VictorJuiz/thesis huggingface dataset:
The Development of Neurodegeneration and Behavioural Alterations following Lithium/Pilocarpine-induced Status Epilepticus in Rats

The lithium/pilocarpine model of epilepsy mimics mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) in humans. Systemic injection of pilocarpine in lithium chloride (LiCL) pretreated adult rats results in an acute episode of severe continuous seizure activity (status epilepticus, SE). SE causes a latent period, whereby the animal appears neurologically normal, with subsequent development of spontaneous recurrent seizures (SRSs). Neuropathological changes that occur during the latent period are believed to contribute to the epileptic condition. The present thesis characterized the development of neuronal death and behavioural alterations in rats after SE induced by the repeated low-dose pilocarpine procedure (RLDP), and investigated the causal relationship between these two processes. Our data demonstrated that the RLDP procedure for the induction of SE results in widespread neurodegeneration and behavioural alterations comparable to the pilocarpine and low-dose pilocarpine (LDP) procedures. However, the advantage to using this protocol was strain-dependent as it reduced mortality in Wistar, but not in Long Evans Hooded (LEH), rats. Stereological analysis of neurons (stained for the neuronal specific marker [NeuN]) at various times (1 hr to 3 months) following SE showed that different brain regions within the hippocampus, amygdala, thalamus and piriform cortex exhibited differential rates of neuronal loss, with the majority of SE-induced neuronal death present by 24 hours. SE resulted in decreased exploratory behavior as assessed in the open field test, increased aggression to handling, increased hyperreactivity as assessed in the touch-response test, and anxiolytic effects as measured in the elevated-plus maze. Furthermore, deficits in search strategies used, as well as impaired spatial learning and memory, contributed to poor Morris water maze (MWM) performance. Partial neuroprotection within the hippocampus (by tat-NR2B9c) had no effect on the number of rats developing SRSs or on behavioural alterations; this argues against a causal relationship between neurodegeneration within this region, genesis of SRSs, and behavioural morbidity.

Keywords: status epilepticus
lithium/pilocarpine
epilepsy
neuroprotection
neurodegeneration
behaviour
Advisor: Milgram, Bill
Gurd, Jim
Le désir et ses stratégies discursives dans les littératures française et québécoise au féminin, 1995-2005

Cette thèse analyse la représentation de sujets désirants féminins dans cinq œuvres contemporaines. La question est abordée dans une perspective féministe et puise des outils théoriques tant du côté de la psychanalyse (Freud, Lacan) que de ses critiques (Deleuze et Guattari, Cixous, Irigaray). Nous faisons appel à la rhétorique pour l’analyse de figures du discours, et examinons comment les sujets et objets grammaticaux correspondent à une répartition des rôles entre sujets désirants et objets désirés. À la suite du chapitre explicitant nos approches théoriques se trouvent cinq chapitres s’appliquant à l’analyse d’une œuvre littéraire. Notre étude sur Folle (2004) de Nelly Arcan explore la posture masochiste construite par la narratrice, grâce à laquelle elle parvient à se représenter simultanément comme l’objet passif du désir masculin et comme un sujet désirant manipulateur. La vie sexuelle de Catherine M. (2001) de Catherine Millet nous a intéressée par l’investissement d’une posture de soumission au désir masculin qui demeure agente et investie de maîtrise. L’analyse de Se perdre (2001) d’Annie Ernaux étudie la configuration du désir ambiguë causée par la passion, où la narratrice se montre à la fois soumise et dominante par rapport à l’amant. Le chapitre sur Baroque d’aube (1995) de Nicole Brossard examine la construction de sujets lesbiens qui ne posent pas leur attirance en tant que désir du même, mais qui encouragent plutôt le déploiement d’une identité féminine plurielle. Enfin, notre étude de La nouvelle pornographie (2000) de Marie Nimier s’attache à la réécriture parodique de la pornographie, démontrant de quelles façons celle-ci permet à la narratrice de critiquer un discours masculin sur le désir et d’en proposer de nouvelles formulations. Au fil de ces analyses, nous interrogeons, à travers la question du désir, les configurations contemporaines du genre sexuel et de la sexualité.

