• (A). Regulation of B-/Z-DNA transition in modified oligonucleotides; (B). Synthesis of cationic BODIPY analogues for antimicrobial and anticancer applications

      Joshi, Dhruval Kumar; Centre for Biotechnology
      A. In this work, LNA-dG was incorporated into d(CG)6 sequence in a site-specific manner through the phosphoramidite chemistry-based solid phase synthesis to investigate the impact of this modification on the B→Z-DNA transition. Circular dichroism study showed that the incorporation of a single LNA-dG unit into d(CG)6 at internal positions virtually suppressed Z-DNA formation at 4 M NaCl concentration, whereas the presence of single LNA-dG unit towards the terminal ends showed only partially inhibition of B→Z-DNA transition. To further understand the influence of chemical modification on B→Z-DNA transition, modification at C8-position on LNA-dG residue was explored. Towards this goal, compounds such as 8-bromo-5′-dimethoxytrityl-N-dimethylformamidine-(2′-O,4′-C-methylene)-guanosine-3′-O-(2-cyanoethyl)-N,N-diisopropy phosphoramidite and 8-bromo-2′-deoxy-5′-O-dimethoxy-N-[(dimethylamino)methylene]-2′-fluoroguanosine-3′-O-(2-cyanoethyl)-N,N-diisopropyl phosphoramidite were synthesized. B. In this study, N,N,N-trimethyl-2-(4,4-difluoro-2,6-diiodo-4-bora-3a,4a-diaza-s-indacen-8-yl) ethylammonium iodide 111 was successfully synthesized. Singlet oxygen generation experiments suggested that BODIPY 111 is ~2.5 times more efficient with respect to Rose Bengal (RB) in generating singlet oxygen. However, based on the cell-culture experiment, BODIPY 111 treated culture plates showed only slight reduction in CFUs compared to Rose Bengal and control plates. BODIPY compounds 107 (iodinated-fluoro-BODIPY), 130 (brominated-fluoro-BODIPY) and 110 (brominated-meso-dimethylamine-fluoro-BODIPY) showed excellent stability both in dark and in light conditions and were found to be very efficient in generating singlet oxygen when compared to RB.
    • A. Discovery of novel reactivity under the Sonogashira reaction conditions B. Synthesis of functionalized BODIPYs and BODIPY-sugar conjugates

      Yalagala, Ravi Shekar; Department of Chemistry
      A. During our attempts to synthesize substituted enediynes, coupling reactions between terminal alkynes and 1,2-cis-dihaloalkenes under the Sonogashira reaction conditions failed to give the corresponding substituted enediynes. Under these conditions, terminal alkynes underwent self-trimerization or tetramerization. In an alternative approach to access substituted enediynes, treatment of alkynes with trisubstituted (Z)-bromoalkenyl-pinacolboronates under Sonogashira coupling conditions was found to give 1,2,4,6-tetrasubstituted benzenes instead of Sonogashira coupled product. The reaction conditions and substrate scopes for these two new reactions were investigated. B. BODIPY core was functionalized with various functional groups such as nitromethyl, nitro, hydroxymethyl, carboxaldehyde by treating 4,4-difluoro-1,3,5,7,8-pentamethyl-2,6-diethyl-4-bora-3a,4a-diaza-s-indacene with copper (II) nitrate trihydrate under different conditions. Further, BODIPY derivatives with alkyne and azido functional groups were synthesized and conjugated to various glycosides by the Click reaction under the microwave conditions. One of the BODIPY–glycan conjugate was found to form liposome upon rehydration. The photochemical properties of BODIPY in these liposomes were characterized by fluorescent confocal microscopy.
    • Adenovirus-based exogenous gene expression in mammalian cells

