Biological Sciences - Theses, Dissertations, and other Required Graduate Degree Essays

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Pregnancy associated plasma protein-a2 (papp-a2) contributes to the regulation of skeletal growth in mice

Author: 
Date created: 
2015-03-17
Abstract: 

Pregnancy associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that cleaves insulin like growth factor binding protein-5 (IGFBP-5), the most abundant IGFBP in bone. Deletion of the Pappa2 gene reduces post-natal growth and skeletal size in mice. This research aimed to further understand the role of PAPP-A2 in skeletal physiology using mice with Pappa2 disrupted constitutively, spatially (in bone), or temporally (in adulthood). I demonstrate that PAPP-A2 produced in bone AND other tissues regulates post-natal growth and skeletal size. Constitutive Pappa2 deletion increases cortical bone mineral density (BMD), whereas disruption of Pappa2 in adulthood decreases trabecular BMD in males alone. PAPP-A2, therefore, appears to play age-specific and potentially site-specific roles. Currently, there is a need for anabolic agents for the treatment of diseases like osteoporosis, making PAPP-A2 an interesting avenue of research.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Julian Christians
Department: 
Science:
Thesis type: 
(Thesis) M.Sc.

Mitochondrial form and function: an investigation of the mechanism and significance of mitochondrial remodelling in rat cortical astrocytes

Author: 
Date created: 
2015-04-02
Abstract: 

Elucidations of the mechanisms that regulate mitochondrial morphology have contributed to a greater understanding of mitochondrial function in eukaryotic cells. To date, mitochondrial morphological changes have mostly been attributed to fission and fusion. Mitochondrial fission is a calcium (Ca2+)/calcineurin mediated process that activates the dynamin related mechanoenzyme DRP1 to cleave the mitochondrial membranes. This thesis explores new evidence that elevations in intracellular calcium produces some mitochondrial fission but the change in morphology is predominately caused by mitochondrial “remodelling”. Mitochondrial remodelling results from a structural change (rounding or elongating) in the membrane of a single mitochondrion without fission or fusion. Due to the nature of tools utilized to assess mitochondrial morphology, remodelling has been largely overlooked in the literature. Using real-time live cell fluorescence microscopy I show that remodelling can occur concomitantly with fission and have provided evidence that the mechanism of remodelling is distinct from fission. Throughout these studies, I used mitochondrially targeted yellow fluorescent protein (mt-eYFP), ratiometric ROS-sensitive GFPs, the mitochondrial membrane potential dye TMRM as well as Ca2+ and ATP FRET probes in rat cortical astrocytes to measure mitochondrial morphological and functional changes in real time. In the first objective chapter, I blocked mitochondrial fission using FK506 and Cyclosporine A and showed that Ca2+ induced mitochondrial remodelling was unaffected. In the second objective, I induced fission and remodelling by applying ROS generating agents such as rotenone and Ca2+ and demonstrated that remodelling was blocked using antioxidants but fission was not attenuated, indicating that remodelling is regulated by ROS. In the final objective chapter, I further investigated the mechanism of remodelling as well as the functional significance of remodelling. I provided evidence that inhibition of glycogen synthase kinase 3β (GSK3β), an enzyme previously associated with fission, induced only mitochondrial remodelling. Furthermore, I showed that remodelling protects cells against some staurosporine induced cell death and that the mechanism of protection may occur through reduced Ca2+ uptake into the mitochondrial matrix. Through exploration of the mechanism and function of mitochondrial remodelling this thesis provides a greater understanding of the role of mitochondria in cellular maintenance and survival.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Gordon Rintoul
Department: 
Science:
Thesis type: 
(Thesis) Ph.D.

Opposing forces: evaluating multiple ecological roles of Pacific salmon in coastal stream ecosystems

Date created: 
2015-03-09
Abstract: 

Resource subsidies can alter the productivity, structure and function of ecosystems. These effects can be particularly strong when the resource is in limited supply within recipient habitats. Migratory species can act as subsidy vectors, transporting vast quantities of nutrients to recipient habitats. They can also significantly disturb the physical, chemical and biological landscape of recipient habitats through their behaviour. This thesis explores how adult spawning salmon affect 1) algal and biofilm biomass, 2) benthic macroinvertebrate biomass, 3) benthic macroinvertebrate diversity and 4) food web structure in streams of the Pacific Northwest. I draw spatial comparisons across multiple streams, compare pre-spawn with post-peak spawning periods, and test for habitat characteristics that mediate these effects. In Chapters 2 and 3, I show that algal and invertebrate biomass in streams decline after salmon spawn, a likely result of substrate disturbance. Through the use of stable isotopes, I also show that algae and invertebrates readily incorporate salmon-derived material. However, only algal biomass in the spring increases with salmon density. Spring invertebrate biomass is low in streams with high salmon densities, despite being enriched in both salmon-derived nitrogen and carbon. This may be due to a slow recovery from the previous fall or in response to salmon nutrients subsidizing higher trophic levels and eliciting a trophic cascade. Chapter 4 reveals that this decline in invertebrate biomass may also be linked to life history traits. Invertebrate family composition shifted significantly across a gradient in salmon density and stream temperature, both prior to and post spawning. However, invertebrate family richness was not related to salmon density; it declined with drainage size, a composite measure of stream and terrestrial habitat measurements. Finally, Chapter 5 reveals that aquatic invertebrates and resident fish species in these coastal streams consume a variety of resources throughout the year and that salmon are an important dietary source for many of these organisms, regardless of season. This thesis demonstrates that salmon are a major structural component of coastal stream food webs, as a resource to benthic production, a major contributor to the diets of freshwater consumers, and as a source of disturbance that contributes to losses in lower trophic levels. Declines in wild Pacific salmon populations would significantly impact how coastal stream food webs function.

