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University of Saskatchewan
1.
Saibu, Yusuf Olayiwola 1989-.
INVESTIGATIONS OF WATERBORNE METAL INTERACTIONS IN THE GILLS OF RAINBOW TROUT USING SYNCHROTRON-BASED TECHNIQUES.
Degree: 2017, University of Saskatchewan
URL: http://hdl.handle.net/10388/7767 
► Most of our current understanding of metal toxicity in aquatic organisms has been based on single metal toxicity. However, metals do not exist singly in…
(more)
▼ Most of our current understanding of metal toxicity in aquatic organisms has been based on single metal toxicity. However, metals do not exist singly in the aquatic environment, but rather as mixtures. As mixtures, they are subject to complex interactions for uptake and/or intracellular handling. An enhanced understanding of intracellular metal interactions could help in developing predictive models (e.g., biotic ligand model) for assessing the toxicity of metals in mixture. To this end, I adopted a suite of synchrotron-based techniques to investigate the acute interactions of waterborne Zn, Cd and Cu in binary mixtures in situ at the gills of a model teleost species, rainbow trout (Oncorhynchus mykiss). Gills (the biotic ligand) of freshwater fish are primary site of toxic action for metals during acute waterborne exposures, and thus were chosen as the target tissue for this investigation. Micro X-ray fluorescence imaging (µ-XRF) and micro X-ray absorption near-edge spectroscopy (µ-XANES) were employed to investigate: (i) the spatial distribution and chemical speciation of Zn and its co-localization pattern with other essential elements (Ca, S and Fe), (ii) the effect of competing metals (Cd and Cu) on Zn distribution and speciation in the gills of rainbow trout. In addition, Fourier transform infrared micro-spectroscopy (FTIRM) was employed to examine the effects of Zn, Cd and Cu, singly and in binary mixtures, on biochemical constituents (e.g., proteins, lipids and nucleic acids) of the gills of rainbow trout. Fish (~200g) were exposed to acutely toxic concentrations (1x 96h LC50) of each metal, alone and in binary combination, in dechlorinated municipal water for 24h. Following exposure, gills were dissected and 10 um thick sections were prepared and analyzed at the VESPERS and Mid-IR beamlines of the Canadian Light Source. My findings indicated that Zn accumulated in high proportions in the primary lamellae (the primary site of mitochondria-rich (chloride) cell localization) of the fish gill. Zinc was also found to predominantly co-localize with Ca and S, but not with Fe, indicating that Ca and S binding intracellular ligands play a crucial role in Zn handling in the gill. The distribution of Zn in the gill was markedly reduced during co-exposure to Cd, but not to Cu, suggesting a competitive interaction between Zn and Cd for uptake. Exposure to Zn, alone and in combination with Cd or Cu, was found to decrease Ca from the gill tissue. The speciation of Zn in the gill was dominated by Zn-phosphate, Zn-histidine and Zn-cysteine; however, the interactions of Zn with Cd or Cu resulted in the loss of Zn-cysteine. The composition of the biochemical constituents of the fish gill was also found to be altered by the exposure to metals, both individually and in binary mixture, and this was apparent both on the primary and secondary lamellae. These alterations were mainly characterized as degradations of proteins and lipids. Generally, exposure to Cu, alone and in mixture with Cd, was found to induce maximum adverse…
Advisors/Committee Members: Niyogi, Som, Wickstrom, Mark, Hecker, Markus, Peak, Derek, Ianowski, Juan.
Subjects/Keywords: Metals; Interactions; Synchrotron; Rainbow trout
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APA (6th Edition):
Saibu, Y. O. 1. (2017). INVESTIGATIONS OF WATERBORNE METAL INTERACTIONS IN THE GILLS OF RAINBOW TROUT USING SYNCHROTRON-BASED TECHNIQUES. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/7767
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Saibu, Yusuf Olayiwola 1989-. “INVESTIGATIONS OF WATERBORNE METAL INTERACTIONS IN THE GILLS OF RAINBOW TROUT USING SYNCHROTRON-BASED TECHNIQUES.” 2017. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/7767.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Saibu, Yusuf Olayiwola 1989-. “INVESTIGATIONS OF WATERBORNE METAL INTERACTIONS IN THE GILLS OF RAINBOW TROUT USING SYNCHROTRON-BASED TECHNIQUES.” 2017. Web. 03 Mar 2021.
Vancouver:
Saibu YO1. INVESTIGATIONS OF WATERBORNE METAL INTERACTIONS IN THE GILLS OF RAINBOW TROUT USING SYNCHROTRON-BASED TECHNIQUES. [Internet] [Thesis]. University of Saskatchewan; 2017. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/7767.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Saibu YO1. INVESTIGATIONS OF WATERBORNE METAL INTERACTIONS IN THE GILLS OF RAINBOW TROUT USING SYNCHROTRON-BASED TECHNIQUES. [Thesis]. University of Saskatchewan; 2017. Available from: http://hdl.handle.net/10388/7767
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
2.
