VictorJuiz/thesis huggingface dataset:
Regulation of the Actin Cytoskeleton by Palmitate: Implications for Lymphatic Endothelial Barrier Function and Skeletal Muscle GLUT4 Translocation

The actin cytoskeleton is a critical component of cells that regulates core cellular processes in diverse cell types. It provides structural and mechanical support, regulates intracellular trafficking, mediates contacts between cells and more. During the development of obesity, cells are exposed to increasing levels of saturated fatty acids (SFAs). SFAs have been implicated in the development of two obesity-associated disorders that I was interested in investigating: lymphatic dysfunction and skeletal muscle insulin resistance, but their precise impact on the actin cytoskeleton in the lymphatic endothelium and skeletal muscle and how it alters their canonical functions (fluid homeostasis and glucose disposal) is incompletely understood. In this dissertation, I identify the actin cytoskeleton as a target of the SFA palmitate (PA) that confers cell type-specific dysfunction in both lymphatic endothelial cells and skeletal muscle cells. In Chapter 3, I describe how PA, but not its unsaturated counterpart palmitoleate (PO), alters the lymphatic endothelial junction by remodelling the actin cytoskeleton. I detail how PA caused the accumulation of actin stress fibres that disrupted cell-cell contacts and compromised wound healing. In Chapter 4, I outline how PA impaired GLUT4 translocation in skeletal muscle cells by abrogating insulin-stimulated actin remodelling and by disrupting the intracellular trafficking of GLUT4. Moreover, I determined that the failure of actin remodelling and GLUT4 mis-localization in these cells are governed by distinct mechanisms, endoplasmic reticulum stress and protein palmitoylation, respectively. In Chapter 5, I uncovered a previously unappreciated role for complexin-2 in insulin-stimulated GLUT4 vesicle fusion with the plasma membrane in skeletal muscle cells that requires actin remodelling. This work establishes PA as a regulator of the actin cytoskeleton in two cell types with unique functional implications for each. My work advances our understanding of how SFAs regulate the cellular actin architecture and how these alterations confer cell type-specific dysfunction. While my work focused on only two cell types, it provides compelling initial evidence that SFAmediated dysregulation of the actin cytoskeleton may represent a common mechanism underlying cellular dysfunction during nutritional excess in additional cell types.

Keywords: actin cytoskeleton
GLUT4
insulin
lymphatic endothelium
palmitate
skeletal muscle
Advisor: Klip, Amira
The Profile of Neuronal Excitability in Epilepsy and Seizure

Seizures are classically described as an epiphenomenon of neuronal hyperexcitabil- ity and hypersynchronicity across brain regions. However, studies of the neurophysi- ological events during the propagation of seizure have revealed a complex transition from a strongly inhibited state of the seizure penumbra to an intensely excitatory state within the seizure core. To better understand the neurobiological mechanisms involved in seizure propagation, it is necessary to characterise a profile of excitability in the seizure penumbra. In this thesis, I used calcium imaging and optogenetics to functionally profile the activation of inhibition relative to seizure propagation in an acute model of focal-onset epilepsy in vivo. First, I find that the activation of in- hibitory neurons during seizure propagation is highly-local to the seizure wavefront. Then, I describe a novel approach of measuring neuronal excitability by combining calcium imaging and optogenetics (all-optical interrogation). This uniquely allows me to perform real-time, in vivo investigations of excitability of neurons distal to the focal-epileptic site. In the acutely epileptic state, the brain becomes susceptible to large synchronous inputs, but in fact single-cell excitability is maintained at baseline levels. During seizure propagation, there is hypoexcitability of neurons only near the seizure wavefront, and not at the larger scale in the seizure penumbra. These experiments provide the first direct, in vivo evidence of the precise spatial scale over which single-cell neuronal excitability evolves during seizure propagation. These re- sults suggest a refined model of seizure propagation based on local inhibition, which advances upon the previous model based on widescale inhibition during seizure.

