VictorJuiz/thesis huggingface dataset:
The Diverse Impact of Bacteriophages on the Bacterial Host

The viruses that infect bacteria, bacteriophages (or phages) are the most abundant biological entities on the planet. Phages are constantly causing bacterial population turnover through infection and lysis, a process that results in the replication of phages and the death of the bacterium. Alternately, phages can integrate into the bacterial genome, at which point the phage is referred to as a prophage. Prophages are abundant in bacterial genomes and are not merely inert entities, as some genes are expressed from the prophage, which can increase host and prophage fitness. Clinical and environmental isolates of the opportunistic human pathogen, Pseudomonas aeruginosa were investigated and found to possess prophages in their genomes which were inducible. I identified many novel phenotypes emerging after prophage acquisition, particularly an array of superinfection exclusion traits that protect the lysogenic host from subsequent phage infection. These traits are likely beneficial in the environment, protecting the bacterium (and the resident prophage) from infection and lysis. In addition to prophages protecting the host from infection, bacteria encode many systems to protect themselves, including the adaptive immune system known as CRISPR-Cas. I demonstrated that the CRISPR-Cas system of P. aeruginosa strain PA14 is active and targets phages and plasmids for degradation. Interestingly, the phages are not passive bystanders in this process and encode genes which inhibit CRISPR-Cas function, called "anti-CRISPRs". Five different anti-CRISPR proteins were discovered which all inactivate the CRISPR-Cas system of P. aeruginosa, thus allowing phages to infect the host and either lyse the bacterium or integrate in the genome. These anti-CRISPRs share no common sequence element and only share the phage genomic position in which they were found. Three of the different anti-CRISPRs were investigated and I show that they utilize completely distinct mechanisms to inactivate the CRISPR-Cas system. These studies shed new light on the arms race between phages and their bacterial hosts and emphasize the complex ecological relationships between them.

Keywords: anti-CRISPR
Bacteriophage
CRISPR-Cas
Lysogen
Prophage
Superinfection
Advisor: Davidson, Alan R
Influence of Climatic and Non-climatic Factors on Range Dynamics and Conservation Priorities of Long-distance Migratory Birds

Understanding factors influencing species' distributions and their dynamics over space and time is a fundamental question in ecology that is receiving renewed interest given increasing threats of global climate change to species persistence. Species are shifting their distributions in response to climate change; however in spite of general directional trends northwards and up in elevation there is substantial interspecific variation. The complexity of species' responses is challenging to explain and limits our predictive capacity to anticipate future consequences of climate change. In addition to climatic factors, species' range dynamics are influenced by non-climatic factors including the biotic interactions, demography, dispersal, and the temporal and spatial scale of threatening processes. The objective of this thesis is to test the role of climatic and non-climatic factors on seasonal range dynamics of long-distance migratory birds over multiple spatial scales, in the recent past, present, and in the future. An understanding of the determinants of Nearctic-Neotropical migratory bird distributions across their interconnected seasonal ranges remains unclear, and few climate change vulnerability assessments consider the complement of habitat dependencies required across their annual cycle. To address these research gaps, I applied multiple modeling methods with outcomes that are increasingly process-oriented. These include correlative species distribution models, dynamic occupancy modeling that account for detection probabilities, and coupled species distribution-metapopulation demographic models. Such modeling approaches allow for deeper inferences regarding the biological processes that actually drive shifts in species distributions over space and time. The main findings of my thesis include: (1) biotic vegetation factors improve species distribution model predictive accuracy measures across both seasonal ranges, and this has non-negligible consequences for spatial conservation priorities under climate change, (2) determinants of seasonal distributions of migratory birds tend to be dominated by abiotic factors, while seasonal differences within species suggest a role for dynamic seasonal niches, (3) short-term habitat changes can more strongly influence local extinction probabilities relative to inter-annual variation in weather suggesting that the temporal scale of climate change and habitat loss requires careful consideration, and (4) accounting for multiple sources of uncertainties is essential for improving models and can help inform robust management actions.

Keywords: climate change
habitat loss
migratory birds
population dynamics
spatio-temporal dynamics
species distributions
Advisor: Fortin, Marie-Josee
Adult Mammalian Central Nervous System Neural Precursors Undergo Rapid and Cathode-Directed Galvanotaxis

