VictorJuiz/thesis huggingface dataset:
Thickness of the Cerebral Cortex and Stress: A Multiscale Analysis

The intricate relationship between stress and the brain varies spatially, across brain regions, and temporally, across the lifespan. It is hypothesized that stress, spanning from the molecular level to environmental level, will be related to cortical thickness and its underlying neurobiology. The research described in this thesis focuses on the neurobiology of cortical thickness and the potential relationship with psychiatric disorders, expression of stress-hormone receptor genes, and potential stress exposure from the socioeconomic environment. The first study investigated what neurobiological features contribute to the variation in cortical thinning during maturation, and how those features may be implicated in psychopathology. Here, dendritic- and myelin-related gene expression both contributed to regional variation in cortical thickness during development, and were also enriched for genes associated with several psychiatric disorders. For the next study, regional variations in expression of the cortisol binding glucocorticoid and mineralocorticoid receptor genes (NR3C1 and NR3C2, respectively) were associated with cortical thickness across the lifespan. The association betweenthe profiles of gene expression and cortical thickness increased rapidly in strength during childhood and adolescence, plateaued in midlife, and decreased during late life. The final study investigated the relationship between cortical thickness and income inequality (in neighborhoods); it used expression of NR3C1 and androgen receptor (AR) in the cerebral cortex to aid interpretation of this relationship. Females, from low-income families living in neighbourhoods with high income-inequality had greater age-related reductions in cortical thickness when compared with females of differing economic conditions. The same group of females displayed a stronger negative association between cortical thinning and both NR3C1 and AR gene expression when compared with other low-income females. This body of research demonstrates how stress, spanning from the molecular level to environmental level, is related to cortical thickness. Overall, this contributes to the understanding of how stressors may contribute to spatial and temporal variations in brain structure, and contribute to the emergence of psychiatric disorders.

Keywords: Cortical Thickness
Gene Expression
Income Inequality
Lifespan
Neuroimage
Stress
Advisor: Paus, Tomas
Brain Endocannabinoid Metabolism and Hippocampus Glutamate Metabolites in Young Adults with and without Psychotic Disorders: Multimodal Imaging with [11C]CURB Positron Emission Tomography and Proton Magnetic Resonance Spectroscopy

The brain’s endocannabinoid neurotransmitter system, the primary target of cannabis, has been implicated in psychosis. The endocannabinoid anandamide is elevated in cerebrospinal fluid of patients with schizophrenia. Fatty acid amide hydrolase (FAAH) controls brain anandamide levels; however, it is unknown if FAAH is altered in vivo in psychosis or related to psychotic symptoms. The endocannabinoid system is a key regulator of neurotransmission throughout the brain including the hippocampus, a major site of glutamate dysfunction in schizophrenia. In vivo neuroimaging studies report alterations in cannabinoid CB1 receptors in psychotic disorders, however, no other endocannabinoid system target has been imaged in vivo in this population. Further, although the endocannabinoid system is related to functional brain activity, the relationship between regional endocannabinoid system markers and brain glutamate remains virtually unexplored. In this work we measured brain FAAH and hippocampal glutamate neurometabolites (glutamate and glutamate-glutamine) using [11C]CURB positron emission tomography (PET) and proton magnetic resonance spectroscopy (1H-MRS), respectively, in patients with psychotic disorders and healthy control participants. Brain FAAH availability did not differ between patients with psychotic disorders and healthy controls, however, low FAAH availability was associated with greater severity of positive dimension psychotic symptoms in patients. FAAH differed across brain regions, with the highest availability observed in hippocampus and striatum. Further, FAAH was higher in females than in males. Hippocampal glutamate metabolites did not differ between patients and healthy controls and were not significantly associated with psychotic symptoms. Combining imaging data from both modalities, we observed that higher FAAH was associated with higher hippocampal glutamate-glutamine and this effect did not differ between patients and healthy control participants or across brain regions. This report provides novel findings that expand the existing picture of endocannabinoid system function in young adults with and without psychotic disorders. Although FAAH did not differ between patients and healthy controls, its relation to psychotic symptom severity may indicate that FAAH serves as a state but not trait biomarker for psychotic symptoms. Regional brain FAAH was associated with hippocampal glutamate metabolite concentrations, providing evidence that the link between glutamate and FAAH activity observed in other species is conserved in humans.