Scott, Gavin Alexander 1988-.
Examining the Roles of Thalamocortical and Frontoparietal Circuitry for Working Memory in the Rat.
Degree: 2019, University of Saskatchewan
URL: http://hdl.handle.net/10388/12476
► Working memory (WM) is the cognitive capacity for short-term maintenance and manipulation of stimuli and goals for the purpose of guiding behaviour. Research in primates…
(more)
▼ Working memory (WM) is the cognitive capacity for short-term maintenance and manipulation of stimuli and goals for the purpose of guiding behaviour. Research in primates has indicated that WM relies on a large network including the prefrontal cortex, various posterior cortical areas, and subcortical nuclei. However, the circuit mapping of WM in rodents is incomplete as it pertains to the specific involvement of thalamocortical and frontoparietal circuitry across WM tasks. In this dissertation, I present the findings of three sets of experiments using two different rodent WM tasks: The odour span task (OST), an incrementing delayed non-matching-to-sample task using odours, and; the Trial-Unique Non-matching-to-Location (TUNL) task, a touchscreen-based visuospatial delayed non-matching-to-sample task. 1) I found evidence that the OST relies on a thalamocortical circuit connecting the medial prefrontal cortex (mPFC) and the mediodorsal thalamus (mdThal). Moreover, the mPFC and mdThal played dissociable roles in the foraging element of the OST, with mdThal inactivation causing a dramatic reduction in exploratory motor activity. 2) I examined the role of the PPC in the OST and found that it is not necessary for OST performance. 3) I found that the PPC is critical for TUNL, confirming that the rodent PPC plays an essential role in visuospatial WM. Additionally, I found that TUNL is independent of NMDA signalling in the PPC and instead depends only on AMPA/Kainate receptors in contrast to previous research showing an important role for NMDA receptors in WM. Overall, the results indicate that thalamocortical and frontoparietal pathways are differentially involved across WM tasks, with frontoparietal circuitry being more sensory modality-specific than thalamocortical circuitry.
Advisors/Committee Members: Howland, John G, Campanucci, Veronica, Lee, Paul, Borowsky, Ron, Ianowski, Juan.
Subjects/Keywords: Working memory; Prefrontal; Posterior Parietal; Thalamus
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APA (6th Edition):
Scott, G. A. 1. (2019). Examining the Roles of Thalamocortical and Frontoparietal Circuitry for Working Memory in the Rat. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/12476
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Scott, Gavin Alexander 1988-. “Examining the Roles of Thalamocortical and Frontoparietal Circuitry for Working Memory in the Rat.” 2019. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/12476.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Scott, Gavin Alexander 1988-. “Examining the Roles of Thalamocortical and Frontoparietal Circuitry for Working Memory in the Rat.” 2019. Web. 03 Mar 2021.
Vancouver:
Scott GA1. Examining the Roles of Thalamocortical and Frontoparietal Circuitry for Working Memory in the Rat. [Internet] [Thesis]. University of Saskatchewan; 2019. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/12476.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Scott GA1. Examining the Roles of Thalamocortical and Frontoparietal Circuitry for Working Memory in the Rat. [Thesis]. University of Saskatchewan; 2019. Available from: http://hdl.handle.net/10388/12476
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Saskatchewan
3.
Givzad, Naseem.
Abnormal electrophysiological properties in sensory neurons from a swine model of cystic fibrosis.
Degree: 2020, University of Saskatchewan
URL: http://hdl.handle.net/10388/13009
► Cystic fibrosis (CF) results from dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. CF has traditionally been considered a pediatric disease, but the…
(more)
▼ Cystic fibrosis (CF) results from dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. CF has traditionally been considered a pediatric disease, but the median predicted survival age in Canada is 55 years. As a result, patients are more likely to experience chronic complications of CF. One such complication is abnormal function of the peripheral nervous system, i.e., peripheral neuropathy. Recent findings from a swine model of CF (CFTR-/-), shows these animals are born with peripheral neuropathy. However, whether a lack of CFTR expression directly affects neuronal function remains to be explored. We hypothesize that the lack of functional CFTR in sensory neurons leads to electrophysiological abnormalities that contribute to the pathology of CF. We propose that malfunction in dorsal root ganglion (DRG) neurons innervating the GI tract contributes to gut-related complications. Using patch clamp electrophysiology, we found that DRG neurons from CFTR-/- (CF) swine had reduced generation of action potentials, compared to wild-type (WT) swine. Additionally, we observed a reduced percentage of neurons with T-type calcium currents in the CF swine, with respect to WT at postnatal day 7. Furthermore, our study showed that DRG neurons from CF swine, which displayed T-type calcium currents, had abnormal activation (G/Gmax) and inactivation () kinetics. Moreover, DRG neurons from CF swine showed a reduction in capsaicin-evoked currents with respect to WT, at both postnatal day 0 and 7. Taken together our data indicate that lack of CFTR expression in sensory neurons is linked to a depression of sensory function in DRG neurons in the first week postnatal. Our data strongly suggest that in
addition to the effects of CF in epithelial cells, impairments in sensory neurons may contribute to the pathology of CF.