Keywords: epilepsy
optogenetics
propagation
seizure
two photon imaging
Advisor: Valiante, Taufik A
Canadian Chinese Graduate Student Occupational Therapist Professional Identities

Occupational therapy (OT) as a field in China and Hong Kong is very different from Western countries like Canada. Not only is the field itself growing at a different pace but the cultural understanding of the role of OT practice also differs. This thesis explores the experiences of five Chinese graduate occupational therapy students, at the halfway point of their Master of OT (M.Sc.OT) programs in Ontario. Specifically, the influences of culture on their understanding of coursework, theories, interactions with peers, faculty, and clients are explored to understand how culture influences their professional identities as student occupational therapists. Seidman’s (2013) three-interview approach is utilized to gather rich data from participants through three separate interviews. Results reveal program and cultural factors that influence participants’ professional identities as student occupational therapists. Program factors include the geographical location of the university, the programs’ teaching philosophy, professional development and mentorship, placement requirements, catchment areas, and unique placement experiences. Cultural factors include the student’s Chinese values and views on health, disability and independence, relationship with preceptors and professors, and the understanding of the scope of occupational therapy. Overall, students had some conflicting views on OT theories which are predominantly westernized, difficulties relating to peers who are not Chinese, and conflicting views on building rapport with professors and preceptors during placements. There were not clear differences between participants from Hong Kong and China related to how long participants had lived in Canada before starting the M.Sc.OT. Despite these conflicting views and challenges, participants are optimistic about their future job prospects. Program level implications include the continued efforts of faculty and educators to incorporate culturally diverse information into case studies, tailoring mentorship programs, and increasing representation of Chinese students, faculty, and preceptors into the program. Research implications include the need for both quantitative and qualitative research studies with a larger population to further understand the cultural influences on graduate Chinese occupational therapy students.

Keywords: Chinese
Culture
graduate students
occupational therapy
Professional identities
Student occupational therapists
Advisor: Childs, Ruth
Genetic and Epigenetic Factors Influencing Population Variability of Allele-Specific Expression

There is a longstanding investigation in human genetics surrounding how individuals with the same genotype display highly variable phenotypes. The impact of gene expression variability is critical for phenotypic variation. Allele-specific expression (ASE) is the preferential expression of one haplotype in an individual. While ASE is associated with several phenotypes and diseases, it remains unknown what genomic and epigenetic factors contribute to variability in ASE. This thesis explores factors contributing to ASE variation, characterized into three categories: population demographics, environment, and age. First, I revealed how population demographics, through effective population size, impact ASE at two levels: i) across populations based on evolutionary histories, and ii) across the genome through recombination and its interaction with natural selection. I demonstrated that recombination rate modulates ASE genome wide, and that loci in regions of high recombination are most efficient at adjusting ASE to protect from harmful mutations. I also demonstrated that genetic ancestry, based on population histories such as recent bottlenecks, contribute to the strength of ASE regulation. Next, I demonstrated that environmental modifiers contribute to ASE regulation, both on a geographic scale, in addition to extrinsic lifestyle factors. I determined differences between French-Canadian individuals based on their local environment, for those whose geographic location is different from their genetic ancestry. I explored medication usage as an extrinsic factor and demonstrated that certain medications are significantly associated with increases in overall levels of ASE. I also detected genes that have significantly different levels of ASE in medicated responders versus non-responders. Lastly, I demonstrated that ASE increases with age in cell types involved in adaptive immunity. I showed that healthy agers have larger increases in ASE as they age, specifically in genes involved in immune response. I also demonstrated that decreases in ASE are associated with cardiometabolic traits such as hypertension and type 2 diabetes. This thesis demonstrates genetic and epigenetic factors contributing to ASE variability, in healthy and disease contexts. My research uncovers scenarios where ASE can act as a protective mechanism, which may be playing a role in healthy aging, and opens the potential for utilizing ASE methodologies in precision medicine approaches for chronic diseases.