Document type: 
Thesis
File(s): 
Senior supervisor: 
John Reynolds
Department: 
Science:
Thesis type: 
(Thesis) Ph.D.

Migratory diversity of juvenile salmon in a threatened estuary

Date created: 
2015-01-16
Abstract: 

Understanding how migratory species such as juvenile salmon (Oncorhynchus spp.) utilize key transition habitats such as estuaries can illuminate their vulnerability to pressures such as habitat alteration or climate change. This thesis examined the diversity of migratory juvenile salmon in the estuary of the vast Skeena River, Canada. First, I compared abundances of different species of juvenile salmon in different regions, and found that sockeye (O. nerka) and Chinook (O. tshawytscha) salmon were most abundant in areas proposed for development. These estuary salmon were genetically linked to dozens of locally-adapted populations from throughout the Skeena watershed and beyond. I also found that downstream migration timing was population-specific and related to the elevation of the different rearing lakes and distance travelled. Different populations encountered different zooplankton communities in the estuary. These results suggest that the Skeena estuary integrates multiple scales of salmon diversity, which could be compromised by impending habitat degradation.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Jonathan Moore
Department: 
Science:
Thesis type: 
(Thesis) M.Sc.

P-Glycoprotein Phosphorylation and Transport Activity in Rainbow Trout (Oncorhynchus mykiss) Hepatocytes.

Date created: 
2014-12-19
Abstract: 

Evidence suggests that P-glycoprotein (P-gp) transport activity can be post-transcriptionally regulated through protein kinase C-mediated phosphorylation. In the present study, P-gp efflux capacity and phosphorylation state were examined in rainbow trout hepatocytes, following protein kinase C (PKC) inhibition with 1-(5-isoquinolinyl-sulfonyl)-3-methyl-piperazine (H-7), or its activation following treatment with Phorbol 12-Myristate 13-Acetate (PMA). Decreased chemical efflux and increased accumulation following H-7 treatment were observed when rhodamine 123 (R123) was used as P-gp substrate, while PMA increased P-gp efflux and decreased the accumulation of daunorubicine (DNR). This substrate-dependent modulation suggests that phosphorylation affects P-gp’s ability to bind to different substrates or, more likely, to its co-substrate ATP. As well, these results raise the possibility that other transporters may be involved, particularly in R123 transport. Immunoblots of solubilized membrane fractions and whole cell extracts following phosphate-affinity SDS-PAGE showed that H-7 and PMA-treated cells produce different P-gp phosphorylation patterns compared to control cells; up to 5 different phosphoisoforms were visualized using the monoclonal antibody C-219. Differences in the distribution, number, and optical densities of bands were visualized, and can be interpreted as PKC activation or inhibition altering the relative abundance of P-gp phosphoisoforms in the cells. Hepatocytes were also treated with H-7 or PMA and radiolabelled in a media containing 32P, were immunoprecipitated, and subjected to conventional SDS-PAGE. The resulting gels confirmed that PMA increased the amount of 32P incorporated into P-gp as compared to controls, while H-7 decreased it, indicating that PKC inhibition prevents or reduces P-gp phosphorylation and the transport of certain substrates, while activation promotes phosphorylation and transport, also in a substrate-dependent manner.

Document type: 
Graduating extended essay / Research project
File(s): 
Senior supervisor: 
Dr. Chris Kennedy
Dr. Margo Moore
Department: 
Science:
Thesis type: 
(Project) M.E.T.

Species richness, abundance and reproductive responses of riparian birds to habitat restoration in the Okanagan Valley

Date created: 
2015-01-26
Abstract: 

In western North America, most riparian habitats have been destroyed or degraded as a result of human settlement and urban development. I examined temporal trends in the abundance, richness and breeding performance of riparian birds in response to restoration of remnant riparian habitat within the south Okanagan Valley, an arid region of Canada. Total abundance and richness increased over the last decade. Restoration increased the abundance of Yellow-breasted Chats (Icteria virens auricollis), the target of management activities, but did not have a detectable effect on the abundance of other songbirds. The habitat characteristics and breeding performance of Yellow-breasted Chats in restored habitat are currently similar to those of Yellow-breasted Chats in reference sites. Habitat characteristics on multiple spatial-scales (shrub cover of the territory and foliage height of the nest patch) influenced the breeding performance of Yellow-breasted Chats. These results provide evidence that limiting grazing is beneficial to some shrub-nesting songbirds.

