30921 research outputs found
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Effect of chronic contractile activity on skeletal muscle-derived extracellular vesicles and their biological activity
No full textRegular exercise evokes numerous systemic benefits, including enhanced mitochondrial function, protection against cardiovascular diseases, and potential anti-tumorigenic effects, among many others. Strong evidence suggests that the systemic adaptative effects of exercise are potentiated in part by the release of myokines during exercise from skeletal muscle. However, the precise molecular mechanisms driving the adaptations of exercise have yet to be fully elucidated. Beyond myokines, extracellular vesicles (EVs), key mediators of intercellular communication, are also released from skeletal muscle during exercise. EVs are small, lipid bilayer-enclosed structures that carry several biomolecules from host cells to recipient cells, thereby modulating the function of target cells. Given the established role of skeletal muscle in exercise-induced responses and the central role of EVs in cell signaling, we hypothesized that skeletal muscle-derived EVs (Skm-EVs) may contribute to the systemic benefits associated with exercise. To investigate this, we employed chronic contractile activity (CCA) on differentiated C2C12 myotubes to mimic exercise in vitro and examined, for the first time, the effects of Skm-EVs on recipient cells. We hypothesized that Skm-EVs derived post-CCA (or CCA-EVs) would mediate the pro-metabolic and anti-tumorigenic effects associated with chronic exercise. In our first study, we observed that CCA led to an increased release of Skm-EVs, which subsequently enhanced mitochondrial biogenesis in C2C12 myoblasts, indicating a potential mechanism for the pro-metabolic benefits of exercise. In the second study, we demonstrated that CCA-EVs increased apoptosis and senescence in Lewis Lung Carcinoma cells, suggesting a role in the anti-tumorigenic effects of exercise. Importantly, in both studies, pre-treatment of CCA-EVs with proteinase K, with or without Triton X-100, reduced their effect on recipient cells, highlighting the significance of the membrane-associated EV protein cargo in mediating these effects. Building on these findings, we conducted a third study to analyze the proteomic content of Skm-EVs and identified potential protein candidates that might be involved in mediating the pro-metabolic and anti-tumorigenic effects of CCA-EVs in the first two studies. Collectively, these findings advance our understanding of the role of Skm-EVs in mediating the systemic benefits of exercise, potentially providing a mechanistic basis for the development of exercise-based therapeutic strategies.February 202
Nature inspired algorithmic strategies for portfolio optimization
No full textPortfolio optimization (PO) entails deciding which assets to invest in order to maximize overall return while minimizing overall risk at the same time. To successfully mitigate loss risk,
the assets within the portfolio need to be diversified among different instruments, industry, etc, so that the risk exposure to any one kind of asset is limited. Another challenge in PO is
finding the optimum weight allocation of funds to the assets within Portfolio. Each investor has their unique risk appetite and earning goals, so apportioning of assets within portfolio is
needed to balance the risk and reward as per individual investor’s goals. With an increase in the number of assets under a portfolio, the optimal asset weight allocation becomes more
complex. It becomes more challenging when there is a vast number of assets to choose from. In recent years, nature inspired algorithms have been considered on a large scale as a first
approach to PO in computational finance literature that provides approximate results which could be improved with deterministic techniques.
By incorporating nature-inspired algorithms, researchers have been able to overcome the limitations of traditional optimization techniques and achieve better performance in terms of
PO. However, there are several issues and challenges associated with using swarm intelligence (a class of nature inspired algorithmic techniques) for PO. Swarm intelligence does not inherently enforce portfolio diversification. Without explicit constraints, these algorithms may generate portfolios that are concentrated towards similar type of assets. Swarm intelligence also face issues when dealing with large-scale portfolio weight optimization. The computational complexity and optimization time increases with the increasing number of assets within a portfolio. These issues hinder the practical applicability of swarm intelligence algorithms for real world portfolio optimization.
Novelty in this thesis is that we improved two different swarm intelligence algorithms and employed an integrative conjunction of these two algorithms: Ant Brood Clustering (ABC) and
Particle Swarm Optimization (PSO) to overcome the issues mentioned above. We improved ABC method with co-integration measure of time series for portfolio diversification which gave clusters of similar stocks based on the co-integration of their closing prices. Subsequently, we fed several diversified portfolios to a novel design of a Set-Based PSO algorithm, synchronous set-based PSO for further stock selection and optimizing the weight allocation of assets within the portfolio.