Keywords: aging
allele-specific-expression
environment
genetic regulation
population genetics
Advisor: Awadalla, Philip
Encoded Bodies: An Analysis of Women of the Hispanic Caribbean Diaspora Performing Identity

The body houses knowledge of lived experiences and functions as an apparatus of storytelling. As women have long been associated in Western culture with the body, this study discusses performances that consider the concrete daily and quotidian experience as reference points. This project explores the representations of ciswomen that inhabit the Hispanic Caribbean diaspora and have had contact with North America who discuss what it means to create, to live and to survive in a culture with hierarchical understandings of identity. I inquire the ways they use their bodies to re/animate and re/insert stories into the collective consciousness, stories ranging from diaspora and migration, abuses of power by regimes and/or governments, racial hierarchies, and simply everyday life. This thesis features works from: María I. Fornés, Alina Troyano, Josefina Báez, Elizabeth Ovalle, Carmen Rivera, Coco Fusco, and Carmen Peláez and considers the following questions: 1) What is performance? 2) How does the body communicate? 3) What are the advantages and disadvantages of an ephemeral medium? 4) What is the role of the audience in these scripted enactments? Targeting liminality, identity, and community, I inquire how performance interacts with the hybrid space of its subjects, exploring embodied language and its contributions to the textual significance of lived experiences of dramatists who belong to countries with distinct colonial histories. I probe the mechanisms which performance uses to shape, parody or interrogate societal norms with examples of opposing subjectivity. This investigation discovers how these texts represent and create community by analyzing the role of the spectator, family, and the wider collective of which these productions are in dialogue. As orality has existed in the Caribbean as a form of intelligence creating countercultures, I outline how these performances and the bodies of these artists exist in direct opposition to homogenous and monolithic understandings of identity. Although they perform fictionalized and constructed narratives, the dramatists of this study often represent autobiographical accounts and thus their body has often lived through the script. The analysis of these narratives is crucial as everyday lived conditions of diaspora and exile are often perceived as unworthy of research.

Keywords: Caribbean
diaspora
latina
migration
performance
theatre
Advisor: Jagoe, Eva-Lynn
Rodríguez, Néstor
Essays in Climate Change and Financial Economics

This thesis contains three papers on how the financial market adjusts to information changes.As economic damages from hurricanes rise due to climate change, banks will need to invest internally to update their risk management framework. Chapter 1 tests whether financial distress affects a bank’s ability to adapt to emerging risks. Distressed banks are 6 percentage points more likely to accept loans exposed to hurricane risk and charge 65 basis points less for risky loans. This increase in risk taking is likely due to an under-investment in assessing hurricane risk, since results are stronger for financially constrained banks. Results are unlikely due to moral hazard, since distressed banks reduce exposure to conventional risks, such as borrower income risk. Financial distress affects a bank’s ability to adapt to emerging risks. Chapter 2 studies the dynamic effect of investors responding to climate risk, using environmental lawsuits as a litigation risk shock. Investors are aware of climate litigation risk and share prices immediately drop by 2% for defendants and 6% for competitors in the same industry. ESG investors exit firms that are exposed to litigation risk and sell approximately 55,000 shares of competitor firms. The net effect of this investor turnover results in a decrease in environmentally-themed shareholder proposals by around 2% for defendants and 1% for competitors. Overall, an increase in climate risk exposure within an industry decreases public environmental engagement. Finally, Chapter 3, based off joint work with Peter Cziraki, Jasmin Gider and Jordi Mondria, studies the dynamics of local investors’ information advantage using local newspaper closures and the trades of local and nonlocal investors. Following the closure of a newspaper, investors are 10 percentage points less likely than nonlocals to trade the shares of firms in the same zip-code, and reduce the share of their local holdings by 8 percentage points. Local investors also make lower risk-adjusted returns on their stock purchases and sales up to 6 months following a local newspaper closure. Our results suggest that local journalism is an important source of local investors’ information advantage, and, therefore, the home bias phenomenon.