      El-Mogy, Mohamed A.; Department of Biological Sciences (Brock University, 2010-03-10)
      Adenoviruses have been used as a model system for understanding gene expression, DNA replication, gene delivery and other molecular biological phenomenon. In this project, adenovirus was used as a model to study exogenous gene expression in mammalian cells. More specifically, several adenoviral components were identified to enhance gene expression together with components needed for viral DNA replication. The adenoviral elements that enhance gene expression were assembled in an expression vector (pEl). These include the viral inverted terminal repeats (ITRs), the El region, the major late promoter (MLP) and the tripartite leader sequence (TPL). The green florescence protein (GFP) was used as a reporter gene. Various aspects of gene expression were examined including DNA delivery and stability inside the cells as well as mRNA transcription and protein expression. First, the effect of DNA quality on its delivery, stability and expreSSIOn III mammalian cells was studied. Five different conditions of the major DNA contaminants were used in this investigation including ethidium bromide (EtBr) , cesium chloride (CsCl), EtBr/CsCl, endotoxins and ethanol. CsCl, EtBr/CsCl and endotoxins affected the delivery process while EtBr affected the expression process but not the delivery. The used EtOH had no significant effect on both. In addition, the effect of all the contaminants was reversible. Next, we looked at the factors that enhance mRNA transcription and translation levels. Three approaches were tested, the first was the co-transfection of pEl and a plasmid that contains adenoviral genes involved in replication (PE2: contains E2 and viral protease). The second was the establishment of a cell line expressing these adenoviral genes involved in replication and the third approach was the super-infection with the wild type adenovirus. The co-transfection did not show any significant increase in gene expression or vector stability. On the other hand, the construction of CHO-E2 cell lines yielded five cell lines but none of them showed expression of all the integrated adenoviral E2 genes or enhancement of stability. Adenoviral super-infection enhanced gene expression. CHO cells showed higher enhancement in intensity and time than human embryonic kidney (HEK) 293 cells. In addition, such enhancement was dependent on the multiplicity of infection (MOl). Finally, this study emphasizes the importance of DNA quality on gene expression. However, the use of adenoviral elements to enhance exogenous gene expression is successful only when the complementary viral proteins and sequences are present. Active expression of the adenoviral proteins does not depend on a few major elements, but depends on the combination of different elements that work in cis or trans to activate gene expression.
    • Affective Traits of Psychopathy and the Role of Early Visual Attention: An Electrophysiological Study

      Weissflog, Meghan; Department of Psychology
      Models of affective processing abnormalities in psychopathy have involved both amygdala abnormalities and attentional deficits to peripheral affective information. Neurophysiological bases for the latter are not currently well understood. Often presented as competing explanations for affective traits of psychopathy, these models may instead be compatible, describing different levels of analysis, with the amygdala playing a role in early attention allocation. To explore this possibility, this dissertation was designed to integrate these two areas of the literature by proposing a neurophysiologically-based model of biases in attention to peripheral affective information in psychopathy. This model is centred on the idea that attentional biases seen in psychopathy may result from reduced responsivity of a subcortical thalamus-amygdala circuit that influences the allocation of attention to salient stimuli in the environment during initial stages of processing. Event-related potential (ERP) components that reflect attention allocation during early stages of visual information processing were used to test the hypothesis that individuals high in psychopathic traits would show reduced attention allocation to peripheral information in the form of reduced and/or delayed ERP responses. Explored were the relations between psychopathic personality traits and early ERP responses to simple stimulation of the visual system (Study 1) and to spatially-filtered emotional faces involving implicit versus explicit processing of the stimuli (Study 2). ERP effects related to overall psychopathic trait severity, but also yielded factor-specific ERP response patterns. Study 1 results were consistent with the present hypotheses. Specifically, higher Factor 1 scores (primary, affect-based traits) were associated with reduced attention-related ERP amplitudes in response to a flash stimulus presented peripheral to task performance. Factor 2 severity (secondary antisocial and behavioural traits) was associated with ERP latencies in primary visual cortex. Study 2 also showed somewhat more complex but Factor-specific patterns of early visual processing. Overall, the results were consistent with a reduced responsivity of the thalamo-amygdalar pathway in psychopathy-related individual differences in attention at early stages of visual information processing, both for affective information and simple sensory stimulation. This raises the question of whether such processing differences are a predisposing factor for the development of psychopathic traits.
    • Affinity for Aloneness and Shyness in Childhood and Adolescence: Differential Longitudinal Associations with Socio-emotional Adjustment

