title: Disrupting the maestro: Tuneful youth insights for engaged music education

contributor: Tilleczek, Kate (Supervisory Committee Member)

contributor: Countryman, June (Supervisory Committee Member)

contributor: Mitchell, Jean (Supervisory Committee Member)

contributor: Tilleczek, Kate (Examination Committee Member)

contributor: Gaztambide-Fernández, Rubén (Examination Committee Member)

contributor: Zinck, Andrew M. (Examination Committee Member)

format: 286 application/pdf PUBLISHED electronic

abstract:
This innovative dissertation research has been designed, implemented, and disseminated through this
written thesis, public performances and a website (http://saswclub.wix.com/saswclub). The research
was undertaken with, for, and by students in one secondary school in Atlantic Canada. The following
research questions were addressed: (a) How do students articulate their perceptions and experiences
of engagement in music-making, (b) How do these student perceptions and experiences figure into
pedagogical practices for teaching music and further engaging in musicmaking and school, and (c)
Are student ideas being heard? Why or why not? To answer these questions, 30 student participants
collaborated with the researcher who is also a music teacher in situ. The research took place over 15
months through sustained and varied critical ethnographic methods. Interviews, documents, reflexive
observations, music-making, and musical performances were collected and analyzed through a
fugue-like process. From this process arose a Song Writer’s Club within the school. Teacher and
student participants collaborated in the duties of recording, production, musical instruction,
accompaniment, and equipment management. Student participants wrote, performed, and recorded
songs. They also spoke about their musicking experiences during two interviews. The ethnographic
processes were shared with student participants via video, songs, journals, and images. Students
provided important insights about teaching and learning music, and about developing engaged
education more generally. They recommended a resolution of current gaps between formal and
informal musicmaking and teaching. They also suggested a need to collaborate across diverse
musical styles and to interrogate maestro-driven educational processes. The dissertation contributes
to the field of Educational Studies by challenging adult-centred education through a new lens of
disrupted maestro and by inviting authentic inclusion of youth in educational research and practice.


title: Semiparametric hierarchical proportional hazards models with applications to animal health data

type: Text Dissertation/Thesis

contributor: Keefe, Greg (Supervisory Committee Member)

contributor: Stryhn, Henrik (Supervisory Committee Member)

contributor: Dohoo, Ian (Supervisory Committee Member)

contributor: Greenwood, Spencer (Supervisory Committee Member)

contributor: Revie, Crawford (Supervisory Committee Member)

contributor: Khedhiri, Sami (Supervisory Committee Member)

contributor: Duchateau, Luc (Examination Committee Member)

contributor: Greenwood, Spencer (Examination Committee Member)

contributor: St-Hilaire, Sophie (Examination Committee Member)

contributor: Khedhiri, Sami (Examination Committee Member)

contributor: McKenna, Shawn (Examination Committee Member)

format: electronic 240 application/pdf PUBLISHED

abstract:
This thesis discusses and applies hierarchical models for survival data in the field of
veterinary medicine. The focus is on hierarchical proportional hazards models when the
baseline hazard is left completely unspecified. Parameter estimation for these models is
explored and the performance of their estimation methods is investigated in terms of
statistical properties such as unbiasedness, robustness, and probability coverage.
The thesis is formed by manuscripts of four studies. The first study compares, via
simulation, the performance of different estimation methods for estimating a random
slope Cox model with and without covariance between the random effects. The
simulation is built to mimic real animal health data. The aim of the study is to establish
some practical guidelines for the choice of appropriate statistical estimation methods for
modeling random slopes in 2-level hierarchical data. Results show that estimating the full
covariance matrix for random effects is always preferable in the analysis and Poisson
maximum likelihood estimation is an adequate approach for this task.
The second study explores the feasibility of a full hierarchical survival analysis for a
large dataset with three levels of hierarchy and time-dependent predictors and
coefficients. To this end, a log-normal nested frailty Cox model is applied to Canadian
Bovine Mastitis Research Network (CBMRN) data to identify risk factors associated with
the hazard of clinical mastitis (CM) during cow lactations. This nested frailty model is
estimated by the Poisson maximum likelihood approach with Gaussian quadrature. The
performance, in terms of bias and efficiency of estimates, of the Poisson maximum
likelihood approach (estimated using either Gaussian quadrature or Laplace approximation) is compared with the performance of the penalized partial likelihood
approach. The Poisson maximum likelihood with Gaussian quadrature produces fairly
robust and adequate estimates while the penalized partial likelihood and the Poisson
maximum likelihood with Laplacian approximation are found to have substantial
drawbacks. Further, the research indicates that some of the herd managerial factors
combined with cow characteristics influence the hazard of CM during the lactation
period; some of these effects are different earlier as compared to later in the lactation.
The third study involves analyzing a dataset on calf loss and mortality in beef cattle in
Western Canada. This dataset has a cross-classified and multiple membership structure
which is a special type of data structure that has only been accounted for in the analyses
of linear and generalized linear models but not in survival analysis. The study objectives
are twofold: the first is to explore and demonstrate the use of Poisson generalized linear
mixed models (GLMMs) in the Bayesian framework for estimating a Cox model with
cross-classified and multiple membership frailties. The second, is to simultaneously
examine the individual, herd management, and environmental factors associated with
beef calf mortality in Western Canada and to estimate the age period where calves are
most at risk. Finally, a simulation study with settings similar to the real data is carried out
to evaluate the estimation approach. The simulation results gave evidence that the
approach used provides valid estimates.
In the fourth study, the robustness of Poisson maximum likelihood estimation was
assessed, through simulation, for a Cox model with normal random effects under
misspecification of the random-effects distribution. The impact of misspecifying the

distribution of random effects is assessed based on two different non-normal distributions for random effects and three different model designs. Some of the factors that might
affect the estimation are also investigated. The study shows that the Poisson maximum
likelihood approach yields robust estimates under misspecification of the random-effects
distribution for within-group fixed effects and in a wide range of situations for betweengroup
fixed effects. For variance components, the approach produces robust estimation
under model misspecification as long as the magnitude of heterogeneity is small, though
misspecification may become a matter of concern when the magnitude of heterogeneity
and group sizes become large.


title: Evaluation of a novel approach to promoting post-ischemic recovery of upper extremity function in the rat

contributor: Wright, Glenda (Supervisory Committee Member)

contributor: Tasker, Andrew (Supervisory Committee Member)

contributor: Doucette, Tracy (Supervisory Committee Member)

contributor: Robertson, Harold (Supervisory Committee Member)

contributor: Kay, Denis (Supervisory Committee Member)

contributor: Kamunde, Collins (Examination Committee Member)

contributor: Tasker, Andrew (Examination Committee Member)

contributor: Doucette, Tracy (Examination Committee Member)

contributor: Montelpare, William (Examination Committee Member)

contributor: Kolb, Bryan (Examination Committee Member)

format: electronic 221 application/pdf PUBLISHED PUBLISHED

rights: In presenting this thesis in partial fulfilment of the requirements for a graduate degree from the University of Prince Edward Island, the author has agreed that the Robertson Library, University of Prince Edward Island, may make this thesis freely available for inspection and gives permission to add an electronic version of the thesis to the Digital Repository at the University of Prince Edward Island. Moreover the author further agrees that permission for extensive copying of this thesis for scholarly purposes may be granted by the professor or professors who supervised the author‘s thesis work, or, in their absence, by the Chair of the Department or the Dean of the Faculty in which the author‘s thesis work was done. It is understood that any copying or publication or use of this thesis or parts thereof for financial gain shall not be allowed without the author‘s written permission. It is also understood that due recognition shall be given to the author and to the University of Prince Edward Island in any scholarly use which may be made of any material in the author‘s thesis.

abstract:
Following stroke, impairments in arm function are common motor deficits in survivors, affecting thousands of people each year. A useful technique used in clinical rehabilitation of patients with arm impairments is to force use of the impaired arm through constraint of the unaffected (or less affected) one. The success of this ‗constraint induced movement therapy‘ (CIMT) is believed to be due to neuroplastic changes that take place on a cellular level in surviving brain tissue, however, little is understood about the mechanisms involved. Appropriate animal models are necessary to study how rehabilitation affects neuroplasticity. Previous literature has described several models of forced use following stroke in rats which have resulted in varying success. Animal stress and lack of behavioural pressure may have contributed to the inconsistency of prior forced use models.
The purpose of the research presented in this thesis was to optimize a surgical model of post-ischemic upper extremity impairment, determine whether it would be possible to force use of the impaired forelimb using a novel appetitively motivated protocol, and then to investigate the effects of this novel model on markers of neuroplasticity. First, the endothelin-1 (ET-1) model of focal unilateral ischemia was optimized by attempting a previously unpublished protocol of injections along the motor cortex and to the striatum. Male Sprague Dawley rats were subjected to ET-1 or sham surgery. Ensuing forelimb functional deficits were measured using a battery of behavioural tests, which were compared to intact sham surgical control performance. The stroke model resulted in reliable and reproducible lesions to forelimb motor regions of the brain, and deficits that lasted up to the end of the 21 day study period in some tests.
Next, this ET-1 stroke surgery was used to evaluate a novel form of forced use rehabilitation in which rats engaged the impaired limb to move voluntarily in commercial pet activity balls. Animals were subjected to ET-1 or sham surgery, and then received either rehabilitation or a control treatment. Behavioural tests revealed that animals receiving rehabilitation recovered to sham levels of performance sooner than animals receiving the control treatment. Stroke, but not rehabilitation, affected the proportion of cells expressing brain derived neurotrophic factor (BDNF) and the presence of doublecortin-positive neuroblasts, but had no effect on the expression of the growth inhibiting protein NOGOA.
Finally, the novel forced use model was developed further to more closely resemble clinical CIMT with the addition of a task-specific reaching component. Animals were subjected to either ET-1 followed by rehabilitation, ET-1 followed by a control treatment, or sham surgery. Again, behavioural tests revealed that animals that had undergone ET-1 surgery had significant deficits that recovered sooner in the group that received rehabilitation. Rehabilitation did not affect the proportion of BDNF-expressing cells, but did appear to cause a shift in the cellular origin of the BDNF that was present. Further, rehabilitation resulted in more doublecortin-positive cells in the damaged hemisphere. This novel approach to rehabilitation represents a useful model of forced use therapy which results in accelerated functional recovery following ischemic injury. The mechanisms underlying this effect may be related to changes in BDNF expression and increased generation or survival of new born cells.