Keywords: cannabinoid
endocannabinoid
neuroimaging
positron emission tomography
psychosis
schizophrenia
Advisor: Mizrahi, Romina
Ross, Ruth A
Therapeutic Instrumental Music Training and Sensory-enhanced Motor Imagery in Chronic Post-stroke Upper-extremity Rehabilitation: A Randomized Controlled Trial

Objectives: To investigate the effectiveness of Therapeutic Instrumental Music Performance (TIMP) training, with or without motor imagery, in upper-extremity rehabilitation for individuals with chronic, post-stroke hemiparesis. Secondary objectives investigate effects of interventions on cognition and affect. Methods: Two baseline assessments, a minimum of one week apart; one final assessment. Nine interventions (3x/wk for 3 wks), facilitated by a qualified Neurologic Music Therapist. Thirty participants were randomized to one of three groups: 45 minutes of active TIMP; 30 minutes of TIMP followed by 15 minutes of metronome-cued motor imagery (TIMP+cMI); 30 minutes of TIMP followed by 15 minutes of motor imagery without cues (TIMP+MI). A selection of acoustic and electronic instruments was used. Results: Thirty participants completed the protocol, ten per arm [14 women; mean age= 55.9; mean time post-stroke= 66.9 months]. Pooled group baseline measures did not significantly differ. There were significant improvements from pre-test 2 to post-test for all groups on the Fugl-Meyer-Upper Extremity (FM-UE) and the Wolf Motor Function Test-Functional Ability Scale (WMFT-FAS), and for TIMP and TIMP+MI on the Motor Activity Log (MAL)-Amount of Use Scale. Comparing percent change differences between groups, TIMP (mean rank = 21.05) scored significantly higher than TIMP+cMI (mean rank = 11.00, p = .032) on the FM-UE. There were no significant percentage change differences between TIMP and TIMP+MI. The TIMP+MI group showed a significant change on the Trail Making Test (TMT)–Part B. The TIMP group showed a significant increase on the Multiple Affect Adjective Checklist (MAACL) Sensation Seeking scale and the Valence and Dominance portions of the Self-Assessment Manikin (SAM); TIMP+cMI showed respective increases and decreases in positive and negative affect on the MAACL, as well as an increase in Valence, Dominance, and Arousal portions of the SAM. There was no statistically significant association between cognitive and affective measures. Conclusions: Implementation of TIMP-based techniques led to significant improvements in paretic arm control. TIMP and TIMP+MI showed greater benefits than TIMP+cMI, suggesting that synchronizing internal and external cues during cMI may pose additional sensory integration challenges. TIMP+MI appeared to increase mental flexibility, while active TIMP interventions appeared to enhance positive affect. Trial Registration: ClinicalTrials NCT03246217

Keywords: affective responding
cognition
motor imagery
music
stroke
upper extremity rehabilitation
Advisor: Thaut, Michael H
Exploring Targets of TET2-mediated Methylation Reprogramming as Potential Therapeutic Targets and Discriminators of Prostate Cancer Progression

Aberrant cytosine methylation is one of the most common alterations in cancer, with global hypomethylation and regional hypermethylation characterizing many different malignancies, including prostate cancer. In normal cells, master methylation regulators, the ten-eleven translocase (TET) family of enzymes, demethylate genes by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine. Although lowered expression of all three TETs is common in prostate cancer, TET2 in particular plays a central role through its interaction with – and repression by – the androgen receptor. Loss of TET2 is associated with decreased cancer-specific survival, while missense alterations of TET2 are linked to metastatic disease. In this thesis, genome-wide targets of TET2 were examined via integrative (hydroxy)methylation and expression analysis to first identify how locus-specific epigenetic patterns affect prostate cancer cells and phenotype. Subsequently, genes regulated by TET2 were assessed to determine their individual and combinatorial utility as potential tumor suppressors or oncogenic factors in disease. In contrast to the paradigm of universal hydroxymethylation loss in cancer, locus-specific intronic retention in genes related to basic cellular function and intergenic gain of hydroxymethylcytosine marks proximal to androgen-related genes was observed in 22Rv1 prostate cancer cell lines. CRISPR-Cas9 based TET2 knockout in prostate cells identified high-confidence genes specifically mediated by TET2 methylation reprogramming. Expression loss of three such genes – ASB2, NUDT10, and SRPX – or increased promoter methylation of NRG1 was significantly (p