      Shapira, Marina; Department of Psychology
      Affinity for aloneness (AFA), a tendency to prefer to spend more time alone rather than with others, is assumed to be driven by low social interest rather than by social fears. This is unlike shyness, which is underpinned by a conflict between high social interest and pervasive social apprehension and weariness. Despite the marked motivational differences between these two subtypes of social withdrawal and their potential differential impact on socio-emotional adjustment in childhood and adolescence, AFA is empirically neglected compared to shyness. Shyness was extensively studied and repeatedly linked to a host of negative socio-emotional correlates such as depression, lower social skills, lower self-esteem and peer maltreatment. However, little is known about the socio-emotional impact of AFA on children and adolescents, particularly longitudinally. Despite clear evidence, AFA was suspected as maladaptive due to its affiliation with social withdrawal, a wide umbrella term that has been tied to internalizing problem and peer difficulties. The generalization of findings regarding social withdrawal as a whole to AFA may lead to a pathologization of a normative behavior, increase instances of unnecessary intervention, and inadvertently negatively impact otherwise intact socio-emotional development of children and adolescents. The scarce available knowledge about AFA stems from several persisting gaps in the literature. First, there is insufficient systematic differentiation among subtypes of social withdrawal, and a lack of deliberate simultaneous measurement of specific constructs such as shyness and AFA. Second, there are very few longitudinal studies of both shyness and AFA across childhood and adolescence. Third, there is a lack of contextual investigation of AFA compared to shyness in common life setting in which children tend to spend much of their time, such as organized sports activities. My doctoral dissertation specifically addressed all of the aforementioned gaps in the literature. Results of Study 1, a longitudinal study spanning from Grade 3 to Grade 5, indicated that only shyness, but not AFA, was significantly related to lower social skills and greater peer victimization across time. Study 2 utilized Latent Class Analysis and results indicated that adolescents in Grades 11 and 12 who were high on AFA and low on shyness did not differ from adolescents low on both AFA and shyness (a non-withdrawn group) on measures of socio-emotional adjustment. In Study 3, results of Structural Equation Modeling (SEM) indicated that only shyness, but not AFA, was related to lower positive activity outcomes through lower psychological engagement in the activity. In aggregate, the findings of the present doctoral studies advance the literature on AFA in meaningful ways. Most notably, AFA emerged as a largely benign form of social withdrawal across middle childhood and adolescence. Moreover, Study 2, which appears to be the first person-centered investigation of AFA in adolescence using Latent Class Analysis, provided novel evidence that AFA and shyness are distinct constructs with unique implication for socio-emotional adjustment. These findings carry applied implication for educators and parents seeking to facilitate optimal developmental contexts for children with an AFA.
    • An after-school literacy program : investigating the experiences of students with literacy difficulties, their volunteer tutors, and the tutors' transition into the teaching profession

      Gallagher, Tiffany L.; Department of Psychology (Brock University, 2005-05-28)
      This research responds to a pervasive call for our educational institutions to provide students with literacy skills, and teachers with the instructional supports necessary to facilitate this skill acquisition. Questions were posed to gain information concerning the efficacy ofteaching literacy strategies to students with learning difficulties, the impact of this training on their volunteer tutors, and the influence of this experience on these tutors' ensuing instructional practice as teacher candidates in a preservice education program. Study #1 compared a nontreatment group of students with literacy difficulties who participated in the program and found that program participants were superior at reading letter patterns and at comprehending the elements of story grammar. Concurrently, the second study explored the experiences of 19 volunteer tutors and uncovered that they acquired instructional skills as they established a knowledge base in teaching reading and writing, and they affirmed personal goals to become future teachers. Study #3 tracked 6 volunteer tutors into their pre-service year and identified their constructions, and beliefs about literacy instruction. These teacher candidates discussed how they had intended to teach reading and writing strategies based on their position that effective teaching ofthese skills in the primary grades is integral to academic success. The teacher candidates emphasized the need to build rapport with students, and the need to exercise flexibility in lesson plan delivery while including activities to meet emotional and developmental requirements of students. The teacher candidates entered their pre-service education with an initial cognition set based on the limited teaching context of tutoring. This foundational ii perception represented their prior knowledge of literacy instruction, a perception that appeared untenable once they were immersed in a regular instructional setting. This disparity provoked some of the teacher candidates to denounce their teacher mentors for not consistently employing literacy strategies and individualized instruction. This critical perspective could have been a demonstration of cognitive dissonance. In the end, when the teacher candidates began to look toward the future and how they would manage the demands of an inclusive classroom, they recognized the differences in the contexts. With an appreciation for the need for balance between prior and present knowledge, the teacher candidates remained committed to implementing their tutoring strategies in future teaching positions. This document highlights the need for teacher candidates with instructional experience prior to teacher education, to engage in cognitive negotiations to assimilate newly acquired pedagogies into existing pedagogies.
    • Age-related errors in the assessment of children

      Veldhuizen, Scott; Applied Health Sciences Program
      Children's functioning can only reasonably be measured relative to that of other individuals of the same age. In practice, age ranges are usually used to group children for this purpose. Examples include school grades, age groups in sports, and age bands used in developmental assessments. Age grouping is associated with systematic errors, often known as relative age effects (RAEs): Within each age group, older children outperform younger ones. This type of assessment error may lead to opportunities and interventions being offered inefficiently or unfairly. This thesis comprises 5 research projects that aim to clarify underlying causes of RAEs, examine their importance in different contexts, and develop analytic methods relevant to their study. I use data drawn from two studies: A prospective cohort study including athletic performance measures (the Physical Health Activity Study Team project) and a validation study undertaken to compare measures of child development (Psychometric Assessment of the Nipissing District Developmental Screener). I develop linear models to characterize age-related variation and then use results to draw conclusions, to inform other analyses, and to generate synthetic datasets. Together, studies demonstrate a set of methods for the exploration and correction of RAEs. They also yield several concrete findings: (1) A simple mathematical interpretation of RAEs can fully explain the errors seen in real datasets, meaning that other explanations are, in at least some contexts, unnecessary. (2) RAEs have different effects in ranking and selection contexts, with ranking errors largest among average individuals but selection errors greatest when more extreme thresholds are used. (3) Age bands cause misclassification in measures of child development, and the error rate rises rapidly with the width of age bands used. (4) The use of different sets of age bands will prevent different assessments from agreeing closely. (5) Age grouping in developmental assessments will create an illusion of longitudinal instability. Finally, I demonstrate the use of alternative scoring approaches and discuss how these can reduce or eliminate errors related to RAEs.
    • alpha-Tocopherol's Antioxidant Role: A Biophysical Perspective

