VictorJuiz/thesis huggingface dataset:
Study of the Physiological and Molecular Mechanisms Underlying Peptide-induced Cell Death and Biofilm Formation in Streptococcus mutans
Keywords: biofilm
competence
Streptococcus
quorum sensing

Biofilms are complex and highly adapted communities of microorganisms found attached to surfaces. Among the best characterized infectious multi-cellular biofilms is the oral community known as dental plaque. Streptococcus mutans resides in the oral biofilm, and is one of the main causative agents of dental caries. Streptococci are known to monitor their population density using a peptide pheromone (CSP)/two component signalling system (ComDE) in a process classically known as quorum sensing (QS). Previous work in S. mutans has implicated the QS system in genetic competence, the stress response, bacteriocin production and biofilm formation. Our objective in this work was to thoroughly characterize the transcriptional and phenotypic response to CSP in S. mutans, and determine its role in biofilm formation. We have shown that the CSP pheromone is more than simply a QS signal, and is also an inducible ‘alarmone’ capable of communicating stress in the population. We have demonstrated that elevated concentrations of CSP such as those that occur during stress trigger autolysis in a fraction of the population. Importantly, we have shown that autolysis in S. mutans occurs via a novel mechanism of action: intracellular accumulation of a self-acting bacteriocin. We have also identified and characterized the autolysis immunity protein, which is differentially regulated from the bacteriocin to allow survival at low cell density. A second regulatory system was shown to govern expression of autolysis immunity in the absence of CSP signaling, and also contribute to the oxidative stress response in the biofilm. Finally, we present evidence that autolysis is involved in the release of DNA in the biofilm, which contributes to the architecture of the extracellular matrix and may provide a mechanism for the dissemination of fitness-enhancing genes under stress. Together, our data provides a mechanistic link between phenotypes previously ascribed to the CSP pheromone in S. mutans.
The Contribution of Physical, Mental and Social Dimensions of Health to Predicting Self-rated Health Over the Course of Recovery Following Total Joint Replacement Surgery
Keywords: Self-Rated Health
Physical Health
Mental Well-Being
Social Health

Background: Self-rated health (SRH) is among the most frequently assessed health perceptions in epidemiological research. While the predominant focus has been the predictive relevance of SRH, there is increasing interest in understanding the nature of SRH. Recently a conceptual interpretation of SRH was proposed. Purpose: To assess the tenability of the recently proposed distinctions of self-rated health, as a spontaneous assessment of overall health, or as an enduring self-concept, or both, and to determine the significance of mental well-being, physical and social health for SRH. Methods: A cohort of individuals undergoing total joint replacement (TJR) for hip or knee osteoarthritis (OA) was followed over 6 months of recovery. Participants (n=449) completed (pre-surgery, 3 and 6 months post-surgery) measures associated with physical health: pain, physical function, sports/recreation, fatigue; mental well-being: anxiety, depression; and social health: social participation, passive/active recreation, community access. Using structural equation modeling, confirmatory factor analyses (CFA) investigated 3 latent health variables, and the responsiveness of SRH to current and changing health status, as well as its predictive significance for future health status was investigated. Results: CFA analyses confirmed relationships between observed health measures and hypothesized latent health dimensions. SRH was responsive to current and changing mental well-being. The effects of physical and social health were mediated through mental well-being. SRH was a strong predictor of future SRH and future health status. Conclusion: SRH displayed features of both an enduring self-concept and spontaneous assessment of health status; evidence is provided that both operate simultaneously. While aspects of physical health have always been perceived as the major determinants of SRH, these findings indicate that mental and social health explain much of the relationship between physical health and SRH. These results are particularly unexpected since this is a sample of individuals undergoing TJR surgery, for which pain and restricted physical function are primary indicators. Since SRH is a significant predictor of health status, TJR outcomes, health care utilization and mortality, this study suggests that health research and care, treatment and management modalities should consider a broad range of health dimensions, not only physical aspects of health, and SRH.
Indigenousness and the Reconstruction of the Other in Guatemalan Indigenous Literature
Keywords: Guatemala
Indigenous Literature
Postcolonialism
Latin American Literature