Keywords: desire
contemporary women's literature
Nelly Arcan
Catherine Millet
Annie Ernaux
Nicole Brossard
Marie Nimier
French literature
Advisor: Havercroft, Barbara
Structural Characterization of Freshwater Dissolved Organic Matter from Arctic and Temperate Climates Using Novel Analytical Approaches

Dissolved organic matter (DOM) is comprised of a complex array of molecular constituents that are linked to many globally-relevant processes and yet this material is still largely molecularly uncharacterized. Research presented here attempted to probe the molecular complexity of this material from both Arctic and temperate climates via multifaceted and novel approaches. DOM collected from remote Arctic watersheds provided evidence to suggest that permafrost-disturbed systems contain more photochemically- and biologically-labile material than undisturbed systems. These results have large implications for predicted increasing temperatures where widespread permafrost melt would significantly impact stores of organic carbon in polar environments. In attempting to address the complexities and reactivity of DOM within global environments, more information at the molecular-level is necessary. Further research sought to unravel the molecularly uncharacterized fraction via use of nuclear magnetic resonance (NMR) spectroscopy in conjunction with hyphenated and varied analytical techniques. Directly hyphenated high performance size exclusion chromatography (HPSEC) with NMR was explored. This hyphenation was found to separate DOM into structurally distinct fractions but proved limited at reducing DOM heterogeneity. Of the many high performance liquid chromatography (HPLC) techniques tested, hydrophilic interaction chromatography (HILIC) was found the most effective at simplifying DOM. HILIC separations utilizing a sample from Florida resulted in fractions with highly resolved NMR signals and substantial reduction in heterogeneity. Further development with a 2D-HILIC/HILIC system to achieve additional fractionation was employed. This method produced fractions of DOM that were homogenous enough to produce excellent resolution and spectral dispersion, permitting 2D and 3D NMR experiments to be performed. Extensive NMR analyses of these fractions demonstrated strong evidence for the presence of highly oxidized sterols. All fractions, however, provided 2D NMR spectra consistent with oxidized polycyclic structures and support emerging data and hypotheses suggesting that cyclic structures, likely derived from terpenoids, are an abundant, refractory and major component of DOM. Research presented within this thesis demonstrates that HILIC and NMR are excellent co-techniques for the analysis of DOM as well as that oxidized sterols and other cyclic components with significant hydroxyl and carboxyl substituents are major constituents in DOM.

Keywords: dissolved organic matter
nuclear magnetic resonance
Arctic
terpenoid-derived
sterols
high performance liquid chromatography
Advisor: Simpson, Andre
Innate Immune Transcription Activator Interferon Regulatory Factor-3 (IRF3) Contributes to Maladaptive Remodeling Post-myocardial Infarction

Cardiovascular disease, and myocardial infarction (MI) in particular, remains a major burden in the developed world today. In fact, the remodeling process, which follows the initial ischemic episode of MI, is a major determinant of heart failure. Although several key mechanistic pathways involving cell growth and death have been identified, there is limited knowledge surrounding the role of the innate immune response as a positive or negative regulator of cardiac remodeling. Recent data strongly support a role for key regulatory components within the toll-like receptor (TLR) family as potent modulators of cardiac remodeling post-MI. It has been demonstrated that targeted gene knockdown of TLR4, as well as downstream adaptor proteins and kinases, significantly improve cardiac function and overall survival. While the well-known NF-κB transcriptional factor that is downstream to TLR4 signaling has been linked to remodeling, there has been no evidence thus far describing a role of the parallel interferon regulatory factor-3 (IRF3) signaling cascade in any facet of this process. Several key findings suggest that IRFs contribute to both cell growth and apoptosis, thus providing an appealing, and novel target for interrogation. In this thesis I describe how IRF3 contributes to maladaptive remodeling post-MI. In my first set of experiments, I demonstrate that IRF3 is acutely upregulated within the cardiomyocyte following MI and that this response contributes to excessive apoptosis post-MI. A targeted deletion of the IRF3 gene enhances cardiac function, decreases infarct size, and improves survival following MI. In the second set of experiments I demonstrate that IRF3 attenuates angiogenesis at the ischemic border zone by upregulating the expression of thrombospondins. I have shown that IRF3 deficiency, which liberates endogenous anti-angiogenic signals, promotes angiogenesis following ischemic injury. These data suggest that IRF3 is a potent regulator of cardiac remodeling and may be an effective therapeutic target to ameliorate maladaptive cardiac repair post-MI.

Keywords: Myocardial Infarction
Cardiac Remodeling
Interferon Regulatory Factor-3
Innate Immunity
Advisor: Liu, Peter
A Role for Bclaf1 in mRNA Processing and Skeletal Muscle Differentiation