Keywords: climate finance
climate risk
financial stability
financial system
investors
risk management
Advisor: Cziraki, Peter
A Musical Chemistry: The Collaboration Between the Pianist/Composer Heather Schmidt and the Cellist Shauna Rolston

Abstract This dissertation consists of an in-depth study of the relationship between the cellist, Shauna Rolston (b. 1967), and the composer and pianist, Heather Schmidt (b. 1974). The heart of the thesis consists of four case studies of works by Schmidt that were written for Rolston: Concerto for cello and orchestra (1998), a three-movement work for cello and orchestra. Rolston premiered and recorded this work. Icicles of Fire, a two-movement piece for cello and piano (2003) that was written for a tour of Iceland by Schmidt and Rolston. This piece was recorded by them on the CD Icicles of Fire (2013), which features three works for cello and piano by Schmidt. Synchronicity for cello and piano was composed in 2007 on commission for the Redstar Films documentary Synchronicity. This 2008 performance film features Rolston and Schmidt and was made for the television network BRAVO. stone leaf shell skin is a work for three dancers, synthesizer, and cello (2014). This composition was created for Peggy Baker Dance Projects and was premiered by Rolston. Schmidt and Rolston worked together closely on these pieces and brought the imagery of their shared interpretations to life. Interviews with Schmidt and Rolston clarify their biography, the role of the performer and the composer in bringing new works to life, and the nature of their collaboration and relationship.

Keywords: Cello and Piano Duo Music
Cello Music
Cello Music of 21st Century
Heather Schmidt
Music and Collaboration
Shauna Rolston
Advisor: Elliott, Robin
The Application of Cell Fusion to Engineer Clinically Relevant Cells for Therapy

Cell fusion plays a central role in tissue development and regeneration at every stage of human life. By combining properties from multiple cells together, cell fusion alters cell fate, developmental potential, and self-renewal capacity. Manipulating cell fusion to create new cells in vitro has led to seminal breakthroughs in research including the generation of hybridomas and somatic cell reprogramming. We hypothesize that cell fusion can be harnessed to generate hybrid cells with clinical potential. To investigate this novel application of cell fusion, we studied hybrid cells derived from fusion of pluripotent stem cells (PSCs). We designed a new “one-way” fusion selection strategy that expands a small repertoire of existing methods of selection. Using this strategy, we showed that mouse PSCs spontaneously fused into hybrid cells that remained phenotypically and functionally pluripotent. Mouse hybrid PSCs demonstrated remarkable chromosomal stability, remaining tetraploid after extensive time in culture. Human hybrid PSCs were effectively isolated with the addition of polyethylene glycol. Despite exhibiting some loss of chromosomes after long-term culture, human hybrid cells could differentiate efficiently into clinically relevant cell types in vitro. Here, we show that we can reliably derive stem cell lines that are a hybrid of two cells and retain the clinical potential of PSCs. Building on these findings, we explored the use of cell fusion to combine or transfer desired genetic modifications from parental cells into human hybrid cells. Specifically, we demonstrated that human hybrid cells inherited a functional FailSafe kill-switch system that allows us to eliminate cells that may become cancerous. As chromosomal stability has been linked to cancer, inheritance of FailSafe is crucial for the safety of hybrid cell-derived therapies. To expand the clinical relevance of this cell fusion application, we demonstrated that hybrid cells inherit and maintain expression of an anti-VEGF biologic that has shown efficacy in treating age-related macular degeneration. In the future, cell fusion could be used to combine other engineered genetic modifications and endogenous properties to create new cells for clinical applications.

