VictorJuiz/thesis huggingface dataset:
The Macro- and Microstructural Alterations Associated with Chronic Stress and Chronic Hyperactivation of the Amygdala: Link to Behavioral Emotionality

Chronic stress exposure is a major risk factor to major depressive disorder (MDD) and anxiety disorders. Chronic stress-based animal models are pivotal for studying brain and behavioral deficits relevant to these disorders. Recent advances in magnetic resonance imaging (MRI) allowing for small animal brain imaging offer the opportunity to investigate with translational approaches the consequences of chronic stress and establish parallels with stress-related disorders in human, while identifying the underlying cellular substrates. In human, MDD is associated with structural alterations within the corticolimbic circuit, and these changes were attributed to synaptic changes particularly in anterior cingulate cortex (ACC) and amygdala (AMY). The AMY is a key brain region characterized by elevated activity as a result of MDD and chronic stress. In this thesis, we assessed in mice the behavioral, MRI volumetric and synaptic alterations induced by chronic stress and chronic hyperactivation of the AMY (cHOA) to establish the links between structural and synaptic changes as well as their role in the expression of behavioral emotionality. Since at the behavioral level the majority of tests used to detect the effects of chronic stress are anxiety tests but are limited in their inability to test anxiety-like deficits longitudinally, we first established a new test allowing to assess anxiety-like behavior repeatedly. Using this assay, we identified that chronic stress resulted in progressive changes in anxiety- and depressive-like behaviors. We then identified MRI structural and synaptic changes induced by chronic stress and found ACC decreased and AMY increased volumes that mapped onto parallel synaptic changes. Further, using a chemogenetic approach to induced cHOA, we demonstrated that cHOA alone resulted in chronic anxiety-like but no depressive-like deficits. We also showed that cHOA did not exacerbate chronic stress effects on anxiety- and/or depressive-like deficits. Lastly, while cHOA increased neuronal activity and synaptic density in the AMY correlated with behavioral deficits, structural changes were not observed. This thesis emphasizes the role of chronic stress in the detrimental morphological deficits associated with MDD, specifically in the ACC and AMY but suggest that AMY hyperactivity and resulting chronic anxiety is not a susceptibility factor for the development of depression.

Keywords: Amygdala
Anxiety
Chronic Stress
Depression
MRI
Synaptic
Advisor: Sibille, Etienne
Banasr, Mounira
“Ainu are not Ecologists!”: Ainu Music, Environmental Activism, and Conceptual Sovereignty for Indigenous People in Japan, 2011-2021

This is an ethnography of contemporary Ainu music; i.e. aural expression in the lives of people who identify as descendants of the original inhabitants of Hokkaido and other regions in and around northern Japan. Many of the Ainu people described here are activists who are committed to preserving their ancestors’ songs, which reference traditional human/animal relationships and pre-colonial ways of life. There are also Ainu people who are ambivalent towards this repertoire but nevertheless connect with their ancestral lands and align with current political debates through aural techniques that their ancestors developed and passed on. Importantly, this research is also about non-Ainu people, particularly environmentalists who are interested in, and committed to, learning Ainu traditions, often directly from Ainu people. In many cases, they view these traditions as closer to nature than their own customs for reasons discussed throughout. In the following pages, I address an influx of support for Ainu music among non-Ainu environmentalists and anti-nuclear activists, especially after the March 2011 Fukushima nuclear accident. I use ethnographic case studies to show how, even when Ainu aural expressions are misunderstood by outsiders, the intellectual legacy of Indigenous ancestors is accessible and presently undergoing rapid development by way of the music-making practices of contemporary Ainu people. While, as one Ainu language teacher put it, “Ainu are not ecologists,” my interlocutors have, indeed, encouraged many people in contemporary Japan to rethink categories like nature, music, and humanity.

Keywords: Ainu
Environmentalism
Indigeneity
Japan
Advisor: Pilzer, Joshua D
Illuminating Outdoor Pedagogy in Early Learning and Child Care: A Collective Case Study in Ontario

This qualitative, collective case study, undertaken through an applied research lens, illuminates outdoor pedagogy by exploring the perspectives and practices of 12 early childhood educators and the relationship between policy and practice in three distinct Early Learning and Child Care (ELCC) programs in Ontario, Canada. Data consisted of educator interviews, field observations, pedagogical planning and documentation artifacts, and centre policies. Drawing on a sociocultural theoretical framework that integrates traditional outdoor learning theory with contemporary literature about Euro-Western approaches to outdoor pedagogy, I employed constant comparison analysis, thematic analysis, and cross-case analysis to identify six themes of outdoor pedagogy: Teamwork, the Role of the Educator, Pedagogical Interactions, the Cycle of Pedagogical Documentation, Environments and Affordances, and Safety and Risk. Further, I determined one overarching theme about the locus of intentionality which informs understanding of the heterogeneity of outdoor pedagogy. I discuss the implications of my findings for practice and policy and for scaling outdoor pedagogy within the impending expansion of ELCC in Canada.

