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Recent Submissions
Effects of Phospholipase A/Acyltransferase-1 (Plaat1) gene deletion on brain molecular and biochemical measures and memory
(University of Waterloo, 2025-10-30) Cocco, Alex
Phospholipase A1/2 and Acyltransferase-1 (PLAAT1) is a small lipid metabolizing enzyme that possesses transacylase activity and is expressed highly in the rodent heart and brain. Recently, our lab has found that in vitro, PLAAT1 is capable of acylating monolysocardiolipin with an acyl chain donated from phosphatidylcholine acyl donors to produce cardiolipin. Cardiolipin is a glycerophospholipid that is essentially exclusive to the mitochondria and is vital for trans-membrane protein stability, inner mitochondrial membrane structure, apoptosis, and more. The de novo synthesis and acyl chain alterations (‘remodeling’) of cardiolipin are important for the health and proper functioning of cells. Previous work in our lab has demonstrated that mice deficient in Plaat1 (Plaat1-/-) had significant deficiencies in cardiac cardiolipin content, suggesting an in vivo role of PLAAT1 in cardiolipin metabolism. However, Plaat1-/- mice are poorly characterized, especially with regards to the brain, and study of this tissue, and
phenotypic changes related to brain function, could help to delineate the role that PLAAT1 may serve there.
Thus, the purpose of this thesis project was to explore the effects of Plaat1-deficiency on mouse brain cardiolipin metabolism and related functions. Lipid analyses of cardiolipin, monolysocardiolipin and phosphatidylcholine revealed small, sex-specific alterations in composition but not content, while analyses of gene expression for relevant biosynthetic and remodeling enzymes exhibited significant transcriptional downregulation in female but not male Plaat1-/- brains. Immunoblotting for mitochondrial protein markers suggested changes to mitochondrial shape in female Plaat1-/- brains, while both male and female Plaat1-/- brains experienced perturbations in subunit content for complexes of the electron transport chain.
Lastly, mouse anxiety and short-term memory behaviour was tested, revealing that female Plaat1-/- mice are relatively anxiolytic (relaxed), while neither male nor female Plaat1-/- mice had altered short-term memory. Taken altogether, the data collected in this project suggests that PLAAT1
acts in a tissue- and sex-specific manner for reasons that were unable to explored within the scope of this thesis project. The present thesis project demonstrates both a cellular and physiological role of PLAAT1 in the female brain, and provides a foundation from which further work on PLAAT1 can be explored. These results have implications for the interaction of sex and cardiolipin metabolism in the function of brain mitochondria and resultant behavioural outcomes.
In silico and In vitro Discovery of Plant-Based Pro-Inflammatory Cytokine Inhibitors
(University of Waterloo, 2025-10-28) Huynh, Cassandra
Purpose: Dry eye disease (DED) is a prevalent condition range between 44.2% to 62.9% of the population, with female sex and aging being the greatest risk factors. The pathogenesis of DED is based on the dysregulation of tear film homeostasis, resulting in a vicious circle of desiccating stress, inflammation, and tissue damage. Mild DED is managed with artificial tears and warm compresses, whereas moderate-to-severe DED require additional anti-inflammatory therapies to break the vicious circle. Anti-inflammatory drugs such as corticosteroids are effective treatments but are associated with adverse side effects including increased risk of cataracts and glaucoma. Discovering novel anti-inflammatory therapeutics with minimal adverse side effects would greatly benefit DED patients who depend on anti-inflammatory treatment to mitigate symptoms. Flavonoids are a class of chemicals found in all vegetation; some are known for their anti-inflammatory effects. The numerous members of the flavonoid class could be leveraged to discover novel inhibitors against inflammatory DED targets. The purpose of this thesis was to discover a novel flavonoid that could act as an anti-inflammatory agent to treat DED.