The primary conclusions drawn from the studies suggest that the resulting portfolio contained diversified stocks and the weights allocated to those stocks minimized the risk while
maximizing the returns. The proposed study presents a promising approach for investors who are aiming to build robust and resilient portfolios to potentially adopt these algorithms across diverse market conditions.Graduate Enhancement of Tri-agency Stipends (GETS), University of Manitoba
International Graduate Student Entrance Scholarship
International Graduate Student Bursary
FAA International Graduate Student Bursary
Robert Eby Graduate Student Scholarship in Computer ScienceMay 202
Characterization of first cut alfalfa grass silage management practice on Canadian dairy farms and their impact on silage quality
No full textThis study was conducted to compare silage management practices on Canadian dairy farms and evaluate their impact on the quality of first cut alfalfa grass silages. In manuscript 1, n=288 responses were collected in the British Columbia (n=21), Prairie (n=32), Central (n=218), and Atlantic (n=17) regions from an online survey distributed in 2020. Forage type (p<0.0001), silo type (p<0.0001), and wilting method (p<0.0001) were the most significantly different among regions. Alfalfa-grass was the most common forage type reported in the Central (93.0%), Atlantic (88.2%), and Prairie (68.8%) regions whereas grass was more common in British Columbia (66.7%). Use of all silo types were reported in the Prairies, Central, and Atlantic regions while only bunkers (52.4%) and baleage (28.6%) were reported in British Columbia. The Central region had the highest response rate for towers (37.2%). Majority of respondents in the Central (78.9%), Prairie (75.9%), Atlantic (71.0%), and British Columbia (55.0%) regions reported wilting forages in windrows. However British Columbia had a sufficient response rate for the use of a tedder (45.0%), which corresponds with the regions high response rate for grass.
In manuscript 2, (n=186) first cut alfalfa, alfalfa-grass, and grass silage samples were collected from British Columbia (n=15), Prairies (n=55), Central (n=34), and Atlantic (n=82) regions. Relative Feed Value (RFV) and Relative Forage Quality (RFQ) were developed to have similar index scales where the minimum value of 125 is recommended for lactating dairy cows. When forages were evaluated with RFV only alfalfa (136.34) met the minimum recommendations. Evaluating forages with RFQ saw all forages meet the minimum recommendation with alfalfa averaging (163.92), alfalfa-grass (158.53), and grass (146.42). The average IVDMD values for alfalfa (66.68 %DM), alfalfa-grass (62.95 %DM), and grass (57.19 %DM) were in line with previous studies, however VolGAS48 averages could not be compared to other studies. This study concluded that (i) there is a large variation in silage quality across Canada, (ii) region and forage type influence quality among other silage management factors (iii) measured estimates such IVDMD and VolGAS48 need further research to standardize the protocol for industry use.February 202
The fourth place within Generation Z's live and work apartment design
No full textThis proposal is for a live and work environment located in the Exchange District of Winnipeg, Manitoba. In the wake of COVID-19, the facility is intended to provide Gen Z with a sense of pride through ownership and build a community through the programming that will take place within as this design aims to merge commercial and residential design. This practicum seeks to use interior design to provide the next generation with a solid foundation and a more permanent space in which they can feel confident, safe and a part of a community they are excited to interact with. While considering the challenges Gen Z is facing this will guide the programming within the apartment design and will help cater events and workshops that will draw in Gen Z.October 202
Experiences of resilience among Indigenous and newcomer students in Winnipeg high schools and CEDA
No full textThere continue to be disparities in education access for Indigenous and newcomer youth across Canada. Indigenous and newcomer youth often encounter unique challenges in educational settings, including racism, bullying, cultural alienation, and inappropriate school curricula. Despite these obstacles, Indigenous and newcomer youth demonstrate resilience and thrive in academic environments. Studies examining the factors contributing to their success and resilience are limited. There is a need to understand these dynamics better to create meaningful interventions that support Indigenous and newcomer youth's experience and success in high school. The Circle of Courage® is a resilience framework rooted in Native American cultures, and experiencing its components enhances positive youth development. This project aimed to explore how the Indigenous and newcomer youth at the Community Education Development Association (CEDA) experienced the Circle of Courage® and related to youth's goals, resilience, and wellness. Nineteen youth participating in the CEDA Pathways to Education program were purposively recruited for the study. Data collection involved one sharing circle with seven participants and eighteen in-depth interviews, allowing for the collection of rich narratives. The findings indicate that Indigenous and newcomer youth experience the Circle of Courage® to varying degrees within school environments, with CEDA promoting its components to a greater extent. Particularly, the Circle of Courage® enhanced positive learning experiences and fostered wellness, resilience, and future orientation among youth. Belonging emerged as the cornerstone of the Circle of Courage®. The study underscored the pivotal role of personal connections and relationships, both within school and at CEDA, in promoting resilience and wellness among youth. It also highlighted CEDA Pathways as an afterschool program that completed learning education and offered additional support where schools may fall short. Notably, the project identified strong similarities between Indigenous and newcomer youth in their experiences related to the Circle of Courage® components, suggesting this framework's universality. These findings contribute to the growing body of evidence supporting that the Circle of Courage® may be applicable to youth of different backgrounds and can be a valuable tool for promoting positive learning experiences, resilience, and wellness among youth in academic settings.Social Science and Humanities Research CouncilOctober 202
Investigating the role of lectins in LAG3 function and T cell activity
No full textDuring prolonged antigen exposure, as in cancer or HIV, surface inhibitory receptors called immune checkpoints (ICs), like Lymphocyte Activation Gene-3 (LAG3) are upregulated on T cells to provoke immunosuppression and evade immune control. Despite well-characterized LAG3-induced T cell exhaustion inhibiting cell function and cytokine responses, much about LAG3 remains elusive.
