Biology

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Access status: Open Access ,
Investigation of Small Molecule Inhibitors Targeting βCatenin/TCF4 Interaction in Ovarian Cancer Cell Lines
(2026-07-24) Yan, Rufei; Sheng, Yi; Peng, Chun
Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy. The development of chemoresistance and relapse is a major challenge in treating ovarian cancer. The Wnt/β-catenin pathway plays critical roles in embryonic development and adult homeostasis. The aberrant activation of β-catenin and its interaction with its co-activator TCF4 is implicated in the progression of EOC; therefore, targeting and inhibiting this interaction is desirable for the development of targeted therapies. Previous studies have identified a small molecule inhibitor of β-catenin known as C10, and novel analogues of C10, C45-C62 have been synthesized in-house. In this study, C45-C62 have been characterized through structure-activity relationship analyses and functional assays to determine their direct binding to β-catenin and antitumour effects. Optimization of C10 and its analogues could lead to potential development of a novel β-catenin/TCF4 inhibitor for ovarian cancer treatment.
Access status: Open Access ,
How do Human-Induced Environmental Changes and Parasitism Influence Plant Traits Governing Bumblebee Foraging?
(2026-07-24) Lis, Shai Semuel; Sharma, Sapna
This thesis examines how environmental changes shape interactions foraging behaviour of bumblebees (Bombus), important ecologically and economically pollinators. A literature review identified floral nutritional and morphological traits as being key for bumblebee attraction. Herbivory generally reduced attractiveness to bumblebees through their effects on these traits, while other environmental factors such as soil moisture or fertilizer use had context-dependent impacts. In an experimental study, I then tested how diet quality and infection with the parasite Crithidia bombi interactively influenced foraging behaviour and sensitivity to herbivore damage. Contrary to predictions, herbivory positively influenced bumblebee visitation, while having no effect on measured floral traits. Infection did not influence foraging decisions, but reduced overall foraging activity in a dose-dependent manner, while diet shaped visitation patterns without having an impact on infection intensity. Colony identity, plant height and floral display size were also key predictors of foraging behaviour. These findings highlight the hierarchical nature of interacting biotic and environmental factors in shaping pollinator foraging ecology.
Access status: Open Access ,
The Future of Lake Ice: Drivers, Trends, and Projections of Ice Phenology and Ice Quality
(2026-07-24) Basu, Aman; Sharma, Sapna
Lake ice is changing rapidly due to climate warming, with significant ecological and societal impacts. Since lake ice provides vital ecosystem services and regulates lake conditions, understanding changing lake ice patterns is critical for managing future risks to ecosystems and communities. However, substantial knowledge gaps exist in lake ice research, including the underrepresentation of small lakes in large-scale ice phenology assessments, the lack of large-scale projections of lake ice quality, and a limited understanding of how locally and regionally altered human landscapes may influence ice dynamics. This thesis addresses these gaps by: (1) forecasting ice phenology with extensively involving representation of lakes (<1 km²) across the Northern Hemisphere (Chapter 2); (2) projecting ice quality, specifically black and white ice thickness, and implications for human safety (Chapter 3); and (3) assessing how local and regional drivers influence ice dynamics (Chapter 4). Chapter 2 reveals that lakes are losing ice faster than previously reported, with a sharp drop in ice-cover duration in the late twentieth century. Including abundant but underrepresented small lakes in predictive models improves forecasts of ice phenology under future climate scenarios. Chapter 3 extends this work by providing the first large-scale assessment of lake ice quality, indicating that warming will reduce total ice thickness and increase the proportion of weaker white ice, heightening hazards for winter travel and other activities. Chapter 4 systematically evaluates how landscape and human pressures affect ice phenology at regional and local scales, shaping ice dynamics in northern U.S. lakes. Collectively, this thesis advances our understanding of lake ice by projecting how both ice timing and ice structure are likely to change through the end of the century and clarifying the extent to which regional and local landscape characteristics may complement broader climate mitigation efforts. These findings highlight lake ice as both a sensitive indicator of climate change and a critical component of freshwater ecosystems and northern livelihoods, underscoring the urgent need for coordinated global, regional, and local responses to preserve the ecological and societal benefits of seasonal lake ice.
