VictorJuiz/thesis huggingface dataset:
Local Delivery of PACAP Attenuates Inflammation and Promotes Functional Recovery in a Mouse Model of Stroke Injury

Ischemic stroke leads to the activation of resident microglia and astrocytes in the brain parenchyma. It was previously thought that immune activation after ischemia is wholly detrimental to stroke recovery. We now know that these cells can activate endogenous repair mechanisms to promote neural regeneration. Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide implicated in both modulation of inflammatory processes and neuroprotection after ischemic stroke. However, its short in vivo half life and dose limiting side effects hinder its therapeutic potential. Here, we address these limitations with a biomaterial-based approach for the local, non-invasive delivery of PACAP to the stroke injured brain. A nanocomposite comprised of poly(lactic-co-glycolic) nanoparticles in a hyaluronan and methylcellulose hydrogel enabled the sustained release of PACAP. The electrostatic interactions between negative PLGA and positive PACAP facilitated encapsulation-free controlled release with nearly 100% peptide loading. The release profile could be tuned over a two-week period by manipulating the surface charge of the nanoparticles, and consequently the adsorption-desorption kinetics between the peptide and nanoparticles in the hydrogel. The vehicle was implanted epicortically in endothelin-1 stroke injured mice, which released PACAP into the tissue over a 10 day period. The epicortical delivery of PACAP improved forelimb strength and motor control one month post stroke. The treatment decreased apoptosis and attenuated both microglia and astrocyte activation within the first week of stroke injury, and drove remaining microglia towards a pro-repair phenotype for the duration of release. These findings suggest that PACAP’s neuroprotective and anti-inflammatory properties improved the functional recovery of treated animals. This work demonstrates that immune modulation with therapeutic peptides is an effective strategy for stroke treatment. This vehicle enables therapeutic peptides and proteins to enter the central nervous system effectively and non-invasively. The electrostatic adsorption controlled release system is amenable to not just stroke treatment, but for disorders of the central nervous system more generally.

Keywords: Electrostatic controlled release
Hydrogel
Inflammation
Nanoparticle
PACAP
Stroke
Advisor: Shoichet, Molly
Economic Insecurity, Work, and Mental Health among Gay, Bisexual, and Queer Men: A Critical Narrative Inquiry into Precarious Work

Precarious employment has proliferated across Western capitalist economies and is associated with economic insecurity and poorer health. This dissertation investigated precarious employment among lesbian, gay, bisexual, transgender, and queer (LGBTQ+) people through an exploration of what is known (scoping review) and what more can be learned from precariously employed LGBTQ+ workers (narrative inquiry).A scoping review guided by an intersectional framework found that LGBTQ+ people were overrepresented in precarious forms of work, including underemployment and part-time work. Additionally, they experienced hostility and discrimination when looking for employment and in the workplace that contributed to increased labour market precarity. A community-engaged narrative inquiry was then conducted among 20 gay, bisexual, and queer men experiencing precarious employment in Toronto, Canada. Guided by political economy frameworks, Polkinghorne’s narrative analysis was used with attention to plotlines, characters, settings, and temporality within and across participants’ stories. A new story was constructed that provides rich insights into lived experiences and the meanings of these experiences among participants, as well as the structural conditions that shape these experiences and meanings. Two analyses were conducted using this method. The first analysis explored labour market experiences and identified the mechanisms that led participants into precarious employment and economic insecurity. Cisheteronormativity, alongside racism, xenophobia, and ableism, shaped participants’ experiences from adolescence to adulthood through LGBTQ+-adversity in adolescence, overt and perceived discriminatory practices in hiring, and harassment and discrimination on the job. Participants’ stories illustrate unique ways that LGBTQ+ people might be particularly susceptible to exploitative labour markets. The second analysis explored the relationship between precarious employment and mental health. Results illustrate a cyclical pattern whereby participant’s adverse adolescent experiences associated with LGBTQ+-related discrimination negatively impacted their mental health, which in turn shaped their employment trajectory. Upon entering the labour market, precarious employment was exacerbated by mental health challenges and, subsequently, precarity exacerbated these challenges. This dissertation addresses the dearth of scholarship in three primary areas: occupational health among LGBTQ+ populations, LGBTQ+ poverty, and LGBTQ+ employment. Implications inform labour market policies and social service and public health practice when supporting LGBTQ+ people experiencing mental health concerns, economic insecurity, and employment challenges.

