• 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.
    • Autonomic Cardiovascular Control in Children and Adolescents

      Chirico, Daniele; Applied Health Sciences Program
      This thesis investigated the impact of pubertal maturation and sex on cardiovagal baroreflex sensitivity (BRS) and arterial properties of the common carotid artery (CCA), and the relationship between CCA arterial properties and BRS. This thesis also investigated the effect of orthostatic stress on arterial properties of the CCA and carotid sinus (CS), as well as their impact on BRS in response to orthostatic stress. Children and adolescents between the ages of 8-18 years were examined. To assess pubertal maturation participants were organized into five pubertal groups based on the criteria of Tanner. BRS was assessed by transfer function analysis in the low frequency range (0.05 – 0.15Hz). Pulse pressure (PP) was measured at the CCA (PPCCA) and CS (PPCS) using applanation tonometry, and at the finger (PPFinger) using photoplethysmography. Ultrasound sonography and applanation tonometry were used to determine the distensibility coefficient (DC) at the CCA (DCCCA) and CS (DCCS). A moderate posture stimulus was implemented by passively moving participants into a 50° seated-recumbent (SR) position. The results demonstrated a sex-by-maturation interaction on BRS (p= 0.019). BRS decreased from early- to post-puberty in males (p<0.01), and remained unchanged in females. Females demonstrated greater BRS compared to males post-puberty (p<0.05). CCA distensibility was not affected by sex or maturation and was not related to BRS. PPCS was greater than PPCCA (p<0.001), while PPFinger was greater than both PPCCA (p<0.001) and PPCS (p<0.001). In response to SR, the relative change in PPFinger was significantly different than the relative change in PPCCA (p<0.001) and PPCS (p<0.001), while the relative change between PPCCA and PPCS were not different. Finally, in response to SR there was a significant decrease in DCCS (p=0.001), but not DCCCA. The relative change in BRS in response to SR was significantly correlated to the relative change in DCCS (p=0.004), but not DCCCA. The findings demonstrated an important sex-dependent maturation effect on BRS in children and adolescents that was not explained by CCA distensibility. Also, the CS and CCA responded differently to orthostatic stress. The CS was more suitable to evaluate the effect of arterial distensibility on BRS in response to posture change.
    • Autonomy and Relatedness in Mainland Chinese Adolescents: Social or Personal? Accommodation or Distinctiveness?

      Zhao, Junru; Department of Psychology (Brock University, 2014-08-01)
      Three studies comprised the current research program, in which the major goals were to propose and validate empirically the proposed two-level (universal and culture-specific) model of both autonomy and relatedness, as well as to develop reliable and valid measures for these two constructs. In Study 1, 143 mainland Chinese adolescents were asked open-ended questions about their understanding of autonomy and relatedness in three social contexts (peer, family, school). Chinese youth’s responses captured universal and culturally distinctive forms of autonomy (personal vs. social) and relatedness (accommodation vs. distinctiveness), according to a priori criteria based on the theoretical frameworks. Also, scenarios designed to reflect culture-specific forms of autonomy and relatedness suggested their relevance to Chinese adolescents. With a second sample of 201 mainland Chinese youth, in Study 2, the obtained autonomy and relatedness descriptors were formulated into scale items. Those items were subject to refinement analyses to examine their psychometric properties and centrality to Chinese youth. The findings of Study 1 scenarios were replicated in Study 2. The primary goal of Study 3 was to test empirically the proposed two-level (universal and culture-specific) models of both autonomy and relatedness, using the measures derived from Studies 1 and 2. A third sample of 465 mainland Chinese youth completed a questionnaire booklet consisting of autonomy and relatedness scales and scenarios and achievement motivation orientations measures. A series of confirmatory factor analysis (CFA) autonomy and relatedness measurement models (first-order and second-order), as well as structural models linking culture-specific forms of autonomy and relatedness and achievement motivation orientations, were conducted. The first-order measurement models based on scale and scenario scores consistently confirmed the distinction between personal autonomy and social autonomy, and that of accommodation and distinctiveness. Although the construct validity of the two culture-specific forms of autonomy gained additional support from the structural models, the associations between the two culture-specific forms of relatedness and achievement motivation orientations were relatively weak. In general, the two-level models of autonomy and relatedness were supported in two ways: conceptual analysis of scale items and second-order measurement models. In addition, across the three studies, I explored potential contextual and sex differences in Chinese youth’s endorsement of the diverse forms of autonomy and relatedness. Overall, no substantial contextual variability or sex differences were found. The current research makes an important theoretical contribution to the field of developmental psychology in general, and autonomy and relatedness in particular, by proposing and testing empirically both universal and culture-specific parts of autonomy and relatedness. The current findings have implications for the measurement of autonomy and relatedness across social contexts, as well as for socialization and education practice.
    • “Because It Breaks Your Heart”: A Study of Transformational Learning Among Adults With Cancer

