• Defence of Agaricus bisporus against toxic secondary metabolites from Trichoderma aggressivum.

      Sjaarda, Calvin; Department of Biological Sciences (Brock University, 2013-09-12)
      Trichoderma spp are effective competitors against other fungi because they are mycoparasitic and produce hydrolytic enzymes and secondary metabolites that inhibit the growth of their competitors. Inhibitory compounds produced by Trichoderma aggressivum, the causative agent of green mold disease, are more toxic to the hybrid off-white strains of Agaricus bisporus than the commercial brown strains, consistent with the commercial brown strain’s increased resistance to the disease. This project looked at the response of hybrid off-white and commercial brown strains of A. bisporus to the presence of T. aggressivum metabolites with regard to three A. bisporus genes: laccase 1, laccase 2, and manganese peroxidase. The addition of T. aggressivum toxic metabolites had no significant effect on MnP or lcc1 transcript abundance. Alternatively, laccase 2 appears to be involved in resistance to T. aggressivum because the presence of T. aggressivum metabolites results in higher lcc2 transcript abundance and laccase activity, especially in the commercial brown strain. The difference in laccase expression and activity between A. bisporus strains was not a result of regulatory or coding sequence differences. Alteration of laccase transcription by RNAi resulted in transformants with variable levels of laccase transcript abundance. Transformants with a low number of lcc transcripts were very sensitive to T. aggressivum toxins, while those with a high number of lcc transcripts had increased resistance. These results indicated that laccase activity, in particular that encoded by lcc2, serves as a defense response of A. bisporus to T. aggressivum toxins and contributes to green mold disease resistance in commercial brown strains.
    • Deindustrialization and Urban Regeneration: Nietzsche, Activism, and Organically Emergent Forms of Civic Engagement in Windsor/ Detroit

      Yocom, Grant Kenneth; Interdisciplinary Humanities Program
      The deindustrialization of cities represents a moment of cultural and political weakness and insecurity about what it means to be urban. Specifically, within Windsor and Detroit the traditionally rooted modes of production and habitation that have framed the cultural and political landscape as well as the identities of these urban centers are in a state of massive transition. Within these urban centers we find engaged residents mobilizing critical, self-critical and projective dispositions capable of meeting the challenges of their context, as well as issuing inquiries that put the inquirer on the spot, produce discomfort, and have potency: the capacity to change the way the inquirer thinks, acts and inhabits urban landscapes. These practices are vital responses to the questions that drive our lived-experience of city life and are in the end matters of survival. This work deploys an interpretation of the new category of philosopher forecasted by Nietzsche in Beyond Good and Evil in order to explore this moment when culture and politics meet at street level in the transitional deindustrializing cities of Windsor and Detroit. This is a difficult moment to make articulate. Many of the criticisms and prescriptions at work in the particular projects that we will examine are expressed as action: performed critique. These urban centers themselves have the capacity to become foxholes of sorts. Cities have a degree of receptivity to urban activism, and thus can become discrete political entities that mediate between culturally rooted criticisms and the larger political landscape. These cities in turn have the capacity to generate larger political effects. Urban activist initiatives, addressed in this project both theoretically and in their particularity, are rooted in the local and the biological in a manner that intimately ties experiences of suffering at the hands of economic and political systems responding to their acts of resistance. Activist collectives aim to inflict a wound to the overall culture, thus inoculating not only the immediate urban culture, but culture more generally with something new and empowering. This work explores the tension between embedded criticisms and proposals performed by urban activists and the trenchant forces that frustrate these actions.
    • Delineation of within-site terroir effects using soil and vine water measurement. Investigation of Cabernet Franc

      Hakimi-Rezaei, Javad; Department of Biological Sciences (Brock University, 2009-01-28)
      . The influence of vine water status was studied in commercial vineyard blocks of Vilis vinifera L. cv. Cabernet Franc in Niagara Peninsula, Ontario from 2005 to 2007. Vine performance, fruit composition and vine size of non-irrigated grapevines were compared within ten vineyard blocks containing different soil and vine water status. Results showed that within each vineyard block water status zones could be identified on GIS-generated maps using leaf water potential and soil moisture measurements. Some yield and fruit composition variables correlated with the intensity of vine water status. Chemical and descriptive sensory analysis was performed on nine (2005) and eight (2006) pairs of experimental wines to illustrate differences between wines made from high and low water status winegrapes at each vineyard block. Twelve trained judges evaluated six aroma and flavor (red fruit, black cherry, black current, black pepper, bell pepper, and green bean), thr~e mouthfeel (astringency, bitterness and acidity) sensory attributes as well as color intensity. Each pair of high and low water status wine was compared using t-test. In 2005, low water status (L WS) wines from Buis, Harbour Estate, Henry of Pelham (HOP), and Vieni had higher color intensity; those form Chateau des Charmes (CDC) had high black cherry flavor; those at RiefEstates were high in red fruit flavor and at those from George site was high in red fruit aroma. In 2006, low water status (L WS) wines from George, Cave Spring and Morrison sites were high in color intensity. L WS wines from CDC, George and Morrison were more intense in black cherry aroma; LWS wines from Hernder site were high in red fruit aroma and flavor. No significant differences were found from one year to the next between the wines produced from the same vineyard, indicating that the attributes of these wines were maintained almost constant despite markedly different conditions in 2005 and 2006 vintages. Partial ii Least Square (PLS) analysis showed that leaf \}' was associated with red fruit aroma and flavor, berry and wine color intensity, total phenols, Brix and anthocyanins while soil moisture was explained with acidity, green bean aroma and flavor as well as bell pepper aroma and flavor. In another study chemical and descriptive sensory analysis was conducted on nine (2005) and eight (2006) medium water status (MWS) experimental wines to illustrate differences that might support the sub-appellation system in Niagara. The judges evaluated the same aroma, flavor, and mouthfeel sensory attributes as well as color intensity. Data were analyzed using analysis of variance (ANOVA), principal component analysis (PCA) and discriminate analysis (DA). ANOV A of sensory data showed regional differences for all sensory attributes. In 2005, wines from CDC, HOP, and Hemder sites showed highest. r ed fruit aroma and flavor. Lakeshore and Niagara River sites (Harbour, Reif, George, and Buis) wines showed higher bell pepper and green bean aroma and flavor due to proximity to the large bodies of water and less heat unit accumulation. In 2006, all sensory attributes except black pepper aroma were different. PCA revealed that wines from HOP and CDC sites were higher in red fruit, black currant and black cherry aroma and flavor as well as black pepper flavor, while wines from Hemder, Morrison and George sites were high in green bean aroma and flavor. ANOV A of chemical data in 2005 indicated that hue, color intensity, and titratable acidity (TA) were different across the sites, while in 2006, hue, color intensity and ethanol were different across the sites. These data indicate that there is the likelihood of substantial chemical and sensory differences between clusters of sub-appellations within the Niagara Peninsula iii
    • Delineation of within-site terroir effects using soil and vine water measurements in Riesling vineyards within the Niagara Peninsula