Keywords: Employment
LGBTQ
Mental Health
Narrative
Poverty
Qualitative
Advisor: Gesink, Dionne
Ross, Lori E.
College Contract Faculty in Ontario: Professional Identities and Precarious Employment

Partial-load college faculty simultaneously occupy insider/outsider positions in their respective higher education institutions. How do they perceive the relationship between their employment status and their work as educators? In recent scholarship, it has been argued that part-time faculty occupy liminal positions as simultaneous professionals and precarious labourers in higher education. None of the literature attends to how part-time college faculty (a cohort that makes up 70%+ of Ontario’s college faculty) who specifically aspire to full-time teaching positions think about their work and professional identities, much less in the context of the province of Ontario, Canada. Through semi-structured and open-ended interviews with ten partial-load college faculty who aspire to full-time teaching positions across three colleges in the Greater Toronto Area (GTA), this study asks faculty to reflect upon the relationship between their conditions of employment and their work as educators. How partial-load college faculty think about their work and professional identities has direct import for what continues to be the foundational mission, purview, and day-to-day activities of colleges – teaching and learning. Holland, Lachicotte, Skinner, and Cain’s (1998) identity theory provides the framework for enabling a nuanced analyses as to how partial-load college faculty think about, make sense of, and narrate their experiences in the liminal space of precarious professionals. The results of this study show that partial-load faculty are largely excluded from the pedagogical communities of their departments and institutions and that every aspect of their work as educators (curriculum development, professional development, and relationships with colleagues) is negotiated and filtered through their precarious status. This research sheds light on the centrality of partial-load college faculty on the enactment of curriculum in colleges as well as explores how various stakeholders can make meaningful change to address the professional goals and curricular inclusion of this significant teaching cohort.

Keywords: College
Faculty
Part-time
Precarious
Professional
Teaching
Advisor: Rolheiser, Carol
Spatial Organization and visual preference of high-level visual brain regions

The human visual system represents visual features in a retinotopic pattern that is quite robust across the visual system hierarchy, from the early visual cortex to the high-level cortical areas. Though high-level areas are functionally distinct, the relationship of pRFs in the high-level visual cortex is consistently organized with a contralateral hemifield bias, corresponding to the topographical organization of the viewing plane. Though the contralateral hemifield bias is a clear sign of retinotopy, the relationship of the size of pRFs to the feature representations in high-level visual areas and memory-related areas is not well understood. In my dissertation, I explore the pRF organization in high-level vision areas, along with memory regions using a large retinotopy dataset. I also explore the relationship of feature specialization to pRF size within memory processing areas, the spatial frequency correspondence with pRF in scene-specialized areas, and finally an analysis of an in silico model of human vision. The organizational pattern extends throughout the human visual system and memory processing areas, which suggests that functional distinctions are organized similarly. Within the hippocampus and scene-specialized regions, the anterior-posterior gradient aligns with functional differences found in these areas. Additionally, the functional distinctions are supported by the decrease in correspondence with the viewing plane via the types of representations indicated by the pRF size within anterior PPA.

Keywords: faces
fMRI
hippocampus
perception
population receptive fields
scenes
Advisor: Bernhardt-Walther, Dirk
Dynamics of National Morality: Negotiating Values and the State

This dissertation promotes a more nuanced understanding of values in state–society relations. The role of values in these relations is examined using a cultural sociology lens combined with concepts from the sociology of morality and of organizations. In these dynamic processes, I argue, a new national morality is constructed, manifesting changes in power structures, social practices, and state bureaucracies. A focus on state institutions highlights negotiation processes for civil-sphere activity and state reactions. I analyze the public discourse regarding three cases of military violence that instigated public debates, using content analysis of 1,500 newspaper stories. First, I examine generalization dynamics transforming a local occurrence into a national crisis, building on societalization theory. I argue that adding the concept of moral legitimacy enables the expansion of values commitments, and the identification of the attempts of social agents to change institutional practices. The analysis shows this broadening of symbolic elements into a scandal, which challenges power structures and threatens national and civil morals. Second, I focus on policy justifications and promote the addition of moral style to the currently dominant economic style. I argue that policies that involve national moral narratives must include values-based justifications. Consequently, using moral reasoning enables the identification of the cultural mechanisms at work, representing civil-sphere action of social change and the state’s ability to maintain continuity. Third, I use the concept of the social contract to argue that moments in which new values transform into contractual agreements represent dynamics in social power structures. The analysis focuses on the military moral contract and discovers tensions and overlapping interfaces between subcontracts. In the negotiation dynamics, commitments and expectations are redefined, constructing a new contractual status quo of citizenship. The overall project challenges the current attention to the impact of values on state and society relations. The chapters emphasize that in the processes of negotiation, there is a dynamic movement between spheres of action, manifesting social changes in power structures and in state bureaucracies. In the negotiation processes, values are redefined, civil solidarity and a collective sense of belonging are enhanced, and a new national morality is constructed.