Neural stem and progenitor cells (neural precursors) exist within the adult mammalian central nervous system, primarily within the brain's neurogenic subependymal and subgranular zones, and in the lining of the spinal cord central canal. Neural precursors are ideal candidates for cell replacement strategies, due to their multipotency and neural stem cells' inherent capacity for self-renewal. Indeed, following neural insult such as ischaemia, endogenous subependymal neural precursors undergo a proliferative and migratory response, whereby they migrate toward the lesion site and differentiate into neural cells. With the goal of enhancing this migratory response in order to facilitate improved neural repair, the work in this thesis has focused on utilizing electrical fields to direct and enhance neural precursor migration and understanding the mechanisms that underlie the effects. We have shown for the first time that primary undifferentiated neural precursors from the adult mammalian brain undergo rapid and cathode-directed migration in the presence of an electrical field, a phenomenon known as galvanotaxis. Strikingly, this response is entirely absent in neural precursors that are induced to differentiate into mature phenotypes. We utilized cross-perfusion techniques to demonstrate that the migratory response is not the result of a chemical gradient that may be electrophoretically generated within the culture media, establishing that the migration is a direct response of the applied electrical field. Second, we have provided evidence that neural precursor galvanotaxis is mediated by epidermal growth factor receptor signalling - one of the mitogens that maintains neural precursors in an undifferentiated state - and by Ca

Keywords: electric fields
galvanotaxis
neural stem cells
neurorepair
Advisor: Morshead, Cindi M
Popovic, Milos R
Text and Image in Contemporary Mexican Narrative: The Effect of Interdisciplinarity in Six Novels

In this thesis I demonstrate that the inclusion of images in Mexican literary texts published during the last twenty years--whether these images are physically present or verbally described--function as a tool of formal and conceptual power. I propose that this tool substantially adds to the text's meaning and possible impact on the reader. The temporal frame for the selection of the literary work stems from a growing attention to the visual arts; in Mexico specifically it is based on the important promotion given to interdisciplinary work since the creation of the National Fund for Culture and Arts (Fondo Nacional para la Cultura y las Artes, FONCA) in 1989. The thesis is divided into three chapters that explore the following works:

Keywords: Appropriation
Contemporary Mexican Literature
FONCA
Interdisciplinarity
Text and Image
Advisor: Sarabia, Rosa
Genetic Contribution to Heterogeneity in Brain Morphology with Applications to Schizophrenia

Schizophrenia is a highly heterogeneous disorder. Differences among patients with schizophrenia have been reported in clinical features, cognitive functioning, and brain structure. This thesis investigates the impact of the well supported genetic risk variants on brain structure and also considers the role of imaging-genetic changes on heterogeneous phenotypes relevant to schizophrenia. In the first study, the genome-wide supported NRXN1 gene, associated with schizophrenia and autism spectrum disorders, was examined with magnetic resonance imaging (MRI) volumetric measures and measures of sensorimotor function. Study two investigated the effect of the genome-wide identified schizophrenia risk variant in the MIR137 gene for association with age-at-onset and brain structures implicated in disease severity, as well as white matter fractional anisotropy (FA) and cortical thickness. Risk allele carriers had earlier age-at-onset and aberrant brain structure suggesting that MIR137 may predict a more severe schizophrenia subphenotype. Study three examined the role of the GAD1 gene on brain structure and executive function. Among patients and controls the GAD1 variant predicted changes in white matter FA and multiple working memory tasks. Using voxel-wise mediation analysis, we were able to infer the functional relevance of GAD1 on structural connectivity by showing these FA changes statistically cause impaired working memory performance. In the final study, we investigated relationships among polygenic additive risk, brain-wide measures, and cognition in schizophrenia patients and healthy controls. Schizophrenia patients with low polygenic risk were similar in brain structure and cognitive performance to healthy controls. In contrast, high polygenic risk in patients led to large reductions in cortical thickness and white matter skeleton FA, in addition to impaired semantic memory and motor functioning. Taken together, these studies suggest that neuroimaging and genetics can be used to meaningful disentangle heterogeneity of schizophrenia phenotypes, and may move towards neurobiological based treatment options.

Keywords: Cognition
Genetics
Heterogeneity
Imaging
Schizophrenia
Symptomology
Advisor: Kennedy, James L
Voineskos, Aristotle N
Lysosomal Targeting and Functions of the LAPTM4 Family of Proteins