Methods: This thesis employed a hybrid approach using network analysis, computational modelling, and in vitro validation. Network analysis was employed to select DED-associated protein targets and candidate flavonoids. “Dry Eye Syndrome” proteins were extracted from the STRING-DISEASE database and were cross-referenced with drug databanks using the functional enrichment analysis tool, ToppFun, for flavonoids. A network analysis tool, Cytoscape (v 3.9.1.), was utilized to visualize and rank DED-associated proteins and flavonoids by number of edge interactions. Two proteins were selected for their distinct roles in the immune response, and two flavonoids were selected for their association with multiple pro-inflammatory DED-associated proteins. Molecular docking and molecular dynamic (MD) simulations modelled and simulated the protein-ligand complex of both protein targets with each flavonoid molecule. Four protein-ligand complexes were assessed for stability and specific residue-ligand interactions. The inhibitory effects of both flavonoids were assessed in vitro with ELISAs against both protein targets. The biocompatibility of the most effective flavonoid inhibitor was assessed with human corneal epithelial cells (HCEC) using an Alamar Blue metabolic activity assay; viability was assessed by evaluating the proportion of live, apoptotic, and dead cells.
Results: The network analysis generated a protein-protein interaction network of 64 DED-associated proteins and a drug-protein network of 108 flavonoids. Tumour necrosis factor (TNF) 𝛂 interactions and interleukin (IL) 17A (14 interactions) were amongst the 5 highly ranked proteins and selected for their roles in the innate and adaptive immune response, respectively. Luteolin (19 interactions) and rutin (17 interactions) were the highest ranked flavonoids associated with DED-associated proteins. Molecular docking and MD simulations predicted that both flavonoids could bind directly to the receptor binding sites of both cytokines. However, ELISAs showed that neither luteolin nor rutin could inhibit TNF-𝛂 and TNF receptor interaction (all p≥0.07). On the other hand, both luteolin (IC50 = 16.54 mM) and rutin (IC50 = 8.73 mM) had inhibitory effects against IL-17A and IL-17A receptor interaction (all p<0.01). Metabolic activity and viability of HCEC remained high (all ≥ 85.95%) below 3.0 mM rutin; no significant difference in metabolic activity and viability were detected in all concentrations of rutin compared to the control (all p>0.06).
Conclusion: This thesis identified rutin as a novel flavonoid inhibitor of IL-17A. These findings suggest that rutin may play a role in anti-inflammatory therapeutics for DED.
Preserving and Generalizing χ-boundedness
(University of Waterloo, 2025-10-27) Chaniotis, Aristotelis
The notion of χ-boundedness, introduced by Gyárfás in the mid-1980s, captures when, for every induced subgraph of a graph, large chromatic number can occur only due to the presence of a sufficiently large complete subgraph. The study of χ-boundedness is a central topic in graph theory. Understanding which hereditary classes of graphs are χ-bounded is of particular importance for advancing our understanding of how restrictions on the induced subgraphs of a graph affect both its global structure and key parameters such as the clique number and the independence number.
Which classes of graphs are χ-bounded? A method that has been used to prove that a class C of graphs is χ-bounded proceeds as follows: we prove that C can be obtained by applying operations that preserve χ-boundedness to already χ-bounded classes. This approach gives rise to the following question: which operations preserve χ-boundedness?
Given k graphs G₁,…,Gₖ, their intersection is the graph (∩{i∈[k]}V(Gᵢ), ∩{i∈[k]}E(Gᵢ)). Given k graph classes G₁,…,Gₖ, we call the class {G : ∀i∈[k], ∃Gᵢ∈Gᵢ such that G = G₁ ∩ ⋯ ∩ Gₖ} the graph-intersection of G₁,…,Gₖ. In the mid-1980s, in his seminal paper “Problems from the world surrounding perfect graphs”, Gyárfás observed that, due to early results of Asplund and Grünbaum, and Burling, graph-intersection does not preserve χ-boundedness in general, and he raised some questions regarding the interplay between graph-intersection and χ-boundedness. This topic has not received much attention since then. In this thesis, we formalize and explore the connection between the operation of graph-intersection and χ-boundedness.