Keywords: early childhood education
outdoor play
pedagogy
risky play
Advisor: Pascal, Charles E
An Integrated Assessment of Changes in Brain Structure and Function among Older Adults with Major Depressive Disorder or Mild Cognitive Impairment

Major Depressive Disorder (MDD) has been associated with an increased risk of developing dementia. In 2008 Butters et al. proposed a mechanistic model by which late-life depression (LLD) may increase the risk for Alzheimer’s disease (AD) consisting of: I) a vascular hypothesis, i.e., structural damage to frontal-executive circuit, II) an inflammation hypothesis, i.e., a high level of stress hormones in depression can lead to hippocampal volume loss (i.e., corticolimbic circuit).In study 1, we conducted a systematic review between 2008 and October 2018 to evaluate the evidence for the conceptual mechanistic model, focusing on frontal-executive and corticolimbic circuits in LLD. Findings from this study revealed inconsistent evidence of alterations in these circuits in LLD (compared to healthy controls; HC). In study 2 and study 3, we assessed structural and functional brain alterations of frontal-executive (i.e., ECN) and corticolimbic (i.e., DMN) circuits in five groups of older adults putatively at-risk for developing dementia: remitted depression with normal cognition (MDD-NC), non-amnestic MCI (naMCI), remitted MDD+naMCI, amnestic MCI (aMCI), and remitted MDD+aMCI. We also examined non-psychiatric HC and individuals with AD. We hypothesized that structural (via T1-weighted imaging & diffusion-weighted imaging) and functional (via resting-state-fMRI) alterations of frontal-executive (i.e., ECN) and corticolimbic (i.e., DMN) circuits would be present among these seven groups of older individuals, with the degree of alterations ranked according to the expected degree of risk for AD. Findings from these studies were contrary to our hypotheses: older individuals with remitted MDD did not show early signs of structural or functional neural alterations in the frontal-executive (i.e., ECN) or corticolimbic (i.e., DMN) circuits associated with preclinical AD. Therefore, remission from depression may protect from the risk of developing AD conferred by depression Taken together, our findings did not fully support the mechanistic ‘multiple pathways model’ linking depression and dementia. In contrast, our findings suggested that treating depression to remission in older adults could potentially reduce the likelihood of developing AD. Future large longitudinal studies should investigate differences in age of onset of depression, treatment-responsiveness, and the effects of antidepressant treatment in relation to risk of developing AD or dementia.

Keywords: Alzheimer's disease
cortico-limbic
frontal-executive
late life depression
mild cognitive impairment
MRI
Advisor: Voineskos, Aristotle
Examining Young Learners’ Emotions and How They Relate to Cognition and Learning

Since the mid-2000s, researchers have embraced a dynamic and multidimensional view of learners, where their cognitive, social, and emotional processes are considered, in addition to their background and experiences that they bring to learning. Together these factors influence students in complex and multifaceted ways, and while tackling all of these interrelated components is impossible, in-depth analyses of contributing factors help elucidate their unique influence. The current study more specifically examines emotion in education. Research on emotion has traditionally focused on anxiety associated with test performance; however, the construct of emotion is multidimensional and developmentally sensitive. There is a dearth of research on the impact of emotion among young learners’, particularly regarding associations within the domains of language and literacy. The present study examined the relationship between task types and young learners’ emotional experience during task performance, examined whether this relationship is further differentiated by the learners’ background characteristics, and further considered the temporality of emotion over time across learning tasks. Students engaged in a comprehensive, multi-task, online learning-oriented assessment platform, Speak and Solve (SnS), targeting oral language and cognition. Multi-channel methods of self-reported emotion and behaviour observation data were used to examine the role of affect in cognitive and linguistic processing for 154 grade 4-6 students engaged in SnS. More specifically, the study utilized latent class analysis, multinomial logistic regression, and latent transition analysis to understand what emotional characteristics are associated with different tasks, what predictive factors (demographic, performance measures) are associated with emotion classes, and the stability of emotion trajectories across tasks. Findings highlight the integrated role that emotions play in young learners’ educational experiences. Additionally, results suggest that while most students’ anxiety peaked prior to and at the beginning of the platform, students that were language learners had anxiety that persisted across tasks. Furthermore, student’s motivational learning orientation appeared to play an important role in emotions experienced during SnS. Findings are contextualized and interpreted using the Control-value theory of achievement emotions.