The Lysosome Associated Protein Transmembrane (LAPTM) family is comprised of LAPTM4 and 5 proteins. LAPTM5 regulates B- and T-cell receptor internalization and pro-inflammatory signaling and its lysosomal sorting was previously characterized. This thesis elucidates the lysosomal sorting determinants of LAPTM4s (LAPTM4a and LAPTM4b) and LAPTM4b function. Here I show that LAPTM4s bind the E3 ubiquitin ligase Nedd4 via their PY motifs and that both Nedd4 and PY motifs are required for their lysosomal sorting. In the absence of PY motifs, LAPTM4 lysosomal localization is reduced and LAPTM4b expression at the plasma membrane is enhanced. Next, PY motifs and Nedd4 are explored as conserved determinants of lysosomal membrane protein (LMP) targeting. Putative PY-motif containing proteins are identified among previously published LMPs. TMEM55B was shown to bind Nedd4 via its PY motif and to utilize this motif for lysosomal targeting, and binding of Nedd4 family members WWP2 and Smurf1 to another PY motif containing LMP (ABCB6) is demonstrated. Lastly, a role for LAPTM4b in mTORC1 signaling is established. mTORC1 activation takes place at the lysosomal membrane, and involves V-ATPase stimulation by intra-lysosomal essential amino acids (EAA, such as Leu) by an inside-out mechanism. How Leu enters the lysosomes is unknown. Here it is shown that LAPTM4b binds the plasma membrane Leu Transporter LAT1-4F2hc and recruits it to lysosomes, leading to uptake of Leu into lysosomes and mTORC1 activation via v-ATPase upon EAA stimulation. These results provide the first demonstration of localization and function of the Leu transporter at the lysosome, and help explain the inside-out activation of mTORC1 by EAA in this organelle.

Keywords: Cell Biology
LAPTM4
Lysosomes
Nedd4
Trafficking
Advisor: Rotin, Daniela
Hybridity in the Fourteenth-century Esther Poems of Israel Caslari

Hybridity in the Fourteenth-Century Esther Poems of Israel Caslari Jaclyn Tzvia Piudik Doctor of Philosophy Centre for Medieval Studies University of Toronto 2014 Abstract The Scroll of Esther, one of the quintessential texts of post-exilic Jewish salvation, was particularly beloved in the European Middle Ages, when the narrative served as a model for redemption from persecution and as a reminder of the threat of expulsion which was part of everyday Jewish life. Among its many medieval adaptations is a pair of texts written by Israel ben Joseph Caslari, a fourteenth-century Jewish physician, living in Papal-ruled Avignon. Israel's retellings of the Purim story are expanded and heavily embellished with material from talmudic and apocryphal sources, medieval medicine and philosophy, and references to popular culture. He composed his first version composed in JudĂŠo-ProvenĂ§al, the southern French vernacular written in Hebrew characters; the second in Hebrew, not a translation, but an adaptation of its predecessor. As individual works, each is a rich intertextual landscape which offers a view into its socio-religious setting and reflects the meeting and melding of cultural influences. If one considers them together, this encounter becomes even more pronounced: the two versions come into conversation, embodying the tensions of their milieu, and of their author, a Jewish intellectual in a Christian-dominated society. The texts are a tapestry of ancient religious legacy and medieval thought, woven from threads of Jewish tradition and secular learning, from medieval belletristic conventions, midrashic literature and medical writings. This dissertation explores issues of biculturalism and religious identity through Israel's compositional strategies and his modifications to the biblical story. It considers first the notion of hybridity in the works through the convergence of their author's professional and religious concerns, in his treatment of gender and language as a representation of cultural boundaries and their transgression. It then examines the multiplicity of literary genres, both religious and secular, that inhabit and inform the texts, while engaging the question of their audiences as the Hebrew version prescribes.

Keywords: Cultural translation
Hebrew literature
Judeo-Provencal
Medieval Jewish literature
Medieval Medicine
Romance
Advisor: Ross, Jill
Statistical Rate Theory Expression for Energy Transported during Evaporation

Statistical rate theory (SRT) uses the quantum-mechanical concept of state transition probabilities to develop an expression for the net evaporation flux. The internal molecular phonons are required in the full SRT expression. Ethanol is a complex molecule with 21 internal molecular phonons and provides a more stringent test of SRT than water or heavy water, which only have 3 internal molecular phonons. When applied to ethanol evaporation, SRT leads to an expression for the saturation-vapour pressure that is both accurate and thermodynamically-consistent since it gives predictions of the evaporative-latent heat and liquid specific heat that agree with independently measured values. The mechanism of evaporation indicated by SRT is that energy must be supplied to excite the molecule's intermolecular bonds for them to escape (evaporate from) the liquid. The internal molecular phonons are not usually known for large molecules. Statistical rate theory is simplified by taking its classical limit and the resulting expression is independent of the internal molecular phonons. The expression is examined experimentally with water and ethanol and gives accurate predictions of the saturation-vapour pressure and of the interfacial temperature discontinuities. The expression also leads to a new physical interpretation of the condensation and evaporation coefficients in the Hertz-Knudsen relation and provides an explanation for the inconsistent coefficient values found in the literature. Statistical rate theory is used to formulate an expression for the net heat flux conducted to the liquid-vapour interface during evaporation. An evaporation constant is found and leads to predictions of the quantum of energy transported across the interface within a time interval. For water, the predicted quantum of energy agrees with the frequency shifts of free O-H stretch and bending modes of interfacial molecules that straddle the liquid-vapour interface. The SRT heat flux expression eliminates the necessity of measuring the temperature gradients at the interface. Statistical rate theory is extended to time-dependent-multicomponent systems to predict temperature and pressure pulsations in evaporating sessile droplets of water, of ethanol and of methanol. The pulsations are due to the heat of solution when one component from the atmosphere adsorbs-absorbs into another liquid, and can be switched on or off by controlling the composition of the atmosphere.