Keywords: Biochemical recurrence
Disease modeling
Epigenetics
Prostate cancer
TET2
Therapeutic targets
Advisor: Bapat, Bharati
Affective Indignities at Work: Exposing the Inequality of Feelings in Canadian Professional Workplaces

Despite the “talk” of diversity and inclusion, power in professional workplaces in Canada remains in the hands of a dominant white network. In order to devise effective strategies to achieve workplace equality, a deeper understanding of how power flows in professional workplaces is needed. In this thesis, I connect the framework of white institutional space, and the concept of feeling rules to explore how 20 foreign-trained South Asian (FTSA) women who occupied professional and/or managerial jobs in the Greater Toronto Area (GTA) conceptualized the power differences that produced and reproduced the form of workplace inequality they experienced. Based on a narrative analysis of the feeling rules experienced and navigated by FTSA women in the professional workplace, I conceptualize the workplace inequality they experienced in two interconnected ways to demonstrate the hegemonic nature of feelings in the professional workplace (i.e., the inequality of feelings). Firstly, through the structural lens afforded by connecting the concept of feeling rules and the framework of white institutional space, I argue that the cumulative impact of years of engaging in multidimensional emotional labour to constantly manage recurring racialized and gendered emotions is a form of workplace inequality. The emotions that FTSA women managed daily did not dissipate each day; instead they accumulated daily and as such are irreducible to invisible work (Daniels, 1987). Secondly, I use Ahmed’s (2004) critical concept of impression and the process of racialization to argue that the accumulation of racialized and gendered emotions through repeated performances of gratitude work, shame work, and empathy work, as directed by the five distinct feeling rules that FTSA women experienced–namely, to be hyper-pleasant, grateful, fearful, not angry, and not lonely–resulted in an intensification of emotions that produced affective associations that racialized their bodies. The impact of these affective associations on an FTSA woman’s bodily and embodied experiences in the workplace is a unique form of workplace inequality as it constrains her agentic actions. I have termed this form of workplace inequality affective indignities as it sustained the racialized relations of power in white institutional spaces that diminished the capacity of FTSA women to act.

Keywords: Affect
Diversity and Inclusion
Emotion Work
Emotional Labour
South Asian Women
White Institutional Space
Advisor: Mirchandani, Kiran
Foaming Effects on Conductivity Percolation Threshold in Conductive Polymer Composites

Conductive filler/polymer composite foams (CPC) with micro-/nano-scale bubbles have attracted much attention due to their various advantages. Understanding the evolution of electrical behavior in CPC foams is important for their functional application. This thesis investigated the foaming effects on the re-alignment of the conductive filler and the subsequent conductivity percolation threshold of CPC foams experimentally and theoretically. The polystyrene (PS) and multiwalled carbon nanotubes (MWCNTs) were selected as the model system for analysis. In the experimental approach, we prepared a series of PS/MWCNTs composite foams using solvent-mixing method to blend PS and MWCNTs followed by the conventional batch foaming. It was found that at a relatively low void fraction, the electrical conductivity can be increased, and the percolation threshold can be decreased. In the theoretical modeling, a novel resistive network model based on Monte Carlo simulation to directly predict the electrical conductivity of CPC foams was developed. The model predictions agreed very well with the experimental data for both the solid and foamed composites. At relatively low void fractions (up to ~30 %), the growth of bubbles with size comparable to the MWCNT length increased the conductivity. The methods and models developed in this work are useful tools for understanding the underlying mechanism of percolation behavior in CPC foams, as well as quantitative tools in the design of CPC foams. Furthermore, the approaches and strategies used to develop such computational model can provide guidelines and useful references for model simulation in other functional polymer composite foams, such as thermally conductive polymer composite foams.