      Marquardt, Drew TC; Department of Physics (Brock University, 2014-10-30)
      I present evidence of an antioxidant mechanism for vitamin E that correlates strongly with its physical location in a model lipid bilayer. These data address the overlooked problem of the physical distance between the vitamin's reducing hydrogen and lipid acyl chain radicals. The combined data from neutron diffraction, NMR and UV spectroscopy experiments, all suggest that reduction of reactive oxygen species and lipid radicals occurs specifically at the membrane's hydrophobic-hydrophilic interface. The latter is possible when the acyl chain adopts conformations in which they snorkel to the interface from the hydrocarbon matrix. Moreover, not all model lipids are equal in this regard, as indicated by the small differences in the vitamin's location. The present result is a clear example of the importance of lipid diversity in controlling the dynamic structural properties of biological membranes. Importantly, these results suggest that measurements of alpha-tocopherol oxidation kinetics, and its products, should be revisited by taking into consideration the physical properties of the membrane in which the vitamin resides.
    • Applications of dihydroarenediols to chemoenzymatic synthesis : approaches to total synthesis of morphine alkaloids

      Finn, Kevin J.; Department of Chemistry (Brock University, 2006-05-28)
      The present studies describe, as a primary goal, our recent progess toward the synthesis of morphine alkaloids from aromatic precursors. Model substrates were synthesized which allowed investigation into Diels-Alder, radical cascade, and palladium-catalyzed bond-forming reactions as possible routes to the morphine alkaloid skeleton. As a secondary objective, three separate series of aromatic substrates were subjected to whole-cell oxidation with Escherichia coli JM 109 (pDTG601), a recombinant organism over-expressing the enzyme toluene dioxygenase. Included in this study were bromothioanisoles, dibromobenzenes, and cyclopropylbenzene derivatives. The products of oxidation were characterized by chemical conversion to known intermediates. The synthetic utility of one of these bacterial metabolites, derived from oxidation of o-dibromobenezene, was demonstrated by chemical conversion to (-)conduritol E.
    • Apprehending Stigma: Towards a Reparative Trauma-informed Decolonial Reading of HIV-related Stigma

      Long, Carmen; Interdisciplinary Humanities Program
      Applying a decolonial trauma-informed framework that brings together different disciplinary systems, this project investigates responses to the stigma associated with the Human Immunodeficiency Virus (HIV) in the literary work of two Canadian and two South African writers. I approach the literary journalism of Stephanie Nolen and Jonny Steinberg and the novels of Tomson Highway and the late Phaswane Mpe as testimony in which Steinberg, Nolen and Mpe contest Western epistemologies and Highway foregrounds Indigenous knowledges. The four texts reframe stigma as operating within much larger systemic violences and operations of power than can be envisioned within a politics of recognition, indexed to the expository logic of Eve Kosofsky Sedgwick’s paranoid position. Locating HIV-related stigma as emerging within the context of intergenerational collective trauma rooted in colonial violence makes possible the kind of reparative work that Sedgwick envisions, as well as an engagement with the infinite possibilities of encounter as an ethical response to this socially polarizing phenomenon that has proven so difficult to dislodge. Attentive to specific racialized and minoritized colonial histories, this project unravels the entanglement of events and conditions that coalesce around HIV in watershed moments when decolonial work collides with ongoing histories of colonial violence. Such a trauma-informed, decolonial lens offers a non-positivist framework to unsettle, potentially, the stasis of stigma reduction.
    • Approaches towards C-10-hydroxylated analogues of narciclasine

      Ticli, Vincenzo; Department of Chemistry
      Discussed in this thesis is the synthesis of a C10-benzyloxy unnatural derivative of narciclasine. The described approach involves the use of homochiral cyclohexadiene diols, products of the biocatalytic transformation of aromatic compounds, as precursors to ring C, and of highly oxygenated aromatic molecules to construct ring A. The document also reports a detailed account of the protocols studied for the intramolecular formation of ring B. Experimental data and spectral data are provided for the novel compounds.
    • The Arabidopsis NPR1 Protein Is a Receptor for the Plant Defense Hormone Salicylic Acid