      Boyko, Susan; Department of Graduate and Undergraduate Studies in Education
      Despite provincial improvement efforts, quantitative patient satisfaction survey results for adults with cancer consistently indicate lower satisfaction with how healthcare professionals address their emotional and information, education, and communication needs. These emotional and cognitive needs greatly influence how adults perceive their care experience. More information is needed about adult cancer patients’ cognitive and emotional needs to understand how to improve their experience and satisfaction with their cancer treatment and care. Qualitative methods such as narrative inquiry have the potential to provide greater insight into adults’ personal experience. This qualitative, arts-informed narrative inquiry examined how illness narratives and arts-based artifacts can deepen understanding of the cognitive and emotional needs of a cohort of adult women with cancer. Purposeful sampling was used to select 6 adult women with cancer who had experienced diagnosis, treatment and were living with cancer. Data collection methods included semi-structured interviews and the researcher’s journal notes. Data analysis revealed additional connections between themes derived from the women’s illness narratives and their arts-based artifacts. These findings were further illustrated by creating a collective body-map. Results demonstrate how arts-based methods expand what is known about the cognitive and emotional needs of adult women with cancer and provide adult educators with direction for planning transformative education. The study discusses implications for transformational adult education practice and educational research, and offers some initial thoughts on the use of arts-based methods to foster perspective transformation. The study will be of particular interest to adult educators who are interested in promoting transformational learning for doctors, other healthcare professionals, and adults with cancer.
    • Behaviour and life history of a large carpenter bee (Xylocopa virginica) in the northern extent of its range

      Prager, Sean Michael.; Department of Biological Sciences (Brock University, 2008-05-28)
      Large carpenter bees (Hymenoptera: Apidae: Xylocopa) have traditionally been thought of as exhibiting solitary or occasionally communal colony social organization. However, studies have demonstrated more complex fonns of social behaviour in this genus. In this document, I examine elements ofbehaviour and life history in a North American species at the northern extreme of its range. Xylocopa virginica was found to be socially polymorphic with both solitary and meta-social or semi-social nests in the same population. In social nests, there is no apparent benefit from additional females which do not perfonn significant work or guarding. I found that the timing of life-history events varies between years, yet foraging effort only differed in the coldest and wettest year of2004 the study. Finally, I that male X virginica exhibit female defence polygyny, with resident and satellite males. Resident males maintain their territories through greater aggression relative to satellites.
    • Behavioural, Pharmacological, and Immunohistochemical Investigation of 50 kHz USVs as an Expression of Positive Emotional Arousal in the Long Evans Rat