Document type: 
Thesis
File(s): 
Senior supervisor: 
David Green
Christine Bishop
Department: 
Science:
Thesis type: 
(Thesis) M.Sc.

Sources and effects of persistent organic pollutants and brominated flame retardants in Cooper’s hawks (Accipiter cooperii) of Vancouver, British Columbia

Date created: 
2014-10-14
Abstract: 

Birds of prey are excellent indicators of environmental health. Since they are top predators, they accumulate a high concentration of persistent organic pollutants (POPs). Cooper’s hawks (Accipiter cooperii) are abundant in urban areas but these environments have been associated with POPs known to cause adverse physiological effects. To investigate the exposure and effects of POPs and flame retardants in Vancouver, British Columbia, we assess the influence of diet, and landscape variables, such as land use and population density on plasma concentrations of pollutants in adult and nestling Cooper’s hawks. We then examined how these pollutant influence thyroid hormones and the fledge success. Our results suggest that: 1) concentrations of DDE are relatively high, 2) urbanized areas were most associated with industrial chemicals; ΣPCB and ΣPBDE, which were also negatively influencing thyroid hormone concentrations, and 3) diet most influenced dieldrin concentrations, which were associated with fledge success.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Ronald Ydenberg
Department: 
Science:
Thesis type: 
(Thesis) M.Sc.

Predicting In Vivo Caffeine/ Angelica dahurica and Caffeine/ Salvia miltiorrhiza Pharmacokinetic Interactions in Humans with In Vitro CYP1A2 Inhibition Data

Date created: 
2014-12-15
Abstract: 

Currently, no existing models allow for holistic predictions of drug-herb interactions. To investigate possible interactions between drugs and current use ‘traditional’ medicines, extracts of Angelica dahurica and Salvia miltiorrhiza were examined in vitro and in vivo for their ability to modify human caffeine metabolism. Consumption of either herbal decoction by volunteers significantly elevated caffeine retention (>200%). Human liver microsomes were treated in vitro with candidate precipitants identified in each herb in addition to ethanolic extracts of the whole herb(s). All treatments reversibly inhibited CYP1A2-mediated caffeine metabolism; Ki values of pure precipitants ranged from 0.28 – 2.55 µM. IC50 values for A. dahurica and S. miltiorrhiza extracts were 1.15e-3 and 1.6e-3 mg/L respectively. Human pharmacokinetic values were estimated for each precipitant and used with in vitro PK data to conservatively predict caffeine retention. This study allows for prediction of hepatic threshold precipitant concentrations associated with clinically relevant inhibition of CYP450 function.

Document type: 
Graduating extended essay / Research project
File(s): 
Senior supervisor: 
Francis Law
Department: 
Science:
Thesis type: 
(Project) M.E.T.

The effect of sulphate on selenium bioaccumulation in two freshwater primary producers and a primary consumer

Author: 
Date created: 
2014-12-16
Abstract: 

Site-specific conditions (e.g. presence of sulphate), may be linked to the variability in the uptake of selenium in organisms at the base of a food chain, potentially affecting the risk of adverse effects in higher trophic-level organisms. In this project, the effect of sulphate on selenate bioaccumulation in two primary producers (Lemna minor and Pseudokirchneriella subcapitata) and a primary consumer (Daphnia magna) was explored. When exposed to selenate, all three species exhibited a decrease in selenium tissue concentration with increasing sulphate. When D. magna were exposed to sulphate and dietary selenium, sulphate did not affect selenium tissue concentrations. The results were used to develop equations estimating selenium tissue concentrations when exposed to selenate and sulphate. The strong predictive ability of the equations suggests that selenate, sulphate, and dietary selenium (applicable to D. magna) are important for describing the relationship between selenate and selenium tissue concentrations.

Document type: 
Graduating extended essay / Research project
File(s): 
Senior supervisor: 
Christopher Kennedy
Department: 
Science:
Thesis type: 
(Project) M.E.T.

Palynology and Paleoecology at Kilgii Gwaay Archaeological Site, Southern Haida Gwaii

Date created: 
2014-11-26
Abstract: 

Buried pond sediments at the Kilgii Gwaay archaeological site on Ellen Island in Gwaii Haanas National Park, were analyzed palynologically to produce a high-resolution record of postglacial vegetation during late glacial and early Holocene time. Seven AMS radiocarbon dates provide a sediment core chronology spanning the period 14,470-10,870 cal yr BP. Four biostratigraphic zones are defined, with a transition from early herb-shrub tundra (14,510 cal yr BP) to a Pinus-dominated forest 14,000 cal yr BP. Pinus is largely replaced by Picea 13,290 cal yr BP, followed by establishment of Tsuga heterophylla 12,420 cal yr BP. Changes in vegetation assemblages and stratigraphy may indicate cooling associated with the Younger Dryas event. Charcoal analysis reveal peak abundance during the known occupation of Kilgii Gwaay (10,700 cal yr BP). Charcoal extends below the known occupation horizon, indicating human presence as early as 11,500 cal yr BP, approximately 800 years earlier than previously documented.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Rolf Mathewes
Department: 
Science:
Thesis type: 
(Thesis) M.Sc.