Access status: Open Access ,
Genomic Insights into Honey Bee Health: Genetics of Immunity and Colony-level Traits
(2026-07-24) Tiwari, Tanushree; Zayed, Amro
Honey bees (Apis mellifera) are essential pollinators in natural and agricultural ecosystems and a key model for studying social behavior. Despite their ecological and economic importance, managed honey bee colonies have experienced persistently high mortality over the past two decades due to interacting stressors, including pests, pathogens, and environmental pressures. Recent national surveys in Canada by the Canadian Association of Professional Apiculturists and Provincial Apiarists reported winter colony losses of 39.3% during 2024–2025, substantially exceeding long-term averages, with Varroa destructor, associated viral infections, weak fall colonies, and poor queen quality identified as major contributors. At the same time, honey bees have substantial phenotypic and genetic diversity across behavioral, immune, and colony-level traits, many of which show measurable narrow-sense heritability. This standing variation provides an opportunity to investigate the genetic basis of colony resilience and immunity. Advances in next-generation sequencing have enabled genome-wide analyses of complex traits at unprecedented scale and resolution. In this dissertation, Chapter 2 establishes the applied and conceptual foundation by reviewing genomic tools for honey bee health management, including stock certification, lineage monitoring, and marker-assisted selection. Building on this framework, Chapter 3 presents a large-scale genome-wide association study (GWAS) of 1,350 colonies spanning behavioral, social, and immune traits, revealing that colony-level traits are heritable yet highly polygenic, shaped by local adaptation, and influenced by extensive pleiotropy. To connect genotype to function further in Chapter 4, protein quantitative trait locus mapping was done to identify loci and genes regulating innate immune protein abundance and pathogen resistance, finding shared loci that influence both protein expression and pathogen load. Integrating these results, Chapter 5 examines the shared genetic architecture of innate immunity, social immunity, and pathogen-associated traits using network analyses, demonstrating that robust honey bee defense is underpinned by interconnected gene networks. Finally, Chapter 6 characterizes understudied short insertion-deletion (InDel) variants and their contribution to colony-level traits, providing complementary evidence to SNP-based analyses. Overall, my dissertation identifies candidate genes, loci, and different genetic variants associated with honey bee health, immunity, and colony performance. These findings highlight key targets for future functional validation and provide a foundation for exploring how natural genetic variation can inform breeding and management strategies aimed at enhancing colony resilience.
Access status: Open Access ,
Causes and Consequences of Eusocial Genome Evolution in the Small Carpenter Bee C. Calcarata and the Honey Bee A. Mellifera
(2026-07-24) Brenman, Dova Batsheva; Zayed, Amro
Bees provide excellent systems for understanding how social behaviour evolves and how it influences the genome, a central question within sociobiological research. Advances in genomic technologies now enable investigation of the evolutionary and molecular mechanisms underlying social complexity. I use genomic and population genetic approaches to investigate the mechanisms that contribute to the emergence of social behaviour and the genomic consequences of advanced eusociality in bees. I first review advances in bee genomics, highlighting how genome sequencing, transcriptomics, and other tools have improved our understanding of bee evolution and behaviour. Then, I suggest that combining molecular and genomic approaches provides a framework for identifying genes and molecular pathways associated with eusocial traits. Using the facultatively social Ceratina calcarata, I investigate genomic patterns linked to early stages of social evolution. Comparisons between social and subsocial colonies show that loci with high genetic differentiation are often located in or near regulatory regions. Comparisons with Ceratina strenua also identify genes under positive selection, particularly in genes involved in regulation and metabolism. Finally, I examine the genomic consequences of longevity in terms of changes in mutation and recombination rate in the advanced eusociality in Apis mellifera. Mutations are more likely to occur in regions with higher recombination and are less common in constrained genomic regions, suggesting that recombination and purifying selection shape patterns of mutation in the honey bee genome. Together, this work demonstrates how genomic approaches can uncover the origins of social behaviour and how eusocial life histories influence genome evolution in bees.