      Willwerth, James Joseph; Department of Biological Sciences (Brock University, 2012-04-04)
      The major focus of this dissertation was to explain terroir effects that impact wine varietal character and to elucidate potential determinants of terroir by testing vine water status (VWS) as the major factor of the terroir effect. It was hypothesized that consistent water status zones could be identified within vineyard sites, and, that differences in vine performance, fruit composition and wine sensory attributes could be related to VWS. To test this hypothesis, ten commercial Riesling vineyards representative of each Vintners Quality Alliance sub-appellation were selected. Vineyards were delineated using global positioning systems and 75 to 80 sentinel vines per vineyard were geo-referenced for data collection. During the 2005 to 2007 growing seasons, VWS measurements [midday leaf water potential ('l')] were collected from a subset of these sentinel vines. Data were collected on soil texture and composition, soil moisture, vine performance (yield components, vine size) and fruit composition. These variables were mapped using global information system (GIS) software and relationships between them were elucidated. Vines were categorized into "low" and "high" water status regions within each vineyard block and replicate wines were made from each. Many geospatial patterns and relationships were spatially and temporally stable within vineyards. Leaf'l' was temporally stable within vineyards despite different weather conditions during each growing season. Generally, spatial relationships between 'l', soil moisture, vine size, berry weight and yield were stable from year to year. Leaf", impacted fruit composition in several vineyards. Through sorting tasks and multidimensional scaling, wines of similar VWS had similar sensory properties. Descriptive analysis further indicated that VWS impacted wine sensory profiles, with similar attributes being different for wines from different water status zones. Vineyard designation had an effect on wine profiles, with certain sensory and chemical attributes being associated from different subappellations. However, wines were generally grouped in terms of their regional designation ('Lakeshore', 'Bench', 'Plains') within the Niagara Peninsula. Through multivariate analyses, specific sensory attributes, viticulture and chemical variables were associated with wines of different VWS. Vine water status was a major contributor to the terroir effect, as it had a major impact on vine size, berry weight and wine sensory characteristics.
    • Demolishing the Competition: The Association between Competitive Video Game Play and Aggression among Adolescents and Young Adults

      Adachi, Paul; Department of Psychology
      The link between video game play and aggression is an important issue as video games The link between video game play and aggression is an important issue as video games are the fastest growing form of entertainment in the world. Past research on this association has been focused primarily on the link between video game violence and aggression; however, this research has confounded the effect of video game violence versus competition on aggression. The main goal of the current dissertation, therefore, was to examine the short- and long-term associations between competitive video game play and aggression. In addition, the longitudinal work on this association to date has been limited to adolescent samples, but not young adults. Thus, the second goal of the dissertation research was to investigate whether video game play predicts aggression in the long-term among young adults in addition to adolescents. To address these goals, three studies were conducted. Study 1 consisted of a series of experiments examining the short-term effect of video game violence versus competition on aggression. Study 2 examined the long-term association between competitive video game play and aggression among adolescents, and Study 3 examined this long-term link among young adults, in addition to adolescents. Taken together, the results of the three dissertation studies converged to suggest that video game competition, rather than violence, may be a stronger predictor of aggression in both the short- and long-term. Overall, the current research represents an important advance in our understanding of the association between video game play and aggression, and leads to a new direction in the video game and aggression literature. are the fastest growing form of entertainment in the world. Past research on this association has been focused primarily on the link between video game violence and aggression; however, this research has confounded the effect of video game violence versus competition on aggression. The main goal of the current dissertation, therefore, was to examine the short- and long-term associations between competitive video game play and aggression. In addition, the longitudinal work on this association to date has been limited to adolescent samples, but not young adults. Thus, the second goal of the dissertation research was to investigate whether video game play predicts aggression in the long-term among young adults in addition to adolescents. To address these goals, three studies were conducted. Study 1 consisted of a series of experiments examining the short-term effect of video game violence versus competition on aggression. Study 2 examined the long-term association between competitive video game play and aggression among adolescents, and Study 3 examined this long-term link among young adults, in addition to adolescents. Taken together, the results of the three dissertation studies converged to suggest that video game competition, rather than violence, may be a stronger predictor of aggression in both the short- and long-term. Overall, the current research represents an important advance in our understanding of the association between video game play and aggression, and leads to a new direction in the video game and aggression literature.
    • Design of Redox-active Ligands: In Pursuit of Stable Radicals, their Complexes, and Assembly of Paramagnetic Coordination Clusters.