Keywords: Emotion
Learning analytics
Learning Oriented Assessment
Oral Language
Young learners
Advisor: Jang, Eunice E
From Dark Matter to Leptoquarks: Phenomenology of Physics Beyond the Standard Model

The Standard Model of particle physics began as a simple ``Model of Leptons" in 1967, but after more than five decades of theoretical development and experimental scrutiny it has grown to become the most successful scientific theory of all time.We begin with a short summary of the features of the Standard Model and a discussion of its explanatory power, taking the modern perspective. We then highlight three particular shortcomings of the SM in its current formulation: the electroweak hierarchy problem, the nature of dark matter, and the growing list of anomalies in the flavour sector, neutrino sector, and elsewhere. These shortcomings form the foundation of the work presented in this thesis. We first show that the electroweak hierarchy problem and the nature of dark matter can be understood through the combination of a general Twin Higgs framework and an additional singlet scalar acting as dark matter. Then we turn our attention to minimal Twin Higgs models and reexamine the twin tau lepton as a dark matter candidate, in light of recent theoretical developments into the UV structure of these models. We find that the scenario is possible and may be discoverable in future direct detection experiments. Lastly, we search for a novel explanation to the MiniBooNE anomaly using scalar leptoquarks to induce lepton flavour violating pion decays, and consider $\mu-e$ conversion experiments as a future probe of important leptoquark couplings.

Keywords: Dark Matter
Flavour Physics
Hierarchy Problem
Naturalness
Twin Higgs
Advisor: Curtin, David R
Developing the Porphysome Nanoparticle for Photodynamic Therapy of Colorectal Cancer

Photodynamic therapy (PDT) is an ablative modality that utilizes a photosensitizing agent, oxygen, and light to generate cytotoxic reactive oxygen species to treat cancer. PDT has not achieved widespread use in clinical practice because of deficiencies in existing photosensitizers. The porphysome (PS) is a multifunctional liposomal nanoparticle containing porphyrin photosensitizer that accumulates in tumours, conferring many potential theranostic applications. Colorectal cancer (CRC) is a deadly disease with a rising incidence. CRC is uniquely amenable to PDT light delivery via endoscopy. The modern treatment of CRC is multimodal, with an increasing demand for neoadjuvant modalities to improve the effectiveness of subsequent surgery. This thesis describes work done to advance the clinical translation of PS-PDT for the treatment of CRC. A systematic review revealed barriers to the use of PDT in CRC, as well as the promise of PDT for CRC producing significant tumour ablation. The ability of PS to act as photosensitizers for PDT was established for the first time, with comparisons made against Photofrin (a clinical photosensitizer). This study found that PS-PDT was equivalent in efficacy and survival, and subsequent studies found reduced skin photosensitivity in PS compared to Photofrin treated animals. Further studies optimized PS-PDT for CRC by investigating the effectiveness associated with changes in drug-light interval, route of administration, and nanoparticle formulation. PS-PDT was most effective when light was delivered 3 hours after administration. PS-PDT was compared to PDT using PS-related nanoparticles (e-porphysomes, ePS), and ePS were shown to be more effective photosensitizers than PS. Peri-tumoural administration of the PS and ePS demonstrated a more targeted effect compared to intravenous administration. The feasibility, safety, and efficacy of intraluminal light delivery to rectal tumours was then investigated using an orthotopic model. This study revealed that intravenous administration of PS resulted in significant off-target effects, and that peri-tumoural administration was required. The thesis concludes with the protocol for a clinical trial of PDT for CRC intended to establish the feasibility of PDT and to inform the design of a future trial of PS-PDT for CRC. Overall, this thesis provides the first evidence that PS-based PDT is possible, describes fundamental discoveries about PS-PDT, and lays the groundwork for future clinical translation of the PS.

Keywords: cancer nanomedicine
colorectal cancer
photodynamic therapy
Advisor: Zheng, Gang
Quereshy, Fayez
Geodesic Envelopes in Teichmuller Space Equipped with the Thurston Metric

The Thurston metric on Teichm\"{u}ller space, first introduced by W. P. Thurston is an asymmetric metric on Teichm\"{u}ller space defined by d_Th(X,Y) = 1/2 log sup_a l_a(Y)/l_a(X). This metric is geodesic, but geodesics are far from unique. In this thesis, we show that in the once-punctured torus, and in the four-times punctured sphere, geodesics stay a uniformly-bounded distance from each other. In other words, we show that the width of the geodesic envelope}, $E(X,Y)$ between any pair of points X,Y in T(S) (where S = S_{1,1} or S = S_{0,4}) is bounded uniformly. To do this, we first identify extremal geodesics in Env(X,Y), and show that these correspond to stretch vectors, proving a conjecture from HOP21. We then compute Fenchel-Nielsen twisting along these paths, and use these computations, along with estimates on earthquake path lengths, to prove the main theorem.

