Biomedical Physiology and Kinesiology - Theses, Dissertations, and other Required Graduate Degree Essays

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Drosophila adducin interacts with synaptic modelling proteins: Draper and Discs-large

Author: 
Date created: 
2015-03-30
Abstract: 

Manipulation of the postsynaptic hu-li tai-shao (hts) transcript can affect synaptic development and plasticity. Hts is an actin-spectrin binding protein that is situated close to the synaptic cell membrane where it can co-localize with many synaptic modelling proteins. Two proteins, Draper (Drpr) and Discs large (Dlg), were found to be regulated by Hts at the postsynaptic membrane of Drosophila 3rd instar larval NMJ. Interestingly, both interacting partners are known to be involved in synaptic remodeling, where Drpr is involved in synaptic pruning and Dlg is involved in the regulation of synaptic cell-cell adhesion. In this study I focused on the characterization of interactions between Hts and Drpr while looking into the possibility that Dlg serves as a mediator between these interactions. I found genetic interaction between hts and drpr, and saw a potential triple-protein-complex between Hts, Dlg and Drpr, which may work together to manipulate synaptic development.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Charles Krieger
Nicholas Harden
Department: 
Science:
Thesis type: 
(Thesis) M.Sc.

Effects of Elevated Core Temperature and Normoxic 30% Nitrous Oxide on Control of Human Breathing during Short Duration, High Intensity Exercise

Author: 
Date created: 
2014-09-17
Abstract: 

It is unresolved how pulmonary ventilation (VE) is influenced by normoxic 30% nitrous oxide (N2O) breathing and hyperthermia during supramaximal intensity exercise. It was hypothesized that normoxic N2O will suppress and hyperthermia will increase exercise ventilation, timing and ventilatory drive during supramaximal intensity exercise. Seven college-aged males volunteered for 4 separate 30 s Wingate cycle ergometer tests. The studies included a 2 x 2 design with factors of Thermal State (normothermia or hyperthermia) and Gas Type (Air or normoxic 30% N2O). A significant interaction (F=8.4, p=0.03) between these 2 factors for VE was explained by a VE from 85 ± 27 L/min (p=0.06) during normothermia with N2O to a VE of 104 ± 23 L/min in hyperthermia with N2O. There were no main effects or interactions for Thermal State and Gas Type for timing components and ventilatory drive. In conclusion, an interaction of Thermal State and Gas Type on VE was explained by its suppression during normothermia relative to its rate in hyperthermia, both during normoxic N2O breathing during supramaximal intensity exercise.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Matthew White
Department: 
Science:
Thesis type: 
(Thesis) M.Sc.

Sugar-sweetened beverages and their relationship to obesity in South Asian children

Date created: 
2014-09-04
Abstract: 

The prevalence of obesity among South Asian (SA) children is increasing in comparison to their ethnic counterparts. This is of great concern given that SA adults have a greater predisposition to cardiovascular disease and type II diabetes. This increase in obesity may be further exacerbated by the adoption of ‘Westernized’ lifestyle behaviours such as dietary changes. Over the past fifty years, consumption of sugar sweetened beverages (SSBs) has dramatically increased to high levels which have led SSBs to become highly scrutinized as a major contributor to the rise in childhood obesity. Evidence suggests the consumption of SSBs is associated with a rise in body mass index (BMI) in young children and adolescents. It is unknown whether this effect is exacerbated in specific populations at high risk of obesity, such as SA children. For this investigation a total of 363 SA children enrolled in grades 2 and 3 were randomly recruited from communities in Vancouver, British Columbia and Hamilton, Ontario. Children were evaluated using the RICH LEGACY Questionnaire that included a comprehensive assessment of the child’s lifestyle and physical measures. Independent multiple linear regression models adjusted for age and sex displayed an association between consumption of SSBs with z-BMI (p=0.02) but not with waist circumference (WC) (p=0.35) and waist to height ratio (W:Ht) (p=0.86). Diet beverages were not associated to z-BMI, WC or W:Ht (p=0.43, 0.46, 0.43, respectively). This new evidence is key in shaping future public health policies and interventions aimed at reducing the prevalence of childhood obesity.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Scott Lear
Department: 
Science:
Thesis type: 
(Thesis) M.Sc.

Molecular Dynamics Based Predictions of the Structural and Functional Effects of Disease Causing Cardiac Troponin C Mutations

Date created: 
2014-05-29
Abstract: 

Human cardiac troponin C (HcTnC), the regulatory calcium-binding component of the troponin complex, is responsible for the regulation of cardiac muscle contraction in response to varying cytosolic calcium levels. Mutations that are shown to increase the cTnC Ca2+ affinity are hypothesized to induce hypertrophic cardiomyopathies (HCM). Several mutations in HcTnC have been selected that are associated with HCM. These mutations include A8V, L29Q, C84Y, E134D, and D145E. The structural effects of these mutations have been modeled through equilibrium molecular dynamics and their functional and structural impacts have been assessed. In each mutant that was analyzed, the equilibrated structures have shown notable deviations from wild-type in the regions known to be cardiac troponin I (cTnI) interaction sites. There were differences in the conformation dynamics of site II and cTnC/cTnI interaction sites. We anticipate these correlations may contribute to Ca2+ affinity either directly or indirectly through cTnI association.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Glen F. Tibbits
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Scaling of sensorimotor control in terrestrial mammals