      Bonanno, Nico Matteo; Department of Chemistry
      This thesis describes the design, synthesis, properties, and coordination chemistry of redoxactive ligands. This thesis also explores new ways of expanding our ligand systems, in order to improve their binding capacities. We accomplished this by utilizing familiar redox-active moieties and structures to those published previously in our group, but with enhanced topological capacities and predictable structural outcomes. Chapter 1 begins with a general outline of the fundamental principles that govern organic radicals including; their reactivity, their properties and applications, and how these can be applied to the design of ligands for polynuclear assembly. Chapter 2 starts with a brief overview of arylazo ligands and the synthesis of a new hydrazone substituted phenalenol ligand (2.1). In the following section (2.2) we use this ligand to produce homoleptic ligand mixed-valence complexes featuring trivalent cobalt and iron metals. The chapter is concluded (2.3) with the synthesis of a new ditopic aryl-azo ligand and its cobalt coordination chemistry involving a neutral tetra-radical/tetra-nuclear molecular grid featuring valence tautomerism. Chapter 3 begins with the design and synthesis of a new ditopic diamino phenol ligand, which was found to oxidize to a neutral stable phenoxyl radical (3.1-3.2). The solution properties, which include reversible pi-dimerization of this stable radical are also described (3.3), and later the substitution chemistry of this new ligand is explored (3.4). In chapter 4, we describe the coordination chemistry of this new ditopic aminophenol ligand, which includes assembly into several coordination clusters involving copper (4.2), iron (4.3), nickel (4.4), and zinc (4.5). These coordination clusters feature the ligand in a variety of oxidation states; including rare examples of dianion “aminyl” radical clusters. In chapter 5, we begin with a description of a new synthetic derivative which can be used for the construction of larger tetratopic or asymmetric diamino phenol ligands. In 5.2 we describe the synthesis of a tetratopic aminophenol ligand along with its reactivity and aerial oxidation to a tri-phenoxyl radical. In 5.3, we conclude the thesis with the use of an asymmetric diamino phenol ligand and it’s Cu(II/III) coordination chemistry, which displayed unique reactivity with molecular oxygen.
    • Design, development and assessment of the Java Intelligent Tutoring System

      Sykes, Edward R.; Department of Graduate and Undergraduate Studies in Education (Brock University, 2006-05-28)
      The "Java Intelligent Tutoring System" (JITS) research project focused on designing, constructing, and determining the effectiveness of an Intelligent Tutoring System for beginner Java programming students at the postsecondary level. The participants in this research were students in the School of Applied Computing and Engineering Sciences at Sheridan College. This research involved consistently gathering input from students and instructors using JITS as it developed. The cyclic process involving designing, developing, testing, and refinement was used for the construction of JITS to ensure that it adequately meets the needs of students and instructors. The second objective in this dissertation determined the effectiveness of learning within this environment. The main findings indicate that JITS is a richly interactive ITS that engages students on Java programming problems. JITS is equipped with a sophisticated personalized feedback mechanism that models and supports each student in his/her learning style. The assessment component involved 2 main quantitative experiments to determine the effectiveness of JITS in terms of student performance. In both experiments it was determined that a statistically significant difference was achieved between the control group and the experimental group (i.e., JITS group). The main effect for Test (i.e., pre- and postiest), F( l , 35) == 119.43,p < .001, was qualified by a Test by Group interaction, F( l , 35) == 4.98,p < .05, and a Test by Time interaction, F( l , 35) == 43.82, p < .001. Similar findings were found for the second experiment; Test by Group interaction revealed F( 1 , 92) == 5.36, p < .025. In both experiments the JITS groups outperformed the corresponding control groups at posttest.
    • Designing, Testing, and Implementing BIAS (Body Image Awareness Seminars): A Positive Body Image Program

      Bailey, Kaytlin Alysse; Applied Health Sciences Program
      Dissatisfaction with the body is prevalent in North America and body image researchers have called this phenomenon a norm, suggesting it is abnormal for people to love their bodies. Positive body image programs are needed now more than ever but currently they are scarce, and this is especially true for individuals outside adolescent and university student populations. This dissertation describes the design, testing, and implementation of a new positive body image program called BIAS (Body Image Awareness Seminars). This program is unique in three ways: 1) it was created by working with participants using action research, 2) it is applicable to a diversity of people including older adults and people with physical disabilities, and 3) it was informed by positive body image research. In study 1, initial interviews and focus group meetings revealed a potential knowledge gap in understanding body image between body image researchers and the non-academic community. Participants described a need to understand body image better in order to improve their body image experiences. This study led to the conclusion that psychoeducation is an important component of a positive body image program which significantly informed the design of BIAS. Study 2 describes the creation of BIAS using action research. Very few body image programs have been designed using participatory methodologies. Instead, most body image researchers create and implement body image interventions without any participant feedback. Study 2 highlights both the advantages and disadvantages of using action research in the design, testing, and implementation of the BIAS program. Study 3 is an evaluation of the effectiveness of BIAS. Using mixed methods, qualitative and quantitative data were analyzed and both concordance and discordance of results were reported. Participants’ body image was found to significantly improve and this improvement was sustained 6-weeks later. Additional findings include participants experiencing self-compassion, greater knowledge about body image, and becoming positive body image advocates. Study contributions to both the body image and mixed methods literature are discussed.
    • Determinants and Consequences of Dehumanization: An Interspecies Model of Prejudice