      Mulvihill, Kevin; Department of Psychology
      The emission of ultrasonic vocalizations (USVs) in Rattus norvegicus is thought to effectively represent an underlying emotional state within the organism manifested at the behavioural level. The main goal of my thesis was to characterize, at multiple levels of analysis, the 50 kHz USVs of the adult rat as an overtly expressed form of positive emotional arousal. In chapter 2, I found evidence of individual differences in 50 kHz emission possibly reflective of a trait that does not merely overlap with approach motivation. The predisposition to emit 50 kHz USVs was found to provide additional information about the USV response to psychostimulant administration beyond approach motivation alone. In chapter 3, I found evidence that various social and non-social behavioural contexts appeared to exert influence on the frequency-modulation characteristics of 50 kHz USVs. My findings suggest that the highest rates of calling and frequency modulation inducible by non-pharmacological stimuli may be observed following exposure of a male rat to a naturally cycling female. Moreover, my research in chapter 3 established that despite context-specific modulation of 50 kHz USVs all such calling could be blocked by antagonism of dopamine receptors. In chapter 4, I utilized microinjections of dopamine into the shell of the nucleus accumbens to establish that dopamine is sufficient to induce 50 kHz USVs. Additionally, my findings from chapter 4 supported the observed association between frequency-modulated 50 kHz USVs and call rate typically induced by psychostimulants. In chapter 5, I used a minimal sensitization protocol with amphetamine to establish that 50 kHz USVs and measures of general ergometric activity could be dissociated. Additionally, in chapter 5 I attempted to find brain region activation patterns associated with calling. My chapter 5 findings failed to find any direct relations between immunostained brain regions and behavioural expression. However, exploratory analyses suggest possible associations between prefrontal and striatal regions may be involved in the USV behavioural response to amphetamine. In aggregate, my empirical findings are consistent with the existence of a putative subcomponent of the ascending mesolimbic dopamine system responsible for positive emotional arousal reflected by emission of 50 kHz USVs in the rat.
    • Beyond the Veil: A Case Study of Context, Culture, Curriculum, and Constructivism at Dubai Women's College

      Lovering, Mary; Department of Graduate and Undergraduate Studies in Education (Brock University, 2012-07-30)
      This case study of curriculum at Dubai Women's College (DWC) examines perceptions of international educators who designed and implemented curriculum for female Emirati higher-educational students in the UAE, and sheds light on the complex social, cultural, and religious factors affecting educational practice. Participants were faculty and supervisors, mainly foreign nationals, while students at DWC are exclusively Emirati. Theories prominent in this study are: constructivist learning theory, trans formative curriculum theory, and sociological theory. Change and empowerment theory figure prominently in this study. Findings reveal this unique group of educators understand curriculum theory as a "contextualized" construct and argue that theory and practice must be viewed through an international lens of religious, cultural, and social contexts. As well, the study explores how mandated "standards" in education-in the form of the International English Language Testing System (IEL TS) and integrated, constructivist curriculum, as taught in the Higher Diploma Year 1 program-function as dual curricular emphases in this context. The study found that tensions among these dual emphases existed and were mediated through specific strategies, including the use of authentic texts to mirror the IEL TS examination during in-class activities, and the relevance of curricular tasks.
    • Bis(dialkylamino)cyclopropeneimine Substituted Proton Sponge Derivatives: Synthesis, Theory, and Application

      Belding, Lee; Department of Chemistry
      The work presented herein describes the synthesis, as well as the experimental and theoretical investigation of hitherto unknown cyclopropenimine containing compounds, mostly within the proton sponge backbone. The properties of these molecules are discussed in the context of other proton sponge derivatives reported in the literature. The superbasicity, catalytic activity, and fluorescent nature of these cyclopropenimine derivatives are also investigated and discussed.
    • Can exergaming improve mental health of university students?

      Santos, Esther; Applied Health Sciences Program
      The academic, financial, and social pressures that emerge when adults begin university may lead them to encounter mental health challenges (American College Health Association [ACHA], 2016). In Ontario, 46.2% of university/college students have reported ‘excessive’ stress whereas 64.5% report ‘overwhelming’ anxiety (ACHA, 2016). One approach that may be useful for enhancing mental health is exergaming which uses motion-sensor technology requiring players to move their bodies to complete the videogame sessions (Huang et al., 2017). However, studies focused on the effectiveness of exergaming for improving mental health of university students are scarce in number and limited in scope. The overall purpose of this dissertation was to examine the role of exergaming in relation to mental health reported by university students. In Study 1, a synthesis of published intervention research using exergaming to change well-being – a psychological concept affiliated with mental health – reported by adults was conducted. Results from Study 1 indicated that less than 50.0% of the coded studies - using either multi- or single-group (pre-post-test) research designs - reported enhanced well-being as a function of exergaming. In Study 2, the link between the amount and intensity of exergaming behaviour per week and mental health reported by university students was evaluated. Results from Study 2 indicated that university students who reported more frequent exergaming behaviour during a typical week displayed lower anxiety and stress plus higher flourishing and vitality. In Study 3, the contributions of exergaming to mental health of university students were investigated using an experimental research design that compared exergaming against other physical activity behaviours and self-management approaches. Results from Study 3 showed that ‘exergamers’ did not present higher or lower mental health scores compared against ‘traditional’ exercisers but displayed less stress and anxiety when compared against pet therapy, as well as, higher vitality plus lower stress and anxiety compared to ‘non-exercisers’. The results from these studies make it apparent that exergaming may not offer anything ‘unique’ as a stimulus beyond more traditional modes of exercise, but it fosters mental health of university students.
    • Cardiac Autonomic Assessment and Diastolic Function in Individuals with Spinal Cord Injury