Advisor: Levi, Ron
The Experiences of Women-Identifying Undergraduate Student Caregivers

This study investigated the experiences of student caregivers through interviews with ten women-identifying undergraduate students at a large urban university, identifying four ways their postsecondary experiences were influenced by the value they placed on their contributions: (1) their sense of autonomy within public and private spaces, (2) experiences of being questioned on the validity of their caregiver identity, (3) expectations from their social circles on what their role should be as a student and caregiver, and (4) their decisions to access support services as being decided by their value. The findings also revealed how students experienced being in the school and home spaces, including feelings of guilt, worry, self-awareness, and forgiveness. The emotional responses from caregiving transformed how students experienced being in postsecondary, including challenges in concentration on academics, varying levels of identity-validation and safety in spaces, and concerns about long-term care responsibilities. The theoretical frameworks that informed this study’s analysis of the findings included the capabilities approach, intersectionality, and social care framework. Interpretative Phenomenological Analysis was used for analysis. Difficulties women-identifying student caregivers experienced included issues of financial instability/insecurity, which affected students’ ability to develop social connections and meet academic demands. Embedded within the issues of financial instability/insecurity were issues related to the provincial financial aid program, as there were many hidden limitations on amounts granted and experiences of losing funds for various reasons (i.e., dropping courses, academic probation, gaps in the students’ studies). Additional issues related to identity-specific circumstances included experiences of racism. Students also identified helpful supports, including academic supports (e.g., student groups), techniques for emotional regulation, the creation of communities of support, and the development of financial strategies. The implications of the study include recommendations for practitioners and policymakers on how to improve programs, resources, and services, including strategies that maintain the student caregiver’s dignity during identity-disclosure or minimize the need for identity-disclosure. Important to any change is acknowledging the effects of one system to another, such as academic probation and suspension’s impact on students’ OSAP funding. Future research directions are also shared for researchers to consider in expanding the literature and knowledge in student caregiving.

Advisor: Childs, Ruth
Successful Aging in Canada: Findings from the Canadian Longitudinal Study on Aging (CLSA)

Background: Successful aging is the desire of older adults and those who have devoted their lives to the care of older adults. Few studies in Canada have focused on the associations between (1) immigrant status; (2) marital trajectories; (3) social participation, and successful aging. This three-paper dissertation introduced an expanded definition of successful aging included the ability to accomplish both activities of daily living (ADLs) and instrumental activities of daily living (IADLs), freedom from mental illness, memory problems and disabling chronic pain, adequate social support and older adults’ self-reported happiness and subjective perception of their physical health, mental health and aging process as good (Ho et al., 2022; Ho et al., 2023). Methods: The first two waves of data from the comprehensive cohort of the Canadian Longitudinal Study on Aging (CLSA) were analyzed. The final samples included 7,600+ respondents defined as “aging successfully” at baseline and were 60 years or older at time 2. Bivariate and multivariable binary logistic regression analyses were conducted. Results: The study found that (1) older immigrants, (2) older adults who were never married or had experienced widowhood, separation and divorce in later life; and (3) older adults who did not engage in volunteer or charity work, and recreational activities had a significantly lower odds of achieving successful aging than their peers. Other significant baseline factors associated with successful aging included being younger, female sex, having higher income, being married, not being obese, not smoking, engaging in moderate or strenuous physical activities, not having sleeping problems and being free of heart disease or arthritis. Conclusions: The study contributed to the body of literature on successful aging by providing an expanded definition of successful aging and studying older immigrants, older adults with different trajectories of marital status, and older adults who have participated in social activities. The findings provided a strong argument that some older adults might achieve successful aging through engaging in activities that promote physical, psychological, mental, social, and self-rated wellness. Practical implications and future research directions were discussed.