LAG3’s extensive N-glycosylation, constitutes a recognition interface for LAG3-expressing cells to communicate and engage with binding partners in their microenvironment. Accordingly, its N-glycosylated residues can coordinate immune interactions and IC function by potentially engaging glycan-binding proteins or lectins such as Galectin-3 or LSECtin, often secreted in these disease contexts. However, the precise mechanisms of this interaction and its functional consequences on LAG3-mediated T cell activity remain a significant knowledge gap. This thesis clarifies that LSECtin and Galectin-3 exhibit dose-dependent specificity for binding LAG3 N-glycans through their carbohydrate recognition domains, affirming the necessity of N-glycosylation in LAG3-lectin engagements.
As an additional immune regulatory layer, this study also resolves that Galectin-3 and LSECtin binding augments LAG3-mediated T cell suppression, with LSECtin yielding stronger inhibitory effects. Contingent on LAG3, these lectin-driven reductions in pro-inflammatory cytokines, IL-2 and IFNγ, may skew and compromise antiviral and antitumor immunity. Conversely, this lectin-induced T cell inhibition is alleviated with N-glycan removal. Addressing a critical research gap in LAG3 literature, this dissertation uncovers a previously underappreciated mechanism of how post-translational N-glycosylation and lectins modulate and instruct LAG3-mediated T cell suppression.
In broadening the scope of LAG3 biology, such insights can spur further research into the complex molecular interplays engendering immune exhaustion and immune escape to better relieve disease progression. By illuminating promising therapeutic targets regarding LAG3-lectin engagements, the research herein can optimize and inform the efficacy of a lectin or LAG3 blockade clinically. Targeted interventions of this nature, alongside current immunotherapies, can refine current cure strategies in addressing undesired immune dysfunction and reinvigorating host immunity for better patient prognosis.May 202
Evaluating the chromatographic behaviour of peptides carrying post-translational modifications for proteomics applications
No full textAmong all types of biomolecules, proteins make up a large portion of the core function of cellular processes. Studying the proteins in a cell is called proteomics, and all the proteins which make up this system, the proteome. Proteomics relies on robust and sophisticated liquid chromatography mass spectrometry (LC-MS) instrumentation with highly developed protocols to achieve confident results in peptide and protein identifications. For such applications, it is useful for the chromatographic and mass spectrometric properties of peptides to be well characterized and consistent across all forms which a peptide can be found. These forms are either native, where peptides are found as simple strings of amino acids or be altered with what are called post-translational modifications (PTMs), where a functional group has been added to the protein endogenously (in the cell) or by chemical treatment. These modifications can have drastic ramifications on the analytical properties of peptides and can even affect the protein identification output by artificially altering the observed abundance of a protein within a sample if the diminished intensities on LC-MS are not taken into consideration. Moreover, endogenous modifications often represent a feature of a protein which is being used to communicate within a signalling pathway or alter the function of that protein in the cell, thereby making PTMs an important choice for biological investigations.