Keywords: ethanol
interfacial temperature discontinuity
kinetic theory
phase change
statistical thermodynamics
thermocapillary flow
Advisor: Ward, Charles A
Negotiating Consensus: Reading Time and Space in Nineteenth-century Novels and Popular Print Genres

Traditionally, the realist novel has been associated with representations of homogeneous time and space, continuous with the world of the reader and measurable in objective units of duration or distance. Cued by characters who attend carefully to schedules, positions, and distances, readers and critics have perhaps overlooked the extent to which novelists use time and space not to represent the consensual, the objective, and the real, but to communicate their characters' desires for consensus. This dissertation explores how nineteenth-century novelists have their characters draw upon symbols and language of time and space to articulate feelings, desires, or values that are difficult to voice or explain, as if a language of time and space might be more easily understood than any other kind of language. In Jane Austen's Mansfield Park and Emma, George Eliot's The Mill on the Floss and Middlemarch, and Henry James's The Portrait of a Lady and The Golden Bowl, representations of time and space are sites of contested meaning, involving negotiations between the private feelings of individuals and the conventions of the community. This dissertation also suggests that novelists have characters draw upon time and space to make subversive desires or abstract ideas comprehensible to others partly because two influential print genres--the almanac and the travel handbook--explicitly associated consensus with time and space. However, almanacs also encouraged readers to distinguish between personal and public time, and to reconcile them in the margins of their texts as they read, while travel handbooks prompted similar negotiations regarding the traveller's personal experiences of public spaces. While apparently authoritative, these print genres were actively and diversely used by readers, provocatively paralleling, and perhaps influencing, the nineteenth-century novel's reliance on time and space to represent negotiations between individuals and their communities.

Keywords: Almanacs
Book history
Nineteenth-century literature
Reading
Space
Time
Advisor: Lynch, Deidre
Cuddy-Keane, Melba
Investigations into UNC-40-Mediated Guidance of Cell Migrations and Cell Extensions

The migration of cells and cell extensions is essential for the proper development of an organism. Guidance receptors at the leading edge of migratory cells interpret and translate various environmental stimuli into spatially restricted cytoskeletal modulations that lead to directed membrane extension. To better understand mechanisms of guidance, I study the midline-oriented guidance of specialized muscle membrane projections found in C. elegans called muscle arms. The guidance of muscle arms to the midline depends on a non-canonical UNC-40/DCC pathway that responds to the novel cue MADD-4. UNC-40 is a transmembrane receptor whose canonical ligand is the UNC-6/netrin cue. We have previously shown that downstream effectors of UNC-40 activity in muscle arm extension include UNC-73/RhoGEF, the WAVE actin polymerization complex GEX-2/GEX-3/WVE-1, and members of the focal adhesion complex. Together, these components act in concert to influence actin-based membrane extension to the midline. We found that the EVA-1 transmembrane receptor likely functions as a co-receptor for UNC-40 to respond to MADD-4 for the guidance of muscle arms and axons. EVA-1 is a conserved transmembrane protein with predicted galactose-binding lectin domains. EVA-1 functions in the same pathway as MADD-4, physically interacts with both MADD-4 and UNC-40, and enhances UNC-40's sensitivity to MADD-4. This enhancement is especially important in the presence of UNC-6, because when EVA-1 is absent, we find that UNC-6 interferes with UNC-40's responsiveness to MADD-4. In the absence of UNC-6, UNC-40's responsiveness to MADD-4 is less dependent on EVA-1. By enabling UNC-40 to respond to MADD-4 in the presence of UNC-6, EVA-1 may increase the precision by which UNC-40-directed processes can reach their MADD-4-expressing targets within a field of the UNC-6 guidance cue. I also identified the involvement of integrins in the guidance of muscle arms and axons. I found that integrin likely forms a complex with EVA-1 and UNC-40 to mediate MADD-4 responses. Disruption of integrin suppresses MADD-4 induced axon dorsalization such that the axons extend in a wild type manner, suggesting that integrins play a role in MADD-4 oriented guidance. The function of integrins may provide a mechanistic link between nascent guided membrane and the maintenance of structural support.

Keywords: Axon guidance
C. elegans
Cell migration
Chemoattraction
DCC
Netrin
Advisor: Roy, Peer J