Keywords: CNT alignment
computational modeling
conductive polymer composite foam
electrical conductivity
MWCNT
Advisor: Park, Chul
Naguib, Hani
Geriatric Traumatic Brain Injury: Outcomes, Costs and Quality of Care

Observational data from an adult traumatic brain injury (TBI) cohort derived from a Level I Trauma Centre (TC) over an eight-year time horizon were analyzed using descriptive statistics and logistic regression in a series of four studies. The first study aimed to assess differences between younger and older TBI patients in injury presentation, hospital resource utilization and short-term outcomes. Older adults were found to have reduced odds for TBI in the presence of multisystem injury (TBI+), direct hospital transport, and trauma team activation (TTA). Older age was also associated with increased odds for assisted living disposition and hospital readmission. The second study sought to assess the impact of different factors related to older and younger patients and factors related to mortality after TBI. It was found that increasing age was associated with increased odds (OR: odds ratio) mortality, as was the presence of comorbidities, severity of injury and receiving surgery. The third study aimed to assess determinants of hospital length of stay (LOS) and associated costs for acute care medical treatment. It was found that the mean LOS was 6.4 days, with intensive care unit (ICU) admissions and alternate level of care (ALC) designated patients accounting for 23% and 13% of total hospital days. The six most influential determinants of acute care hospital LOS were discharge destination, hospital acquired complications, ICU management, Geriatric Trauma Consultation Service (GTCS) exposure, physician service, and TBI+ diagnosis. The mean acute care hospital cost for patients in the cohort was $20,148 CAN (SD: $32,800). TBI+ presentation accounted for 20% of all hospital bed-days and 23% of all hospital expenditures, despite its representation in only 10% of the entire cohort. The fourth study was designed to measure associations between GTCS and hospitalization outcomes for geriatric TBI patients. GTCS patients were matched to those without GTCS (UC: usual care) using propensity scores. GTCS management was significantly associated with increased rate of in-hospital complications, ICU- and ALC-management and prolonged total LOS Among GTCS survivors, there was significant increased disposition to in-patient rehabilitation (IR) (OR 1.37 CI 1.00-1.88), compared to UC patients.

Keywords: Clinical Care Pathways
Geriatric
Observational
Resource Use
Trauma Center
Traumatic Brain Injury
Advisor: Burnham, McIntyre
Rizoli, Sandro
Experiences of Secondary Long-term Occassional Teachers Seeking Permanent Employment in Ontario

This study analyses how Long-term Occasional Teachers (LTO) interface with permanent teachers, students and the administration as they seek to gain permanent employment. It also focuses on Internationally Educated Teachers (IETs) who are LTOs as they seek integration into the Ontario teaching workforce as permanent teachers. The study utilized a general qualitative research methodology with interviews to obtain participant data and is undergird by notions of Post-Fordism, communities of practice and equity education. Data were collected from 15 participants who self-identified as LTOs. Of the 15 LTOs 4 identified as IETs who sought employment as full-time teachers in Ontario. Findings reveal that (a) LTOs and in particular those who were internationally trained (IETs) felt that they were required to continuously reinvent themselves to become marketable for the Ontario education system; (b) their knowledge seems to be less appreciated than that of permanent contract teachers and; (c) there are challenges achieving permanent employment. This study also reports on the insecurities and low self-esteem caused by extended periods of job search as well as the impact of different forms of discrimination on their ability to obtain full time employment. This study relies on the extant literature on the experiences of LTOs and IETs to build greater awareness of the challenges they experience while seeking employment in Ontario as full-time teachers.

Keywords: Equity
Hierarchy
Invisible Influence
Nepotism
Permanent Employment
Advisor: Lopez, Ann AL
CityPlace and City Space: An Investigation into Toronto's Changing Skyline