      Sharif, Hisham; Applied Health Sciences Program
      The primary purpose of this thesis was to examine the validity and reproducibility of the QT-variability index (QTVI) as a measure of cardiac autonomic function in individuals with spinal cord injury (SCI). The secondary purpose was to investigate the influence of cardiac autonomic activity and blood volume on diastolic function in individuals with SCI. Results from Study 1 showed that the QTVI increased when participants performed a cardiovascular (CV) stress maneuver, and subsequently returned to baseline after blocking sympathetic outflow via metoprolol. Moreover, while participants were resting, the QTVI increased after blocking parasympathetic activity via atropine. These results suggest that the QTVI may reflect both cardiac sympathetic and parasympathetic activity in those with incomplete SCI, depending on the autonomic state of the individual. Results from Study 2 demonstrate high day-to-day reproducibility of the QTVI in participants with SCI, regardless of injury level, and also in those with high level injuries who may have reduced cardiac sympathetic regulation. Results from Study 3 showed that indices of cardiac parasympathetic activity (HRV and QTVI) were correlated with left ventricular filling in able-bodied individuals but not in individuals with SCI, suggesting a disconnect between cardiac parasympathetic activity and diastolic function after SCI. In addition, for the able-bodied group, the cold face test (CFT) increased vagal activity which was associated with bradycardia and augmentation of diastolic filling. However, for the SCI group, the increase in vagal activity during the CFT was associated with no change in heart rate and an attenuation of diastolic function. Results from Study 4 showed that although individuals with SCI were hypovolemic, resting diastolic velocities were similar compared to the able-bodied group. This maintenance of diastolic function appeared to be attributed to the cardiac atrophy that manifests following SCI. In addition, there was no between-group difference in the diastolic response to rapid saline infusion. Findings from this dissertation suggest that the QTVI is a valid and reliable tool for non-invasively estimating cardiac autonomic regulation in individuals with SCI. In addition, although the mechanical aspect of diastolic function is preserved after SCI, atypical vagal-diastolic interactions may impair ventricular filling in this population.
    • A case study investigation of the learning needs of the Niagara grape and wine community

      Ker, Kevin Warren; Department of Graduate and Undergraduate Studies in Education (Brock University, 2010-10-26)
      The Niagara Grape and Wine Community (NGWC) is an industry that has undergone rapid change and expansion as a result of changes in governmental regulations and consumer preferences. As a result of these changes, the demands of the wine industry workforce have changed to reflect the need to implement new strategies and practices to remain viable and competitive. The influx of people into the community with little or no prior practical experience in grape growing (viticulture) or winemaking (oenology) has created a need for additional training and learning opportunities to meet workforce needs. This case study investigated the learning needs of the members of this community and how these needs are currently being met. The barriers to, and the opportunities for, members acquiring new knowledge and developing skills were also explored. Participants were those involved in all levels of the industry and sectors (viticulture, processing, and retail), and their views on needs and suggestions for programs of study were collected. Through cross analyses of sectors, areas of common and unique interest were identified as well as formats for delivery. A common fundamental component was identified by all sectors - any program must have a significant applied component or demonstration of proficiency and should utilize members as peer instructors, mentors, and collaborators to generate a larger shared collective of knowledge. Through the review of learning organizations, learning communities, communities of practices, and learning networks, the principles for the development of a Grape and Wine Learning Network to meet the learning needs of the NGWC outside of formal institutional or academic programs were developed. The roles and actions of members to make such a network successful are suggested.
    • A Case Study of Doctoral Research Assistantships: Access and Experiences of Full-Time and Part-Time Education Students