Keywords: Geodesic
Stretch path
Surfaces
Teichmuller
Thurston
Topology
Advisor: Rafi, Kasra
Hexokinase 2 Localizes to the Nucleus and Regulate s Stemness in AML through a Kinase Independent Mechanism

Leukemia stem cells are responsible for the initiation and recurrence of AML. Cell differentiation requires the coordination of metabolic state and gene expression programs. It is known that metabolic intermediates can serve as cofactors in epigenetic modifications in the nucleus to regulate the function and differentiation of leukemic and normal stem cells. However, it is less understood how mitochondrial enzymes localize to the nucleus to control stem cell function. We screened for mitochondrial metabolic enzymes that localize to the nucleus of AML stem cells. We discovered that the mitochondrial metabolic enzyme Hexokinase 2 (HK2) localizes to the nucleus in leukemic cell lines and primary patient samples. To determine whether nuclear HK2 was functionally important for AML stem cells, we overexpressed HK2 tagged with a nuclear localizing sequence (PAAKRVKLD, PKKKRKV). Overexpression of nuclear localized HK2 enhanced clonogenic growth and engraftment into immune deficient mice. Likewise, overexpression of nuclear localized HK2 blocked differentiation after treatment with all-trans retinoic acid (ATRA). Overexpression of nuclear HK2 increased leukemic stem cell (LSC) properties, independent of its kinase or metabolic activity. The nuclear localization of HK2 required active import through the importin, IPO5 and exportin XPO1, respectively. HK2 interacted with nuclear proteins that regulate chromatin openness, transcription and DNA repair. ATAC-sequencing demonstrated that nuclear HK2 increased chromatin accessibility at sites associated with the LSC+ signature. Nuclear HK2 was found to interact with the bHLH E-Box binding protein MAX (MYC associated factor X) by ChIP sequencing. Given that HK2 interacted with DNA repair proteins and increased accessibility at sites of DNA repair, we examined the role of nuclear HK2 in the DNA damage response. Overexpression of nuclear HK2 decreased double strand breaks and conferred chemoresistance in AML. This enhanced DNA damage response may contribute to the mechanism by which LSCs resist DNA damaging agents. Thus, we describe a non-canonical mechanism by which mitochondrial enzymes influence gene expression and stem cell function in AML, independent of their metabolic function.

Keywords: Acute myeloid leukemia
Leukemia
Leukemia stem cells
Advisor: Schimmer, Aaron D
Reading Comprehension in English-French Bilinguals: The Roles of Syntactic and Morphological Awareness

This dissertation examines the roles of two types of metalinguistic awareness – syntactic and morphological awareness – in the reading comprehension of children enrolled in early Canadian French immersion programs. The first study investigated the contributions of syntactic awareness to concurrent reading comprehension within and across children’s first and second languages. Seventy-two emerging English-French bilingual children in Grade 3 completed measures of syntactic awareness, reading comprehension, word reading, and vocabulary in both languages, as well as a measure of nonverbal reasoning. Results revealed that French syntactic awareness made a significant unique contribution to French reading comprehension beyond controls. French syntactic awareness also contributed cross-linguistically to English reading comprehension after accounting for English controls, including English syntactic awareness. In contrast, no significant unique relations were found between English syntactic awareness and reading comprehension in either language beyond controls.The second study examined the development of morphological awareness, as well as its role in reading comprehension, in emerging English-French bilinguals. Using a longitudinal design, 115 participants were assessed in both languages on morphological awareness, reading comprehension, word reading, and vocabulary in Grade 2 and again in Grade 3. A measure of nonverbal reasoning was also collected. Results highlight the influence of phonological structure and cognate status on children’s development of morphological awareness in each language. Within-language results revealed that French morphological awareness contributed to concurrent French reading comprehension in both Grades 2 and 3 after controls, while English morphological awareness contributed to English reading comprehension in Grade 3 only. Longitudinally, Grade 2 morphological awareness predicted gains in Grade 3 reading comprehension within each language, beyond a stringent autoregressive control. Cross-language results indicated that French morphological awareness made significant contributions to English reading comprehension concurrently in Grade 3, and longitudinally from Grade 2 to Grade 3. In contrast, English morphological awareness did not contribute to French reading comprehension concurrently or longitudinally. Taken together, the findings of this dissertation add to our understanding of the roles of syntactic and morphological awareness in the reading comprehension of bilingual children. The findings underscore the importance of cultivating children’s metalinguistic awareness during the early stages of bilingual reading instruction.

Keywords: Bilingualism
Education
French immersion
Morphological Awareness
Reading Comprehension
Syntactic Awareness
Advisor: Chen, Xi Becky