title:
Assessment of the diversity of Algicolous Fungi from Prince Edward
Island, new species discovery and antimicrobial screening of selected isolates

contributor: Kerr, Russell (Supervisory Committee Member)

contributor: Malloch, David (Examination Committee Member)

contributor: Saleh, Tarek (Supervisory Committee Member)

contributor: Burka, John (Supervisory Committee Member)

contributor: McConkey, Sandra (Supervisory Committee Member)

contributor: Zhang, Junzeng (Supervisory Committee Member)

contributor: Sims, David (Examination Committee Member)

contributor: Kerr, Russell (Examination Committee Member)

contributor: Lacroix, Christian (Examination Committee Member)

contributor: Zhang, Junzeng (Examination Committee Member)

format: electronic 231 application/pdf PUBLISHED

rights:
In presenting this thesis in partial fulfillment of the requirements for a postgraduate
degree from the University of Prince Edward Island, I agree that the Libraries of this
University may make it freely available for inspection. I further agree that permission
for extensive copying of this thesis for scholarly purposes may be granted by the
professor or professors who supervised my thesis work, or, in their absence, by the
Chair of the Department or the Dean of the Faculty in which my thesis work was done.
It is understood any copying or publication or use of this thesis or parts thereof for
financial gain shall not be allowed without my written permission. It is also understood
that due recognition shall be given to me and to the University of Prince Edward Island
in any scholarly use which may be made of any material in my thesis.

abstract:
The field of fungal taxonomy has been enduring in recent years due to the progress
and application of molecular tools used in concert with morphological analysis. The
fungal kingdom is extremely diverse and estimated to include 1.5 million species. Only
11% of these fungi are currently described in the literature. Marine-derived fungi are an
ecological group of fungi that have been under focus lately for the purpose of drug
discovery as they produce structurally unique secondary metabolites, most of which
display promising biological and pharmacological properties against many human and
crop diseases. Fungi derived from Prince Edward Island (PEI) marine habitats represent
a potentially valuable resource and have not been investigated for the purpose of
discovering both new species and new pharmacologically active secondary metabolites.
Thus, the strategy of this thesis research was to isolate algicolous fungi from the south
shore of PEI and examine some of the promising isolates for the production of
antimicrobial metabolites. The biological diversity in this study encompasses 130 fungal
isolates belonging to 35 diverse genera. Almost one third of these isolates are still
awaiting discovery and description. A comparative study between sediment and algal
fungal content showed that algae present valuable resourceful hosts for the purpose of
new species discovery.
Prolonged usage of broad spectrum antibiotics has led to the emergence of drug
resistance, necessitating the discovery of novel antimicrobial agents. The rich taxonomic
diversity obtained from the biodiversity study initiated investigations into the production
of secondary metabolites from selected fungal isolates with the intent to discover novel antimicrobial metabolites, ultimately to be used as lead structures for antimicrobial drug
development. Forty-seven isolates were fermented on four nutritionally different media.
The extracts were fractionated prior to bioassay and then tested against three
―superbugs‖ in addition to four human pathogens. Fractions from 22 isolates showed
moderate to high activity against the selected pathogens. Some of the activity was
attributed to previously known metabolites, however this study is thought to be the first
report for their activity against the ―superbugs‖. The 47 isolate fermentations has
resulted in a total of 531 fractions, this library of fractions is available for the purpose of
other biological activity or chemical investigations.
New species discovery with a focus upon algicolous fungi from PEI, was one of the
goals of this study. By integrating molecular biology and chemistry, a new fungal
species was discovered with the capability of producing secondary metabolites with
activity against the ―superbugs‖ methicillin-resistant Staphylococcus aureus and
vancomycin-resistant Enterococcus. The new species was named Westerdykella
reniformis Ebead & Overy sp. nov.; isolated from the red alga Polysiphonia sp. When
comparing the chemical and biological profile of this new species relative to other
members of the genus, it was obvious that the new species possessed a different natural
product biosynthetic gene cluster not previously found in its genus. This finding proves
that biodiversity is translated into chemical diversity.


title:
Proteomic and biochemical approaches to investigate the
interactions between the Eastern Oyster, Crassostrea virginica and the MSX
parasite, Haplosporidium nelsoni

contributor: Markham, Frederick (Supervisory Committee Member)

contributor: Chu, Fu-Lin E. (Examination Committee Member)

contributor: Markham, Frederick (Examination Committee Member)

contributor: Davidson, Jeffery (Examination Committee Member)

contributor: Fast, Mark (Examination Committee Member)

contributor: Conboy, Gary (Examination Committee Member)

contributor: Ross, Neil (Supervisory Committee Member)

contributor: Kibenge, Frederick (Supervisory Committee Member)

contributor: Berthe, Franck (Supervisory Committee Member)

contributor: Davidson, Jeffrey (Supervisory Committee Member)

format: electronic 179 application/pdf PUBLISHED

rights:
In presenting this thesis in partial fulfilment of the requirements for a postgraduate degree
from the University of Prince Edward Island, I agree that the Libraries of this University
may make it freely available for inspection. I further agree that permission for extensive
copying of this thesis for scholarly purposes may be granted by the professor or
professors who supervised my thesis work, or, in their absence, by the Chair of the
Department or the Dean of the Faculty in which my thesis work was done. It is
understood any copying or publication or use of this thesis or parts thereof for financial
gain shall not be allowed without my written permission. It is also understood that due
recognition shall be given to me and to the University of Prince Edward Island in any
scholarly use which may be made of any material in my thesis.

abstract:
The host parasite system of the MSX parasite, Haplosporidium nelsoni, in the eastern
oyster, Crassostrea virginica, poses many challenges for experimental study. The
interactions that are involved in the development of the typically high prevalence and
intensities of disease encountered in certain environments have not been characterized .
The parasite is not-culturable and its life cycle outside of the oyster host remains
unknown, as such the field is the only source of infective tissues available for study.
The main goals of this research were to first, explore of potential protein targets involved
in infection; second, investigate the tissues that provide optimal comparative value and
third, test methodologies that allow for clear comparative analysis. In order to investigate
this host parasite system it was first necessary to develop an experimental design that
enabled the consistency of samples and reliable diagnosis of their disease state. Arriving
at an experimental design involved the implementation of several laboratory protocols
including one and two dimensional protein gel electrophoresis, enzymatic assays, the use
of two diagnostic methods, field sampling and experimental field infection, in order to
determine the most promising approach to describing the host parasite interaction.
Two environmental systems in which MSX infects the eastern oyster were studied, the
Bras d’Or lakes, Cape Breton, Nova Scotia, Canada and the York river system of the
Chesapeake Bay, Virginia, USA. Within the Bras d’Or lakes samples, a population of
oysters was discovered in which parasite pressure was present but the manifestation of
disease within the tissues of oysters from this population was not found. The
identification of a differential response to parasite pressure led to the comparison of
proteins involved in disease from the three Bras d’Or lakes populations sampled. The
new landscape of the parasite’s presence in the Bras d’Or along with the targeting of
several tissues and the comparison of different individuals with different disease states
highlighted the need to control for variability in protein profiles.
The concentration of further comparative protein analyses to the Chesapeake Bay system
allowed for the experimental field infection of naïve oysters and thus the comparison of
proteins from the same individual oyster’s haemolymph over time. Once collected, these
samples were grouped based on final infection intensity and the comparison of protein
profiles indicated the presence of a protein after exposure to an MSX impacted area. This
differentially expressed protein was identified as actin and was consistently observed in
the cell free haemolymph lysates from all intensity classes studied. The comparison of
proteolytic activity of haemolymph over time and between final infection intensity
classes identified a protease present within the initial haemolymph samples (naive
individuals) occurring at a significantly higher frequency within those individuals that
went on to develop high intensity infections. This finding suggests a protein
differentiation found within the naïve population that impacts the outcome of infection of
these individuals. The potential of this protease as a marker for heightened disease
susceptibility may provide insight into the overall disease process of H. nelsoni within
this host. Enzymatic activity also differed significantly among infection intensity classes,
XI
as alkaline phosphatase increased over time within intensity groups, as well as
comparatively between infection intensities. The monitoring of this activity may allow
for the disease to be tracked more readily in populations through testing of haemolymph
over time.
Having established some technical protocols that aided in clearly displaying constituent
proteins from oyster tissue samples, the experimental field trial was established to
compare the haemolymph of the same individual over time and exposure to MSX. This
led to the identification of protein, protease and enzymatic changes associated with
infection intensity. The success of this approach can aid in further characterization of
infection as well as establish important indicators of the point at which disease may
occur.