      Wu, Yue; Department of Biological Sciences
      Systemic Acquired Resistance (SAR) is a type of plant systemic resistance occurring against a broad spectrum of pathogens. It can be activated in response to pathogen infection in the model plant Arabidopsis thaliana and many agriculturally important crops. Upon SAR activation, the infected plant undergoes transcriptional reprogramming, marked by the induction of a battery of defense genes, including Pathogenesis-related (PR) genes. Activation of the PR-1 gene serves as a molecular marker for the deployment of SAR. The accumulation of a defense hormone, salicylic acid (SA) is crucial for the infected plant to mount SAR. Increased cellular levels of SA lead to the downstream activation of the PR-1 gene, triggered by the combined action of the Non-expressor of Pathogenesis-related Gene 1 (NPR1) protein and the TGA II-clade transcription factor (namely TGA2). Despite the importance of SA, its receptor has remained elusive for decades. In this study, we demonstrated that in Arabidopsis the NPR1 protein is a receptor for SA. SA physically binds to the C-terminal transactivation domain of NPR1. The two cysteines (Cys521 and Cys529), which are important for NPR1’s coactivator function, within this transactivation domain are critical for the binding of SA to NPR1. The interaction between SA and NPR1 requires a transition metal, copper, as a cofactor. Our results also suggested a conformational change in NPR1 upon SA binding, releasing the C-terminal transactivation domain from the N-terminal autoinhibitory BTB/POZ domain. These results advance our understanding of the plant immune function, specifically related to the molecular mechanisms underlying SAR. The discovery of NPR1 as a SA receptor enables future chemical screening for small molecules that activate plant immune responses through their interaction with NPR1 or NPR1-like proteins in commercially important plants. This will help in identifying the next generation of non-biocidal pesticides.
    • Aspects of spatial and habitat ecology of multiple Anopheles species (Diptera: Culicidae): malaria vectors in the highlands and foothills of Ecuador

      Pinault, Lauren; Department of Biological Sciences (Brock University, 2012-07-30)
      The resurgence of malaria in highland regions of Africa, Oceania and recently in South America underlines the importance of the study of the ecology of highland mosquito vectors of malaria. Since the incidence of malaria is limited by the distribution of its vectors, the purpose of this PhD thesis was to examine aspects of the ecology of Anopheles mosquitoes in the Andes of Ecuador, South America. A historical literature and archival data review (Chapter 2) indicated that Anopheles pseudopunctipennis transmitted malaria in highland valleys of Ecuador prior to 1950, although it was eliminated through habitat removal and the use of chemical insecticides. Other anopheline species were previously limited to low-altitude regions, except in a few unconfirmed cases. A thorough larval collection effort (n=438 attempted collection sites) in all road-accessible parts of Ecuador except for the lowland Amazon basin was undertaken between 2008 - 2010 (Chapter 3). Larvae were identified morphologically and using molecular techniques (mitochondrial COl gene), and distribution maps indicated that all five species collected (Anopheles albimanus, An. pseudopunctipennis, Anopheles punctimacula, Anopheles oswaldoi s.l. and Anopheles eiseni) were more widespread throughout highland regions than previously recorded during the 1940s, with higher maximum altitudes for all except An. pseudopunctipennis (1541 m, 1930 m, 1906 m, 1233 m and 1873 m, respectively). During larval collections, to characterize species-specific larval habitat, a variety of abiotic and biotic habitat parameters were measured and compared between species-present and species-absent sites using chi-square tests and stepwise binary logistic regression analyses (Chapter 4). An. albimanus was significantly associated with permanent pools with sand substrates and An. pseudopunctipennis with gravel and boulder substrates. Both species were significantly associated with floating cyanobacterial mats and warmer temperatures, which may limit their presence in cooler highland regions. Anopheles punctimacula was collected more often than expected from algae-free, shaded pools with higher-than-average calculated dissolved oxygen. Anopheles oswaldoi s.l., the species occurring on the Amazonian side of the Andes, was associated with permanent, anthropogenic habitats such as roadside ditches and ponds. To address the hypothesis that human land use change is responsible for the emergence of multiple highland Anopheles species by creating larval habitat, common land uses in the western Andes were surveyed for standing water and potential larval habitat suitability (Chapter 5). Rivers and road edges provided large amounts of potentially suitable anopheline habitat in the western Andes, while cattle pasture also created potentially suitable habitat in irrigation canals and watering ponds. Other common land uses surveyed (banana farms, sugarcane plantations, mixed tree plantations, and empty lots) were usually established on steep slopes and had very little standing water present. Using distribution and larval habitat data, a GIS-based larval habitat distribution model for the common western species was constructed in ArcGIS v.l 0 (ESRI 2010) using derived data layers from field measurements and other sources (Chapter 6). The additive model predicted 76.4 - 97.9% of the field-observed collection localities of An. albimanus, An. pseudopunctipennis and An. punctimacula, although it could not accurately distinguish between species-absent and speciespresent sites due to its coarse scale. The model predicted distributional expansion and/or shift of one or more anopheline species into the following highland valleys with climate warming: Mira/Chota, Imbabura province, Tumbaco, Pichincha province, Pallatanga and Sibambe, Chimborazo province, and Yungilla, Azuay province. These valleys may serve as targeted sites of future monitoring to prevent highland epidemics of malaria. The human perceptions of malaria and mosquitoes in relation to land management practices were assessed through an interview-based survey (n=262) in both highlands and lowlands, of male and female land owners and managers of five property types (Chapter 7). Although respondents had a strong understanding of where the disease occurs in their own country and of the basic relationship among standing water, mosquitoes and malaria, about half of respondents in potential risk areas denied the current possibility of malaria infection on their own property. As well, about half of respondents with potential anopheline larval habitat did not report its presence, likely due to a highly specific definition of suitable mosquito habitat. Most respondents who are considered at risk of malaria currently use at least one type of mosquito bite prevention, most commonly bed nets. In conclusion, this interdisciplinary thesis examines the occurrence of Anopheles species in the lowland transition area and highlands in Ecuador, from a historic, geographic, ecological and sociological perspective.
    • Aspergillus flavus infections in Galleria mellonella : a pathogen-host model system for the study of emerging diseases