      Costello, Kimberly; Department of Psychology (Brock University, 2013-01-14)
      Dehumanizing ideologies that explicitly liken other humans to “inferior” animals can have negative consequences for intergroup attitudes and relations. Surprisingly, very little is known about the causes of dehumanization, and essentially no research has examined strategies for reducing dehumanizing tendencies. The Interspecies Model of Prejudice specifies that animalistic dehumanization may be rooted in basic hierarchical beliefs regarding human superiority over animals. This theoretical reasoning suggests that narrowing the human-animal divide should also reduce dehumanization. The purpose of the present dissertation, therefore, was to gain a more complete understanding of the predictors of and solutions to dehumanization by examining the Interspecies Model of Prejudice, first from a layperson’s perspective and then among young children. In Study 1, laypeople strongly rejected the human-animal divide as a probable cause of, or solution to, dehumanization, despite evidence that their own personal beliefs in the human-animal divide positively predicted their dehumanization (and prejudice) scores. From Study 1, it was concluded that the human-animal divide, despite being a robust empirical predictor of dehumanization, is largely unrecognized as a probable cause of, or solution to, dehumanization by non-experts in the psychology of prejudice. Studies 2 and 3 explored the expression of dehumanization, as well as the Interspecies Model of Prejudice, among children ages six to ten years (Studies 2 and 3) and parents (Study 3). Across both studies, White children showed evidence of racial dehumanization by attributing a Black child target fewer “uniquely human” characteristics than the White child target, representing the first systematic evidence of racial dehumanization among children. In Study 3, path analyses supported the Interspecies Model of Prejudice among children. Specifically, children’s beliefs in the human-animal divide predicted greater racial prejudice, an effect explained by heightened racial dehumanization. Moreover, parents’ Social Dominance Orientation (preference for social hierarchy and inequality) positively predicted children’s human-animal divide beliefs. Critically, these effects remained significant even after controlling for established predictors of child-prejudice (i.e., parent prejudice, authoritarian parenting, and social-cognitive skills) and relevant child demographics (i.e., age and sex). Similar patterns emerged among parent participants, further supporting the Interspecies Model of Prejudice. Encouragingly, children reported narrower human-animal divide perceptions after being exposed to an experimental prime (versus control) that highlighted the similarities among humans and animals. Together the three studies reported in this dissertation offer important and novel contributions to the dehumanization and prejudice literature. Not only did we find the first systematic evidence of racial dehumanization among children, we established the human-animal divide as a meaningful dehumanization precursor. Moreover, empirical support was obtained for the Interspecies Model of Prejudice among diverse samples including university students (Study 1), children (Studies 2 and 3), and adult-aged samples (Study 3). Importantly, each study also highlights the promising social implication of targeting the human-animal divide in interventions to reduce dehumanization and other prejudicial processes.
    • Development of a bacteriophage-based biopesticide for fire blight

      Lehman, Susan M.; Department of Biological Studies (Brock University, 2007-05-28)
      Fire blight is an economically important disease of apples and pears that is caused by the bacterium Erwinia amylovora. Control of the disease depends on limiting primaly blosson1 infection in the spring, and rapidly removing infected tissue. The possibility of using phages to control E.amylovora populations has been suggested, but previous studies have. failed to show high treatment efficacies. This work describes the development of a phage-based biopesticide that controls E. amylovora populations under field conditions, and significantly reduces the incidence of fire blight. This work reports the first use ofPantoea agglomerans, a non-pathogenic relative ofE. amylovora, as a carrier for E. amylovora.phages. Its role is to support a replicating population of these phages on blossom surfaces during the period when the flowers are most susceptible to infection. Seven phages and one carrier isolate were selected for field trials from existing collections of 56 E. amylovora phages and 249 epiphytic orchard bacteria. Selection of the . /' phages and carrier was based on characteristics relevant to the production and field perfonnance of a biopesticide: host range, genetic diversity, growth under the conditions of large-scale production, and the ability to prevent E. amylovora from infecting pear blossoms. In planta assays showed that both the phages and the carrier make significant contributions to reducirig the development of fire blight symptoms in pear blossoms. Field-scale phage production and purification methods were developed based on the growth characteristics of the phages and bacteria in liquid culture, and on the survival of phages in various liquid media. Six of twelve phage-carrier biopesticide treatments caused statistically signiflcant reductions in disease incidence during orchard trials. Multiplex real-time PCR was used to simultaneously monitor the phage, carrier, and pathogen populations over the course of selected treatments. In all cases. the observed population dynamics of the biocontrol agents and the pathogen were consistent with the success or failure of each treatment to control disease incidence. In treatments exhibiting a significantly reduced incidel1ce of fire blight, the average blossom population ofE.amylovora had been reduced to pre-experiment epiphytic levels. In successful treatments the phages grew on the P. agglomerans carrier for 2 to 3 d after treatment application. The phages then grew preferentially on the pathogen, once it was introduced into this blossom ecosystem. The efficacy of the successful phage-based treatnlents was statistically similar to that of streptomycin, which is the most effective bactericide currently available for fire blight prevention. The in planta behaviour ofE. amylovora was compared to that ofErwinia pyrifoliae, a closely related species that causes fire blight-like synlptoms on pears in southeast Asia. Duplex real-time PCR was used to monitor the population dynamics of both species on single blossonls. E. amylovora exhibited a greater competitive fitness on Bartlett pear blossoms than E. pyrifoliae. The genome ofErwinia phage <l>Ea21-4 was sequenced and annotated. Most of the 8-4.7 kB genome is substantially different from previously described sequences, though some regions are notably similar to Salmonella phage Felix 01 . Putative functions were assigned to approximately 30% of the predicted open reading frames based on amino acid sequence comparisons and N-terminal sequencing of structural proteins.
    • Developmental and gonadal regulation of hypothalamic-pituitary-adrenal axis function in adolescent and adult rats