      Niemczyk, Ewelina; Department of Graduate and Undergraduate Studies in Education
      Graduate students’ development as researchers is a key objective in higher education. Research assistantships provide distinctive spaces where graduate students can be nurtured and shaped as novice researchers as they develop theoretical and methodological knowledge. However, few scholars have investigated graduate student research assistants’ experiences and the ways these experiences are influenced by institutional regulations, informal practices, and social relations. The purpose of this case-within-a-case study was to explore the research assistantship experiences of full-time and part-time doctoral students in Education at an Ontario university. I present separate subcases for full-time and part-time students, and an overarching case of research assistantships in one program at a specific period of time. The main question was how do institutional regulations, informal practices, and social relations influence full-time and part-time doctoral students’ access to and experiences within research assistantships. My objective was to draw from interviews and documents to acquire a thorough understanding of the organizational characteristics of research assistantships (i.e., structures of access, distribution, and coordination of participation) to explore the ways institutional regulations, informal practices, and social relations promote, prevent, or limit full-time and part-time students’ legitimate peripheral participation in research assistantships. Although I devoted particular attention to the ways students’ full-time and part-time status shaped their decisions, relationships, and experiences, I was conscious that other factors such as gender, age, and cultural background may have also influenced doctoral research assistant experiences.
    • Cell wall degrading enzymes and interaction between Trichoderma Aggressivum and Agaricus Bisporus

      Abubaker, Kamal Salem; Department of Biological Sciences (Brock University, 2010-10-26)
      Agaricus bisporus is the most commonly cultivated mushroom in North America and has a great economic value. Green mould is a serious disease of A. bisporus and causes major reductions in mushroom crop production. The causative agent of green mould disease in North America was identified as Trichoderma aggressivum f. aggressivum. Variations in the disease resistance have been shown in the different commercial mushroom strains. The purpose of this study is to continue investigations of the interactions between T. aggressivum and A. bisporus during the development of green mould disease. The main focus of the research was to study the roles of cell wall degrading enzymes in green mould disease resistance and pathogenesis. First, we tried to isolate and sequence the N-acetylglucosaminidase from A. bisporus to understand the defensive mechanism of mushroom against the disease. However, the lack of genomic and proteomic information of A. bisporus limited our efforts. Next, T. aggressivum cell wall degrading enzymes that are thought to attack Agaricus and mediate the disease development were examined. The three cell wall degrading enzymes genes, encoding endochitinase (ech42), glucanase (fJ-1,3 glucanase) and protease (prb 1), were isolated and sequenced from T. aggressivum f. aggressivum. The sequence data showed significant homology with the corresponding genes from other fungi including Trichoderma species. The transcription levels of the three T. aggressivum cell wall degrading enzymes were studied during the in vitro co-cultivation with A. bisporus using R T -qPCR. The transcription levels of the three genes were significantly upregulated compared to the solitary culture levels but were upregulated to a lesser extent in co-cultivation with a resistant strain of A. bisporus than with a sensitive strain. An Agrobacterium tumefaciens transformation system was developed for T. aggressivum and was used to transform three silencing plasmids to construct three new T. aggressivum phenotypes, each with a silenced cell wall degrading enzyme. The silencing efficiency was determined by RT-qPCR during the individual in vitro cocultivation of each of the new phenotypes with A. bisporus. The results showed that the expression of the three enzymes was significantly decreased during the in vitro cocultivation when compared with the wild type. The phenotypes were co-cultivated with A. bisporus on compost with monitoring the green mould disease progression. The data indicated that prbi and ech42 genes is more important in disease progression than the p- 1,3 glucanase gene. Finally, the present study emphasises the role of the three cell wall degrading enzymes in green mould disease infection and may provide a promising tool for disease management.
    • Cell-selective modulation of the neuromuscular system in Drosophila