Access status: Open Access ,
An Examination of Mechanisms Contributing to Cell Death Induced by Metabolic Stress in Cardiomyoblasts and Immune Cells
(2026-07-24) Ahmed, Saher Maham; Sweeney, Gary
Metabolic syndrome is an underestimated, growing global health crisis, plaguing millions of people worldwide. In this thesis, I assessed mechanisms of two important features of metabolic dysregulation; hyperglycemia and iron overload. This was accomplished across three projects; 1) examining mechanisms of adiponectin action in attenuating high glucose-induced cell death in cardiac cells and tissue, 2) observing inflammatory response in macrophages upon combining high glucose and iron treatments and 3) examining shifts in frequency of immune cell subsets in PBMCs treated with high glucose and iron. Briefly, results from study #1 revealed that an adiponectin mimetic, ALY688, was able to successfully attenuate high glucose-induced cell death in cardiomyoblasts and ventricular mouse tissue, in an autophagy-dependent manner. Interestingly, inflammatory agents released from cardiomyoblasts were eliciting inflammatory pathway activation in macrophages, which led to the formation of study #2. This study explored how two relevant metabolic stressors, high glucose and iron, could induce inflammation in macrophages. This study found that combining high glucose and iron led to significant activation of key inflammatory pathways, cytokine release and cell death in bone marrow-derived macrophages. These findings became the foundation for the next study to elucidate whether this robust response would be observed in primary human immune cells; peripheral blood mononuclear cells (PBMCs). Results from this study found no significant difference in frequency of T cells, though frequency of natural killer T cells were elevated upon treatment with high glucose and iron. In addition, combining high glucose and iron in PBMCs resulted in a profound increase in cytokine production, oxidative stress, mitochondrial dysfunction, and cell death. Overall, this thesis elucidates mechanisms of cellular damage induced by highly relevant metabolic stressors in cardiomyoblasts and immune cells. It further evaluates a therapeutic intervention and provides insight into axes that can be investigated to combat adverse metabolic outcomes.
Access status: Open Access ,
Characterization of the Toxicity of Carbon-Coated Iron Oxide Nanoparticles in Zebrafish: Neurophysiological Effects and Underlying Molecular Mechanisms
(2026-07-24) Mahtab Zonouzi-Marand; Kwong, Raymond W. M.
Iron oxide nanoparticles (IONPs) are widely utilized in biomedical, industrial, and environmental applications; however, their increasing release into aquatic systems raises concerns regarding their potential neurotoxic effects on aquatic organisms. This study investigated the physiological, behavioural, molecular, and electrophysiological impacts of early life IONP exposure in zebrafish (Danio rerio) to elucidate concentration-dependent and developmental outcomes. Zebrafish embryos were exposed to sublethal concentrations of IONPs (0, 1, and 5 mg IONPs/L) from 4 hours post-fertilization to 6 days post-fertilization (dpf), and raised to 30 dpf under normal conditions, to assess potential persistent effects. Physiological analyses revealed no significant mortality or deformity, suggesting the absence of gross morphological toxicity. Nevertheless, trace metal analysis revealed elevated Fe accumulation in tissues, consistent with nanoparticle uptake and bioavailability. Behavioural assessments were consistent with increased locomotor activity and elevated thigmotaxis in 6 dpf larvae exposed to 1 mg/L IONPs, whereas larvae exposed to 5 mg/L exhibited locomotor activity comparable to controls while maintaining elevated thigmotaxis. Overall, behavioural effects appeared more pronounced at the lower exposure concentration. In juveniles (30 dpf), behavioural effects persisted in a nonlinear manner: 1 mg/L exposure caused hypoactivity and anxiety-like responses, while 5 mg/L exposure induced hyperactivity and reduced social preference. At the molecular level, IONP exposure altered the transcript abundance of oxidative stress-related genes (Superoxide dismutase 1, Catalase, and Glutathione S-transferase) and dopaminergic markers (Tyrosine hydroxylase)). Larvae exhibited elevated cat and gstp1.2 mRNA expression, consistent with increased oxidative stress, while juveniles showed th1 upregulation and gstp1.2 downregulation, consistent with altered dopaminergic and antioxidant defence pathways, respectively. Electrophysiological analyses using multi-electrode arrays revealed significantly increased local field potentials, burst event frequencies and higher number of electrical spikes in 5 mg/L larvae, potentially suggesting enhanced neural excitability. Collectively, these findings demonstrate that early-life exposure to environmentally relevant concentrations of IONPs may induce lasting, life stage- specific neurophysiological and behavioural alterations. This integrated assessment underscores the potential ecological and developmental risks of IONPs and emphasizes the need for long-term, multilevel evaluations in nanoparticle toxicology.