      Green, Matthew; Department of Psychology
      The hypothalamic-pituitary-adrenal (HPA) axis regulates the release of stress hormones and its function is dependent on various factors including prior exposure to stressors, circulating gonadal hormones, and developmental status. The overarching goal of this thesis was to uncover the potential mechanisms mediating developmental changes in HPA function and its regulation by gonadal hormones during adolescence and early adulthood. In Chapter 2, I found that pre-pubertal (postnatal day [P]35) and post-pubertal (P45) adolescents responded to an acute stressor with greater release of corticosterone (the main stress hormone in rodents) compared with adults (P75). To determine whether differences in corticosterone release were related to ongoing maturation of HPA feedback, I investigated glucocorticoid receptor (GR) activity and mRNA expression of receptors (Nr3c1, Nr3c2) and their co-chaperones (Fkbp5, Fkbp4, Bag1) in the hippocampus. I provide novel evidence that P35 males have more, not less, GR translocation from the cytosol to the nucleus in response to stress compared with P75 males. Gene expression remained relatively stable across development, except for Fkbp4, which codes for a pro-translocation protein and was up-regulated in P35 males relative to expression in P75 males. Thus, there are developmental shifts in the hormonal response to stress that are likely unrelated to GR activity in the hippocampus. In Chapter 3, I investigated whether differences in HPA function are explained by gonadal status; in adult males, testosterone reduces HPA function. Age-related differences in corticosterone release persisted when orchiectomized (OCX) males at each age were administered testosterone. Moreover, the effect of testosterone changed across the adolescent period; relative to those that got blank implants, testosterone had no effect on post-stress concentrations of corticosterone at P35, increased concentrations at P45, and tended to reduce concentrations at P75. Testosterone reduced expression of AVP in the PVN at all ages, but did not affect Fos (a marker of neuronal activation) expression. I hypothesized that the age-specific effects of testosterone on corticosterone were related to differential conversion to metabolites (e.g., estradiol), which I tested using androgen receptor (AR) and estrogen receptor (ER) antagonists (flutamide and tamoxifen, respectively) in the presence of testosterone or dihydrotestosterone (DHT). Testosterone produced a similar, albeit non-significant, age-specific pattern of effects on corticosterone as described above, and I found little evidence for effects of receptor antagonists. Androgens reduced post-stress concentrations of progesterone in all age groups, and flutamide prevented the effect. Together, this study provides evidence for developmental shifts in stress responses and their regulation by gonadal hormones. In Chapter 4, I examined the influence of estradiol on HPA function in adult female rats as a first step toward understanding developmental shifts. Ovariectomy (OVX) reduced post-stress concentrations of corticosterone compared with sham OVX and OVX females given estradiol alone or in combination with progesterone. I also found that OVX females had greater cytosolic expression of GR, possibly increasing sensitivity to corticosterone. In a second experiment, I found that progesterone partially mitigated the effect of estradiol on corticosterone release and that gene expression of stress hormone receptors (Nr3c1, Nr3c2), their co-chaperones (Fkbp5, Fkbp4, Bag1), and a co-activator (Src-1) did not change as a function of ovarian hormones. Together, these studies build on previous research investigating developmental and gonadal regulation of HPA activity and provide novel findings regarding potential mechanisms underlying their actions.
    • Developmental differences in locomotor responsiveness to amphetamine in rats

      Mathews, Iva; Department of Psychology (Brock University, 2011-10-14)
      The developmental remodelling of motivational systems that underlie drug dependence and addiction may account for the greater frequency and severity of drug abuse in adolescence compared to adulthood. Recent advances in animal models have begun to identify the morphological and the molecular factors that are being remodelled, but little is known about the culmination of these factors in altered sensitivity to psycho stimulant drugs, like amphetamine, in adolescence. Amphetamine induces potent locomotor activating effects in rodents through increased dopamine release in the mesocorticolimbic dopamine system, which makes locomotor activity a useful behavioural marker of age differences in amphetamine sensitivity. The aim of the thesis was to investigate the neural basis for age differences in amphetamine sensitivity with a focus on the nucleus accumbens and the medial prefrontal cortex, which initiate and regulate amphetamine-induced locomotor activity, respectively. In study 1, I found pre- and post- pubertal adolescent rats to be less active (i.e., hypoactive) than adults to a first injection of 0.5, but not of 1.5, mg/kg of intraperitonealy (i.p.) administered amphetamine. Although initially hypoactive, only adolescent rats exhibited an increase in activity to a second injection of amphetamine given 24 h later, indicating that adolescents may be more sensitive to the rapid changes in amphetamineinduced plasticity than adults. Given that the locomotor activating effects of amphetamine are initiated in the nucleus accumbens, age differences in response to direct injections of amphetamine into this brain region were investigated in study 2. In contrast to i.p. injections, adolescents were more active than adults when amphetamine was given directly into the nucleus accumbens, indicating that hypo activity may be attributed to the development of regulatory regions outside of the accumbens. The medial prefrontal cortex (mPFC) is a key regulator of the locomotor activating effects of amphetamine that undergoes extensive remodelling in adolescence. In study 3, I found that an i.p. injection of 1.5, and not of 0.5, mg/kg of amphetamine resulted in a high expression of c-fos, a marker of neural activation, in the pre limbic mPFC only in pre-pubertal adolescent rats. This finding suggests that the ability of adolescent rats to overcome hypo activity at the 1.5 mg/kg dose may involve greater activation of the prelimbic mPFC compared to adulthood. In support of this hypothesis, I found that pharmacological inhibition of prelimbic D 1 dopamine receptors disrupted the locomotor activating effects of the 1.5 mg/kg dose of amphetamine to a greater extent in adolescent than in adult rats. In addition, the stimulation of prelimbic D 1 dopamine receptors potentiated locomotor activity at the 0.5 mg/kg dose of amphetamine only in adolescent rats, indicating that the prelimbic D1 dopamine receptors are involved in overcoming locomotor hypoactivity during adolescence. Given my finding that the locomotor activating effects of amphetamine rely on slightly different mechanisms in adolescence than in adulthood, study 4 was designed to determine whether the lasting consequences of drug use would also differ with age. A short period of pre-treatment with 0.5 mg/kg of amphetamine in adolescence, but not in adulthood, resulted in heightened sensitivity to an injection of amphetamine given 30 days after the start of the procedure, when adolescent rats had reached adulthood. The finding of an age-specific increase in amphetamine sensitivity is consistent with evidence for increased risk for addiction when drug use is initiated in adolescence compared to adulthood in people (Merline et aI., 2002), and with the hypothesis that adolescence is a sensitive period of development.
    • A DFT Guided/Experimental Approach to Asymmetric Allylation and Phase-Transfer Catalysis