      Ormerod, Kiel; Department of Biological Sciences
      The capacity for all living cells to sense and interact with their environment is a necessity for life. In highly evolved, eukaryotic species, like humans, signalling mechanisms are necessary to regulate the function and survival of all cells in the organism. Synchronizing systemic signalling systems at the cellular, organ and whole-organism level is a formidable task, and for most species requires a large number of signalling molecules and their receptors. One of the major types of signalling molecules used throughout the animal kingdom are modulatory substances (e.x. hormones and peptides). Modulators can act as chemical transmitters, facilitating communication at chemical synapses. There are hundreds of circulating modulators within the mammalian system, but the reason for so many remains a mystery. Recent work with the fruit fly, Drosophila melanogaster demonstrated the capacity for peptides to modulate synaptic transmission in a neuron-specific manner, suggesting that peptides are not simply redundant, but rather may have highly specific roles. Thus, the diversity of peptides may reflect cell-specific functions. The main objective of my doctoral thesis was to examine the extent to which neuromodulator substances and their receptors modulate synaptic transmission at a cell-specific level using D. melanogaster. Using three different modulatory substances, i) octopamine - a biogenic amine released from motor neuron terminals, ii) DPKQDFMRFa - a neuropeptide secreted into circulation, and iii) Proctolin - a pentapeptide released both from motor neuron terminals and into circulation, I was able to investigate not only the capacity of these various substances to work in a cell-selective manner, but also examine the different mechanisms of action and how modulatory substances work in concert to execute systemic functionality . The results support the idea that modulatory substances act in a circuit-selective manner in the central nervous system and in the periphery in order to coordinate and synchronize physiologically and behaviourally relevant outputs. The findings contribute as to why the nervous system encodes so many modulatory substances.
    • Cellular Mechanisms of Resveratrol's Interaction with Mitochondrial Reactive Oxygen Species Metabolism

      Robb, Ellen; Department of Biological Sciences (Brock University, 2013-05-14)
      Resveratrol, a polyphenol found naturally in red wines, has attracted great interest in both the scientific community and the general public for its reported ability to protect against many of the diseases facing Western society today. While the purported health effects of resveratrol are well characterized, details of the cellular mechanisms that give rise to these observations are unclear. Here, the mitochondrial antioxidant enzyme Mn superoxide dismutase (MnSOD) was identified as a proximal target of resveratrol in vitro and in vivo. MnSOD protein and activity levels increase significantly in cultured cells treated with resveratrol, and in the brain tissue of mice given resveratrol in a high fat diet. Preventing the increase in MnSOD levels eliminates two of resveratrol’s more interesting effects in the context of human health: inhibition of proliferative cell growth and cytoprotection. Thus, the induction of MnSOD is a critical step in the molecular mechanism of resveratrol. Mitochondrial morphology is a malleable property that is capable of impeding cell cycle progression and conferring resistance against stress induced cell death. Using confocal microscopy and a novel ‘cell free’ fusion assay it was determined that concurrent with changes in MnSOD protein levels, resveratrol treatment leads to a more fused mitochondrial reticulum. This observation may be important to resveratrol’s ability to slow proliferative cell growth and confer cytoprotection. Resveratrol's biological activities, including the ability to increase MnSOD levels, are strikingly similar to what is observed with estrogen treatment. Resveratrol fails to increase MnSOD levels, slow proliferative cell growth and confer cytoprotection in the presence of an estrogen receptor antagonist. Resveratrol's effects can be replicated with the specific estrogen receptor beta agonist diarylpropionitrile, and are absent in myoblasts lacking estrogen receptor beta. Four compounds that are structurally similar to resveratrol and seven phytoestrogens predicted to bind to estrogen receptor beta were screened for their effects on MnSOD, proliferative growth rates and stress resistance in cultured mammalian cells. Several of these compounds were able to mimic the effects of resveratrol on MnSOD levels, proliferative cell growth and stress resistance in vitro. Thus, I hypothesize that resveratrol interacts with estrogen receptor beta to induce the upregulation of MnSOD, which in turn affects cell cycle progression and stress resistance. These results have important implications for the understanding of RES’s biological activities and potential applications to human health.
    • Characterisation and optimisation of the flavour of health-promoting, plantderived bitterants in functional beverages.