title: Study of prevalence, risk factors, and lifetime impacts of infection with bovine leukemia virus in the Canadian dairy industry

contributor: Keefe, Greg (Supervisory Committee Member)

contributor: VanLeeuwen, John (Supervisory Committee Member)

contributor: Hanna, Paul (Supervisory Committee Member)

contributor: Kelton, David (Supervisory Committee Member)

contributor: Sanchez, Javier (Supervisory Committee Member)

contributor: Stryhn, Henrik (Supervisory Committee Member)

contributor: Spangler, Liz (Examination Committee Member)

contributor: Hanna, Paul (Examination Committee Member)

contributor: Vanderstichel, Raphael (Examination Committee Member)

contributor: VanLeeuwen, John (Examination Committee Member)

contributor: Erskine, Ronald (Examination Committee Member)

format: electronic 183 application/pdf PUBLISHED

abstract:
The overall goal of the research described in this thesis was to lay a proper foundation for designing and conducting efficient control and eradication programs for infection with bovine leukemia virus (BLV) in the Canadian dairy industry.
The objective in Chapter 2 was to identify potentially important risk factors for BLV infection in Canadian dairy herds. Of 272 study herds, from 8 provinces of Canada and tested during 1998-2003, 78% were BLV-positive. Over 15 management determinants for the infection were evaluated. Herds with clinical cases of leukosis during the 12 months prior to sampling, as well as herds which purchased animals with unknown BLV infection status in the last five years, had a significantly increased proportion of BLV-positive cows. Herds from eastern provinces and those not purchasing cows in the last five years were more likely to be free from BLV compared to western provinces and farms purchasing cows in the last five years.
The objective in Chapter 3 was to determine the lifetime effects of BLV infection on milk production and longevity of dairy cows in Canada. Overall, 4052 cows from 348 herds were enrolled in a historical cohort study, based on test results from 1998-2003 and lactation and culling records post-testing until 2013. Positive cows to BLV had consistently greater probability of being culled (or dying) than the negative cows (over lifetime lactations 2-7). Only BLV-positive cows with short longevity (2 and 3 lifetime lactations) had a significantly lower lifetime milk production compared with their negative counterparts. As the cows lived longer (> 3 lactations), the difference in milk production between the two cohorts was no longer significant. The objectives of Chapter 4 were: 1) to assess the potential for carryover of antibodies against BLV in milk samples obtained from shared meters; and 2) to determine if adjustment of the diagnostic test cut-off value would improve the test characteristics for meter-collected milk ELISA results. The study included 236 paired milk samples from 8 dairy farms in Prince Edward Island collected in 2013. Two simultaneous milk samples, one hand-collected at the beginning of milking, and the other from the corresponding milk meter, were taken from all lactating cows that were milked at the selected meters. The sequence of cows using each meter was recorded. Carryover of BLV antibodies at shared milk meters was significant. For low-titer cows, the carryover effect was positively associated with the titer of the preceding cows. This could result in generating false-positive results in the BLV antibody-ELISA test on meter-collected samples from dairy herd improvement (DHI) procedures. Based on a new optimal cut-point, a suspicious category on the ELISA titers was defined, and a retest on the samples falling within this range was recommended to reduce the false positive rate.
The objectives for Chapter 5 were: 1) to determine the prevalence of BLV infection at the herd level using a bulk-tank milk (BTM) antibody ELISA in the Maritime region of Canada ; and 2) to develop applied statistical models for predicting within-herd prevalence of BLV infection using the BTM antibody levels. To detect BLV infection and the antibody levels, a census was implemented on BTM samples from all dairy farms in the Maritime region in 2013 (3 monthly rounds of sampling on 623 farms). Another round of BTM sampling was coincided with individual cow sampling (all cows that contributed milk to the fourth BTM) in 90 selected herds. Herd-level prevalence of BLV in the Maritime region was 90.8%. In the individual testing, 30.4% of cows were positive. The statistical models developed in this study were able to predict true within-herd prevalence of BLV reasonably well based only on the BTM results. The model including all BTM tests (4 rounds of sampling) as the predictor had the best fit, although the models using 2 and 3 BTM tests provided similar results to 4 repeated tests.
The focus for Chapter 6 was to assess the diagnostic performance of a commercially available ELISA for detecting BLV antibodies in BTM samples collected from dairy herds in Eastern Canada in 2013. Of 133 tested herds, 108 herds were found to be truly infected. At the resulting optimal cut-point, sensitivity and specificity of the BTM ELISA were estimated at 0.972 (0.921 – 0.994) and 1 (0.863 – 1), respectively.
With the high prevalence of BLV infection across Canada and its detrimental economic impacts, pursuing broad-based control programs is necessary. All of the findings in the present research could contribute to designing and conducting efficient BLV control programs.


title:
Assessment of the face
validity, construct validity, and etiological validity of a novel animal model of
schizophrenia

contributor: Doucette, Tracy (Supervisory Committee Member)

contributor: Ryan, Catherine (Supervisory Committee Member)

contributor: Hurta, Robert (Supervisory Committee Member)

contributor: Sweeney-Nixon, Marva (Supervisory Committee Member)

contributor: Kay, Denis (Supervisory Committee Member)

contributor: Doucette, Tracy (Examination Committee Member)

contributor: Ryan, Catherine (Examination Committee Member)

contributor: Hurta, Robert (Examination Committee Member)

contributor: Sweeney-Nixon, Marva (Examination Committee Member)

contributor: Kay, Denis (Examination Committee Member)

contributor: MacDonald, Dany (Examination Committee Member)

format: electronic 173 application/pdf PUBLISHED

rights:
In presenting this thesis in partial fulfillment of the requirements for a postgraduate
degree from the University of Prince Edward Island, I agree that the Libraries of this
University may make this thesis freely available for inspection and give
permission to add an electronic version of the thesis to the Digital Repository at the
University of Prince Edward Island. Moreover the author agrees that permission for
extensive copying of this thesis for scholarly purposes may be granted by the professor or
professors who supervised my thesis work, or, in their absence, by the Chair of the
Department or the Dean of the Faculty in which my thesis work was done. It is
understood any copying or publication or use of this thesis or parts thereof for financial
gain shall not be allowed without my written permission. It is also understood that due
recognition shall be given to me and to the University of Prince Edward Island in any
scholarly use which may be made of any material in my thesis.

abstract:
Schizophrenia is a devastating neurological disorder that affects approximately 1% of the
population and is characterized by positive, negative, and/or cognitive symptoms.
Positive symptoms are associated with increased glutamate (Glu) and/or dopamine (DA)
signaling in the nucleus accumbens (NAcc) while negative and cognitive symptoms are
related to decreased Glu and/or DA signaling in the medial prefrontal cortex (mPFC) and
hippocampus. The etiology of the disorder remains unknown, yet it is believed to be the
result of a combination of genetic and neurodevelopmental factors. In order to improve
our understanding of schizophrenia it is important to develop and further characterize
animal models with relevance to the human condition.
Prior research has demonstrated that rodents exposed to neonatal treatment with domoic
acid (DOM) (20 ìg/kg), a kainate (KA) receptor (KAR) agonist, during a critical period
of brain development (i.e. post-natal day (PND) 8-14) produces animals that exhibit
several behavioural, neurochemical, and neuroanatomical abnormalities that are
characteristic of schizophrenia.
The purpose of this thesis is to further examine the potential of DOM treatment in
producing an animal model of schizophrenia by assessing cognitive functioning (i.e. face
validity) using the attentional set-shifting and puzzle box paradigms, employing
immunohistochemistry to examine dopamine transporter (DAT), D1 receptor, and D2
receptor as markers of the DA system in the mPFC (i.e. construct validity), and by assessing active caspase-3, an executioner caspase in cellular apoptosis, in the mPFC (i.e.
etiological validity).
Behavioural results indicate improved cognitive flexibility among DOM-treated males in
the attentional set-shifting paradigm and improved short-term memory and problem
solving ability among DOM-treated females in the puzzle box. Neurochemical results
indicate increased DAT staining in the right PRL of DOM-treated females, decreased
caspase-3 staining, as evidenced by optical density measurement, in the right PRL among
DOM-treated males, and decreased caspase-3 staining, as evidenced by cell count
measurement, in the right PRL among DOM-treated females. These results serve to
strengthen the face validity, construct validity, and etiological validity of the model as
they demonstrate cognitive alterations, neurochemical alterations in adulthood which are
associated with behavioural symptomatology, and neurochemical alterations during
development.


title: Where there's a will, there's a way: Identifying important factors of physical activity among older adults

contributor: MacDonald, Dany (Supervisory Committee Member)

contributor: Weeks, Lori (Supervisory Committee Member)

contributor: Montelpare, William (Supervisory Committee Member)

contributor: Weeks, Lori (Examination Committee Member)

contributor: Montelpare, William (Examination Committee Member)

contributor: Meisner, Brad (Examination Committee Member)

contributor: Quijon, Pedro (Examination Committee Member)

format: electronic 99 application/pdf PUBLISHED

rights: In presenting this thesis in partial fulfillment of the requirements for a postgraduate degree from the University of Prince Edward Island, I agree that the Libraries of this University may make this thesis freely available for inspection and give permission to add an electronic version of the thesis to the Digital Repository at the University of Prince Edward Island. Moreover the author agrees that permission for extensive copying of this thesis for scholarly purposes may be granted by the professor or professors who supervised my thesis work, or, in their absence, by the Chair of the Department or the Dean of the Faculty in which my thesis work was done. It is understood any copying or publication or use of this thesis or parts thereof for financial gain shall not be allowed without my written permission. It is also understood that due recognition shall be given to me and to the University of Prince Edward Island in any scholarly use which may be made of any material in my thesis.

abstract: Older adults in Canada are largely sedentary and do not meet the recommended amount of daily physical activity. It has been suggested that older adults preferences for physical activities move from those characterized by high intensity and competition, to those of lower intensity and higher social components. However, limited research has examined which elements of physical activity influence participation or non-participation in the older adult population. Therefore, the purpose of this research was to determine which of these elements, or "factors", influence older adult's selection of physical activity. A two-phase design was used to collect data. Phase one consisted of a committee of seven older adults who generated a list of 25 factors affecting participation. Phase two consisted of 45 older adults who used the list of factors created by phase one to rank the most important factors across four categories: group structured, group unstructured, individual structured, and individual unstructured activities. The Cochran–Mantel–Haenszel chi–square test was used to investigate the differences between categories on the order of ranks. Results of this analysis show that there is a significant difference in rank orders of factors across the quadrants (χ2 = 75.9, p < 0.001). The second analysis used confidence intervals to investigated differences within categories to determine which factors were most important to older adults. Level A factors (most important) were identified as fun, satisfaction, commitment, and energize. Level B factors included safety, learning, awareness, and productive while level C factors were related to meaningful contribution, intensity, and motivation. In general, it was found that certain factors are more important than others when selecting physical activity during older adulthood. Results are discussed in light of these findings and it is concluded that including these factors into physical activity may lead to higher participation rates.