Let r ≥ 2 be an integer. We denote by Kᵣ the complete graph on r vertices. The Kᵣ-free chromatic number of a graph G, denoted by χᵣ(G), is the minimum size of a partition of V(G) into sets each of which induces a Kᵣ-free graph. Generalizing χ-boundedness, we say that a class C of graphs is χᵣ-bounded if there exists a function f:ℕ→ℕ such that for every G∈C and every induced subgraph G′ of G, we have χᵣ(G′) ≤ f(ω(G′)), where ω(G′) denotes the clique number of G′. We study the induced subgraphs of graphs with large Kᵣ-free chromatic number.
Finally, we introduce the fractional Kᵣ-free chromatic number, and for every r ≥ 2 we construct K_{r+1}-free intersection graphs of straight-line segments in the plane with arbitrarily large fractional Kᵣ-free chromatic number.
Data-Driven Decision-Making Under Uncertainty: An Empirical Study of U.S. Wildfire Management
(University of Waterloo, 2025-10-24) Garros, Gong
Wildfire management in the United States faces prediction accuracy, cost efficiency, and fiscal sustainability issues. This dissertation integrates three interrelated research topics to develop integrated decision models applicable to each stage of wildfire management. The first study evaluates the role of social media analytics (SMA) and Web 3.0 technologies towards improving wildfire prediction, real-time tracking, and response decisions. The study reviewed current social media analytics tools for crisis response, showing how they support crisis tracking, response timing, and crisis communication. The same functionality can presumably be applied to wildfire management. The second study introduces a temporal gravity model that links population- and location-weighted social media activity to wildfire response costs per acre. The model captures behavioral visibility prior to operational deployment and demonstrates stronger informational value than tweet volume alone. The third study investigates how federal budget changes relate to the accuracy of state preparedness decisions. Higher funding is associated with improved accuracy in the short term, but this association weakens in later budget cycles. The analysis treats federal budgets as exogenous inputs and uses panel methods with robustness checks to evaluate decision dynamics under fixed fiscal constraints. Across all three essays, the dissertation highlights the importance of integrating behavioral data and fiscal signals to better inform wildfire planning. It provides empirical evidence that public attention, budget expectations, and institutional coordination jointly influence the quality of response decisions. These findings suggest that effective wildfire management requires models that account for informational uncertainty, fragmented authority, and the timing structure of operational and fiscal systems.
Keywords: Wildfire Management, Decision Science, Behavioral Operations Management, Crisis Informatics, Public Finance, Panel Data Analysis, Gravity Model, Time Series Analysis.
Cybersickness: Linking Postural Control to User Discomfort in a Virtual Roller Coaster
(University of Waterloo, 2025-10-23) Gulifeire, Alimu
Cybersickness (CS) remains a major obstacle to the widespread use of Virtual Reality (VR), with leading explanations emphasizing sensory conflict, sensory reweighting, and postural instability. Prior research has shown that individuals who flexibly reweight visual, vestibular, and body cues report lower CS, particularly in interactive VR tasks where users can move freely. Whether this relationship generalizes to more passive, visually intense VR experiences is less clear. This thesis examined sensory cue reweighting and postural control as predictors of CS during an immersive roller coaster simulation. Nineteen younger adults completed the Oriented Character Recognition Task (OCHART) before and after VR exposure to estimate perceptual upright and quantify cue weightings. During VR exposure, postural movement was recorded using markerless motion capture, and participants reported symptoms using the Fast Motion Sickness (FMS) scale after each trial. Contrary to findings from interactive VR contexts, sensory reweighting was not significantly associated with CS in this passive roller coaster environment. In contrast, measures of postural control, particularly total path length, were robust predictors of sickness severity, with greater displacement linked to higher FMS scores. These findings suggest that in visually dominant VR tasks with limited bodily engagement, postural instability provides a more reliable marker of CS than sensory reweighting. This work clarifies that the predictive value of sensory reweighting is context dependent, emerging more clearly in interactive than passive VR tasks. It further points toward movement-based strategies for mitigating discomfort in VR experiences where movement is restricted but visual conflict is high.