“Indigenousness and the Reconstruction of the Other in Guatemalan Indigenous Literature” examines the production of a contemporary Indigenous literature in Guatemala. With the aid of a multidisciplinary approach informed by cultural, feminist, gender, socio-anthropological, and postcolonial studies, I analyze the emergence and ongoing struggle of Maya writers in Guatemala to show how the production of an alternate ideology contests official notions of nationhood and promotes a more inclusive space. I argue that Maya writers redefine Indigenous identity by reinstating Indigenous agency and self-determination, and deconstructing and rearticulating ethnicity, class and gender, among other markers of identity. I begin by examining the indio as the basis of colonial and national narratives that logically organize the Guatemalan nation. I then observe the emergence of a contemporary Indigenous literature in Guatemala in the 1970s, a literature that, I argue, isolates and contests the position that was assigned to the indio and proposes a literature written by and for the Indigenous peoples of Guatemala. I posit that the inauguration of a Maya cultural space occurs with Luis de Lión’s novel El tiempo principia en Xibalbá (1985) and Gaspar Pedro González’ La otra cara (1992). I then observe the destabilization of traditional Maya female roles and symbols in the recent work of female Indigenous poets, Calixta Gabriel Xiquín and Maya Cu. Lastly, in the work of Víctor Montejo and Humberto Ak’abal I identify a negotiation of heterogeneity and essentialism for the development of a cultural project that looks to the formation of a pluricultural, plurinational Guatemalan state.
Role of Osteopntin during Dextran Sulphate Sodium-induced Colitis
Keywords: Osteopontin
Colitis
Dextran Sulphate Sodium

Osteopontin (OPN) is a matricellular cytokine found in most tissues and body fluids. It is involved in a variety of cell processes by binding to integrins and CD44 receptors, and it modulates immune responses. To investigate the functions of OPN during colitis the DSS acute colitis model in OPN-/- and WT control mice was utilized. OPN-/- mice were more susceptible to DSS-induced colitis than the DSS-treated WT control mice. The increased susceptibility of the OPN-/- mice was characterized by greater intestinal crypt destruction; high myeloperoxidase activity of infiltrating neutrophils; lack of differentiation of inflammatory cells such as lymphocytes subsets (CD4+, CD8+) and macrophages (F4/80); reduced production of certain cytokines, especially TNF-alpha; and non-programmed cell death of enterocytes. It is postulated that the hyperactivity of neutrophils may explain the increased tissue destruction during experimental colitis in the absence of OPN. Analysis of OPN’s impact on neutrophil function showed that while OPN may be important for the recruitment and migration of neutrophils, the expression of OPN by neutrophils is not required for manifestation of their destructive capabilities. This would suggest that OPN administration may protect the intestines from the adverse effects of colitis. Exogenous bovine milk OPN (20 μg/ml), administered for 8 days dissolved in the drinking water, ameliorated DSS-induced colitis. It diminished signs of disease, with a greater impact in the WT than the OPN-/- mice. It reduced the levels of neutrophils, macrophages, and pro-inflammatory mediators in the colon tissue. Recombinant OPN failed to reproduce the beneficial effects of milk OPN, which suggests that post-translational modifications of OPN are crucial to ameliorate experimental colitis. Collectively, these studies demonstrate that OPN has a protective effect during experimental colitis and that the oral administration of bovine milk OPN (20 μg/ml) ameliorates acute DSS-induced colitis. The results of this study also imply that the protective effect probably depends on a post-translationally modified form of OPN, and may require intracellular-OPN as a cofactor for significant attenuation of colitis. Future research could concentrate on more detailed investigation of these latter findings to determine OPN’s mechanism of action.
Unraveling the Causative Defects in X-linked Myopathy with Excessive Autophagy
Keywords: skeletal muscle, autophagy, vacuolar ATPases, splicing, autophagic vacuolar myopathy, mutation screening, hypomorphic alleles, X-linked myopathy with excessive autophagy

X-linked myopathy with excessive autophagy (XMEA) is a skeletal muscle disorder inherited in recessive fashion, affecting boys and sparing carrier females. Onset is in childhood with weakness of the proximal muscles of the lower extremities, progressing slowly to involve other muscle groups. Pathological analysis of skeletal muscle biopsies shows no inflammation, necrosis or apoptosis. Instead, forty to 80% of fibers exhibit giant autophagic vacuoles with heterogeneous degradative content. Numerous critical functions of all cells are compartmentalized in particular pH environments established by the intracellular transmembrane V-ATPase proton pump complex. Assembly of this complex, directed by the Vma21p chaperone, is well-studied in yeast but completely unknown in other organisms. The aim of my project was a better understanding of XMEA pathogenesis, with a focus on finding the disease-causing gene. In this thesis, I identify mutations in XMEA patients in a novel, previously uncharacterized gene, which we name VMA21. Most of the mutations are located in splicing-relevant positions and decrease splicing efficiency. After establishing that XMEA is caused by hypomorphic alleles of the VMA21 gene, I show that VMA21 is the diverged human orthologue of the yeast Vma21p protein, and that like Vma21p, it is an essential assembly chaperone of the V-ATPase. Decreased VMA21 reduces V-ATPase activity, resulting in altered lysosomal pH and a blockage at the degradative step of autophagy. Towards understanding disease pathogenesis, I show evidence of compensatory autophagy upregulation consecutive to the impaired clearance. Accumulated autolysosomes due to increased autophagy continue to face the degradative block and are slow to disappear. Instead, they merge to each other and form the characteristic giant XMEA vacuoles. These results uncover a novel mechanism of disease, namely macroautophagic overcompensation leading to cell vacuolation and tissue atrophy. This work describes the clinical outcome at the cusp of tolerable reduction in V-ATPase, with implications on common diseases like osteoporosis and cancer metastasis, where increased V-ATPase activity is an important component. Our XMEA patients show that the safety margin of reducing V-ATPase activity in humans is wide, increasing the potential to utilize chemical or biological V-ATPase inhibitors as possible therapies.
The Seven Last Words from the Cross
Keywords: sacred music
choral music