Bcl-2 associated factor 1 (Bclaf1; previously known as Btf) is a nuclear protein that was originally identified as an interacting partner for the adenoviral anti-apoptotic Bcl-2 family member E1B-19K. Surprisingly, Bclaf1 does not share structural homology with the Bcl-2 family of proteins, but rather exhibits protein structure and subcellular distribution patterns reminiscent of proteins that regulate mRNA processing. In addition, Bclaf1 appears to be expressed at high levels in skeletal muscle and was recently shown to associate with emerin, a protein linked to muscular dystrophy. Despite these observations, roles for Bclaf1 in RNA processing and/or skeletal muscle differentiation remain to be elucidated. In an effort to identify new roles for Bclaf1 I conducted protein-protein interaction screens to identify candidate interacting proteins and pathways. I identified p32 and 9G8 as novel interacting partners for Bclaf1. Additional subsequent experiments demonstrated an interaction of Bclaf1 with tip associated protein (Tap) and association of Bclaf1 with ribonucleoprotein complexes. Given that all of these proteins have been linked to mRNA processing, a role for Bclaf1 in this pathway was investigated. Using several approaches, I demonstrated that Bclaf1 is able to associate with splicing complexes and mRNA species at various stages of processing. The function of Bclaf1 in the context of skeletal muscle differentiation was also explored using skeletal muscle cell lines and primary mouse myoblasts. Skeletal muscle differentiation led to a dramatic decrease in nuclear Bclaf1 steady-state protein, with the unexpected appearance of smaller Bclaf1 protein species that accumulated in the cytoplasm during differentiation due to cleavage by caspases. Furthermore, Bclaf1 depletion in a myoblast cell line led to increased myoblast fusion and myofiber dimensions during differentiation. Overall our findings indicate roles for Bclaf1 in the skeletal muscle differentiation program and in molecular events that regulate pre-mRNA splicing and related events.

Keywords: Bclaf1
myoblasts
pre-mRNA processing
skeletal muscle
yeast two-hybrid
apoptosis
Advisor: McPherson, John Peter
Evolution and Ecology of Flyingfishes (Teleostei:Exocoetidae)

The flyingfishes (Teleostei: Exocoetidae) are a family of 53 epipelagic marine species distributed throughout tropical and subtropical surface waters. They form a key mid-trophic link between zooplankton and predators, and have evolved special adaptations to survive in the open ocean. However, little is known about their basic evolutionary history and ecology. Here, I apply a multidisciplinary approach to better understand the evolution and ecology of flyingfishes. I propose the first species-level phylogenetic hypothesis for the group, based on nuclear and mtDNA sequences, and show that the most speciose genus (Cheilopogon) is paraphyletic. Gliding evolved progressively from two- to four-wing strategies, and habitat preference is correlated with species range size. I also analyzed patterns of genetic diversity within the most abundant genus, Exocoetus, and found no evidence of cryptic species. Instead, I found that this genus likely consists of three genetically distinct species (in contrast to the five currently recognized) and two indistinct species that diverged very recently. Population genetic analysis of Exocoetus volitans (266 samples from 97 localities) indicates a single, circum-tropical population that is well connected; yet the Isthmus of Panama and an Equatorial barrier limit gene flow. Finally, I investigated species abundance, richness, diversity, and distributions within the eastern tropical Pacific Ocean (11,125 specimens). My results provide critical updates on species distributions and habitat preferences. Predictive modeling indicates that sea surface temperature is important for defining flyingfish habitat. This thesis addresses central issues concerning both evolution and ecology in the epipelagic zone, and highlights the need for better understanding remote marine regions and organisms.

Keywords: phylogenetics
speciation
population genetics
habitat modeling
epipelagic
flyingfish
Advisor: Lovejoy, Nathan
Knowledge Sharing: An Empirical Study of the Role of Trust and Other Social-cognitive Factors in an Organizational Setting

Effective knowledge sharing within project teams is critical to knowledge-intensive professional service firms. Prior research studies indicate a positive association between trust, social-cognitive factors, and effective knowledge sharing among co-workers. The conceptual framework proposed here builds on these studies, and draws from theoretical foundations from the organizational behavior, psychology, information studies, sociology, and management literature on organizational trust and knowledge sharing, and identifies the most significant factors found to influence organizational knowledge sharing directly and indirectly through trust. The study makes methodological contributions in the form of conceptualizations for knowledge sharing behavior, trust, and tie strength. Also, it provides a more nuanced and focused analysis, by factoring for knowledge type and co-worker working relationship. Data were collected from 275 knowledge workers (‘legal professionals’ and paralegals) engaged in shared legal project work, at one of Canada’s largest multijurisdictional law firms. The nature of their work required a significant reliance on co-workers, for both explicit and tacit knowledge. Multiple regression analysis, among other statistical techniques, was used to test the hypotheses and determine significant relationships. Of the factors examined in the study, the three found to have the strongest effect on respondents’ trust in their co-workers were shared vision, shared language, and tie strength. Furthermore, the two factors found to have the strongest effect on organizational knowledge sharing behavior were trust and shared vision. Overall trust was also found to have a mediating effect between shared vision and knowledge sharing behavior, and between shared language and knowledge sharing behavior. A significant implication for practitioners is that effective knowledge sharing among co-workers requires a nurturing manager to work on developing co-worker trust and shared vision. Furthermore, a manager wanting to promote trust between co-workers must nurture shared language and shared vision.