Date created: 
2013-12-17
Abstract: 

Terrestrial mammals span a wide range of sizes, with the largest elephant being several million times more massive than the smallest shrew. This huge size range results in small and large animals experiencing very different physical challenges, yet all animals must effectively interact with their environment to survive. In order to sense and respond to stimuli with similar speed and precision, small and large animals may need to control their movement in different ways. To begin to understand whether and how small and large animals coordinate their movement with similar effectiveness despite their different physical challenges, I investigated how size influences the physiological mechanisms underlying sensorimotor control. My general hypothesis was that the sensorimotor systems of larger animals have longer delays and lower precision than those of smaller animals. To investigate the scaling of delays, I combined my own electrophysiology measurements with data from the literature to determine how total response time and its component delays changed with animal mass. To investigate the scaling of precision, I combined my own histology measurements with data from the literature to determine how nerve fiber number and size distribution changed with animal mass. As part of this, I developed a supervised image analysis method to measure nerve fiber characteristics in scanning electron microscope images. I found that larger animals have longer absolute delays and more nerve fibers than smaller animals. However, changes to movement times with animal size almost entirely compensate for increases in absolute delays, resulting in similar relative delays for all sizes of animals. Nerve fiber number increases more slowly than animal mass, area, and muscle force, suggesting that larger animals have relatively fewer sensors and motor units than smaller animals. Nerve fiber size distribution becomes more bimodal as animal size increases, ameliorating the potential tradeoff between speed and precision in peripheral nerves. While small and large animals seem to be able to sense and respond to stimuli within the same relative time, large animals may face challenges in situations requiring short absolute delays and high precision, and may need to rely more heavily on predictive methods of control.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Max Donelan
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Dissertation) Ph.D.

In vivo Measurements of Biophysical Properties of a Heart and Aorta in a Mouse Model of Marfan Syndrome

Author: 
Date created: 
2014-05-28
Abstract: 

In Marfan Syndrome (MFS) patients cardiovascular complications are the most life-threatening manifestations and death is often sudden due to aortic dissection and rupture. Echocardiography is critical in the diagnosis and follow-up of MFS patients to detect and evaluate their cardiovascular phenotype. High frequency echocardiography was used to investigate the structural and functional properties on 6- and 12-mo WT and MFS [Fbn1 (C1039G/+)] mice (n = 8). The data show that Pulse Wave Velocity (PWV) was significantly increased in 6-mo MFS vs. WT (366.6 ± 19.9 vs. 205.2 ± 18.1 cm/s; p < 0.001) and 12-mo MFS vs. WT (459.5 ± 42.3 vs. 205.3 ± 30.3 m/s; p = 0.001) and the PWV increased directly in proportion to age in MFS mice but not in WT mice. LV mass (3.06 ± 0.16 vs. 2.46 ± 0.09 μm/g; p = 0.007) was significantly increased in 6-mo MFS mice compared with WT. We also found a significantly enlarged aortic root, decreased E/A ratio, prolonged isovolumic relaxation time and increased myocardial performance index in MFS mice compared with WT for both age groups. This study shows significant aortic dilation and central aortic stiffness in the MFS mice which are associated with LV hypertrophy, systolic and diastolic dysfunction. Moreover, the symptoms progressed with increasing age from six months to twelve months.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Glen Tibbits
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Effects of physiological, pharmacological, and toxic factors on cell transport

Date created: 
2014-04-22
Abstract: 

Endocytic transport is a fundamental cell function involved in nutrient assimilation, signal transduction, growth, and other cellular activities. Disruption of this transport has been associated with aging and some chronic diseases. There is growing interest in possible regulation of the endocytic machinery by physiological factors, and in pathological processes. In this project, I analyzed effects of (a) pro-oxidative factors such as ROS and amyloidogenic polypeptide aggregates, (b) physiological factors such as EGF and steroid hormones, and (c) select pharmacological or phytochemical compounds, on different endocytic pathways within a cell, and among different cell types. The results provide evidence that pro-oxidants can inhibit endocytic transport in different cell types; and the pathways can exhibit differences in sensitivity to a pro-oxidant. Select physiological and pharmacological factors can also stimulate or inhibit some of these transport pathways in different cell types. Further screening and testing of pharmacological modulators may identify possible therapeutic compounds.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Amandio Vieira
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Computational models of chronic diseases: understanding and leveraging complexity

Peer reviewed: 
No, item is not peer reviewed.
Date created: 
2014-04-14
Abstract: 