      Gaudette, Nicole J.; Applied Health Sciences Program (Brock University, 2012-07-30)
      Flavour is a combination of taste, odour, and chemesthetic sensations. Close associations exist between these sensory modalities, and thus, the overall flavour of a food or beverage product can change when the intensity of one or more of these sensations is altered. Strategies to modify flavour are often utilized by the food industry, and are central to the engineering of new and reformulated products. For functional food and beverages, flavour modification is particularly important, as fortifying agents can elicit high levels of less than desirable sensations, such as bitterness and astringency. The application of various flavour modifying strategies can decrease the perceived intensity of these sensations, and in tum, improve the sensory profile of the product. This collection of studies describes the sensory characteristics of experimental functional beverages fortified with trans-resveratrol, (+)-catechin, and/or caffeine, and examines the impact of novel flavour modifying strategies on the perceived flavour of these beverages. In the first study, results demonstrate that the flavour profile of Cabemet Sauvignon wines fortified with 20 mglL and 200 mg/L of trans-resveratrol is not perceived as different compared to control wine (0 mglL). However, Riesling wine fortified with 200 mg/L is perceived as significantly higher in bitterness compared to 20 mglL and control. For some functional food formulations, alternative strategies for flavour modification are needed. Traditional methods, such as the addition of sucrose and sodium chloride, may decrease the perceived 'healthiness' of a product, and thus, may be sub-optimal. In a second study, high and low concentrations of five different bitter inhibiting compounds - 'bitter blockers' - (B-cyclodextrin, homoeridictyol sodium salt, carboxymethylcellulose - low viscosity, zinc sulfate, magnesium sulfate) were tested for their efficacy towards decreasing the bitterness of high and low concentrations of caffeine and (+)catechin - two health-relevant, plant-derived bitterants. B-cyclodextrin and homoeridictyol sodium salt were the most effective blockers at decreasing (+ )-catechin and caffeine, respectively. In addition to bitter blockers, additional flavour modifying strategies, either alone or in combination - may also be successful in functional food formulations. Both sucrose and rebaudioside A - a plant-derived sweetener - were effective at decreasing the bitterness of (+)catechin. When added to (+)-catechin along with B-cyc1odextrin, both sweeteners provided the most effective decrease in bitterness compared to binary, ternary, or quaternary mixtures of (+)catechin together with bitter blockers, sweeteners, andlor odourants. The perceived intensity of sensations elicited by sweeteners and odourants was not affected by the addition of bitter blockers, and thus, their impact within these complex matrices is minimal. In addition, withinmodal (taste-taste) compared to cross-modal (taste-odour) sensory interactions were more effective at decreasing the bitterness of (+ )-catechin. Overall, results from these studies demonstrate that certain novel, alternative flavour modifying approaches may be successful towards lowering the bitterness and astringency elicited by (+ )-catechin and caffeine in aqueous solutions.
    • Chemoenzymatic Formal Total Syntheses of Tetrodotoxin and an Approach to Daphenylline

      Baidilov, Daler; Department of Chemistry
      This thesis describes chemoenzymatic formal total syntheses of tetrodotoxin and a concise synthetic approach to daphenylline. Advanced intermediates for the syntheses of tetrodotoxin reported by the groups of Fukuyama, Alonso, and Sato were prepared. Key steps included toluene dioxygenase-mediated dihydroxylation of either iodobenzene or benzyl acetate and a [4+2] hetero-Diels-Alder cycloaddition/Kornblum–DeLaMare rearrangement sequence to construct a common enone intermediate. The resulting key enone was transformed into Fukuyama's intermediate in four steps, into Alonso's intermediate in six steps, and into Sato's intermediate in seven steps. Fukuyama’s route employed a highly stereoselective allyl cyanate-to-isocyanate rearrangement to install the nitrogen atom at C8a. This protocol was also successfully applied in designing a synthetic avenue to daphenylline. The ABC tricyclic skeleton of daphenylline was successfully constructed in just eight steps starting from readily available (S)-carvone.
    • Chemoenzymatic synthesis of amaryllidaceae alkaloids and their C-1 analogues : symmetry based approach to total synthesis of thebaine