Access status: Open Access ,
Impact of the Tumor ECM Niche On AML Drug Sensitivity: A Comparative Screening Study
(2026-07-24) Kabir, Samira; Sachlos, Eleftherios
Acute myeloid leukemia (AML) progression and drug resistance are strongly shaped by interactions between leukemic cells and the extracellular matrix (ECM) within the bone marrow niche. These ECM-driven signals promote cell survival and reduce therapeutic sensitivity, contributing to treatment failure and relapse. Traditional two-dimensional polystyrene cultures do not recapitulate these microenvironmental cues, limiting their predictive value for preclinical drug screening. Scaffold-based culture systems offer a more physiologically relevant model by mimicking ECM architecture and enabling cell–matrix interactions. However, quantifying drug responses in these complex systems is challenging, as conventional assays including plate-based viability, flow cytometry and high-content imaging, have distinct limitations. In this study, we optimized and compared these methods to evaluate AML drug responses in both polystyrene and ECM-mimicking scaffolds. Flow cytometry enabled reliable assessment of cell viability and revealed clear differences in drug sensitivity between the two platforms. This comparative approach highlights the impact of the ECM microenvironment on therapeutic responses, improving the evaluation of candidate AML drugs.
Access status: Open Access ,
The Regulation of Fatty Acid Metabolism by the NHR-14/HNF 4aplha Transcription Factor in Caenorhabditis Elegans
(2026-07-24) Hadi, Rawan Saad; Kubiseski, Terrance J.
Energy production through metabolic reactions is essential for life in all organisms. Proper metabolic regulation strongly influences aging, as disruptions in these reactions can impair cellular homeostasis and stress response pathways. Lipid metabolism is a central metabolic process that contributes to energy balance and cellular function; however, disturbances in lipid regulatory pathways can increase susceptibility to oxidative damage and negatively affect organismal health and longevity. Accordingly, many organisms have evolved transcriptional regulators that coordinate metabolic activity with stress resistance. Our lab uses Caenorhabditis elegans to study the role of SKN-1/Nrf2 and its protective functions in conjunction with other, yet unknown, transcription factors. We have previously shown that transcription factors can influence stress resistance through detoxification gene regulation. I focused on the transcription factor NHR-14 and its role in oxidative stress responses. RNA-seq analysis of the nhr-14(tm1473) deletion showed downregulation of multiple fatty acid degradation genes, suggesting that NHR-14 functions as a positive regulator of metabolic pathways. I found that the mutation in the nhr-14(tm1473) gene resulted in decreased survival under oxidative stress, reduced brood size, and shortened lifespan. My investigation of NHR-14’s function, along with characterization of its role as a positive regulator, provides new understanding into the mechanisms that maintain stress resistance and highlights important implications for longevity.
Access status: Open Access ,
Audiovisual Integration after Late Monocular Enucleation
(2026-07-24) Qureshi, Faizaan Ahmad; Steeves, Jennifer K.
People who underwent monocular enucleation, the surgical removal of one eye, exhibit altered sensory processing compared to people with binocular vision. Most research has focused on early monocular enucleation, which occurs during critical periods in visual development and leads to more balanced processing of audiovisual stimuli. I investigated whether audiovisual integration is altered after late monocular enucleation, which occurs after completed visual development. Susceptibility to the sound-induced flash illusion and the McGurk effect was compared between people who underwent late monocular enucleation and binocular viewing control participants. People who underwent late monocular enucleation were less susceptible to the sound-induced flash illusion but were susceptible to the McGurk effect, whereas control participants were susceptible to both. These findings suggest altered audiovisual integration for low-level audiovisual stimuli but unaltered audiovisual integration for high-level audiovisual speech stimuli. This may reflect compensatory adaptations and underscores the importance of timing in monocular enucleation research.