      Scully, Lisa R.; Department of Biological Sciences (Brock University, 2007-05-28)
      To study emerging diseases, I employed a model pathogen-host system involving infections of insect larvae with the opportunistic fungus Aspergillus flavus, providing insight into three mechanisms ofpathogen evolution namely de novo mutation, genome decay, and virulence factoracquisition In Chapter 2 as a foundational experiment, A. flavus was serially propagated through insects to study the evolution of an opportunistic pathogen during repeated exposure to a single host. While A. flavus displayed de novo phenotypic alterations, namely decreased saprobic capacity, analysis of genotypic variation in Chapter 3 signified a host-imposed bottleneck on the pathogen population, emphasizing the host's role in shaping pathogen population structure. Described in Chapter 4, the serial passage scheme enabled the isolation of an A. flavus cysteine/methionine auxotroph with characteristics reminiscent of an obligate insect pathogen, suggesting that lost biosynthetic capacity may restrict host range based on nutrient availability and provide selection pressure for further evolution. As outlined in Chapter 6, cysteine/methionine auxotrophy had the pleiotrophic effect of increasing virulence factor production, affording the slow-growing auxotroph with a modified pathogenic strategy such that virulence was not reduced. Moreover in Chapter 7, transformation with a virulence factor from a facultative insect pathogen failed to increase virulence, demonstrating the necessity of an appropriate genetic background for virulence factor acquisition to instigate pathogen evolution.
    • The Associations Among Sleep Problems, Emotion Dysregulation and Adjustment Over Time Among University Students

      Semplonius, Thalia; Department of Psychology
      Young adults experience a variety of changes when entering university (e.g., leaving home for the first time). Although some students adjust well to university, others may experience difficulties. Two problems that may be experienced are sleep problems and difficulties regulating emotion; importantly, both of these factors are associated with a variety of adjustment indicators. Throughout this dissertation, the three adjustment indicators that were of interest were physical activity, depressive symptoms and alcohol use as all three are common throughout university. As little work has examined the direction of effects between all of these factors, a longitudinal dataset was used to examine the relationships among these factors in two ways. Participants included 1132 first year undergraduate students (Time 1 Mage = 19.06 years, SD = 11.17 months). The first method was the use of a variable-centered analysis which was used in Studies 1 and 2. Study 1 focused on the relationships among sleep problems, emotion dysregulation, and physical activity and Study 2 focused on the relationships among sleep problems, emotion dysregulation, depressive symptoms, and alcohol use. Study 3 used a person-centered analysis which allowed for the examination of heterogeneity in the patterns of association between variables. Specifically, this study involved examining heterogeneity in the associations between sleep problems and emotion dysregulation, and how these patterns were related to depressive symptoms and alcohol use in both the short- and longterm. Overall, these studies indicate that sleep and emotion dysregulation are both bidirectionally related over time and also co-occur for a subgroup of individuals. The results also indicate that difficulties in adjustment experienced early on in university may have lasting effects.
    • Astringency and other oral sensations : biological sources of individual variation and association with food and beverage behaviour