title: Simulation modeling of zoonotic diseases between swine and human populations for informing policy decisions

contributor: McClure, J Trenton (Supervisory Committee Member)

contributor: Revie, Crawford (Supervisory Committee Member)

contributor: Sanchez, Javier (Supervisory Committee Member)

contributor: Forzán, María (Supervisory Committee Member)

contributor: McNab, Bruce (Supervisory Committee Member)

contributor: Poljak, Zvonimir (Supervisory Committee Member)

contributor: Spangler, Elizabeth (Examination Committee Member)

contributor: Deardon, Rob (Examination Committee Member)

contributor: Sanchez, Javier (Examination Committee Member)

contributor: Hurnik, Dan (Examination Committee Member)

contributor: Forzán, María (Examination Committee Member)

format: electronic 382 application/pdf PUBLISHED

rights: In presenting this thesis in partial fulfillment of the requirements for a postgraduate degree from the University of Prince Edward Island, I agree that the Libraries of this University may make it freely available for inspection. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the professor or professors who supervised my thesis work, or, in their absence, by the Chairman of the Department or the Dean of the Faculty in which my thesis work was done. It is understood any copying or publication or use of this thesis or parts thereof for financial gain shall not be allowed without my written permission. It is also understood that due recognition shall be given to me and to the University of Prince Edward Island in any scholarly use which may be made of any material in my thesis.

abstract:
Approximately 60% of human pathogens and emerging infectious diseases are zoonotic. Simulation models are increasingly being used to investigate the spread of diseases, evaluate intervention strategies and guide the decisions of policy makers. In this thesis a systematic review of modeling methods and approaches used for zoonotic influenza in animals and humans was conducted, and knowledge gaps were identified. Furthermore, the disease spread and intervention parameters used in these studies were summarized for ready reference in future work.
Building on this review work, the research presented in this thesis evaluated the effects of transmissibility of the pandemic H1N1 2009 (pH1N1) virus at the swine- human interface and the control strategies against its spread in swine and human populations as a case study for zoonotic disease modeling. The feasibility of North American Animal Disease Spread Model (NAADSM) for modeling directly transmitted zoonoses was also assessed. Population data based on swine herds and households (categorized as rural households with or without swine workers, and urban households without swine workers) of a county in Ontario, Canada was used. The swine workers served as a bridging population for the spread of the virus between swine herds and households. Scenarios based on the combinations of the transmissibility of the virus (low (L), medium (M), and high (H)) from swine-to-human and human-to-swine (LL, ML, HL, MM, HM, LL), and targeted vaccination of swine worker households (0% to 60%) were evaluated. The results showed that lowering the influenza transmissibility at
the interface to low level and providing higher vaccine coverage (60%) had significant beneficial effects on all outcome measures. However, these measures had little or negligible impact on the total number of rural and urban households infected. A set of models evaluating the combination of control strategies indicated that a moderate speed of the detection (within 5 to 10 days of the first infection), combined with the quarantine of detected units alone, contained the outbreak within the swine population in most simulations. However, a zone-based quarantine strategy was more effective when the detection was delayed until around three weeks after initial infection. Ring vaccination had no added beneficial effect. This work suggested that NAADSM can be used for modeling the directly transmitted zoonotic diseases under similar simplifying assumptions adopted in these studies. However, this needs to be evaluated further with more accurate parameters and influenza outbreak data.
To fill in some of the gaps identified in the review study, network analyses of swine shipments among farms, and between farms and abattoirs were conducted. This provided network metrics and parameters necessary for disease modeling and risk-based disease management in swine in Ontario for the first time. Finally, agent-based network models assessing the spread and control of pH1N1 in swine established the importance of explicitly incorporating appropriate contact network structures into such models to increase their validity. It also demonstrated the benefits of targeted control strategies against highly connected farms. In conclusion, the modeling tools developed in this thesis can assist decision makers in preparedness and response of outbreaks of infectious diseases as more information become available for the parameterization of models.


title: Effects of environmental enrichment and behavioural style on stress responses in singly housed shelter cats (Felis catus)

contributor: Cockram, Michael (Supervisory Committee Member)

contributor: Stryhn, Henrik (Supervisory Committee Member)

contributor: Ryan, Cathy (Supervisory Committee Member)

contributor: Spears, Jonathan (Supervisory Committee Member)

contributor: Mason, Georgia (Examination Committee Member)

contributor: McClure, J Trenton (Examination Committee Member)

contributor: McNiven, Mary (Examination Committee Member)

contributor: Ryan, Cathy (Examination Committee Member)

format: electronic 264 application/pdf PUBLISHED

rights: In presenting this thesis in partial fulfillment of the requirements for a postgraduate degree from the University of Prince Edward Island, I agree that the Libraries of this University may make it freely available for inspection. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the professor or professors who supervised my thesis work, or, in their absence, by the Chair of the Department or the Dean of the Faculty in which my thesis work was done. It is understood any copying or publication or use of this thesis or parts thereof for financial gain shall not be allowed without my written permission. It is also understood that due recognition shall be given to me and to the University of Prince Edward Island in any scholarly use which may be made of any material in my thesis.

abstract: Shelters are potentially stressful environments for singly housed cats. The behaviour and faecal glucocorticoid metabolite (FGM) responses were examined in six shelter cats caged singularly for 30 days. Raised faecal glucocorticoid metabolite (FGM) concentrations and Cat-Stress-Scores (CSS) together with increased grooming and reduced eating indicated a stress response that tended to decrease with time. Environmental enrichment (EE) of the cages may help reduce this stress. However, the efficacy of different types of EE may be reliant on whether a cat is bold or shy, and may be related to the EE preferences expressed. A test was developed to discriminate between bold and shy cats. Nine cats were tested for latency to emerge from a carrier, and percentage of time spent in a carrier during a 5-min test in an empty arena. These measures were found to be significantly different across individuals and not significantly different across time. Seventeen cats were then subjected to a similar test, with similar results. Combining these results, it was determined that latency to emerge from carrier with a cut-point of 10 s was the most appropriate test for discriminating between bold and shy cats in a shelter setting. It correctly classified a high percentage of cats overall, was quick and easy to administer, and best suited to correctly identify shy individuals, which were less represented in this population and arguably could derive greater benefit from identification and extra attention. A final behavioural style study subjected 84 cats to this test, which showed acceptable cross-context consistency and correctly classified a high percentage of cats. Cats’ visit frequency to and time allocation with different types of EE were assessed using a plus-shaped choice chamber, in which each external compartment contained a different type of EE. Entrance to each chamber was gained through a cat-flap door monitored remotely using a HOBO data-logger. Usage of the shelf compartment was not significantly different from any other compartment. A significantly higher percentage of time was allocated to the compartment containing the hiding box compared to the toy compartment and to the empty control compartment, suggesting a hiding box may be a valued resource. A final experiment housed 72 bold or shy cats singly in cages enriched with either a hiding box or a shelf, or in an empty control cage. The amount of food eaten and the percentage of time spent eating increased across time, and percentage of time spent grooming decreased over time. Cats in the hiding box group had significantly lower FGM and higher food intake than cats in the control group, indicating that the type of EE used most in the choice test reduced stress. Shy cats used the hiding box significantly more than bold cats, and had a significantly higher CSS until day 5. There was no evidence that bold and shy cats benefited from different types of EE. The results indicated that the stress of caging is experienced more intensely by shy cats, but it can be reduced by the inclusion of a hiding opportunity in cats expressing either mode of this behavioural style.


title: Investigation of the microbial diversity and characterization of new natural products produced by fungi and actinobacteria of Frobisher Bay

contributor: Kerr, Russell (Supervisory Committee Member)

contributor: Greenwood, Spencer (Supervisory Committee Member)

contributor: Kerr, Russell (Examination Committee Member)

contributor: Ahmed, Marya (Examination Committee Member)

contributor: Greenwood, Spencer (Examination Committee Member)

contributor: Sorensen, John (Examination Committee Member)

contributor: Tasker, Andy (Examination Committee Member)

contributor: Kirby, Chris (Supervisory Committee Member)

contributor: McCallum, Jason (Supervisory Committee Member)

contributor: McClure, J. (Supervisory Committee Member)