Access status: Open Access ,
Mechanism of Adiponectin-Mediated Prevention of Cardiometabolic Diseases and Therapeutic Potential
(2026-07-24) Tang, Jia-Ling; Sweeney, Gary
Myocardial ischemia-reperfusion (IR) injury remains a major contributor to cardiomyocyte loss and heart failure progression despite advances in revascularization. Adiponectin, a cardioprotective adipokine reduced in cardiovascular disease and obesity, has well-recognized benefits, yet the mechanisms underlying adiponectin receptor–mediated protection during IR injury remain incompletely defined. This thesis investigates the multi-layered cardioprotective actions of ALY688, a synthetic adiponectin receptor agonist, with a focus on extracellular vesicle (EV)-mediated communication, metabolic organellar coupling, and autophagy regulation. Four integrated studies employed complementary in vivo (rat and mouse myocardial infarction models) and in vitro (H9c2 cardiomyocytes and human iPSC-derived cardiomyocytes) approaches. Mechanistic interrogation utilized CRISPR-mediated gene editing, mass spectrometry-based proteomics, lipidomic profiling, real-time autophagy flux assays, and advanced imaging techniques including fluorescence molecular tomography and cryo-electron microscopy. Study 1 demonstrated that ALY688 reduces infarct size and preserves cardiac function through dual mechanisms: direct cardiomyocyte protection, characterized by reduced oxidative stress, restored autophagy flux, and attenuated apoptosis, and Rab8a-dependent EV biogenesis. Genetic ablation of Rab8a abolished EV-mediated cardioprotection, identifying Rab8a as a critical regulator. Study 2 showed that ALY688 reprograms EV cargo toward cardioprotective phenotypes, enriching EVs with adiponectin, metabolic enzymes, and autophagy-related proteins. Systemic delivery of ALY688-derived EVs reduced infarct size, improved cardiac function, and normalized mitochondrial dynamics in both lean and obese mice, supporting the therapeutic potential of EV-based strategies. Study 3 uncovered a previously unrecognized role for Rab8a in maintaining lipid droplet–mitochondria coupling, essential for long-chain fatty acid utilization during ischemic stress. Hypoxia–reoxygenation suppressed Rab8a, disrupting metabolic coupling and promoting lipotoxicity, whereas ALY688 preserved Rab8a via AMPK-dependent signaling, restoring metabolic homeostasis in a Rab8a-dependent manner. Study 4 demonstrated that adiponectin deficiency exacerbates ischemia-induced cardiac dysfunction through impaired autophagy flux. CRISPR-mediated ATG7 deletion confirmed autophagy as mechanistically essential for adiponectin-mediated cytoprotection. This thesis identifies adiponectin receptor signaling as a hierarchically organized cardioprotective network integrating direct cellular signaling, Rab8a-dependent EV biogenesis and cargo remodeling, preservation of lipid droplet-mitochondria metabolic coupling, and context-dependent autophagy regulation. Rab8a emerges as a central hub linking vesicular trafficking with metabolic resilience. These findings support the development of ALY688 and EV-based modalities as multi-mechanistic therapies for acute myocardial infarction and heart failure prevention.
Access status: Open Access ,
Lipid Remodeling Links Iron and Adiponectin to Ferroptosis, Inflammation, and Metabolic Regulation.
(2026-07-24) Cho, SungJi; Sweeney, Gary
Cardiometabolic diseases (CMD) impose a substantial global health burden marked by chronic metabolic stress, oxidative imbalance, and low-grade inflammation. While disturbances in iron metabolism, lipid metabolism and adipokine signaling are increasingly recognized in CMD, how these processes converge to influence cellular vulnerability and intercellular metabolic regulation remains incompletely understood. This dissertation investigated the roles of iron-induced ferroptosis and adiponectin-associated extracellular vesicles (EVs) in linking lipid remodeling to cardiometabolic pathology. Study 1 demonstrated that enrichment of ω-6 polyunsaturated fatty acid (PUFA)–containing membrane phospholipids, particularly phosphatidylethanolamines, markedly sensitized cardiomyocytes to iron-induced lipid peroxidation, mitochondrial dysfunction, sterile inflammatory signaling, and ferroptotic cell death. These findings establish membranous lipid composition, rather than lipid abundance alone, as a critical determinant of cellular vulnerability under metabolic stress. Building on this mechanistic framework, Study 2 extended lipid-mediated cellular vulnerability to the level of intercellular communication. Integrated EV lipidomic and functional analyses in murine models and human metabolic syndrome cohorts identified a conserved PUFA-enriched EV lipid signature associated with adiponectin deficiency. EVs carrying this lipid signature modulated recipient cell phenotypes by promoting oxidative and inflammatory signaling in macrophages, impairing mitochondrial energetics and insulin signaling in skeletal muscle cells, and disrupting glucose-stimulated insulin secretion in pancreatic β-cells. These findings indicate that EV lipid composition can regulate metabolic and inflammatory responses in recipient cells. Collectively, these findings demonstrate that metabolic stress is associated with PUFA-driven membrane lipid remodeling at the cellular level and with corresponding changes in the lipid composition of EVs. Adiponectin deficiency is linked to EV lipid remodeling and altered metabolic and inflammatory regulation in recipient cells. Together, these observations identify lipid remodeling, iron homeostasis, and EV-associated pathways as interconnected features of CMD biology with implications for biomarker discovery.