      Bajec, Marth R.; Department of Biological Sciences (Brock University, 2011-10-14)
      Orosensory perception strongly influences liking and consumption of foods and beverages. This thesis examines the influence of biological sources of individual variation on the perception of prototypical orosensory stimuli, food liking, self-reported alcohol liking and consumption, and indices of health. Two orosensory indices were examined: propylthiouracil (PROP) responsiveness, a genetically-mediated index of individual variation associated with enhanced responsiveness to orosensory stimuli often expressed as PROP taster status (PTS); and thermal taster status (TTS), a recently reported index of orosensory responsiveness. Taster status in PTS and/or TTS confers greater responsiveness to most orosensory stimuli. Gender, age, ethnicity, and fungiform papillae (FP) density were not associated with orosensory responsiveness to tastants, an astringent, and a flavour. Unlike PROP responsiveness, FP density was not associated with TTS. Both PROP responsiveness and TTS were associated with increased responsiveness to orosensory stimuli, including temperature and astringency. For PROP, this association did not hold when stimuli were presented at cold or warm temperatures, which are ecologically valid since most foods and beverages are not consumed at ambient temperature. Thermal tasters (TTs), who perceive 'phantom' taste sensations with lingual thermal stimulation, were more responsive to stimuli at both temperatures than thermal non-tasters (TnTs). While PTS, TIS, and gender affected self-reported liking and consumption of some alcoholic beverages, gender associated with the greatest number of beverage types and consumption parameters, with males generally liking and consuming alcoholic beverages more than females. Age and gender were the best predictors of alcoholic beverageAiking and consumption. As expected, .. liking of bitter and fatty foods and cream was inversely related to PROP responsiveness. TTS did not associate with body mass index or waist circumference, and contrary to previous studies, neither did PROP responsiveness. Taken together, TnTs' greater liking of cooked fruits and vegetables and high alcohol, and astringent alcoholic beverages than TTs suggests differences between TTS groups may be driven by perceived temperature and texture. Neither an interaction between PTS and TTS nor a TTS effect on PROP responsiveness was observed, suggesting these two indices of individual variation exert their influences on orosensory perception independently.
    • Attention capture: Stimulus, group, individual, and moment-to-moment factors contributing to distraction

      Stokes, Kirk; Department of Psychology
      Over four studies, some containing multiple experiments, attention capture is explored in a variety of experimental contexts. The over-arching goals were to better understand attention capture at the stimulus level (Chapter 2), the group and the individual-differences level (Chapters 3 and 4), and in terms of moment-to-moment fluctuations in susceptibility to distraction by task-irrelevant stimuli (Chapter 5). Rare or unexpected stimulus changes are known to capture attention and disrupt behavioural performance. Detection is typically thought to depend on changes to the physical properties (e.g., tone pitch) of a stimulus. Chapter 2 explores whether physical change is a necessary antecedent for attention capture. Here, evidence suggests that unexpected semantic change is sufficient to produce a distraction effect and that an accompanying physical/acoustic change is not required to induce semantic processing of task-irrelevant stimuli even when the semantic deviants are unrelated to the primary task. Attention capture is typically robust at the group level and has been observed in a variety of popular paradigms. Chapter 3 explores whether attention capture can be viewed as a stable and generalizable individual trait. The study examined involuntary attention capture across a set of prototypical stimulus-driven capture tasks and contingent-capture tasks in both spatial and/or temporal paradigms. Results showed the expected pattern of capture in each of the tasks as well as modest to good test-retest reliability over the span of one week for each of the capture measures. However, no evidence is found for a common attention capture factor providing evidence that attention capture within an individual is reliable but not generalizable. Chapter 4 extends the results of Chapter 3 and shows that attention capture in these tasks is not related to off-line self-report measures of attentional ability and day-to-day functioning. The lack of evidence for a common factor that can predict attention capture in one or more paradigms suggests that attention capture is not characterized by trait individual differences in executive function or predicted by individuals’ meta-awareness of their own attentional ability. Chapter 5, however, shows that attention capture can be characterized by moment-to-moment lapses of attention as it varies trial-to-trial as a function of internally generated task-irrelevant thought (i.e., mind-wandering). Mind-wandering slowed RTs overall and increased non-contingent, but not contingent, forms of capture providing evidence that some forms of attention capture are exacerbated by moment-to-moment lapses of attention. Self-reports on a dispositional mind-wandering scale did not predict capture when mind-wandering was used as an individual differences variable. Results suggest that attention capture may be better explained by cognitive processes engaged moment-to-moment rather than individual dispositions.
    • Augmented Video Self-Modeling as an Intervention Technique for Young Children with Selective Mutism: An Explanatory Sequential Study