Keywords: Canadian Longitudinal Study on Aging (CLSA)
Immigrant status
Marital trajectories
Older adults
Social participation
Successful aging
Advisor: Fuller-Thomson, Esme
Mark of the Non-Conviction Record: Managing Stigma and Confronting the Consequences of Recorded Police Contact in Canada

This dissertation investigates the experiences of people with non-conviction records (NCR) in Canada and how they contend with the stigma of this police record type. Minimal sociological and criminological research focuses on NCR holder experiences despite tens of thousands of NCRs being generated in Canada annually, and NGOs and legal scholars reporting that NCR exposure has similar stigma-induced repercussions to disclosing a conviction record (CR). I address this literature gap by investigating whether, why, and how recorded police contact leads to challenges for NCR holders, and how NCR holders address record-related repercussions. I draw on interviews with twenty-two NCR holders and twelve key informants across Ontario to understand NCR holder perceptions of NCR consequences, NCR holder strategies for contending with record stigma, and how NCR holder experiences compare to those of CR holders in other studies. I argue that the mark of an NCR can affect NCR holders in similar ways to CR holders, as indicated by the NCR-induced collateral consequences they experience, the record-induced discrimination they anticipate, and their use of strategies to prevent stigmatization. Interviews revealed diverse NCR exposure experiences and repercussions, including social, professional, and economic marginalization. All NCR holder participants anticipated, and most experienced, consequences in at least one area of their lives, including employment, financial security, volunteering, career training, U.S. travel, personal relationships, and sense of well-being. Collateral consequences resulted from NCRs appearing on security checks as well as NCR holders holding back from opportunities due to their perceived risk of record exposure and stigma-induced rejection. NCR holders used stigma avoidance tactics to retreat from opportunities with exposure and rejection potential; alternatively, they used stigma management strategies to resist consequences through impression management and information control. Strategy choice was primarily related to perceptions of when and where NCR consequences may occur. The findings suggest Canadians are not guaranteed the right to be considered “innocent until proven guilty” since the mere mark of police contact can have long-term detrimental effects on people who were never convicted of a crime. Overall, this dissertation contributes to broader discussions about criminal record stigma and record disclosure reform.

Keywords: Collateral consequences
Non-conviction records
Stigma
Stigma avoidance tactics
Stigma management strategies
Advisor: Welsh, Sandy
Adaptive Biology, Driven by Metabolic Reprogramming, in Soft Tissue Sarcoma

Soft tissue sarcomas (STS) are mesenchymal tumors. Undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), and leiomyosarcoma (LMS) are common types of adult STS, while rhabdomyosarcoma (RMS) is a common pediatric STS. Treatment is multimodal, yet survival rates have remained largely unchanged in the last decade. Metabolic reprogramming is the ability of cancer cells to alter their metabolism to provide energy and building blocks to support aberrant growth. Adaptation to the tumor microenvironment, such as that created by hypoxia or during metastasis, can influence growth kinetics. Therefore, metabolic pathways, such as the PI3K/mTOR pathway, are attractive targets. An understanding of how metabolic reprogramming drives adaptive STS biology may improve outcomes for these patients. To find novel therapeutic agents, we performed a drug screen on UPS cell lines. Simvastatin, which inhibits the mevalonate pathway, was a top hit at reducing the viability of UPS and LMS through a reduction in proliferation and increase in cell death. In UPS and possibly LMS cell lines, the mechanism of action occurs through a reduction in PI3K/mTOR signaling. In vivo toxicity precluded determining if simvastatin + doxorubicin, a current standard of care for patients with advanced STS, was efficacious. To model metastatic disease, we endeavored to drive STS metastasis in mice through surgical (resection or amputation) or systemic (tail vein or jugular injection) methods. While both amputations and tail veins led to metastases, we focused on amputation as this most accurately represents human disease. We established metastatic models of LMS and RMS (alveolar and embryonal), which can be used to better understand the metastatic cascade of STS and test novel therapeutics. To comprehend what drives aggressive biology in extremity UPS and MFS, we quantified hypoxia and associated epigenetic changes. Hypoxia, detected by FAZA-PET/MRI, was correlated to a worse disease-free survival. Methylation did not appear to be changed by hypoxia. In summary, we targeted metabolic pathways in UPS and LMS with simvastatin. Metabolic reprogramming may be driven by hypoxia, which we were able to quantify in UPS and MFS with two exogenous markers. With our metastatic models we can investigate the mechanism of metastasis and evaluate novel therapeutics.

Keywords: Adaptive Biology
Hypoxia
Metabolic Reprogramming
Metastatic Model
Soft Tissue Sarcoma
Statins
Advisor: Gladdy, Rebecca A