As the largest master-planned residential community in Toronto, the case of CityPlace offers an important and dramatic study of physical, social, and symbolic transformation. The towers of CityPlace altered the skyline of downtown Toronto, created a new residential and commercial neighbourhood on previously unused rail land, and established a community of nearly 18,000 people. The unique features, context, and scale of CityPlace condominiums offer a profoundly interesting case for understanding a variety of policies and processes, including: social mix and creative city planning strategies; the narrative of Toronto as a city of neighbourhoods; and the form and function of community through both online and offline geographies. The rapid construction of this neighbourhood raises critical and timely questions about the profound transformation of Toronto through the building of CityPlace, and the role of this development in shaping new neighbourhoods and identities. My dissertation engages with many themes embedded in these transformations, connecting the development of CityPlace to concepts of urban neoliberalism and development, new-build gentrification, the performance and perception of neighbourhood and community, and the production of space in the urban realm. This project investigates CityPlace in the contexts and confluences of the site’s development and evolution: production and promotion of the condominium complex within neoliberal paradigms of benevolent gentrification, creativity, and social mix; complex negotiations of Toronto’s narrative as a Jane Jacobsian city-of-neighbourhoods; strategies and sites of community life and novel perspectives on the physical and virtual locality of neighbourhood connection. CityPlace condos are reflective and constitutive of broader geo-political forces such as urban neoliberalism, place-making and gentrification, and the production of a symbolic economy – concepts that must be carefully applied to a timely and meaningful analysis of this site. Extending this analysis further, CityPlace is also a site of negotiation and nuance, where challenging, contradictory, and variegated practices, policies, processes, and perceptions complicate but also enrich our contemplation of this neighbourhood. In this dissertation, I utilize a multimethods approach to explore case and context: the production, policies, and practices of CityPlace condominiums, and how this neighbourhood operates within and informs a landscape of narratives about urban space.

Keywords: condominiums
creative cities
Facebook
gentrification
neighbourhood and community
urban neoliberalism
Advisor: Leslie, Deborah
Molecular Mechanisms Involved in the Regulation of Agouti-related Peptide and Neuropeptide Y by Endocrine Disrupting Chemical Bisphenol A in Hypothalamic Neurons

Bisphenol A (BPA), a ubiquitous endocrine disrupting chemical found in plastics and receipts, is a disruptor of reproductive function and is a known ‘obesogen’ as it is linked to increased body mass index in humans and leads to weight gain in animal models. The hypothalamus houses orexigenic NPY/AgRP neurons, which integrate peripheral hormones and nutritional signals, to increase food intake and decrease energy expenditure. NPY neurons are also afferent regulators of the hypothalamic-pituitary gonadal axis, and thus reproductive function. This thesis investigated whether the NPY/AgRP neurons, and particularly Npy and Agrp expression, are altered by BPA. We hypothesized that BPA increases Npy and Agrp gene expression in hypothalamic neurons and that this effect is mediated through nuclear receptor activation, induction of cellular stress and subsequent transcription factor activation or circadian dysregulation. We demonstrated that BPA increased Agrp mRNA expression in mHypoA-59 and mHypoE-41 cells. Inhibition of AMPK and knock-down of transcription factor ATF3 prevented the BPA-mediated increase in Agrp expression in the mHypoA-59 cells. ATF3 was also required for BPA-mediated increase in Npy in the mHypoE-41 cells. We also described subpopulation-specific changes in Npy expression in response to BPA. While BPA induced Npy expression in mHypoA-59, -2/12 and mHypoE-41, -42 neurons, Npy expression was downregulated in mHypoE-46 and -44 neurons. Inhibition of AMPK with compound C or oxidative stress with antioxidants and vitamin B6 prevented the BPA-mediated induction in Npy in the mHypoA-59 cells, whereas antagonism of ERß or GPER prevented the decrease in Npy mRNA in the mHypoE-46 cells. Finally, we showed that circadian gene dysregulation occurred with BPA exposure and using hypothalamic cell lines lacking BMAL1, demonstrated that the BPA-mediated induction of Npy, but not Agrp, required BMAL1. Accordingly, treatment with BPA increased BMAL1 binding to the Npy promoter. These findings illustrate distinct mechanisms responsible for the BPA-mediated changes in appetite-increasing Npy and Agrp gene expression, suggesting that NPY/AgRP neurons are susceptible to the endocrine disrupting effects of BPA. Furthermore, we describe potential targetable pathways to combat the obesogenic or reproductive dysfunction-inducing effects of BPA at the hypothalamic level.

Advisor: Belsham, Denise D