The Seven Last Words from the Cross is structured as a kind of loose double theme and variations. Movements II, IV, VI, VIII, IX, XI and XII present Jesus’ words as recorded in the four Gospels, and the remaining movements (which set related biblical and non-biblical texts) treat related themes and serve as choral and orchestral responses to Jesus’ words. The Gospel movements use a gradually expanding collection of pitches that frame a central pitch. This pitch (with a few deliberate exceptions) is generally reserved for Jesus’ actual utterances, which are sung by the four vocal soloists together, and which mostly use contrasting pitch material: a quasi-diatonic collection presented as pairs of intervals that move in contrary motion around the central pitch. The movements that respond to the Gospel texts take these interval pairs as their primary musical material, adapting them in symbolically and musically significant ways. The unison that is used to set Christ’s words fractures into a minor second when sung by the chorus, and his minor seventh expands to the more dissonant major seventh. The major third and perfect fifth, however, are common to both versions of the primary intervallic material, and both are used in shaping the large-scale form of these movements. Symmetry, both of pitch and rhythm, is also important to these movements’ structures. The opening and closing movements frame the main body of the work and are deliberately linked in their texts and musical material. The text of the first movement deals with the problem of corporate and individual human sin, of God’s wrath at humankind’s misdeeds and our own frustration and grief at our inability to consistently do what is right. The answer to this problem of sin, Christians believe, is the cross, and so in the last movement God’s anger, which was “poured out like fire” in the first movement, is quenched in a fountain of mercy. God’s rejection of sinning humanity and our rejection of God are ended. The Lord hears his people and answers them, and they in turn call out to him, acknowledging him as their God. In the seventh movement, a setting of a portion of the Stabat mater, the verse “Tui Nati vulnerati/ tam dignati pro me pati/ poenas mecum divide” (in part, “Let me share the pains of your wounded Son”) is given particular emphasis. The reason for this emphasis is explained in the eighth movement, “My God, my God, why have you forsaken me?” in which the piece’s previously established pattern breaks down. The words of Jesus are sung by the full chorus with the soloists, instead of by the soloists alone, and use the more dissonant version of the paired intervals, which was previously reserved for the response movements. The setting of the Gospel text and its response (excerpts from Psalm 22) are also combined into one movement for the first and only time in the piece. The purpose of these alterations was to draw a connection between Jesus’ sense of abandonment by God, the psalmist he was quoting, and the universal experience of human suffering.
Living in the Shadow of an "Obesity Epidemic": The Discursive Construction of Boys and Their Bodies
Keywords: fatness
obesity epidemic
boys
embodiment
masculinity
discursive construction
race
social class

This dissertation is about boys and fatness. In it I explore the central discourses that shape young men’s (13-15 years) experiences of their bodies, particularly in relation to body size, shape, and fatness. A central objective is to listen, hear, and take seriously the embodied health rationalities of young men as they negotiate the multiple and contesting discourses that confront them in their daily lives. I employ a feminist poststructural lens to account for the nuanced, alternative, and contextually specific ways young men think about and do health. Data collection was divided into three phases (non-participant observation, photo(focus) groups, and interviews) and was implemented at two Toronto area sites, including an exclusive private school and a publicly funded parks and recreation community centre. I demonstrate that there is not one way of experiencing fatness and masculinity, rather the young men’s constructions of fatness and health were fluid, shifting, contradictory and cross cut by other salient identity categories such as gender, race, ethnicity, social class, and age. Using Michel Foucault’s concept of governmentality, I show how obesity discourse provides a set of resources by which young men are able to construct themselves as autonomous, rational, neoliberal subjects, and how these subjectivities are differentially constituted depending on social and cultural positioning. I also reveal how differently raced and classed young men take up and embody normative ideals of the lean muscular male body through culturally appropriate masculine technologies of the self (i.e. sport and heterosexuality). The multiplicity of health and body discourses available to the young men gave rise to contested and ambivalent experiences and practices, such that dominant discourses were not always articulated in a straightforward and predictable manner, but were imbued with alternative and, in some cases, subversive meanings. To date, the social sciences have neglected to account for the relationship boys and men have with fatness discourses. By centering the analysis on the embodied experiences of diverse racialized and classed youth, this research demonstrates that weight and shape is more than a biomedical problem to be eradicated, but a discursively compelled embodiment that exists at the crossroads of the social, cultural, psychic, and biologic.
Involvement of Nitric Oxide in Osteoclastogenesis and Orthodontic Tooth Movement
Keywords: Nitric oxide, osteoclasts, orthodontic