format: electronic 339 application/pdf

abstract:
Natural products (NPs) are an important source of pharmaceutical agents and are produced by a wide range of micro and macro organisms. Microorganisms, specifically bacteria within the order Actinomycetales and fungi, are prolific producers of NPs and are responsible for upwards of 70% of all clinically approved antibiotics. Due to the intensive investigation of these microorganisms, specifically from the terrestrial environment for NP discovery, the rate of reisolation of known compounds is high. One way to overcome this issue is to investigate unexplored and underexplored environments as a source of biodiverse microorganisms for natural product discovery.
Canada’s Arctic remains a vast and largely undiscovered landscape due to its inaccessibility and harsh environment. Being so, the Arctic provides a unique niche, where members of the microbial community have evolved to “fit” this distinctive environment and must be capable of withstanding extreme cold, limited environmental resources and a range of other physical and biological factors. It is hypothesized Arctic microorganisms will have a unique secondary metabolome compared to their tropical counterparts based on environmental selection. Due to a lack of investigation of Canada’s Arctic for natural products, Frobisher Bay was selected as the study location for this investigation. The aims of this thesis were to characterize the bacterial and fungal community of Frobisher Bay and to discover new NPs from these microorganisms.
In order to assess the microbial community within Frobisher Bay, 454-pyrosequencing of the 16S rRNA gene and ITS region was used to determine the bacterial and fungal diversity respectively within sediment samples from Frobisher Bay. In order to achieve greater sequencing depth within the prolific NP producing Actinobacteria, Actinobacteria-specific 16S rRNA primers were used in addition to universal 16S rRNA primers. Overall, sites within Frobisher Bay were found to host high levels of taxonomically diverse microorganisms. The presence of large numbers of unknown phylotypes and the immense taxonomic diversity uncovered, make this region an intriguing area to explore from a NPs perspective.
Using a variety of isolation techniques, Actinobacteria and fungi were cultured from sediment samples collected from Frobisher Bay. In total, 90 Actinobacteria representing 25 distinct species, and 354 fungal isolates representing 54 species were cultured from this region. Of the fungal isolates, 9 appeared to be putatively novel based on sequencing of barcoding genes and morphological investigations. These isolates were particularly interesting from a NPs perspective, as they offered an untapped resource for NP discovery.
In order to prioritize isolates based on the production of new NPs, an LC-HRMS based screening method was used. This resulted in the isolation and characterization of several new NPs including a new hirsutellic acid analog obtained from Simplicillium aogashimaense RKAG 563, a new reduced perylene quinone compound obtained from Cadophora viticola RKAG 170 and two new cameronic acid analogs from Botrytis caroliniana RKAG 208. Investigation of the putatively novel fungal isolates was particularly fruitful for natural product discovery and resulted in the isolation of 17 new natural products. Investigation of Mortierella sp. RKAG 110 resulted in the characterization of mortiamides A-D, new cyclic heptapeptides containing five amino acids in the non-natural D-configuration. Examination of Sesquicillium spp. RKAG 571 and 186 led to the isolation of the new 11 residue peptaibols, tariuqins A-F containing the non-proteogenic amino acids (R)- and (S)-isovaline and aminoisobutyric acid, and to the isolation of the new cyclic decapeptides, auyuittuqamide A-D, containing three N-methylated amino acids. Lastly, exploration of putatively novel Tolypocladium species led to the isolation of several new tetramic acid containing compounds, iqalisetin A and B, and tolypoalbin.
Due to the permanently cold environment from which they were isolated, the effect of fermentation temperature on NP product production in Actinobacteria from Frobisher Bay was investigated. As most standard lab fermentations occur at a non-ecologically relevant temperature of 30°C, fermentations at colder, more ecologically relevant temperatures (4°C and 15°C) was undertaken. Differences in NP production at each fermentation temperature were assessed using an LC-HRMS based chemical metabolomics method on a subset of cultured actinomycetes. Within the 15°C fermentations, the de novo induction of actinomycin was observed in Streptomyces sp. RKAG 337 and the upregulated production of two new compounds, landomycin AA and AB from Streptomyces sp. RKAG 290 was observed. Due to this upregulation, sufficient material was produced to enable structural characterization of these two compounds. The use of fermentation temperature to induce or increase the production of NPs is a useful tool to access previously inaccessible chemical diversity.
Overall, Frobisher Bay is a rich resource for microorganisms as assessed by culture independent and dependent methods. The isolation of a large number of new NPs from microorganisms from this region, highlights the Arctic as a promising resource for NP discovery, reinforcing the notion that investigating unexplored environments for NP discovery is a very valuable tool in NPs research.


title: Caribbean Small Island States and United States Hegemony in the Caribbean Region

contributor: Bartmann, Barry (Examination Committee Member)

contributor: Srebrnik, Henry (Examination Committee Member)

contributor: Sutton, Paul (Examination Committee Member)

format: electronic 212 application/pdf PUBLISHED

rights: In presenting this thesis in partial fulfilment of the requirements for a graduate degree from the University of Prince Edward Island, the author has agreed that the Robertson Library, University of Prince Edward Island, may make this thesis freely available for inspection and gives permission to add an electronic version of the thesis to the Digital Repository at the University of Prince Edward Island. Moreover the author further agrees that permission for extensive copying of this thesis for scholarly purposes may be granted by the professor or professors who supervised the author’s thesis work, or, in their absence, by the Chair of the Department or the Dean of the Faculty in which the author’s thesis work was done. It is understood that any copying or publication or use of this thesis or parts thereof for financial gain shall not be allowed without the author’s written permission. It is also understood that due recognition shall be given to the author and to the University of Prince Edward Island in any scholarly use which may be made of any material in the author’s thesis.

abstract: The emergence of Caribbean small island states (SIS) through the 'demonstration effect‘ has resulted in even some of the smallest Caribbean islands achieving sovereignty. Past conventional security threats, such as the 1983 coup and intervention in Grenada, have resulted in the US Commonwealth Caribbean relations being interpreted in the context of US hegemony. Such an interpretation has been pejoratively interpreted as being negative, and therefore having a negative impact on Commonwealth Caribbean SIS. However, increasing recognition of unconventional security threats in the Caribbean (such as drug trafficking, illegal immigration, money laundering and gun smuggling) have led to the direct and indirect involvement of the United States (US) in the region‘s security agenda through increased regional cooperation. Despite negative connotations of US hegemony in the Commonwealth Caribbean, the US role in Commonwealth Caribbean SIS security can be considered that of a mentor state. This thesis will argue pejorative negative interpretations of US hegemony, in the context of the 1983 US invasion of Grenada, to assert that non-conventional threats are the predominant security threat to Commonwealth Caribbean SIS.


title: The truth about stories: An autoethnography towards earth consciousness

contributor:
DesRoches, John Darrell (author)
Walton, Fiona (Thesis advisor)
Thomas, Suzanne (Thesis advisor)
(Committee member)
(Signature Project Advisor)
(Supervisory Committee Member)
(Examination Committee Member)

format: print PUBLISHED 158 application/pdf

rights: In presenting this thesis in partial fulfillment for a postgraduate degree from the University of Prince Edward Island, I agree that the libraries of this University may make it freely available for inspection. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the Professors who supervised my thesis work, or, in their absence, by the Dean of the Faculty of Education. It is understood that any copying or publication or use of this thesis or parts thereof for financial gain shall not be allowed without my written permission. It is also understood that due recognition shall be given to me and to the University of Prince Edward Island in any scholarly use which may be made of any material in my thesis.

abstract:
The present ecological crisis reflects a crisis in human consciousness, especially in the western world, where our relationship with the earth and cosmos has been largely shaped and influenced by the stories we have been told in our culture. The old stories, as manifested in the myths and world views of our western cultural, philosophical and religious belief systems, emphasized humanity‟s dominion over nature and the benefits of economic, scientific and technological progress that regard the earth as having value in meeting our own ends.
A series of autoethnographic narratives and reflections suggest that technological progress alone will not curb the current ecological destruction of the earth. There is a need for new stories; for a re-storying about the earth that includes our interconnectedness with the planet. Earth consciousness is described as a relational and embodied understanding of ourselves vis-à-vis the earth. Earth consciousness fosters an understanding that humanity is part of the earth, part of the universe, not a separate entity. Respect, relationship and reciprocity are suggested as our best hope for the future, lying in our capacity for an attitude of reverence, wonder and awe at the creative, life-sustaining power of the universe.


title: Characterization and stability of gold nanocages for use as contrast agents in optoacoustics

contributor: Whelan, William (Supervisory Committee Member)

contributor: Bissessur, Rabin (Supervisory Committee Member)

contributor: Grabtchak, Serge (Supervisory Committee Member)

contributor: Wagner, Brian (Supervisory Committee Member)

contributor: Whelan, William (Examination Committee Member)

contributor: Bissessur, Rabin (Examination Committee Member)

contributor: Grabtchak, Serge (Examination Committee Member)

contributor: Wagner, Brian (Examination Committee Member)

contributor: Montelpare, William (Examination Committee Member)

contributor: Quijon, Pedro (Examination Committee Member)

format: 185 application/pdf PUBLISHED electronic

abstract:
Optoacoustic (OA) imaging is a new technique for cancer detection and non-invasive monitoring of cancer therapeutics. This technique is the combination of both optical and ultrasound modalities, in which tissue is irradiated with nanosecond laser pulses. The delivered optical energy is absorbed and converted into heat, leading to thermaoelastic expansion, which produces acoustic waves. Generated sound waves are then detected by ultrasonic transducers to form an image. In order to enhance optoacoustic signals in tissues, gold nanocages (AuNCs) can be used as contrast agents due to their tuneable optical properties in the near infrared region. Gold nanoparticles are biocompatible and their surface chemistry is well known, therefore they can be easily functionalized to targeting specific cells.
This work involved three linked investigations involving the synthesis, stability testing and optoacoustic contrast capabilities of AuNCs.  Silver nanocubes were synthesized to be used as templates for AuNCs synthesis. More then 95% purity was required but only 20-30% purity was achieved in our experiments due to the sensitivity of the reaction. Gold nanocages of 40-45nm were acquired from Dr. Younan Xia (Georgia Tech).
For all OA investigations the system consisted of a Nd:YAG pumped Ti:S laser, which can operate at either 775 nm or 1064 nm, an 8 element annular array transducer with 5 MHz central frequency and bifurcated optic fibre bundles to introduce light to the target. A 6 ns pulse duration and 10 Hz repetition rate were used. For the stability study, different pulse energies (5mJ, 10mJ) were used and at each energy, three different AuNCs concentrations were exposed for 1 min, 3 min and 5 min. Optical absorption measurements and TEM imaging confirmed conformational changes in AuNCs at both energies. For contrast investigations, three different AuNCs concentrations (8.0 X 1011 particles/ml, 2.7 X 1011 particles/ml and 1.6 X 1011 particles/ml) were tested against fluence, of 0.016 J/cm2 at 775nm using seven 1% Intralipid phantoms with different background absorption, μa (0.03cm-1, 0.1 cm-1, 0.5 cm-1, 1.0 cm-1, 1.5 cm-1, 2.0 cm-1, 4.0 cm-1). For the proof of principle study, pork loin tissues of 5mm 10mm thickness were used as background phantoms. A single AuNCs concentration (2.66 X 1011 particles/ml) and 9.2mJ laser energy (0.014 J/cm2) at 775nm was used. Results demonstrate that AuNCs show relevant contrast, even at the highest absorbing background (4.0 cm-1) and for the maximum pork loin thickness (10mm) tested. Results from 1% Intralipid also demonstrate that there were no conformational changes in AuNCs after the illumination. Therefore, the contrast study indicates that AuNCs could be used as contrast agents by knowing specific parameters, such as background optical properties, AuNCs concentration and required laser fluence.