      Mirabdolbaghi, Roya; Department of Chemistry (Brock University, 2014-09-10)
      The Dudding group is interested in the application of Density Functional Theory (DFT) in developing asymmetric methodologies, and thus the focus of this dissertation will be on the integration of these approaches. Several interrelated subsets of computer aided design and implementation in catalysis have been addressed during the course of these studies. The first of the aims rested upon the advancement of methodologies for the synthesis of biological active C(1)-chiral 3-methylene-indan-1-ols, which in practice lead to the use of a sequential asymmetric Yamamoto-Sakurai-Hosomi allylation/Mizoroki Heck reaction sequence. An important aspect of this work was the utilization of ortho-substituted arylaldehyde reagents which are known to be a problematic class of substrates for existing asymmetric allylation approaches. The second phase of my research program lead to the further development of asymmetric allylation methods using o-arylaldehyde substrates for synthesis of chiral C(3)-substituted phthalides. Apart from the de novo design of these chemistries in silico, which notably utilized water-tolerant, inexpensive, and relatively environmental benign indium metal, this work represented the first computational study of a stereoselective indium-mediated process. Following from these discoveries was the advent of a related, yet catalytic, Ag(I)-catalyzed approach for preparing C(3)-substituted phthalides that from a practical standpoint was complementary in many ways. Not only did this new methodology build upon my earlier work with the integrated (experimental/computational) use of the Ag(I)-catalyzed asymmetric methods in synthesis, it provided fundamental insight arrived at through DFT calculations, regarding the Yamamoto-Sakurai-Hosomi allylation. The development of ligands for unprecedented asymmetric Lewis base catalysis, especially asymmetric allylations using silver and indium metals, followed as a natural extension from these earlier discoveries. To this end, forthcoming as well was the advancement of a family of disubstituted (N-cyclopropenium guanidine/N-imidazoliumyl substituted cyclopropenylimine) nitrogen adducts that has provided fundamental insight into chemical bonding and offered an unprecedented class of phase transfer catalysts (PTC) having far-reaching potential. Salient features of these disubstituted nitrogen species is unprecedented finding of a cyclopropenium based C-H•••πaryl interaction, as well, the presence of a highly dissociated anion projected them to serve as a catalyst promoting fluorination reactions. Attracted by the timely development of these disubstituted nitrogen adducts my last studies as a PhD scholar has addressed the utility of one of the synthesized disubstituted nitrogen adducts as a valuable catalyst for benzylation of the Schiff base N-diphenyl methylene glycine ethyl ester. Additionally, the catalyst was applied for benzylic fluorination, emerging from this exploration was successful fluorination of benzyl bromide and its derivatives in high yields. A notable feature of this protocol is column-free purification of the product and recovery of the catalyst to use in a further reaction sequence.
    • Diastereoselective Synthesis of Planar Chiral N-Substituted Ferrocenes Derived from Epimeric Imidazolones and their Application to Asymmetric Hydrogenation of Quinolines

      John, Joshni; Department of Chemistry (Brock University, 2015-03-02)
      This thesis describes the synthesis and use of an N-substituted ferrocene bearing a proline-derived chiral directing group and diastereoselective lithiation-electrophile quench of the pro-Sp hydrogen of the ferrocene to give planar chiral products in >95:5 dr. The auxiliary group is found to be stable to lithium bases of types RLi and R2NLi giving the same diastereoselectivity. The anti- epimer of the previously mentioned syn auxiliary induces lithiation of pro Rp rather than pro Sp hydrogen in >95:5 dr. Upon electrophile quench and elimination, the enantiomer of the syn-derived planar chiral imidazolone is obtained. Hence, this method provides a practical way to prepare planar chiral enantiomers in this series without the use of a more expensive D-proline derived starting material. The syn and anti epimers have β, γ-stereogenic centers and the origin of stereoselectivity in lithiation appears to be driven by the conformational bias exerted by the β-silyloxy moiety in each chiral auxiliary. In the thesis, this conclusion is supported using insensitivity of lithiation selectivity to the bulkiness of the base, comparison of enantiomers, deuteration experiments, nOe difference studies and computational modeling of the ground states and lithiation transition states for both substrates. The products are then converted to ligand precursors to make iridium and rhodium complexes. Among them, one of the cationic iridium complex is found to be effective in the asymmetric hydrogenation of 2-substituted quinolines with enantioselectivities up to 80% at pressures as low as 5 atm.
    • Discovery of a novel cytochrome P450, (+)-vincadifformine 19-hydroxylase (V19H), distinguishes separate branch pathways forming aspidosperma-type monoterpenoid indole alkaloids in Catharanthus roseus roots