Access status: Open Access ,
Causes and Consequences of Desert Ant Community Assembly
(2026-07-24) Jenna Lee Braun; MacDonald, Suzanne E.
Understanding the mechanisms that maintain species coexistence and determine patterns of community assembly are fundamental topics of community ecology. This dissertation examines the drivers of ant community assembly mechanisms along environmental stress gradients in dryland ecosystems. This work positions facultative mutualisms and positive interactions alongside competition as key drivers of community structure. To start, I used experimental resource addition to show that the identity of mutualist ant defenders on silver cholla is a consequence of coexistence processes (here, resource partitioning of individual plants based on EFN resource availability). Investment into EFN resources is worthwhile for plants because ant defense benefits silver cholla; however, this investment is mediated by competition within the ant community. I then examined the importance of the EFN-bearing plant community for ant community assembly at macroecological scales using stacked species distribution models. The EFN-bearing plant community predicted the geographic distribution and diversity of the nectar-feeding ant community. However, interactions between the groups are vulnerable to climate change because of the predicted decrease in geographic overlap between ant-EFN-bearing plant pairs under future climate scenarios. I then examined the relative importance of environmental and biotic assembly mechanisms for ants along a desert stress gradient. The functional structure of the ant community was significantly more diverse than expected which is consistent with the mechanisms of limiting similarity and suggests the importance of competition to ant community structure. The strength of this mechanism decreased with increasing stress, demonstrating that environmental and biotic assembly mechanisms jointly and non-independently structure the ant community. Finally, I asked if environmental filtering on the functional trait composition of the plant and granivorous ant communities scales to shape ant-seed interactions. Ant functional traits responded to both environmental stress and to the functional traits of the plant community. However, seed size-dependent foraging choices arose from ant population size and not the functional structure of either community. This work showed that ant-plant interactions are integral to community assembly for both dryland communities.
Access status: Open Access ,
Investigating the Drivers and Consequences of Individual Dietary Specialization in an Arctic Marine Top Predator
(2026-03-10) Finkbeiner, Griffin; Thiemann, Gregory W.
Due to climate warming, reduced sea-ice extent and concentration in the Arctic has altered prey availability and limited foraging opportunities for polar bears (Ursus maritimus). My thesis examined individual foraging patterns across the Foxe Basin and Davis Strait subpopulations to identify drivers and consequences of dietary specialization. Using quantitative fatty acid signature analysis and proportional similarity (PSi) scores, I assessed how dietary specialization varies across intrinsic and extrinsic factors, and its relationship to body condition. Results revealed distinct diets and differing levels of specialization influenced by intrinsic and extrinsic variables. Sea-ice metrics were linked to variations in prey choice and individual specialization, suggesting altered access to preferred prey. Differences in individual specialization corresponded to variations in body condition, suggesting demographic groups experience energetic costs differently. These findings emphasize the role of individual-level variation in a warming Arctic, and underscore the importance of continued monitoring for polar bear conservation and management.
Access status: Open Access ,
Spatiotemporal Variation in the Foraging Ecology, Habitat Use, and Distribution of Arctic Marine Mammals in Relation to Sea Ice
(2026-03-10) Roberts, Jessica Michelle; Thiemann, Gregory W.
The Arctic is shifting under climate change, with loss of sea ice altering marine ecosystem structure. This thesis examined two Arctic marine mammals: Bowhead whales (Balaena mysticetus) and ringed seals (Pusa hispida), both being at risk of the effects of sea ice loss. Using biomarker analysis for bowhead whales (δ13C, δ15N, fatty acids) and observations from aerial surveys for ringed seals, this study investigated spatiotemporal variability in (1) foraging of bowheads from 1993-2023 in the eastern Canadian Arctic and (2) density and distribution of ringed seals from 1994 to 2024 in Western Hudson Bay, Canada. The biomarker results indicated spatiotemporal shifts in bowhead whale diet, including a nonlinear relationship between δ13C and sea ice concentration, declining δ15N values, narrowing of isotopic niche widths, and shifts in fatty acid profiles- especially in Hudson Bay. Ringed seal density declined from 1994-2024, with sea ice and distance to shore as key predictors.