Nitric oxide (NO) is a short lived free radical regulating bone turnover and bone cell function (1, 2). Osteoclasts are multinucleated bone resorbing cells which form by fusion of pre-osteoclasts. In addition, NO is a signaling molecule in mechanical loading of the bone (3), and in orthodontic tooth movement (OTM) (4). In OTM, force is applied to the tooth and transferred to the bone resulting in bone remodeling leading to tooth movement. This project has two parts: 1) NO in osteoclastogenesis: a) An intense NO signal was observed in pre-osteoclasts preceding cell fusion. b) Osteoclastogenesis increased when cells were exposed to the NOS inhibitor, L-NMMA, during their differentiation phase. c) In contrast, pre-osteoclast fusion decreased in presence of to L-NMMA during the fusion phase. d) NOS inhibitors, decreased osteoclast formation. e) The inhibitory effect of L-NMMA on osteoclast formation was abolished with increasing concentrations of sRANKL. f) NO donors increased osteoclast formation. g) An increase in NO production coincided with pre-osteoclasts fusion. h) Inhibiting fusion decreased osteoclast formation and NO production. i) L-NMMA decreased, while NO donors increased actin free barbed ends. Conclusion: While NO initially negatively regulates pre-osteoclast differentiation, it later facilitates the fusion of mononuclear pre-osteoclasts, possibly by up regulating actin remodeling. 2) Involvement of NO in OTM: Differential expression of NOS isoforms was investigated in periodontal ligament (PDL) and bone in tension and pressure sides using immunohistochemistry with NOS isoforms in a rat model of OTM. a) Expression of all isoforms was increased in the tension side. b) iNOS and nNOS expressions in the pressure side with the cell free zone were decreased while in the pressure side without the cell free zone were increased. c) The intensity of eNOS staining was increased in the tension side. d) Duration of force only changed the pattern of nNOS expression. e) Osteocyte NOS expression did not change. Conclusion: All NOS isoforms are involved in OTM with different expression patterns between the tension and pressure with nNOS being more involved in early OTM. PDL cells, rather than osteocytes are the mechanosensors in early OTM with regards to NO signaling.
The Dynamic Atmospheres of Classical Cepheids: Studies of Atmospheric Extension, Mass Loss, and Shocks
Keywords: Cepheids
Stars
Stellar Atmospheres
Stellar Mass Loss

In this dissertation, we develop new tools for the study of stellar atmospheres, pulsating stellar atmospheres and mass loss from pulsating stars. These tools provide new insights into the structure and evolution of stars and complement modern observational techniques such as optical interferometry and high resolution spectroscopy. In the first part, a new spherically symmetric version of the Atlas program is developed for modelling extended stellar atmospheres. The program is used to model interferometric observations from the literature and to study limb-darkening for stars with low gravity. It is determined that stellar limb-darkening can be used to constrain fundamental properties of stars. When this is coupled with interferometric or microlensing observations, stellar limb-darkening can predict the masses of isolated stars. The new SAtlas program is combined with the plane-parallel hydrodynamic program Hermes to develop a new spherically-symmetric radiative hydrodynamic program that models radial pulsation in the atmosphere of a star to depths including the pulsation-driving regions of the stars. Preliminary tests of this new program are discussed. In the second part, we study the recent observations of circumstellar envelopes surrounding Cepheids and develop a mass-loss hypothesis to explain their formation. The hypothesis is studied using a modified version of the Castor, Abbott, & Klein theory for radiative-driven winds to contain the effects of pulsation. In the theory, pulsation is found to be a driving mechanism that increases the mass-loss rates of Cepheids by up to four orders of magnitude. These mass-loss rates are large enough to explain the formation of the envelopes from dust forming in the wind at large distances from the surface of the star. The mass-loss rates are found to be plausible explanation for the Cepheid mass discrepancy. We also compute mass-loss rates from optical and infrared observations of Large Magellanic Cloud Cepheids from the infrared excess and find mass loss to be an important phenomena in these stars. The amount of infrared excess is found to potentially affect the structure of the infrared Leavitt law.