Advisors/Committee Members: Campanucci, Veronica, Ianowski, Juan, Howland, John, Verge, Valerie, Mckinney, Martha.
Subjects/Keywords: cystic fibrosis; neuropathy
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APA (6th Edition):
Givzad, N. (2020). Abnormal electrophysiological properties in sensory neurons from a swine model of cystic fibrosis. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/13009
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Givzad, Naseem. “Abnormal electrophysiological properties in sensory neurons from a swine model of cystic fibrosis.” 2020. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/13009.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Givzad, Naseem. “Abnormal electrophysiological properties in sensory neurons from a swine model of cystic fibrosis.” 2020. Web. 03 Mar 2021.
Vancouver:
Givzad N. Abnormal electrophysiological properties in sensory neurons from a swine model of cystic fibrosis. [Internet] [Thesis]. University of Saskatchewan; 2020. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/13009.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Givzad N. Abnormal electrophysiological properties in sensory neurons from a swine model of cystic fibrosis. [Thesis]. University of Saskatchewan; 2020. Available from: http://hdl.handle.net/10388/13009
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Saskatchewan
4.
Wright, Nathan D.
Plasma factors, antibiotic therapy, and sputum bacteria associated with alteration of circulating neutrophils in individuals with cystic fibrosis.
Degree: 2020, University of Saskatchewan
URL: http://hdl.handle.net/10388/13203
► Cystic fibrosis (CF) is a genetic disease with pathology highly focused on pulmonary complications. Infection and colonisation of CF airways by well established pathogens (e.g.,…
(more)
▼ Cystic fibrosis (CF) is a genetic disease with pathology highly focused on pulmonary complications. Infection and colonisation of CF airways by well established pathogens (e.g., Pseudomonas aeruginosa, Staphylococcus aureus) are continual issues, and these infections are commonly managed through prolonged use of multiple antibiotics. Neutrophils respond to pulmonary bacterial infections. In CF, however, altered airway physiology and neutrophil function contribute to inflammation, tissue remodeling, and fibrosis. It has been established that circulating neutrophils from individuals with CF are functionally altered, either intrinsically or from the inflammatory environment of the airways, and this alteration appears to involve increased neutrophil survival and reduced apoptosis. Furthermore, this alteration in neutrophil physiology has been related to undefined mediators present within plasma from individuals with CF. Therefore, to better understand disease pathogenesis and improve CF patient management, it is important to identify the plasma factors causing these alterations of the CF neutrophil. With these concerns in mind, the primary objective of this research was to identify plasma factors that altered the physiology of circulating neutrophils in CF, and to determine which neutrophil signaling pathways were stimulated by these factors. A further objective was to investigate how these plasma factors and altered neutrophil functions related to disease progression and medical chart data for individuals with CF.
To address my research objectives, blood samples were collected from 22 adult volunteers with CF who were ΔF508 homozygotes, and from 11 age and sex matched non-CF control volunteers. This study did not incorporate inclusion or exclusion criteria based on clinical assessment of stability for the volunteers with CF. Plasma samples were first screened for the capacity to stimulate the NF-κB pathway using the THP1-Dual cell, NF-κB reporter assay. In addition, proteins present in a plasma sample collected from a volunteer with CF were analysed using mass spectrometry. Plasma samples were also analysed for specific factors known to have stimulatory effects on neutrophils. These factors included G-CSF and CXCL1, which were measured using enzyme-linked immunosorbent assay (ELISA) methodology, and endotoxin, which was measured using the limulus amebocyte lysate (LAL) endotoxin assay. Neutrophils from these blood samples were also isolated and the number of neutrophils isolated/ml of blood were calculated. Some of these circulating neutrophil samples were analysed for gene expression of several pro-inflammatory factors using reverse transcription - quantitative real-time polymerase chain reaction (RT-qPCR). In addition, expression of the anti-apoptotic protein XIAP and phosphorylated XIAP were evaluated through western blotting analysis of neutrophil lysates. Finally, intracellular signaling in circulating neutrophil samples was analysed using kinome arrays and the resulting data was subjected to pathway…
Advisors/Committee Members: Gordon, John R, Tam, Julian, Griebel, Philip, Gerdts, Volker, Ianowski, Juan.