Keywords: Knowledge Sharing
Trust
Knowledge Sharing Behavior
Homophily
Shared Perspective
Shared Language
Shared Vision
Tie Strength
Relationship Length
Social-Cognitive Factors
Trust as a Mediating Factor
Willingness to Share Knowledge
Willingness to Use Knowledge
Perceived Receipt of Useful Knowledge
Organizational Behavior
Professional Service Firm (PSF)
Knowledge Workers
Empirical Study
Advisor: Choo, Chun Wei
Individual Differences and the Learning of Two Grammatical Features with Turkish Learners of English

This study investigated relationships between individual learner differences and the learning of two English structures that differed in their grammatical difficulty. Using a quasi-experimental design, 66 secondary-level learners of English as a foreign language from three intact classes were provided with four hours of instruction on two L2 structures –one considered relatively easy to learn (i.e., past progressive) and the other relatively difficult to learn (i.e. passive construction). The participants were pretested on their knowledge of both structures and posttested immediately after the instruction. Learners’ progress was measured via written grammaticality judgment tests (GJT) and oral production tasks (OPT). The instruments to measure individual learner differences included a computerized language aptitude test, an L1 metalinguistic awareness test, a motivation questionnaire, a backward digit span test, and a learner retrospection questionnaire. The results revealed that aptitude and motivation were the two variables that significantly contributed to learners’ gains with respect to the ‘passive’ and that L1 metalinguistic awareness explained significant variation in learners’ gains regarding the ‘past progressive’. These relationships were observed with learners’ performance on the written but not oral measures. A detailed analysis of the aptitude test components revealed that the grammatical inferencing subtask was significantly related to L2 gains on the ‘passive’ – again only with respect to learners’ performance on the written GJT. The results also revealed that learners with different aptitude profiles (i.e., low, medium, high) benefited differently from instruction on the two target features. High aptitude learners performed better than low aptitude learners on the ‘passive’ as measured by the GJT posttest. With respect to the ‘past progressive’ only learners in the medium aptitude profile group improved significantly on the written GJT. These findings confirm that language aptitude holds a role in language learning but that there are other factors (i.e., motivation and L1 metalinguistic awareness) that also contribute to L2 progress. These results also provide evidence from a classroom-based study that the grammatical difficulty of what is to be learned is a factor in determining what cognitive abilities L2 learners rely on in their efforts to learn a new language.

Keywords: Language teaching
instructed second language acquisition
English as a foreign language
individual learner differences
Advisor: Spada, Nina
Determining Lineage Fate, Survival and Proliferation of Differentiating Thymocytes: Interplay between Notch, TCR, PI3K and MAPK Pathways

A common bipotent thymocyte precursor gives rise to both lineages of T cells, αβ and γδ. This thesis addresses how the interplay between intrinsic T cell receptor (TCR) signals and cell extrinsic signals provided by Notch and TCR ligands help to assign and support a final lineage fate decision. Emerging data supports a model in which differential TCR signaling capacity plays an instructional role in specifying lineage fate, particularly through induction of the ERK - early growth response gene (Egr) - inhibitor of DNA binding 3 (Id3) pathway. In particular, Id3 expression serves to regulate adoption of the γδ fate. Moreover, Id3 is both necessary and sufficient to enable γδ-lineage cells to differentiate independently of Notch signaling and become competent interferon (IFN)-γ-producing effectors. These findings identify Id3 as a central player that controls both adoption of the γδ fate and their maturation in the thymus. While loss of Notch signaling in γδTCR-expressing CD4-CD8- (DN)3 cells does not affect development, Notch signals are critical for pre-TCR-bearing cells to transition to the CD4+CD8+ (DP) stage of αβ T cell development. Notch signals affect the activation of the PI3K/Akt pathway, which is required for pTα/TCRβ (pre-TCR)-induced survival, differentiation and proliferation of developing αβ-lineage thymocytes. Here, I identify the key molecular players responsible for the interaction between the Notch and PI3K pathways at this critical developmental stage. Notch induction of Hes1 expression is necessary to repress the expression of the PI3K/Akt pathway inhibitor, PTEN, which in turn facilitates pre-TCR-induced differentiation. c-Myc, another critical target of Notch, is required for proliferation during β-selection. Lastly, I find that the majority of DN3 cells expressing both pre-TCR and γδTCR follow the signal strength model for lineage development, and commit and mature along the γδ-lineage. However, manipulation of signal strength, through γδTCR ligand availability or Id3 expression, can skew this development outcome. Taken together, the results from this thesis provide a detailed examination of the molecular mechanisms that are instrumental in determining lineage fate, survival, and proliferation of differentiating thymocytes. Central to these outcomes is the interplay between the Notch, TCR, PI3K, and MAPK signaling pathways.

Keywords: T cell development
Notch signaling
Advisor: Zuniga-Pflucker, Juan Carlos