Keywords: cell fusion
cell therapy
pluripotent stem cell
Advisor: Nagy, Andras
Understanding Travel Behaviours and Overcoming Barriers: Case Studies of Achieving Equitable Public Transit for Disadvantaged Groups in Canada

Having access to transportation is essential for everyone to participate in daily activities, such as employment, healthcare, education, or social interaction. Socially disadvantaged groups, including low-income earners, single parents, immigrants, and people with disabilities often encounter travel barriers that prevent them from participating in activities, negatively impacting their well-being and quality of life.Public transit plays an important role in providing accessibility for socially disadvantaged groups. Many transit agencies are establishing partnerships with private companies to enhance their services, such as collaborating with technology companies to deliver on-demand transit services and collaborating with accessible taxi companies to increase the capacity of paratransit. Understanding the social impacts of these transit services is crucial. This dissertation aims to improve our understanding of the travel behaviour of socially disadvantaged groups, and how public transit serves these groups. It uses three empirical case studies to explore the travel patterns of people who use on-demand transit and paratransit, and investigate the social impacts of these services. In chapter 2, I conduct a case study in Belleville, Canada, with the aim of describing the user profile of on-demand transit and examining user satisfaction with the services. Additionally, the chapter shows there is a positive association between user satisfaction and activity participation among socially marginalized groups. Chapter 3 and chapter 4 place particular emphasis on people with disabilities, a significant subset of socially disadvantaged groups. The primary objective of these two chapters is to obtain a better understanding of the travel patterns of people with disabilities who use paratransit services. Chapter 3 investigates where and when individuals with disabilities travel using accessible taxis, and identifies the factors that influence wait and in-vehicle times. Chapter 4 categorizes paratransit users into five distinct groups, and investigates the changes in travel patterns before and during the COVID-19 pandemic. This thesis offers significant insights into the understanding of how public transit serves socially disadvantaged groups and helps mitigate transport-related social exclusion. It also has a practical contribution to policymakers seeking to enhance transport equity.

Advisor: Farber, Steven
Coagulation/Flocculation-Ultrafiltration Optimization in Drinking Water Treatment

Coagulation/flocculation is applied prior to ultrafiltration (UF) to reduce fouling and increase natural organic matter (NOM) removal. A lack of knowledge exists regarding the selection of optimal conditions to satisfy these treatment objectives. The present research includes three studies which provide guidance for the design and operation of coagulation/flocculation-UF by: i) development of a bench-scale approach for process evaluation, ii) elucidating impacts of coagulation mechanisms and coagulation/flocculation configurations on UF performance, and iii) evaluating the retention of microplastics (MPs) and release by cleaning during coagulation/flocculation-UF treatment. Bench-scale continuous-flow systems allow evaluation of coagulation/flocculation-UF over consecutive permeation cycles, but require high flowrates to achieve hydraulic retention times (HRTs) typical of full-scale rapid mixing. To reduce flowrates, the present research evaluated a typical 2 min HRT vs. 20 min in terms of impacts on particle properties and UF performance; 20 min represents HRTs previously considered during bench-scale investigations. Increases in particle size/concentration and reduced UF fouling resistance at a 20 min HRT, suggest that HRTs equivalent to those typically applied during full-scale rapid mixing must be considered during bench-scale studies in order to produce results relevant to full-scale. In the subsequent study, previous knowledge regarding alum dosages and pH values which promote specific coagulation mechanisms was utilized as a framework to select coagulation conditions applied during coagulation/flocculation-UF. In cases where fouling control is required, conditions that promote adsorption destabilization are optimal, whereas in cases where NOM removal is required, conditions that promote sweep are optimal. Inclusion of flocculation (vs. coagulation alone) increased NOM removal while reducing irreversible fouling resistance, despite increased NOM retention by the membrane. In the final study, when compared to raw water, alum addition increased hydraulically irreversible accumulation of MPs on the membrane from 50% to 80% of those present in UF feed water. Chemical cleaning released 20% to 60% of MPs which had accumulated on the membrane during previous permeation cycles. While positive correlations were observed between the release of MPs and foulants, the release of MPs was consistently lower. Accumulation of MPs on the membrane may increase UF fouling over extended operating periods.

Keywords: Coagulation
Floc
Flocculation
Fouling
Membranes
Ultrafiltration
Advisor: Andrews, Robert C
Bérubé, Pierre R