VictorJuiz/thesis huggingface dataset:
Transitions between Marine and Freshwaters in Fishes: Evolutionary Pattern and Process
Keywords: macroevolution
biogeography
phylogenetics
fishes

Evolutionary transitions between marine and freshwater habitats are rare events that can have profound impacts on aquatic biodiversity. The main goal of my thesis is determining the processes involved in transitions between marine and freshwater biomes, and the resulting patterns of diversity using phylogenetic approaches. To test hypotheses regarding the geography, timing, frequency, and mechanisms regulating biome transitions I generated multi-locus time-calibrated molecular phylogenies for groups of fishes that include both exclusively marine and freshwater species. My analysis of anchovies demonstrated that Neotropical freshwater anchovies represent a monophyletic radiation with a single origin in South American freshwaters. I used a phylogeny of herring and allies (Clupeiformes) to investigate the evolution of diadromy, a migratory behavior in which individuals move between oceans and freshwater habitats for reproduction and feeding. These analyses do not support the hypothesis that differences in productivity between marine and freshwater explain the origins of diadromous lineages. Diadromy has been considered an evolutionary pathway for permanent biome transitions, however I found that diadromy almost never produces a fully marine or freshwater clade. Marine lineages often invade continental freshwaters during episodes of marine incursion. In South America, the rich diversity of marine derived fish lineages invaded during Eocene marine incursions from either the Pacific or the Caribbean, and Oligocene marine incursions from the Caribbean. I falsified the highly cited Miocene marine incursion hypothesis, but found that the Pebas Mega-Wetland catalyzed diversification in some marine derived lineages. Using diversification analyses, I investigated the evolutionary processes that have generated disparate patterns of diversity between continents and oceans. I found that freshwater silversides have higher speciation and extinction rates than marine silversides. Lineages accumulation plots suggest ecological limits are not regulating clade growth in either marine or freshwater biomes. Overall, biome conservatism is a widespread pattern among fishes, and this pattern is largely driven by competition in clades that are physiologically capable of biome transitions. Biome transitions are facilitated by rare paleogeographic events, such as marine incursions. Finally, a difference in net diversification rate is the macroevolutionary mechanism that best explains the difference in diversity between continents and oceans.
Mathematics Coaching to Improve Teaching Practice: The Experiences of Mathematics Teachers and Coaches
Keywords: Teacher Emotions
Mathematics

The purpose of the study is to determine how coaching can be used effectively to improve instruction and student achievement while exploring teachers’ specific emotions during mathematics education reform initiatives that challenge the teacher’s beliefs about teaching and learning in mathematics. It also examines how teachers incorporate the reform changes into their practice in order for the new instructional practices to have the expected effect. I explored teacher learning which refers to the correct use of reform strategies by mathematics teachers so that they have the intended effects on student achievement with the support of a coach during reform initiatives. Through questionnaires, interviews, observations and archival material, the study determines the relationship between teachers’ specific emotions, teacher learning and teacher coaching in secondary school mathematics classrooms. As a result, the study highlights the issues associated with the implementation of mathematics education reform initiatives and implications. The findings show that mathematics education reforms produce emotional responses that can be described as both negative and positive. For example, some emotions include pride, joy, fear, feeling drained and ineffective. The four teachers in the study experienced these emotions because of factors such as a lack of knowledge of how to implement mathematics reform, beliefs about teaching and learning in mathematics that were inconsistent with the reform initiatives, the nature of coaching, and gains in student achievement and engagement. They also experienced negative emotions because of favorable in-school factors such as an administration that supported teacher efforts to implement mathematics reforms. The study shows that: a) coaching may not help teachers reconstruct their professional self-understanding when it fails to address their self-image issues; b) teacher learning may occur even when the teacher’s beliefs are inconsistent with reform initiatives; and c) even when teacher learning results from coaching, reforms do not present themselves as expected in the classroom. Coaches experienced positive and negative emotions as a result of how well the reforms were being implemented by teachers. The experiences of the two coaches during mathematics reforms indicate a need to support coaches as they help teachers use the reform strategies. The directions for future research are described.
Mapping Genetic Interaction Networks in Yeast
Keywords: genetic interactions
networks
yeast