Access status: Open Access ,
The Effects of Modulated Global Levels of Sumoylation on Gene Expression
(2026-03-10) Moallem, Marjan; Rosanina, Emanuel
Hundreds of proteins are modified by SUMO (small ubiquitin-like modifier) peptides, the majority of which are nuclear and involved in gene expression. Through SUMO chromatin immunoprecipitation sequencing (ChIP-seq), sumoylated proteins can be readily detected at numerous distinct chromatin sites. This includes promoters of protein-coding genes thus linking sumoylation with transcription regulation. Cells can coordinately modulate levels of sumoylation globally. For example, there is a surge in SUMO conjugation in response to heat shock, an effect that we attribute here to the degradation of the major SUMO protease, Ulp1, in budding yeast. Whereas the effects of sumoylation have been examined for many individual target proteins, not much is known about how coordinated global changes to sumoylation levels impact transcription. To address this, we investigated whether changing cellular sumoylation levels in yeast impacts (1) cell growth in normal and stress conditions, and (2) global transcription and gene expression patterns. Primarily, this was accomplished using strains that express mutant forms of Ubc9, the sole E2 conjugating enzyme, or Ulp1, which harbour constitutively reduced or elevated sumoylation levels, respectively. We find that cells with dramatically reduced levels of sumoylation grow near-normally in optimal, non-stress conditions. While they tolerate multiple stress conditions very well, they show strong sensitivity to heat shock specifically. Both reduced and elevated sumoylation levels lead to widespread changes to transcription, but intriguingly, both result in a gene expression pattern that resembles that of stressed cells. Therefore, heat-shock genes have high levels of expression, even in non-stress conditions. This indicates that both sumoylation and desumoylation are important for suppressing stress response gene expression in non-stress conditions, and paradoxically, our results correlate constitutive expression of stress response genes with temperature sensitivity. Finally, our data implicate activation of the key stress response factors, Msn2 and Hog1, in driving the inappropriate induction of heat-shock genes in Ubc9 and Ulp1 mutants even in the absence of stress.
Access status: Open Access ,
Interplay of Iron and Hydrogen Sulfide in Pathophysiology of Vascular Damage
(2026-03-10) Arif, Hassan Mustafa; Wang, Rui
Hydrogen sulfide (H₂S) and iron are fundamental regulators of redox biology, exerting opposing influences on oxidative stress and vascular homeostasis, yet their mechanistic interplay remains unresolved. This dissertation addresses this gap through a series of studies spanning molecular, mitochondrial, cellular, and whole-animal levels. The molecular basis of H₂S–iron interactions in vascular smooth muscle cells was defined, demonstrating that endogenous H₂S upregulates ferritin expression, balances apoptosis–autophagy signaling, and protects against iron overload–induced cellular dysfunction. These findings were then extended to mitochondrial physiology, showing that CSE-derived H₂S safeguards mitochondrial respiration, spare respiratory capacity, and membrane potential under iron stress, thereby enhancing cellular resilience. To enable accurate translational assessment, a high-performance liquid chromatography method using a methylene blue/methylene green (MBMG) system was developed, establishing a robust, sensitive, and stable platform for plasma H₂S quantification with broad research applicability. Applying this method in murine models of acute iron overload demonstrated that CSE deficiency led to impaired ferritin upregulation, increased vascular iron deposition, elastin degradation, inflammatory remodeling, and severe vasomotor dysfunction—effects that were mitigated in wild-type mice via compensatory CSE/H₂S induction. Collectively, these studies establish a continuum of evidence linking H₂S to iron metabolism and vascular adaptation, from cellular and mitochondrial mechanisms to systemic physiology. By integrating conceptual review, mechanistic cell studies, methodological innovation, and translational animal models, this thesis identifies endogenous H₂S as both a biomarker and a therapeutic target for iron-related vascular disease.
