assessed CIN-associated phenotypes, including changes in nuclear areas and increases in micronucleus formation. Subsequent direct tests in non-malignant colonic epithelial cell lines confirmed that silencing 10 prioritized genes, including USP4 and SKP2, induces significant changes in chromosome numbers and thus, CIN. As USP4 copy number losses occur in ~16% of CRC cases and correspond with worse patient outcomes relative to diploid counterparts, heterozygous and homozygous CRISPR/Cas9 USP4-knockout clones were generated in two non-malignant colonic epithelial cell lines (Chapter 5). Although these knockout clones did not form subcutaneous tumours in mice within the constraints of this study, they exhibited dynamic CIN and cellular transformation phenotypes, suggesting USP4 copy number loss may be an early etiological event in CRC pathogenesis. Parallel research in our laboratory showed that reduced SKP2 expression induces CIN through mechanisms not fully explained by the established substrates Cyclin E1 and P27. To expand these findings, TurboID was employed, which identified the actin-binding proteins Caldesmon and Transgelin as putative SKP2 substrates (Chapter 6). These data implicate novel roles for SKP2 in modulating actin dynamics that may impact chromosome stability. Collectively, these findings provide novel insights into how aberrant ubiquitin regulation impacts CIN and may contribute to CRC pathogenesis.Paul Albrechtsen Research Institute
University of Manitoba
Research Manitoba
Graduate Enhancement of Tri-Council Stipends
Canadian Institute of Health Research
Caroline A. Cope Award for Excellence in Oncology Research
Paul Albrechtsen Research Institute CancerCare Manitoba Major Student Research Award.February 202
A follow up study
No full textIn the summer of 2021, older Manitobans (65 years and older) were surveyed about their experiences using online exercise throughout the first year of the COVID-19 pandemic. Participants were recruited through various community organizations (e.g., exercise organizations, senior centres, retiree organizations). This study is a follow up study to a survey conducted in the summer of 2020, investigating the experiences of older adults in Manitoba using online exercise at the beginning of the COVID-19 pandemic
A genome-wide association study of methamphetamine use among people with HIV
Full text linkAbstract Background Amphetamine-like stimulants are the most used psychostimulants in the world; methamphetamine use is the most prevalent in people with HIV. Prolonged methamphetamine use can cause lasting damage to the heart, gut, and brain, as well as auditory hallucinations and paranoid thinking. However, relatively little is known about methamphetamine use and its genetic contributors. Methods Using genetic information from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, we conducted a multi-ancestry genome-wide association study (GWAS) of methamphetamine use among people with HIV (n = 1,196 reported ever use, n = 4,750 reported never use). Results No single nucleotide polymorphism was statistically associated with methamphetamine use at the genome-wide level (p 0.05 in our analysis). Discussion Our study suggests that there is no single strong genetic contributor to lifetime use of methamphetamine in people with HIV enrolled in CNICS. Larger studies with more refined outcome assessment are warranted to further understand the contribution of genetics to methamphetamine use and use disorder. Investigation into social and environmental contributors to methamphetamine use are similarly necessary
The effectiveness of new urban trail infrastructure on physical activity and active transportation: a systematic review and meta-analysis of natural experiments
Full text linkBackground Cities in Western countries are investing billions of dollars in new cycling infrastructure (urban trails) to support active transportation (AT) and leisure-type physical activity (PA). Little empirical evidence exists on the effectiveness of urban trails on changes in AT or PA. Design and methods We searched CINAHL, OVID, SPORTDiscus, Transport Research International Documentation (TRID), Web of Science Core Collection and Google Scholar for articles published from 2010 to 2023. We included controlled experimental studies that reported PA, AT or trail counts as outcome measures before and after construction of an urban trail. A modified risk of bias tool was employed to assess the methodological quality of each selected study (Prospero ID: CRD42023438891). Results Three independent reviewers screened abstracts from 3936 articles identified in the original search and identified 24 articles that met inclusion criteria: 11 studies (n = 11,464) that measured changes in PA, 8 studies (n = 92,001) that measured changes in cycling traffic and 5 studies (n = 4,958,203) that measured changes in rates of AT/cycling. Meta-analysis revealed that new trails increased PA levels among individuals in proximity to one, compared to those living in control areas (SMD = 0.12; 95% CI: 0.04, 0.20; I2 = 73%; n = 11,464). This effect was marginally stronger when data were restricted to individuals living in closest proximity to trails (SMD = 0.14; 96% CI: 0.06 to 0.25, I2 = 74%; n = 8234). Meta-analyses were not possible for measures of AT and cycling counts. All studies were at high risk of bias due to a failure to adhere to reporting guidelines for quasi-experimental studies. Conclusions There is limited but intriguing evidence that the addition of protected urban trails increases daily PA for individuals living in neighbourhoods that receive them. The strength of this evidence could be enhanced with the application of and adherence to principles of causal inference and increased diversity of individuals included in study designs
Impact of age and mean intracranial pressure on the morphology of intracranial pressure waveform and its association with mortality in traumatic brain injury
Full text linkAbstract Background Morphological analysis of intracranial pressure (ICP) pulse waveforms provides indirect information on cerebrospinal compliance, which might be reduced by space-occupying lesions but also by intracranial hypertension and aging. This study investigates the impact of age and mean ICP on the shape and amplitude of ICP pulse waveform in traumatic brain injury (TBI). Additionally, it explores the association between morphological parameters and mortality after TBI. Methods ICP recordings from 183 TBI patients (median age: 50 (30, 61) years) from the CENTER-TBI database were retrospectively analyzed. ICP morphology was assessed using the artificial intelligence-based pulse shape index (PSI) and peak-to-peak amplitude of ICP pulse waveform (AmpICP). The impact of mean ICP, age, and their interaction on PSI and AmpICP were estimated using factorial ANOVA. To account for influence of disturbance in the intracranial volume on AmpICP and PSI, a multiple regression analysis was performed using age, mean ICP, and the Rotterdam CT score as explanatory variables. The associations of AmpICP and PSI with six-month mortality were assessed using the area under the ROC curve (AUC). Results Age had a predominant influence on PSI (p < 0.01), accounting for 33.1% of its variance, while mean ICP explained 6.6% (p < 0.01). Conversely, mean ICP primarily affected AmpICP (p < 0.01), explaining 22.8% of its variance, with age contributing 8.0% (p < 0.01). A combined effect of age and mean ICP on AmpICP (p = 0.01) explained 11.7% of its variance but did not influence PSI. After accounting for Rotterdam CT score, the results remained consistent, indicating that advanced age has the strongest impact on PSI (β = 0.342, p < 0.01) while elevated mean ICP has dominant influence on AmpICP (β = 0.522, p < 0.01). Both AmpICP and PSI were moderately associated with mortality (AUC: 0.76 and 0.71, respectively). Conclusions AmpICP and PSI capture distinct aspects of cerebrospinal compliance. PSI appears to reflect age-related stiffening of the cerebrovascular system, while AmpICP, influenced by mean ICP, indicates acute volume compensatory changes. Combined, they provide a more comprehensive assessment of cerebrospinal volume–pressure compensation. Both morphological metrics are associated with mortality after TBI. As cerebrospinal compliance declines with age, older TBI patients become more susceptible to uncontrolled rises in ICP, which can worsen their outcome