      Williams, Danielle; Centre for Biotechnology
      Investigation of Catharanthus roseus monoterpenoid indole alkaloid (MIA) biosynthesis and accumulation has been important in elucidating the formation of the antineoplastic drugs, vinblastine and vincristine. These pharmaceuticals are formed by the condensation of the MIAs catharanthine and vindoline, which accumulate in C. roseus leaves. While we had completed and expressed the seven-step pathway from the aspidosperma-type MIA (-)-tabersonine to vindoline in yeast, little was known about the reactions involved in the metabolism of aspidosperma-type MIAs in roots. C. roseus roots convert (-)-tabersonine to lochnericine, the precursor for a major root alkaloid hörhammericine, and the reasons for the production of different aspidosperma MIAs in above and below ground plant organs is unknown. The molecular and biochemical characterization of minovincinine-19-O-acetyltransferase (MAT), tabersonine-19-hydroxylase (T19H), tabersonine-6,7-epoxidase (TEX1/2), and tabersonine 19-O-acetyltransferase (TAT) suggests that biosynthesis of hörhammericine and its derivative, 19-O-acetyl-hörhammericine, involves an ordered series of reactions. Bioinformatic analysis led to the identification of a root specific homolog of tabersonine-3-oxygenase (T3O), a cytochrome P450 (P450) involved in the formation of tabersonine 2,3-epoxides, as part of the vindoline pathway in leaves. Characterization of the T3O-homolog revealed that it converts (+)-vincadifformine to its 19-hydroxyderivative, (+)-minovincinine, and it was named (+)-vincadifformine 19-hydroxylase (V19H). V19H did not accept (-)-tabersonine or tabersonine-derived (-)-vincadifformine. T19H, another root-specific P450, hydroxylates (-)-tabersonine and its derivatives, including (-)-vincadifformine, to their respective 19-hydroxyderivatives, but does not accept (+)-vincadifformine. TAT will only acetylate the (-)-tabersonine derivatives, whereas MAT only turns over the (+)-vincadifformine derivative to form (+)-echitovenine. This shows that two distinct aspidosperma pathways exist in C. roseus since endogenous vincadifformine must be the (+)-enantiomer instead of the tabersonine derived (-)-vincadifformine. Modelling studies revealed that V19H activity is competitively inhibited by (-)-vincadifformine, suggesting that the (-)-aspidosperma backbone could still be incorporated into the binding site, albeit without hydroxylation. Models of T3O and T19H were generated to compare their binding pockets with that of V19H, and there were four conserved residues in T3O and T19H that were missing in V19H. Using site-directed mutagenesis (SDM) of V19H at those four residues, the binding pocket became more T3O-like, and V19H gained T3O-like activity without the loss of V19H activity.
    • Dispositional Forgiveness and Health in Romantic Relationships: An Exploration of Sex Differences, Actor Effects, and Partner Effects

      Green, Michelle; Department of Psychology (Brock University, 2012-07-30)
      The individual and dyadic associations between dispositional forgiveness of self, others, and situations and mental and physical health in individuals involved in romantic relationships were examined. Sex differences in the relationship between dispositional forgiveness and health were examined. Sex differences in the dyadic relationship between forgiveness and health were also examined. The dispositional forgiveness scores of 297 partners involved in a romantic relationship were used to predict their own as well as their partners' physical and mental health. Both members of the relationship separately completed an Internet-based questionnaire assessing personality traits, relationship variables, and physical and mental health. The couple was provided with monetary compensation. Analyses revealed that women's dispositional forgiveness of self, others, and situations were positively associated with their own physical and mental health. Similarly, men's dispositional forgiveness of self, others, and situations were positively associated with their own mental and physical health. At the individual level, there were no sex differences in the relationship between dispositional forgiveness and health, nor were there sex differences in men and women's reports of dispositional forgiveness. Analyses revealed that men's forgiveness of others and situations were positively associated with their female partners' mental health. There were no partner effects for women or for physical health. The implications of these results for research in the forgiveness-health literature and research on forgiveness in romantic relationships were discussed as were directions for future research.
    • Distinct forms of depression and somatization following head injury: A neuropsychological framework and exploratory treatment paradigm for somatic symptoms and executive dysfunction following mild head injury

      Robb, Sean; Department of Psychology
      Psychiatric symptoms following traumatic brain injury (TBI) pose a significant barrier to neurorehabilitation and impact survivor’s life satisfaction following injury. Depressive and somatization symptoms are common clinical presentations postinjury; however, due to the paucity of etiological models to explain these symptoms, treatment approaches are predominately “borrowed” from non-neurally compromised populations with similar clinical presentations. The orbitofrontal cortex (OFC) is particularly vulnerable in TBI, and serves to modulate autonomic arousal states. Varying severities of TBI have been linked to autonomic underarousal as measured by electrodermal activation (EDA). In a series of studies examining persons with mild head injury (MHI), the phenomenological presentation of depressive and somatization symptoms was examined in persons with and without MHI, and the relationship between these symptoms and autonomic underarousal was explored. In study one, MHI were found to be autonomically underaroused, reporting more somatic depressive symptoms relative to their no-MHI cohort, and the relationship between their injury severity and the intensity of their somatic depressive complaints was completely mediated by underarousal. Investigating somatization revealed MHI status as a moderator of the relationship between somatization and post-concussive symptoms, with MHI having a stronger positive association. Autonomic underarousal was found to be a complete mediator between the relationship between injury severity and their somatization symptoms. In study two, we experimentally manipulated autonomic arousal through brief cardiovascular exercise and evaluated whether this concomitantly improved somatic-based psychiatric complaints and neurocognitive functioning in persons with MHI. Study two replicated the somatic depressive mediation model of study one, and revealed that the experimental manipulation was effective in increasing autonomic arousal, and improving somatic-psychiatric complaints and neurocognitive status. Collectively, these findings suggest that depressive and somatization symptoms postinjury are phenomenologically and etiologically different in persons with a history of head injury relative to their non-neurally compromised counterpart, and autonomic underarousal and OFC dysfunction is a strong candidate for continued investigation as an etiological model for psychiatric symptoms postinjury. Reversal of underarousal may serve as an important therapeutic goal. Lastly, we propose the term “somatic underarousal” to describe this symptomatology as a means to avoid confusion with the historical roots of the term somatization.
    • A domain-general perspective on medial frontal brain activity during performance monitoring