title: Eastern oyster, Crassostrea virginica: Productivity and physiology under varying temperature and salinity conditions

contributor: Stryhn, Henrik (Supervisory Committee Member)

contributor: Davidson, Jeffrey (Supervisory Committee Member)

contributor: Landry, Thomas (Supervisory Committee Member)

contributor: Comeau, Luc (Supervisory Committee Member)

contributor: Burka, John (Supervisory Committee Member)

contributor: MacMillan, Kathleen (Examination Committee Member)

contributor: Bushek, Dave (Examination Committee Member)

contributor: St. Hilaire, Sophie (Examination Committee Member)

contributor: Comeau, Luc (Examination Committee Member)

contributor: Burka, John (Examination Committee Member)

format: electronic 165 application/pdf PUBLISHED

rights: In presenting this thesis in partial fulfillment of the requirements for a postgraduate degree from the University of Prince Edward Island, I agree that the Libraries of this University may make it freely available for inspection. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the professor or professors who supervised my thesis work recorded herein or, in their absence, by the Chairman of the Department or the Dean of the Faculty in which my thesis work was done. It is understood any copying or publication or use of this thesis or parts thereof for financial recognition shall not be allowed without my written permission. It is also understood that due recognition shall be given to me and to the University of Prince Edward Island in any scholarly use which may be made of any material in my thesis.

abstract:
In the early 1990s, the introduction of suspended culture methods and the development of a market for cocktail oysters (65–75 mm) propelled the oyster aquaculture industry in New Brunswick forward, now producing over 140,000,000 oysters (337,000 floating bags) on 2,649 hectares of private shellfish leases. Recently, the industry has been threatened by an oyster disease outbreak, known as MSX in the Bras D’Or Lakes region (Nova Scotia). The possibility of the MSX parasite spreading into New Brunswick waters, as well as an increasing number of aquatic invasive species in the area, is a real concern for the industry and has prompted an investigation on possible mitigation strategies.
The benefits of incorporating an upriver site into the production cycle of oyster aquaculture operations were evaluated. Seed (~ 26 mm shell height) and adult (~ 66 mm shell height) oysters were taken from downriver (salinity ~ 20–30‰) aquaculture sites and transferred upriver (salinity ~ 5–20‰) and monitored for shell and meat growth (May-October). At the same time, the impact of the relay fishery (harvest of oyster in closed marginally contaminated areas for relay to tenures in open areas) on oyster productivity was evaluated; wild upriver oysters were transferred downriver and monitored. Productivity data revealed that seed transferred upriver grew and survived as well as seed that remained downriver, while the mortality rates of adult oysters were lower at the upriver site. Meat content was unaffected in adult oysters transferred upriver. However, adult oysters transferred upriver had a gain in shell height (least squares means ± standard error) over the oysters that remained downriver (2.7 ± 0.5 mm vs. 1.8 ± 0.5 mm) and, in shell width (Median [95% CI]; 2.8 mm [1.9, 3.6] vs. 1.0 mm [0.3, 1.2]). Final organic meat content were approximately 35% less in adult oysters transferred downriver compared to those that remained upriver, confirming anecdotal reports from fishers of the relay fishery. Stress response of adult oysters was also assessed (80 and 150 days post transfer). Stress response measured revealed that regardless of their origin (upriver, downriver), oysters maintained upriver showed high levels of lysosomal destabilization and tissue atrophy. By contrast, the transfer downriver had the opposite effect, i.e. low lysosomal destabilization and low tubule atrophy. Results suggest that there exists no association between productivity parameters and the level of stress response measured by the biomarkers.
The field investigation prompted further exploration on the impact of hemolymph fluid osmolality on neutral red retention assay (NRA) outcome. The prescribed saline solution for the assay assumes animals are isosmotic to surrounding water; however oysters sampled were hyperosmotic. Hemolymph osmolality was manipulated under laboratory conditions by subjecting adult oysters to temperature (0, 5, 10, 15, 20ºC) and salinity (6, 27‰) regimes. At 10–20ºC, oysters remained isosmotic to ambient waters, while hyperosmotic at 0–5ºC. When mimicking spring freshets (salinity 6‰), hyperosmotic condition was observed in all temperature groups, and was inversely proportional to temperature. Monitoring of valve activity confirmed a restricted exchange at 6‰ salinity (e.g. spring freshet). With these laboratory results, use of filtered hemolymph fluid (NRAMOD) is recommended instead of the prescribed standard solution (standard NRA) adjusted to ambient seawater.


title: Cyclodextrin-based biodegradable polymer stars: Synthesis, degradation and fluorescence studies

contributor: Shaver, Michael (Supervisory Committee Member)

contributor: Wagner, Brian (Supervisory Committee Member)

contributor: Etkin, Nola (Supervisory Committee Member)

contributor: Linkletter, Barry (Supervisory Committee Member)

contributor: Briand, Glen (Supervisory Committee Member)

contributor: Polson, James (Examination Committee Member)

contributor: Shaver, Michael (Examination Committee Member)

contributor: Linkletter, Barry (Examination Committee Member)

contributor: Etkin, Nola (Examination Committee Member)

contributor: Briand, Glen (Examination Committee Member)

format: electronic 149 application/pdf PUBLISHED

rights:
In presenting this thesis in partial fulfillment of the requirements for a postgraduate
degree from the University of Prince Edward Island, I agree that the Libraries of this
University may make it freely available for inspection. I further agree that permission for
extensive copying of this thesis for scholarly purposes may be granted by the professor or
professors who supervised my thesis work, or, in their absence, by the Chair of the
Department or the Dean of the Faculty in which my thesis work was done. It is
understood any copying or publication or use of this thesis or parts thereof for financial
gain shall not be allowed without my written permission. It is also understood that due
recognition shall be given to me and to the University of Prince Edward Island in any
scholarly use which may be made of any material in my thesis.

abstract:
In controlled release, each patient’s body displays different pharmacokinetics for
the degradation of the drug delivery system affecting the release of the bioactive
compound. The proposed research aims to develop polymeric systems based on a
host/guest core capable of indicating controlled release by fluorescence. Specifically, this
involves the development of a prototype material based on a cyclodextrin molecule that
serves as a framework for biodegradable polymer arms.
Binding constant and correlation studies were successfully conducted with β-
cyclodextrin and heptakis(2,6-di-O-methyl)-β-cyclodextrin with 7-methoxycoumarin
using solvent systems of water and methanol and pure water. Studies on β-CD in H2O
gave a binding constant of 238 M-1 and an R2 value of 0.9580. Stronger binding and a
better correlation was obtained with heptakis(2,6-di-O-methyl)-β-CD in H2O with a
binding constant of 306 M-1 and R2 value of 0.998. Binding in H2O/MeOH was also
tested with heptakis(2,6-di-O-methyl)-β-CD resulting in a weaker binding constant of
120 M-1 and lower correlation value of 0.986 due to the decrease in solution polarity.
Polymer stars were synthesized based on core- and arm-first methods. For corefirst
synthesis, stars based on a heptakis(2,6-di-O-methyl)-β-cyclodextrin core that
supports 7 polymer arms of poly(lactic acid) (PLA), poly(3-hydroxybutyrate) (PHB) or
poly(lactic-co-glycolic acid) (PLGA) were synthesized by ring-opening polymerization
with variation in both the polymer microstructure and arm length. Use of Sn(Oct)2 as a
catalyst yielded polymers with high PDI values and poor molecular weight correlation.
Switching to the Al[salen] system yielded polymers with excellent PDI values but low
molecular weight correlation.
For arm-first synthesis, copper-catalyzed azide-alkyne cycloaddition was used to
synthesize 7 arm stars based on a β-CD-(N3)7 and acetylene terminated polymers of PLA,
PHB, PCL and PLGA. Excellent levels of control and good molecular weight correlation
was obtained from arm-first synthesis. However, isolation of these stars was challenging,
resulting in low yields.
Analysis of these polymers by 1H NMR spectroscopy revealed the polymer
composition whilst differential scanning calorimetry gave glass, melt and crystallization
temperatures. Decomposition temperatures were also investigated by thermogravimetric
analysis. Molecular weights and polydispersities of these polymers were determined by
using gel permeation chromatography coupled with light scattering detectors as well as
1H NMR spectroscopy.
A 7-methoxycoumarin fluorophore was used to demonstrate the controlled release
characteristics of these novel materials by fluorescence spectroscopy by uncatalyzed and
enzyme catalyzed degradations, showing that they have potential as controlled release
vectors.


title: Immunotoxic effects of benzo[a]pyrene on rainbow trout (Oncorhynchus mykiss)

contributor: van den Heuvel, Michael (Thesis advisor)

contributor: van den Heuvel, Michael (Supervisory Committee Member)

contributor: Kamunde, Collins (Supervisory Committee Member)

contributor: Hogan, Natacha (Supervisory Committee Member)

contributor: van den Heuvel, Michael (Examination Committee Member)

contributor: Hogan, Natasha (Examination Committee Member)

contributor: Kamunde, Collins (Examination Committee Member)

contributor: Fast, Mark (Examination Committee Member)

contributor: Giberson, Donna (Examination Committee Member)

format: electronic 86 application/pdf PUBLISHED

rights:
In presenting this thesis in partial fulfillment of the requirements for a postgraduate
degree from the University of Prince Edward Island, I agree that the Libraries of this
University may make this thesis freely available for inspection and give permission to
add an electronic version of the thesis to the Digital Repository at the University of
Prince Edward Island. Moreover, I further agree that permission for extensive copying of
this thesis for scholarly purposes may be granted by the professor or professors who
supervised my thesis work, or, in their absence, by the Chair of the Department or the
Dean of the Faculty in which my thesis work was done. It is understood any copying or
publication or use of this thesis or parts thereof for financial gain shall not be allowed
without my written permission. It is also understood that due recognition shall be given to
me and to the University of Prince Edward Island in any scholarly use which may be
made of any material in my thesis.