      Collins, Jonathan A.; Department of Chemistry (Brock University, 2010-10-26)
      Described herein is the chemoenzymatic total synthesis of several Amaryllidaceae constituents and their unnatural C-I analogues. A new approach to pancratistatin and related compounds will be discussed along with the completed total synthesis of 7 -deoxypancratistatin and trans-dihydrolycoricidine. Evaluation of all new C-l analogues as cancer cell growth inhibitory agents is described. The enzymatic oxidation of dibromobenzenes by Escherichia coli 1M 109 (pDTG60 1) is presented along with conversion of their metabolites to (-)-conduritol E. Investigation into the steric and functional factors governing the enzymatic dihydroxylation of various benzoates by the same organism is also discussed. The synthetic utility of these metabolites is demonstrated through their conversion to pseudo-sugars, aminocyclitols, and complex bicyclic ring systems. The current work on the total synthesis of some morphine alkaloids is also presented. Highlighted will be the synthesis of several model systems related to the efficient total synthesis of thebaine.
    • Chemoenzymatic Total Synthesis of ent-Oxycodone

      Makarova, Mariia; Department of Chemistry
      This thesis describes the approach towards chemoenzymatic total synthesis of ent-dihydroisocodeine and chemoenzymatic total synthesis of ent-oxycodone as well as the development of a new method for the preparation of rearranged allylic isocyanates. The synthesis of ent-dihydroisocodeine started from phenethyl acetate and included a microbial oxidation of phenethyl acetate by E. coli JM109 (pDTG601A), a Mitsunobu reaction to the couple A- and C-rings, Heck cyclization to construct the E-ring and Henry reaction to introduce the nitrogen functionality as key steps. The construction of the B-ring proved to be challenging and neither radical cyclization nor attempts to perform photochemistry or nucleophilic opening of an epoxide gave any positive results. The chemoenzymatic total synthesis of ent-oxycodone was accomplished starting from phenethyl acetate in 23 steps. The tricyclic intermediate was furnished in the same manner as described above. The olefin to ketone conversion and a double Henry reaction allowed the construction of the B-ring. Unfortunately, it was established that the resulting hydroxyl group at C14 and amino group at C9 were of the undesired trans stereochemistry. To complete the morphine skeleton the transformation of the side chain at C13 to an N-methyl-p-toluenesufonamide via Mitsunobu reaction as well as the elimination of the amino group at C9 via formation of an N-oxide were performed. Subsequent radical cyclization of the side chain at the C9 position formed the last D-ring. The silyl ether deprotection followed by oxidation provided ent-oxycodone. The other approach to construct the D-ring was based on the formation of a lactone and the elimination of the amino group via an N-oxide. The nitrogen functionality was reinstalled using sodium azide and was accompanied by the introduction of the C10 hydroxyl group. Reduction of the azide and subsequent formation of the amide allowed access to the core skeleton of the target compound. The removal of the C10 hydroxyl group accomplished the synthesis. The last project involved the development of a new method for the preparation of rearranged allylic isocyanates from allylic alcohols using 1-cyano-4-dimethylaminopyridinium as the source of electrophilic cyanide. Experimental and spectral data are provided for all the compounds.
    • Chemoenzymatic Total Synthesis of Morphine alkaloids: Synthesis of Dihydrocodeine and Hydrocodone via a Double Claisen Strategy and ent-Hydromorphone via an Oxidative Dearomatization/intramolecular [4+2] Cycloaddition

      Varghese, Vimal; Department of Chemistry (Brock University, 2015-01-15)
      This thesis describes the chemoenzymatic synthesis of three morphine alkaloids. The total synthesis of dihydrocodeine and hydrocodone was accomplished starting from bromobenzene in 16 and 17 steps, respectively. The key steps included a microbial oxidation of bromobenzene by E. coli JM109 (pDTG601A), a Kazmaier-Claisen rearrangement of glycinate ester to generate C-9 and C-14 stereo centers, a Johnson-Claisen rearrangement to set the C-13 quaternary center, and a C-10/C-11 ring closure via a Friedel-Crafts reaction. In addition, the total synthesis of ent-hydromorphone starting from β-bromoethylbenzene in 12 steps is also described. The key reactions included the enzymatic dihydroxylation of β-bromoethylbenzene to the corresponding cis-cyclohexadienediol, a Mitsunobu reaction, and an oxidative dearomatization followed by an intramolecular [4+2] cycloaddition.