Global quantitative analysis of genetic interactions provides a powerful approach for deciphering the roles of genes and mapping functional relationships amongst path-ways. Using colony size as a proxy for fitness, I developed a method for measuring ge-netic interactions from high-density arrays of yeast double mutants generated by synthet-ic genetic array (SGA) technology. I identified several experimental sources of systematic variation and developed normalization strategies to obtain accurate fitness measurements. I used this scoring method to map quantitative genetic interactions among 5.4 million yeast double mutants and generated the first functionally unbiased genetic interaction map of a eukaryotic cell. My map produced an unprecedented view of the cell in which genes of similar biological processes cluster together in coherent subsets and functionally interconnected bioprocesses map next to each other. We discovered several physiological and evolutionary gene features that are characteristic of genetic interaction hubs, and explored the relationship between genetic and protein-protein interaction networks. In particular, by comparing quantitative single and double mutant phenotypes, we identified specific cases of positive genetic interactions, termed genetic suppression, and constructed a global network of suppression interactions among protein complexes. I also demonstrated that an extensive and unbiased mapping of genetic interactions provides a key for interpreting chemical-genetic interactions and identifying drug targets. In addition, I used genome-wide SGA data to map profiles of genetic linkage along all sixteen yeast chromosomes. These linkage profiles recapitulated previously identified recombination patterns and uncovered an unexpected correlation between chromosome length and the extent of centromere-related recombination repression. These findings suggest a chromosome size-dependent mechanism for ensuring proper chromosome segregation and highlight the SGA methodology as a unique approach for systematic analysis of yeast meiotic recombination.
Validation and Functional Characterization of Novel Neurofibromin Interacting Proteins
Keywords: Neurofibromatosis Type 1
Leigh's Syndrome, French Canadian variant
Neurofibromin
Leucine Rich Pentatrico Peptide Repeat motif-Containing protein

Neurofibromin (NF1) is a 2,818aa protein encoded by the very large NF1 tumour suppressor gene located on chromosome 17q11.2. Loss of function mutations and deletions in NF1 underlie Neurofibromatosis type-1 (NF-1) - the most common inherited syndrome of the nervous system in humans with a birth incidence of 1:3,000. The most visible feature of NF-1 is the neoplastic manifestations known as neurofibromas, however, the syndrome is also characterized by pigmentary defects, peripheral motor dysfunction, learning disabilities and several developmental abnormalities. The molecular etiology of many of these non-neoplastic phenotypes remains unknown. Here we demonstrate that the Tubulin Binding Domain (TBD) of NF1 is a binding partner of the Leucine Rich Pentatrico Peptide Repeat motif-Containing protein (LRPPRC) and cytoplasmic Dynein Heavy Chain (DHC). The NF1-LRPPRC interaction is of high significance as it links NF-1 with Leigh’s Syndrome, French Canadian variant (LSFC) – an autosomal recessive neurodegenerative disorder that arises due to mutations in the LRPPRC gene. This interaction occurs as part of an RNA granule complex, and use of transgenic mouse models establishes an important role of NF1 and LRPPRC in peripheral nerve development. The NF1-DHC interaction is of importance in melanocytes where our studies suggest a possible role in melanosome localization, disruptions in which may underlie the abnormal pigmentary features known as café-au-lait macules that are commonly associated with NF-1. The validation of LRPPRC and DHC as novel NF1 interactors reveal new roles of NF1, which open the door to better understanding the molecular mechanisms that underlie the myriad of NF-1 manifestations.
Identification of a Novel G-protein Interactor, RADIL, and Functional Characterization of its Role in Cancer Cell Motility
Keywords: G protein
Cell motility
Radil
Cancer
Gbetagamma
Rap1

Cell adhesion and migration play crucial roles in development of multicellular organisms, immune surveillance, wound repair and cancer metastasis. The Gβγ subunits of heterotrimeric G-proteins have been implicated in signalling activities that promote cell adhesion and migration but the molecular mechanisms are unclear. Using a mass-spectrometry based proteomic approach we identified a protein complex between Gβγ and Rap1a that is bridged by a novel Rap1 effector, Radil. Overexpression of constitutively active Rap1a, Gβγ or stimulation of cells with the GPCR ligand fMLP triggers recruitment of Radil to the plasma membrane. Exogenous expression of Radil promotes cell spreading through Rap1-dependent inside-out activation of integrins leading to enhanced cell-matrix adhesion. Structure function experiments demonstrated that the RA and PDZ domains of Radil are required for its ability to promote cell adhesion. Using phage-display and mass-spectrometry we identified the kinesin family protein KIF14 as a novel interacting partner for Radil. Both KIF14 and Radil colocalized on microtubules in a PDZ-dependent manner. Depletion of KIF14 or disruption of microtubules led to accumulation of Radil at the cell membrane. Functionally, KIF14 is a negative regulator of Radil signalling as its depletion increased cell spreading and integrin activation and both phenotypes are rescued by simultaneous knockdown of Radil. Knockdown of KIF14 affects focal adhesion dynamics, which we determined is due to delayed adhesion disassembly. Depletion of either KIF14 or Radil dramatically decreased breast cancer cell migration and invasion in vitro. Additionally, knockdown of Radil compromised the ability of cells to metastasize to the lung and reduced tu-mor growth in xenograft mouse models. Collectively, these studies describe a functional re-quirement for the Gβγ-Rap1a-Radil complex during GPCR signalling for the control of integrin-mediated cell adhesion, cell motility and cancer progression.
Phenotypic Classification of Paediatric Inflammatory Bowel Disease
Keywords: Inflammatory bowel disease
paediatric
classification
phenotype