Unfortunately, despite the importance in studying PTMs, their chromatographic characteristics are rarely reported. In this thesis, the chemical characteristics of various PTMs, general and specific, were uncovered and reported, permitting explanations for standard and ‘anomalous’ retention behaviours for peptides carrying PTMs. The general features across all PTMs studied in our lab over the last 10 years were summarized, while more specific behaviours based on peptide primary structure and the position of the modified amino acid were elucidated for peptides carrying deamidations and HexNAc glycosylations. Moreover, one mode which largely showed promise in investigating PTMs, electrostatic repulsion-hydrophilic interaction chromatography (ERLIC), was studied for its retention properties. This led to the development of a retention time prediction algorithm which explained the sequence-specific behaviour of peptides and general features of PTMs in ERLIC.February 202
Using workshops to enhance parent understanding of and beliefs about reform-based mathematics teaching and learning
No full textAs a middle school teacher, I often find that parents are concerned about the quality of their children’s mathematics education, especially when they are confronted with unfamiliar methods and teaching practices. The topic of mathematics education is often the subject of public scrutiny (Chernoff, 2019; Herrera & Owens, 2001), but it has also been well-researched. In this study, I investigated the experiences of parents of middle school students who attended a series of three workshops on mathematics teaching and learning. I used positioning theory to analyze how they positioned themselves in relation to the discourse on mathematics education. After attending the workshops, listening to explanations of key concepts, and participating in hands-on activities, I found that many participants felt better equipped and empowered to help their children with mathematics. They expressed a sense of trust in teachers and the education system and seemed to have an enhanced understanding of the value of reform-oriented mathematics teaching and learning. At the same time, their views of the centrality of fact fluency seemed more resistant to change. This study provides valuable insight for researchers looking to further investigate the use of parent workshops in a middle school context, as well as teachers, administrators, and school divisions looking to perform outreach in their communities in the area of mathematics education.October 202
A scoping review of the links between early childhood caries and clean water and sanitation: the Sustainable Development Goal 6
No full textIntroduction
The United Nation’s Sustainable Development Goal (SDG) 6 calls for universal access to clean water, sanitation and hygiene (WASH), which are crucial elements of health and well-being and fundamental for a life in dignity. Early childhood caries (ECC) is a preventable disease affecting health and quality of life of millions of young children worldwide. This scoping review aims to explore the connection between ECC and access to clean water and sanitation.
Methods
This scoping review, registered on the Open Science Framework and following PRISMA-ScR guidelines, conducted a thorough search in databases (PubMed, Web of Science, Embase, Google Scholar, SciELO) and websites (via Google) in November 2023. The search, without date limitations, targeted studies in English and Spanish linking ECC to SDG6. Exclusions were made for studies solely focusing on ECC without a direct connection to clean water and sanitation. Descriptive statistics summarized the retrieved papers.
Results
The initial search yielded 303 articles. After removing duplicates, 264 articles remained for title and abstract screening after which 244 were excluded and one report was added through citation searching. The 21 remaining articles underwent full text review. There were no studies on a direct association between access to clean water and sanitation and the prevalence of ECC. There were nine studies that showed indirect associations between ECC and access to clean water and sanitation through the links of: water and sanitation access as a marker for poverty (n = 1), water consumption as a feeding practice (n = 4), and the effectiveness of water fluoridation (n = 4). These were used to develop a conceptual model.
Conclusions
While it is conceivable that a direct link exists between ECC and access to clean water and sanitation, the available body of research only offers evidence of indirect associations. The exploration of potential pathways connecting water access to ECC warrants further investigation in future research
Beyond Blood Sugar Control: A Review of Metformin’s Therapeutic Potential in Age-Related Disease
No full textEvidence has suggested that the pharmacokinetic mechanisms of metformin may show benefit in the etiology of chronic disease beyond that of diabetes control. This review investigates various clinical trials and analyses the efficacy of metformin in non-diabetic individuals focusing on cardiovascular disease, neurodegenerative disease, and lung neoplasm. Findings suggest an overall neutrality in the effects of metformin across the three analyzed aspects of chronic disease. Specifically, 38% of participants in the cardiovascular disease studies exhibited a favorable response to metformin. These benefits were observed in blood pressure control, left ventricular mass and NT-pro-BNP, with some evidence indicating an improved lipid profile. Additionally, 39% of participants in the neurodegenerative disease trials demonstrated positive outcomes. Significant enhancements were observed in cerebral blood flow within the orbitofrontal region, as well as executive function in Alzheimer’s disease patients. Mechanical power and duration in gait analysis in those with Myotonic dystrophy demonstrated beneficial outcomes. However, among participants with lung neoplasm, only 12% displayed overall benefit with metformin as an adjunct therapy. Findings suggested of six-month progression-free survival; however, conflicting data suggested a negative trend to the same parameter as well as overall survival. These findings may underscore the nuanced effects of metformin across different stages of disease and highlight the importance of considering various factors when evaluating therapeutic potential. In conclusion, while metformin shows promise in certain aspects of chronic disease, further research is needed to provide further insight into metformin’s role in chronic disease and prolonging health span