abstract:
Polycyclic aromatic hydrocarbons (PAHs) are a group of compounds with
immunotoxic and carcinogenic potential that may pose a threat to fish populations. The
mechanism underlying immune toxicity of PAHs in fishes remains unclear. Some
evidence supports the requirement for metabolism to more toxic metabolites. This twopart
study aims to utilize a newly developed fish immunotoxicology model to determine
the immune tissue/cell population level effects of PAHs on rainbow trout, using
benzo[a]pyrene (BaP) as a representative immunotoxic PAH. In the first part of the study,
intraperitoneal injection of 25 or 100 mg/kg BaP resulted in sustained exposure as
indicated by biliary fluorescence at BaP wavelengths for up to 42 d. A new flow
cytometry method for absolute counts of differential leukocyte distributions in spleen,
blood, and head kidney was developed by combining absolute quantitative counts of total
leukocytes in the tissue (3,3′-dihexyloxacarbocyanine iodide (DiOC6) dye) with relative
differential counts using monoclonal antibodies for B cells, T cells, myeloid cells, and
thrombocytes. Experiments indicated dose- and time-dependent decreases in the absolute
number of B cells, myeloid cells, or T cells in blood, spleen, or head kidney after 7, 14 or
21 d of exposure. There was no change in the absolute numbers of erythrocytes or
thrombocytes in any tissue. When rainbow trout were exposed to inactivated Aeromonas
salmonicida after a 21 d exposure to 100 mg/kg BaP, circulating antibody concentrations
were decreased by 56%. It was concluded that BaP has a cell lineage-specific toxic effect
on some immune cells of rainbow trout, and causes a decrease in circulating antibody
levels. The second part of the study examined whether intraperitoneal exposure of
rainbow trout to BaP caused leukocyte mRNA expression changes in five cytochrome P450 (CYP) enzymes; to their transcription factor, AhR; or to an extrinsic pathway
apoptosis checkpoint, p53. mRNA expression was analyzed in immunomagnetically
isolated B cells and thrombocytes from blood, spleen, or head kidney in an effort to
clarify the tissue and cell specific toxicity of BaP. Significant inductions above control
levels were observed in CYP1A1 in liver, blood B cells, and blood thrombocytes;
CYP1B1 in blood B cells, and blood thrombocytes; CYP1A3 in liver, blood and spleen B
cells; and AhR in spleen thrombocytes. No significant changes were found in CYP1C1,
CYP1C2, or p53. Increased mRNA expression was observed 14 d after exposure,
indicating a prolonged physiological effect of a single BaP injection. Although there were
differences in expression, it was concluded that variations in the presence or induction of
CYP enzymes is not enough to explain the difference in toxicity observed between B
cells and thrombocytes. An induction of AhR in thrombocytes is interesting, but difficult
to explain given current knowledge on endogenous AhR regulation and the limited
toxicity in thrombocytes. Overall, our findings provide support for a complex mechanism
of toxicity for chronic PAH exposure, and suggest that CYP expression profiles do not
fully explain these effects.


title: Assessment of balance behaviour, eye-movement, and attention: A step towards a more comprehensive concussion return-to-play protocol

contributor: Montelpare, William (Supervisory Committee Member)

contributor: Reed-Jones, Rebecca (Supervisory Committee Member)

contributor: Zerpa, Carlos (Supervisory Committee Member)

contributor: Montelpare, William (Examination Committee Member)

contributor: Reed-Jones, Rebecca (Examination Committee Member)

contributor: Zerpa, Carlos (Examination Committee Member)

contributor: Livingston, Lori (Examination Committee Member)

contributor: Quijon, Pedro (Examination Committee Member)

format: electronic application/pdf PUBLISHED

abstract: Concerns associated with head injuries have come to the forefront as head trauma events in the National Hockey League (NHL) and National Football League (NFL) bring to light the prevalence and effects of concussions. Accordingly, proper assessment and management of head injuries are growing areas of interest among the general public and researchers. At this point, most sports leagues and teams have established the need for concussion protocols and have set standards that must be met when an injury occurs or is suspected. In an effort to make assessments accessible to the general public, many tests are simplified to computer tests that require very little training or cost to administer. However, these assessment protocols are often not thorough enough to detect the various potential deficits and symptoms that can occur after a head injury. Of the various possible symptoms of a concussion, the highest testable deficits are balance dysfunction and dizziness. Further, most tests used to evaluate athletes comprehensively, are not ecologically relevant. The increased challenges athletes incur through their participation in sport in their everyday lives must be considered when developing baseline testing. The present research study aimed to aid in the correction of the previously mentioned inadequacies. A test-retest design used 4 instruments to evaluate 20 healthy individuals ranging in age from 17-25. The BESS, ANT, Wii Fit Balance Board, and Mobile Eye XG glasses were used to measure static and dynamic balance, attention, and gaze. The results indicate that the selected measures were stable and consistent with traditionally used protocols for healthy individuals. By analyzing the test-retest reliability of the Soccer Heading Game on the Wii Fit Balance Board while wearing an eye-tracking device, a more ecologically relevant and comprehensive test is available to assess an athlete's balance.


title: Effects of neonatal domoic acid treatment and social isolation rearing on measures of attentional processing in rats: An investigation of the “two-hit” hypothesis of psychiatric disease

contributor: Tasker, Andrew (Supervisory Committee Member)

contributor: Doucette, Tracy (Supervisory Committee Member)

contributor: Hartwig, Sunny (Supervisory Committee Member)

contributor: Hurta, Robert (Supervisory Committee Member)

contributor: Ryan, Catherine (Supervisory Committee Member)

contributor: Dawson, Susan (Examination Committee Member)

contributor: Tasker, Andrew (Examination Committee Member)

contributor: Doucette, Tracy (Examination Committee Member)

contributor: Stevens, Don (Examination Committee Member)

contributor: Hurta, Robert (Examination Committee Member)

contributor: Kostrzewa, Richard M (Examination Committee Member)

format: electronic 282 application/pdf PUBLISHED

rights: In presenting this thesis in partial fulfilment of the requirements for a graduate degree from the University of Prince Edward Island, the author has agreed that the Robertson Library, University of Prince Edward Island, may make this thesis freely available for inspection and gives permission to add an electronic version of the thesis to the Digital Repository at the University of Prince Edward Island. Moreover, the author further agrees that permission for extensive copying of this thesis for scholarly purposes may be granted by the professor or professors who supervised the author’s thesis work, or, in their absence, by the Chair of the Department or the Dean of the Faculty in which the author’s thesis work was done. It is understood that any copying or publication or use of this thesis or parts thereof for financial gain shall not be allowed without the author’s written permission. It is also understood that due recognition shall be given to the author and to the University of Prince Edward Island in any scholarly use which may be made of any material in the author’s thesis.

abstract:
Neuropsychiatric disorders affect a significant number of people across the globe and are a serious economic and social burden. As a class of diseases they are often poorly understood, difficult to treat, and can lead to a significant decline in normal function and quality of life. Recent evidence supports the notion that many neuropsychiatric disorders are neurodevelopmental in foundation, originating at least in part from abnormal activity during critical periods of brain development. Attentional processing is a higher order cognitive behaviour fundamental to many important brain processes and is known to be affected in a number of human neuropsychiatric disorders. The purpose of the research described herein was to better understand how changes in early brain development can have a long lasting effect on the central nervous system relevant to the etiology of neuropsychiatric disorders, and to utilize a novel approach to investigate the “two-hit” hypothesis of psychiatric disease by probing the effects of chemically (neonatal low-dose domoic acid [DOM] treatment) and/or environmentally (social isolation rearing) induced changes in attentional processing.
First, adult untreated rats were used to develop a latent inhibition (LI) paradigm that resulted in both deficient and abnormally persistent LI. Next, utilizing both the newly-developed LI protocol and previously established protocols for prepulse inhibition (PPI), the behavioural consequences of neonatal DOM administration and social isolation housing, both alone and in combination, were measured. Results indicated a number of behavioural alterations in both sexes and across all treatment groups indicating that neonatal DOM treatment and isolation rearing affect both of these measures of attentional processing although not in identical ways. Subsequently, the regional expression profiles of various proteins involved in dopaminergic and GABAergic neurotransmission were quantified by Western blot analysis to investigate the potential molecular alterations responsible for the observed behavioural changes. No significant effects on these markers were observed in any treatment group, although large inter-individual variations were noted. A preliminary post-hoc analysis of correlations between changes in PPI and protein expression resulted in a number of significant correlations and suggested that the various experimental manipulations were differentially affecting the signalling pathways involved.
In conclusion, both neonatal low-dose DOM treatment and social isolation rearing affect the development of attentional processing in rats. However, each paradigm may exert these effects through different neuronal signalling systems and these different systems may be responsible for different aspects of the behavioural changes that were observed. Finally, this work illustrates the potential of a novel “two-hit” method for studying the development of neuropsychiatric disease as well as the complex interconnected processes that are affected by altered brain development.


title: Resistance to emamectin benzoate in sea lice

contributor: Burka, John (Supervisory Committee Member)

contributor: Bate, Luis (Examination Committee Member)

contributor: Fast, Mark (Supervisory Committee Member)

contributor: Wright, Glenda (Supervisory Committee Member)

contributor: Kamunde, Collins (Supervisory Committee Member)

contributor: Westcott, Jillian (Supervisory Committee Member)

contributor: Siah, Ahmed (Supervisory Committee Member)

contributor: Burka, John (Examination Committee Member)

contributor: Fast, Mark (Examination Committee Member)

contributor: Whyte, Shona (Examination Committee Member)

contributor: Greenwood, Spencer (Examination Committee Member)

contributor: Prichard, Roger (Examination Committee Member)

format: electronic 242 application/pdf PUBLISHED

rights:
In presenting this thesis in partial fulfillment of the requirements for a postgraduate degree from
the University of Prince Edward Island, I agree that the Libraries of this University may make it
freely available for inspection. I further agree that permission for extensive copying of this
thesis for scholarly purposes may be granted by the professor or professors who supervised my
thesis work, or, in their absence, by the Chair of the Department or the Dean of the Faculty in
which my thesis work was done. It is understood any copying or publication or use of this thesis
or parts thereof for financial gain shall not be allowed without my written permission. It is also
understood that due recognition shall be given to me and to the University of Prince Edward
Island in any scholarly use which may be made of any material in my thesis.