This thesis explores aspects pertinent to the phenotypic classification of paediatric patients with inflammatory bowel disease (IBD). In the current era it has never been more important to have rigourous phenotypic classification to facilitate genotype-phenotype correlation studies as well as to optimize design of clinical trials of emerging therapies, where frequently response may differ according to phenotype of disease. The first study examined the reliability of the Montreal Classification for classifying paediatric IBD patients. This is the first study exploring the reliability of phenotypic classification in a paediatric population. The reliability of assigning an overall diagnosis of type of IBD was good, but not excellent. Amongst Crohn’s disease patients, reliability of assigning disease behaviour was excellent, while the reliability of assigning disease location categories varied from fair to good. The percentage agreement when describing disease extent for ulcerative colitis was high. The second study described the evolution of disease phenotype in a cohort of paediatric IBD patients. Similar to observations in adult-onset IBD, disease location was found to be relatively stable, while Crohn’s disease behaviour evolves from an inflammatory to a stricturing and/or penetrating phenotype in 20% of patients by 5 years of follow-up. The final study explored the association between 2 polymorphisms in the NOD2 gene with the requirement for intestinal resection (a surrogate marker of complicated disease) in models that included and excluded disease duration. Although no difference was found, this may have been influenced by data quality, which was suboptimal. In conclusion, this thesis has demonstrated that imprecision exists in the phenotyping of paediatric IBD patients, in whom phenotypic characteristics evolve over time. It is pertinent that disease duration be considered in any study attempting to make phenotypic correlations.
School Travel Mode Choice Behaviour in Toronto, Canada
Keywords: Built environment
Active travel
Children
School transportation
Physical activity
Intra-household interaction

Interest in school transportation has emerged in response to concern over the reduced levels of physical activity among children and youth. Recent Canadian policies emphasize population health intervention to encourage active travel among this younger population; urban planners and public health professionals have also highlighted the importance of the neighbourhood built environment. However, this “child-youth friendly” turn in policy and planning practice, particularly in Canada, has arguably occurred in advance of conclusive and generalizable knowledge about the relationship between the built environment and children’s travel. Within this context, this thesis is the first quantitative research that examines school transportation mode choice behaviour in the largest Canadian city, the City of Toronto. At first, a Behavioural Model of School Transportation was outlined. This exercise was followed by three empirical studies that explored school travel by children and youth, using travel data from Transportation Tomorrow Survey. The first of these three studies investigated the association between the built environment and the likelihood of walking or being driven, for journeys to and from school. The next study focused on a measurement issue; the potential influence of the modifiable areal unit problem on statistical modelling of the built environment - mode choice relationship was examined. Lastly, the potential influence of travel interactions among household members, the built environment, and unobservable spatial dependency (i.e., spatial auto-correlation), on school travel outcome of children and youth, were examined. The results indicated that caregiver availability may influence travel mode choice. The built environment near both home and school locations was associated with the likelihood of walking. In addition, the correlates of mode choice were different between children and youth, which perhaps, reflects a child’s cognitive development with age as an independent traveller. These findings suggest the need for neighbourhood-wide improvement in the built environment, and age-specific population health interventions at schools and in the communities.
The Development of Neurodegeneration and Behavioural Alterations following Lithium/Pilocarpine-induced Status Epilepticus in Rats
Keywords: status epilepticus
lithium/pilocarpine
epilepsy
neuroprotection
neurodegeneration
behaviour

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.
Le désir et ses stratégies discursives dans les littératures française et québécoise au féminin, 1995-2005
Keywords: desire
contemporary women's literature
Nelly Arcan
Catherine Millet
Annie Ernaux
Nicole Brossard
Marie Nimier
French literature

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.
Structural Characterization of Freshwater Dissolved Organic Matter from Arctic and Temperate Climates Using Novel Analytical Approaches
Keywords: dissolved organic matter
nuclear magnetic resonance
Arctic
terpenoid-derived
sterols
high performance liquid chromatography

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.