      van Noordt, Stefon; Department of Psychology
      Activity of the medial frontal cortex (MFC) has been implicated in attention regulation and performance monitoring. The MFC is thought to generate several event-related potential (ERPs) components, known as medial frontal negativities (MFNs), that are elicited when a behavioural response becomes difficult to control (e.g., following an error or shifting from a frequently executed response). The functional significance of MFNs has traditionally been interpreted in the context of the paradigm used to elicit a specific response, such as errors. In a series of studies, we consider the functional similarity of multiple MFC brain responses by designing novel performance monitoring tasks and exploiting advanced methods for electroencephalography (EEG) signal processing and robust estimation statistics for hypothesis testing. In study 1, we designed a response cueing task and used Independent Component Analysis (ICA) to show that the latent factors describing a MFN to stimuli that cued the potential need to inhibit a response on upcoming trials also accounted for medial frontal brain responses that occurred when individuals made a mistake or inhibited an incorrect response. It was also found that increases in theta occurred to each of these task events, and that the effects were evident at the group level and in single cases. In study 2, we replicated our method of classifying MFC activity to cues in our response task and showed again, using additional tasks, that error commission, response inhibition, and, to a lesser extent, the processing of performance feedback all elicited similar changes across MFNs and theta power. In the final study, we converted our response cueing paradigm into a saccade cueing task in order to examine the oscillatory dynamics of response preparation. We found that, compared to easy pro-saccades, successfully preparing a difficult anti-saccadic response was characterized by an increase in MFC theta and the suppression of posterior alpha power prior to executing the eye movement. These findings align with a large body of literature on performance monitoring and ERPs, and indicate that MFNs, along with their signature in theta power, reflects the general process of controlling attention and adapting behaviour without the need to induce error commission, the inhibition of responses, or the presentation of negative feedback.
    • Dreams of the Deceased: Who Has Them and Why?

      Black, Joshua; Department of Psychology
      The limited research on dreams of the deceased is a cause for concern for those working with bereaved persons. This research addressed four questions: 1. Why do some bereaved individuals dream of the deceased while others do not? 2. Why are some dreams of the deceased a positive experience, while others are negative? 3. Are dreams of the deceased a form of continuing bond? 4. Are continuing bonds helpful for grief recovery? Four studies were conducted. In one, participants were 268 U.S. residents who had a romantic partner or spouse die in the prior 12 to 24 months. The second study had 199 U.S. residents whose dog or cat had died in the prior six months. The third study had 226 U.S. residents who experienced a stillbirth or miscarriage in the prior year. The fourth study had 218 participants, mostly U.S. residents, who had a romantic partner or spouse die in the prior 6 to 24 months. Participants completed all questionnaires online. Study 1 and 2 focused primarily on the issue of predicting the frequency of dreams of the deceased and found that frequency of general dream recall (all dreams, not just dreams of the deceased) was the primary predictor. In addition, grief intensity, openness to experience, and attachment security all showed indirect effects. All four studies, but especially studies 2 through 4, addressed the questions about the quality of dream experience, the relation of dreams of the deceased to continuing bonds, and the adaptiveness of continuing bonds. In general the findings from all four studies, but especially study 4, support the idea that there are multiple types of continuing bonds with differing impacts on grief recovery, and there are differing forms of dreams of the deceased, not all of which represent continuing bonds.
    • Dynamic DNA Nanotechnology for Probing Single Nucleotide Variants and DNA Modifications

      Wang, Guan; Department of Chemistry
      In the last decades, various DNA hybridization probes have been developed that attempt to conquer the challenge of single-nucleotide-variants (SNVs) detection. Even though a powerful toolbox including the toehold-exchange reaction, the dynamic ‘sink’ design, and the polymerase chain reaction (PCR) has been built, it still faces practical problems. For example, the natural DNA is usually in double-stranded form whereas most hybridization probes aim for single-stranded targets; the concentration of extracted DNA samples is totally unknown thus may lay outside the optimal design of probes/primers. To achieve ultra-high sensitivity and specificity, expensive and sophisticated machines such as digital droplet PCR and next-generation-sequencing may be inapplicable in rural areas. Therefore, the quantitative PCR method is still the gold standard for clinical tests. Thus motivated, my PhD career was mainly focused on the fundamental understanding of the challenges in SNVs discrimination and developing robust, versatile, and user-friendly probes/strategies. In this thesis, Chapter 1 provides a general introduction of dynamic DNA nanotechnology and its representative applications in discriminating SNVs. Chapter 2 to 4 describe three completed projects that aim to understand the thermodynamic and kinetic properties of strand displacement reactions and to circumvent the challenges of discriminating SNVs through finely tuned probes/assays.