abstract:
Effective control of parasitic sea lice (including Lepeophtheirus salmonis and Caligus
elongatus), is a major challenge currently facing sea cage salmon aquaculture. Emamectin
benzoate (EMB; SLICE®), a macrocyclic lactone (ML), has been the drug of choice for sea lice
treatment over the past decade due to its ease of administration, as well as efficacy, on all
parasitic stages of the salmon parasite. This over-reliance led to increased tolerance to the drug
and a consequent decline in its use. Macrocyclic lactone resistance has been linked to ATPbinding
cassette (ABC) transporters such as P-glycoprotein (P-gp) in arthropods and nematodes.
The present study investigated the role of P-gp in sea lice resistance to EMB. Analysis of
bioassay results indicated a 4 to 26 fold higher EMB EC50 for L. salmonis samples collected from
salmon farms in the Bay of Fundy, New Brunswick (NB), in 2011 compared with a similar study
carried out between 2002 and 2004, suggesting loss of EMB efficacy in sea lice in this region.
An assay for ATPase activity (utilizing SB-MDR1-Sf9 membranes over-expressing P-gp), as
well as a competitive inhibition test, showed that EMB interacts with this transporter.
Emamectin benzoate caused a significant concentration-dependent increase in P-gp mRNA
expression in L. salmonis. Also, results indicated a temporal increase in P-gp mRNA levels in
archived L. salmonis collected from 2002 to 2011. These findings suggest that EMB is a
substrate for P-gp, will induce higher expression of the transporter, and that the latter is likely
involved in loss of EMB efficacy in L. salmonis. Contrary to initial prediction that prior host
immunostimulation would enhance EMB efficacy in the parasite, sea lice attached to salmon
with a history of immunostimulation exhibited greater survival and significantly higher P-gp
mRNA expression compared with control groups (P < 0.05). Prior host immunostimulation likely caused increased expression of P-gp which could have consequently caused decreased
EMB efficacy.
The present study also investigated (using bioassays and RT-qPCR) reports of differences
in sea lice EMB sensitivity in salmon farming regions in the Bay of Fundy. Lepeophtheirus
salmonis collected from Grand Manan [Bay Management Area (BMA) 2b] recorded >2 fold
lower EMB EC50 values compared with BMAs 1 and 2a populations, confirming the presence of
relatively EMB-sensitive sea lice in BMA 2b. Laboratory-reared sea lice maintained their EMB
sensitivity status for up to three filial generations. Caligus elongatus, collected from BMA 2a,
also showed >2 fold lower EMB EC50 values compared with L. salmonis collected from the same
site, indicating species differences in sensitivity to the parasiticide. Attempts to localize sea lice
P-gp protein and mRNA in situ using immunohistochemistry and in situ hybridization
techniques, respectively, were not successful. Similarly, the quantification of P-gp in L.
salmonis using ELISA and Western blot techniques was unsuccessful. This could be due to low
P-gp expression at mRNA and protein levels and/or poor antigenic specificity of the antibodies
used.
Results in this study strongly support the hypothesis that the efflux transporter, P-gp, is
involved in reduced sensitivity of L. salmonis to EMB, and that this occurs over time due to drug
selection of resistant strains of the parasite. However, there is a need to develop sensitive tools,
e.g. probes and antibodies, which will localize and quantify L. salmonis P-gp mRNA and protein
production. This will allow for a greater understanding of the role of P-gp in sea lice resistance
to EMB as well as a greater ability to monitor resistance development to the parsiticide.
Changes in the expression of resistance-associated genes, such as those for P-gp, can be
monitored and used in the diagnosis of resistance development to parasiticides. Knowledge of the timing for resistance development will inform necessary changes to treatment options to
prevent treatment failure. Further comparisons between EMB-sensitive and -resistant strains of
L. salmonis may be necessary to verify the degree to which P-gp is involved in the loss of
parasite sensitivity to the drug. More investigations on the nature of the species differences in
EMB sensitivity in sea lice, as well as the heredity of EMB resistance mechanisms, is necessary
for a better understanding of how this parasite strives to survive its control.


title: Mitochondrial bioenergetics: An integrated platform to study interactions of multiple stressors

contributor: Kibenge, Frederick (Supervisory Committee Member)

contributor: Stevens, Don (Supervisory Committee Member)

contributor: MacCormack, Tyson (Examination Committee Member)

contributor: Kamunde, Collins (Examination Committee Member)

contributor: Aburto, Enrique (Examination Committee Member)

contributor: Hanna, Paul (Examination Committee Member)

format: electronic 289 application/pdf PUBLISHED

abstract:
Animals must expend energy to deal with a wide array of stressors associated with
environmental change. Because mitochondria produce >90% of the energy requirement of the
cell, they are likely the fundamental drivers of responses to environmental change. The primary
goal of my thesis was to explore the interactions of three common stressors in aquatic systems –
temperature, metals (copper: Cu) and hypoxia– on mitochondrial bioenergetics. To achieve this,
I first performed a series of in vitro experiments using rainbow trout, Oncorhynchus mykiss liver
mitochondria energized with complex I and II substrates to characterize the acute interactive
responses of temperature and Cu on mitochondrial function. These studies revealed that Cu
altered the basal and maximal mitochondrial oxidation rates differently depending on the metal
dose and temperature. Mechanistically, I showed that Cu impairs oxidative phosphorylation in
part by inhibiting the electron transport system (ETS) enzymes, stimulating proton leak, inducing
mitochondrial permeability transition pore and dissipating inner membrane potential.
Importantly, temperature exacerbated the effects of Cu suggesting that environmental warming,
e.g., due to climate change, may sensitize fish to Cu toxicity.
The next study combined in vitro and in vivo approaches to shed light on how persistent elevated
temperature (warm acclimation) modulates the effects of acute temperature increase, hypoxiareoxygenation
(HRO) and/or Cu on mitochondrial function. Sequential inhibition and activation
of mitochondrial ETS enzyme complexes permitted the measurement of respiratory activities
supported by ETS complexes I-IV in one run and allowed me to identify segments/components
of the ETS that are resilient or susceptible to single and combined effects of temperature, Cu and
HRO. This study also revealed that warm acclimation blunted the sensitivity of the ETS to acute
temperature rise and, together with HRO, sensitized the ETS to Cu. My fourth study examined how warm acclimation influences the ability of fish to handle
individual and joint effects of subsequent acute temperature shifts, hypoxia and Cu stress by
exposing fish in vivo to the three stressors. Here I measured mitochondrial oxidation and apical
endpoints indicative of stress and organismal energy status to assess the relevance of energy
metabolism endpoints in vivo. I showed that warm acclimation reduced fish condition, promoted
anaerobic metabolism, decelerated the ETS and altered the responses of fish to acute temperature
shifts, hypoxia and Cu. Moreover, Cu and hypoxia showed reciprocal antagonistic interaction on
the ETS and plasma metabolites, with modest additive actions limited to proton leak.
The final study highlighted the functional-biochemical and transcriptional responses of fish to
warm acclimation and short-term exposures to Cu and hypoxia. In this in vivo study, activities of
ETS enzyme complexes and targeted analyses of transcripts encoding for proteins involved in
mitochondrial oxidation, metals detoxification/stress response and energy sensing were done in
isolated liver mitochondria and in whole liver and gill tissues by RT-qPCR. Warm acclimation
inhibited activities of ETS enzymes while effects of Cu and hypoxia depended on the enzyme
and thermal acclimation status. The genes encoding for proteins involved in mitochondrial
oxidation, metals detoxification/stress response and energy sensing were all strongly regulated
by warm acclimation while Cu and hypoxia clearly increased transcript levels of genes encoding
for proteins involved in metals detoxification/stress response. Overall, the studies I carried out
not only provided the mechanistic underpinnings of responses of fish to thermal stress, hypoxia
and Cu, but unveiled novel interactive effects of multiple stressors. Importantly, I showed that
mitochondria are a viable platform for integrating effects of multiple stressors.


title:
Young writers as philosophers: teaching writing through natural inquiry and
community dialogue

contributor: McAuley, Alexander (Supervisory Committee Member)

contributor: Courtenay-Hall, Pamela (Supervisory Committee Member)

contributor: McAuley, Alexander (Examination Committee Member)

contributor: Courtenay-Hall, Pamela (Examination Committee Member)

format: electronic 205 application/pdf PUBLISHED

rights:
In presenting this thesis in partial fulfillment of the requirements for a
postgraduate degree from the University of Prince Edward Island, I agree that the
Libraries of this University may make it freely available for inspection. I further
agree that permission for extensive copying of this thesis for scholarly purposes
may be granted by the professor or professors who supervised my thesis work, or,
in their absence, by the Chair of the Department or the Dean of the Faculty in which
my thesis was done. It is understood any copying or publication or use of this
thesis or parts thereof for financial gain shall not be allowed without my written
permission. It is also understood that due recognition shall be given to me and to
the University of Prince Edward Island in any scholarly use which may be made of
any material in my thesis.

abstract:
Current school culture places excessive emphasis on children reaching a
minimum standard impairing their ability to reach their greatest potential. Students need
to be challenged individually in authentic learning opportunities so that they can be
supported to thrive as individuals. Teaching philosophically is one method that can
address students’ needs including those requiring enrichment and additional support.
Students are able to sustain thinking on subjects of authentic interest and reflect and
assist one another through a recursive process of dialogue in the community of inquiry
and writing. A qualitative study based on a three-month intervention in a grade two
classroom revealed that philosophical activity and writing instruction can be reciprocally
beneficial for primary student learning. Data sources include the participant teacher’s
reflective journal, student-written reflections, assessed student work, video and a rubric
measuring philosophical understanding.
Teaching writing philosophically provides an authentic and student-centred way
of challenging students to deepen their reasoning skills, understanding and capacity for
critical, creative and caring thinking. Philosophy can be taught within a subject so time
allotment in the curricular timetable can be met. The study is significant in Prince
Edward Island because there is currently no documentation of any such initiatives to
share with other teachers. An engaging and evocative stimulus, community of inquiry
scaffolding, reflection, metacognition, narrative as genre and an effective working
environment are necessary to ensure students are secure participating in challenging
activities. Philosophical activity can engage and deepen grade two students’ thinking,
while allowing them to play with ideas and imagine novel possibility.