      Bork, Poling Marianne; Department of Graduate and Undergraduate Studies in Education
      This mixed methods study examined efficacy of augmented video self-modeling (VSM) as an intervention technique for young children with selective mutism (SM). Participants included 3 children aged 8 (including a set of twins) and their parents and classroom teachers. The first, quantitative phase was guided by Kehle, Madaus, Baratta, and Bray (1998), who proposed using augmented VSM as an intervention package comprising a combination of video self-modeling, stimulus fading, and reinforcement behavioural techniques. The second, qualitative phase was to identify participants’ experience and perspective on augmented VSM, and to examine contexts and individual cases of SM and results obtained from the first phase of the study. Parents, teachers, and the researcher conducted a comprehensive assessment of participants’ verbal behaviour across multiple settings and throughout baseline, intervention, post-intervention, and 1-month follow-up. Interviews with open-ended questions elicited perspectives of parents and teachers, while close-ended post-intervention questionnaires with the children revealed individual experience with the intervention. Statistical analyses indicated participants’ verbal communicative behaviour increased significantly during post-intervention, and their progress was maintained at 1-month follow-up. Communication scores increased significantly for all children. All parents and teachers rated the intervention as effective, with one parent further commenting that intervention results exceeded her expectations. A recent meeting with the school board’s Speech Language Pathologist revealed the 3 participants are speaking freely inside the school, and that the twins are indistinguishable from other children 1 year post-study. Limitations of the study and future research implication and direction are discussed.
    • Autonomic and electrocortical indices of performance monitoring and source memory discrimination in older and younger adults

      Mathewson, Karen Janet.; Department of Psychology (Brock University, 2009-05-28)
      Reduced capacity for executive cognitive function and for the autonomic control of cardiac responsivity are both concomitants of the aging process. These may be linked through their mutual dependence on medial prefrontal function, but the specifics ofthat linkage have not been well explored. Executive functions associated with medial prefrontal cortex involve various aspects ofperformance monitoring, whereas centrally mediated autonomic functions can be observed as heart rate variability (HRV), i.e., variability in the length of intervals between heart beats. The focus for this thesis was to examine the degree to which the capacity for phasic autonomic adjustments to heart rate relates to performance monitoring in younger and older adults, using measures of electrocortical and autonomic activity. Behavioural performance and attention allocation during two age-sensitive tasks could be predicted by various aspects of autonomic control. For young adults, greater influence of the parasympathetic system on HRV was beneficial for learning unfamiliar maze paths; for older adults, greater sympathetic influence was detrimental to these functions. Further, these relationships were primarily evoked when the task required the construction and use of internalized representations of mazes rather than passive responses to feedback. When memory for source was required, older adults made three times as many source errors as young adults. However, greater parasympathetic influence on HRV in the older group was conducive to avoiding source errors and to reduced electrocortical responses to irrelevant information. Higher sympathetic predominance, in contrast, was associated with higher rates of source error and greater electrocortical responses tq non-target information in both groups. These relations were not seen for 11 errors associated with a speeded perceptual task, irrespective of its difficulty level. Overall, autonomic modulation of cardiac activity was associated with higher levels of performance monitoring, but differentially across tasks and age groups. With respect to age, those older adults who had maintained higher levels of autonomic cardiac regulation appeared to have also maintained higher levels of executive control over task performance.
    • Autonomic and Electrophysiological Correlates of Cognitive Control in Aging

      Capuana, Lesley; Department of Psychology (Brock University, 2014-08-21)
      This thesis tested a model of neurovisceral integration (Thayer & Lane, 2001) wherein parasympathetic autonomic regulation is considered to play a central role in cognitive control. We asked whether respiratory sinus arrhythmia (RSA), a parasympathetic index, and cardiac workload (rate pressure product, RPP) would influence cognition and whether this would change with age. Cognitive control was measured behaviourally and electrophysiologically through the error-related negativity (ERN) and error positivity (Pe). The ERN and Pe are thought to be generated by the anterior cingulate cortex (ACC), a region involved in regulating cognitive and autonomic control and susceptible to age-related change. In Study 1, older and younger adults completed a working memory Go/NoGo task. Although RSA did not relate to performance, higher pre-task RPP was associated with poorer NoGo performance among older adults. Relations between ERN/Pe and accuracy were indirect and more evident in younger adults. Thus, Study 1 supported the link between cognition and autonomic activity, specifically, cardiac workload in older adults. In Study 2, we included younger adults and manipulated a Stroop task to clarify conditions under which associations between RSA and performance will likely emerge. We varied task parameters to allow for proactive versus reactive strategies, and motivation was increased via financial incentive. Pre-task RSA predicted accuracy when response contingencies required maintenance of a specific item in memory. Thus, RSA was most relevant when performance required proactive control, a metabolically costly strategy that would presumably be more reliant on autonomic flexibility. In Study 3, we included older adults and examined RSA and proactive control in an additive factors framework. We maintained the incentive and measured fitness. Higher pre-task RSA among older adults was associated with greater accuracy when proactive control was needed most. Conversely, performance of young women was consistently associated with fitness. Relations between ERN/Pe and accuracy were modest; however, isolating ACC activity via independent component analysis allowed for more associations with accuracy to emerge in younger adults. Thus, performance in both groups appeared to be differentially dependent on RSA and ACC activation. Altogether, these data are consistent with a neurovisceral integration model in the context of cognitive control.