People struggle to implement interventions that create a significant and sustainable weight loss. This suggests that we need to move beyond viewing obesity as a mere matter of diet and exercise. Instead, we need to accept that the system giving rise to obesity is complex and re-think the ways in which we have approached weight management. This thesis is concerned with the development of microsimulation models that address three features of this complexity at the level of individual food and physical activity behaviours: heterogeneity of individuals and environments, many interactions and loops found between drivers and nonlinearity of the relationships between behaviours. These models were used to explore the dynamics of behaviours, and to support `what-if' scenarios in which we can assess the virtual consequences of possible interventions. In particular, we found that social influences can be as important as environmental influences in changing individuals' weight. However, simulations suggested that intervening in social influences has a larger impact on changing weights by promoting healthy eating than either tax-based or zoning interventions. Our models demonstrated that the structure of communities can be a confounder, as strongly-linked communities reduce the effectiveness of interventions based on social influences. We also highlighted the potential of models to generate social theories. Taking binge drinking as a case study, we generated a set of hypotheses that explains the behaviour of half of the binge drinkers and 4 out of 5 non-binge drinkers. This thesis also made several technical advances. First, we presented an innovative computational framework that supports modelers in expressing how social influences are mediated by the specificities of each individual's context. This is a major improvement over previous microsimulation models that were limited to viewing obesity as contagious. The framework was demonstrated for insurgencies and obesity. Second, we designed and evaluated novel techniques to address heterogeneity when performing a randomized controlled trial for behaviour change. Software was created for both. Finally, we created a system to support practitioners in navigating the maze of factors relevant to their patients, and we used health games to empower patients into the management of their own well-being.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Diane Finegood
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) Ph.D.

Automatic pacing: on the use of external timing cues to regulate speed during human walking and running

Author: 
Date created: 
2013-12-16
Abstract: 

Out of all parameters used to describe gait, overground speed is one of the most important. The importance of gait speed is highlighted when used as a measure of performance during exercise, or as a measure of function when walking ability is compromised. Because the ability to control gait speed is imperative to reach optimal results in both exercise and gait rehabilitation, a system that helps people to control their overground speed more accurately might be beneficial. Developing an overground speed control system was the main goal of this thesis. To gain insight in the performance enhancing effects that can be expected from such a system, my colleagues and I first determined the ability of recreational runners to accurately control their own speed. We then used a simulation approach to estimate the effect of pacing inaccuracy on optimal running performance. Our simulation results suggested that the existing pacing error (2.3±4.6%) would decrease optimal performance by approximately 5% for an average recreational runner. These results indicate that the performance of recreational runners could be improved by minutes for typical race distances, simply by helping them achieve and maintain their optimal speed. To determine the viability of controlling overground speed by prescribing step frequency, we quantified the dynamic response in walking and running speed following controlled perturbations in prescribed metronome frequency. We found that perturbations in metronome frequency triggered rapid and predictable changes in speed, suggesting that overground speed is indeed controllable by prescribing step frequency. However, due to the variability present in the speed response, both within and between individuals, accurately controlling overground speed using an open-loop speed control system is not possible. To improve speed control performance we developed and built a closed-loop speed control system, which made the metronome frequency directly dependent on the instantaneous speed error. We tested the performance of this system in both walking and running, and found that the speed control accuracy of a closed-loop system was significantly better compared to self-paced running and an open-loop speed control system. Finally, we translated the speed control system into a training tool available to the general public.

Document type: 
Thesis
File(s): 
Senior supervisor: 
J. Maxwell Donelan
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Dissertation) Ph.D.

Biomechanics of Falls and Hip Fractures in Older Adults

Date created: 
2013-09-05
Abstract: 

Over 90% of hip fractures are due to falls. Yet, only 1-2% of falls result in hip fracture. This suggests that there exist factors that determine injurious and non-injurious falls, but we have limited information on this area. My PhD research addresses this issue through three related studies. My first study examined age-related changes in the dynamic compressive properties (stiffness and damping) of soft tissues over the hip region. My results indicate that the soft tissues of older adults absorb 70% less energy than those of young adults, thereby requiring more energy to be absorbed in the underlying skeletal components, with corresponding increase in fracture risk. My second study determined the effect of hip abductor muscle forces and knee boundary conditions on bone stress at the femoral neck during simulated falls. My results show that physiologically feasible increases in muscle force can reduce peak compressive and tensile stresses by up to 24 and 47%, respectively. These effects are similar to the magnitude of decline in fracture strength associated with osteoporosis. Therefore, muscle contraction at impact may be as important as bone density in determining hip fracture risk during a fall. My third study analyzed the kinematics of real-life falls in older adults, as captured by surveillance cameras, to estimate velocity of the pelvis at impact -- a primary determinant of impact force and fracture risk. Results show that the pelvis impact velocity averages 2.08 m/s, which is 48% below simple free-fall predictions based on fall height ((2gh)^0.5) and 20% below average previously reported for young adults. Results also show that several mechanisms contribute to reducing the pelvis impact velocity, including hand impact and attempts to recover balance by stepping. Collectively, these findings should add important pieces to the puzzle of whether a particular fall will result in hip fracture, and informs future direction for clinical and laboratory-based research on hip fracture prevention.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Stephen Robinovitch
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Dissertation) Ph.D.