Access status: Open Access ,
Assessing the Role of Maternal Social Network Inheritance in the Social Integration of Immature Vervet Monkeys (Chlorocebus Pygerythrus)
(2026-03-10) Dupuis, Margaux Cyrielle Eleonore; Schoof, Valerie A.
Specific mechanisms of social network integration in juvenile animals are still largely obscure. However, much research indicates that mothers have a wide range of effects on their offspring, including on their sociality. Using a Bayesian framework, I investigated factors of social integration, such as maternal proximity, network influences (i.e., inheritance), age, dominance rank, and offspring traits from May-July 2025 in wild vervet monkeys (Chlorocebus pygerythrus) at Lake Nabugabo, Uganda. My results suggest that maternal influences exist mainly in proximity but less in grooming networks. Older offspring were more distant from their mothers and less central in proximity networks than younger offspring. Notably, offspring sex was a strong predictor of social ontogeny in vervet monkeys, with daughters being more integrated in grooming networks than sons. Overall, these results provide insight into the importance of mothers in social ontogeny, while also highlighting the pivotal role of offspring sex on their social integration.
Access status: Open Access ,
Modelling Bone Marrow Extracellular Matrix Interactions Reveal CD36-Dependant Vulnerabilities in Acute Myeloid Leukemia
(2026-03-10) Cifligu, Zhaklina; Sachlos, Terry
Understanding how the bone marrow microenvironment influences metabolic dependencies is crucial for improving therapeutic strategies in acute myeloid leukemia (AML). CD36, a fatty acid transporter associated with lipid uptake and chemoresistance in AML, may be functionally influenced by interactions with the extracellular matrix (ECM). This thesis investigated whether ECM engagement alters CD36-dependent responses in AML. OCI-AML2 cells were cultured on either standard polystyrene (PS) or an ECM-based scaffold and assessed following CD36 inhibition using flow cytometry. Scaffold-cultured cells exhibited reduced viability, fatty acid uptake, and clonogenic capacity under CD36 inhibition compared to PS culture. Primary AML samples were then evaluated to assess patient-specific responses. ECM scaffold culture revealed phenotypic adaptations following CD36 inhibition, including reduced fatty acid uptake and increased CD11b expression for two patient samples, suggestive of enhanced ECM interaction and myeloid differentiation. Overall, these findings demonstrate that ECM interactions modulate CD36-dependent vulnerabilities in AML not evident under standard PS culture conditions.
Access status: Open Access ,
Unlocking Phytoalexin Biosynthesis Using Multigene Engineering
(2026-03-10) Ly, Melissa Thanh; Kovinich, Nikola
Plants have evolved sophisticated defense mechanisms to balance growth and immunity, with phytoalexins and lignin playing central roles in pathogen resistance. In Arabidopsis thaliana, the jasmonate repressor JAZ1 and transcription factor ANAC042 act as opposing regulators of this process. The regulation of phytoalexin biosynthesis is highly complex, and manipulating individual transcription factors has generally proven insufficient to fully activate the pathway. To address this limitation, this study investigates whether the knockout of JAZ1 in combination with the overexpression of ANAC042 can more effectively unlock phytoalexin biosynthesis. While JAZ1 knockout promoted systemic lignification under prolonged stress, while ANAC042 overexpression alone did not strongly induce phytoalexins. However, their combination enhanced accumulation of hydroxyindole-3-carbonyl nitrile and monolignols. Transcriptional analysis revealed altered regulation of WRKY33 and MYB15, suggesting that JAZ1 and ANAC042 are a part of a broader defense regulatory network. Growth-defense trade-offs showed growth penalties in all tested genotypes under Flg22 elicitation, except in ANAC042 overexpression lines, where growth was unaffected by the elicitor, highlighting the metabolic costs associated with sustained immunity. Extending these findings to soybean, a dual-gene plasmid (pGEMINI-B) was constructed to co-overexpress two positive regulators of glyceollin biosynthesis, while silencing GmJAZ1 genes. Collectively, these findings demonstrate that manipulating antagonistic regulatory factors simultaneously can unlock levels of phytoalexin accumulation that are unattainable through single-gene modifications. The underlying shifts in gene expression and metabolism driving this effect are unconventional and warrant deeper investigation, as elevated phytoalexin biosynthetic gene expression does not directly account for the observed increases in phytoalexin levels.

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