Subjects/Keywords: Immunology; Neutrophil; Cystic Fibrosis; Translational Research
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APA (6th Edition):
Wright, N. D. (2020). Plasma factors, antibiotic therapy, and sputum bacteria associated with alteration of circulating neutrophils in individuals with cystic fibrosis. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/13203
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wright, Nathan D. “Plasma factors, antibiotic therapy, and sputum bacteria associated with alteration of circulating neutrophils in individuals with cystic fibrosis.” 2020. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/13203.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wright, Nathan D. “Plasma factors, antibiotic therapy, and sputum bacteria associated with alteration of circulating neutrophils in individuals with cystic fibrosis.” 2020. Web. 03 Mar 2021.
Vancouver:
Wright ND. Plasma factors, antibiotic therapy, and sputum bacteria associated with alteration of circulating neutrophils in individuals with cystic fibrosis. [Internet] [Thesis]. University of Saskatchewan; 2020. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/13203.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wright ND. Plasma factors, antibiotic therapy, and sputum bacteria associated with alteration of circulating neutrophils in individuals with cystic fibrosis. [Thesis]. University of Saskatchewan; 2020. Available from: http://hdl.handle.net/10388/13203
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Saskatchewan
5.
Hassan, Noman 1990-.
The Role of Intracellular Calcium Signaling in Regulating Transepithelial Ion Transport by the Malpighian Tubules of Rhodnius prolixus.
Degree: 2016, University of Saskatchewan
URL: http://hdl.handle.net/10388/7519
► Intracellular ion and volume homeostasis is fundamental to epithelial cells during water and solute transport. When homeostasis is disrupted, it may result in pathological consequences,…
(more)
▼ Intracellular ion and volume homeostasis is fundamental to epithelial cells during water and solute transport. When homeostasis is disrupted, it may result in pathological consequences, e.g. cystic fibrosis. We use Rhodnius prolixus Malpighian tubules as a model epithelium to study the mechanisms of intracellular homeostasis in epithelial cells. Previously published research indicates that intracellular calcium (Ca2+) signal may be involved in the intracellular homeostasis in some vertebrate epithelia by mediating the crosstalk between ion transporters. In this thesis, (I) we investigate if Ca2+ oscillations are part of crosstalk mechanism between apical and basolateral membrane transporters and, (II) use mass spectrometry (MS)-based proteomics to decipher proteins involved in crosstalk mechanism.
Calcium imaging experiments revealed that the amplitude and the frequency of the intracellular Ca2+ oscillations displayed by Malpighian tubule cells correlated with the fluid transport rate. As the transport rate decreased with increasing concentration of the transport blocker, bumetanide, the Ca2+ oscillations displayed smaller amplitudes and frequency. Similarly, changes in transcellular potassium (K+) flux, while maintaining constant fluidsecretion rate, caused a concentration-dependent decrease in amplitude and frequency of Ca2+oscillations. These results are consistent with the hypothesis that Ca2+ oscillations may code information on ion transport flux that could be a part of the crosstalk mechanism.
To further test the role of Ca2+ in regulating intracellular ion homeostasis, we measured intracellular potassium using imaging. Our results show that inhibiting intracellular Ca2+ oscillations blocked the ability of the tubule cells to maintain a constant intracellular K+ concentration after the cells were experimentally forced to instantaneously reduce transcellular K+ flux. This indicates that in the absence of Ca2+ oscillations, the cells are unable to maintain intracellular K+ homeostasis, suggesting that Ca2+ may be involved in regulating the ability of apical and basolateral transporters to crosstalk.
We induced diuresis with serotonin to simulate crosstalk, which is fundamental to diuresis. MS-based proteomics were used to compare serotonin-stimulated samples with control. The results revealed several proteins of interest with a change in the proteome profile, suggesting a potential involvement in crosstalk mechanism. Of these proteins, we validated the roles of WNK and CAMKII, using conventional techniques. Inhibition of WNK significantly reduced fluid transport and reduced amplitude and frequency of Ca2+ oscillations in a dose dependent manner. Whereas, inhibition of CAMKII significantly reduced fluid transport but failed to affect the cell’s ability to keep an internal ion homeostasis with low K+ challenge. This suggests that the WNK pathway may be fundamental to the crosstalk mechanism, whereas CAMKII might not be involved.
In conclusion, there exists a crosstalk mechanism between basolateral and apical…
Advisors/Committee Members: Mulligan, Sean, Ianowski, Juan P, Katselis, George, Campanucci, Veronica, Bekar, Lane, Noyogi, Som.
Subjects/Keywords: Epithelial physiology; Epithelial cell crosstalk; Calcium oscillations; MS-based proteomics; Kinases; Calcium binding proteins
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APA (6th Edition):
Hassan, N. 1. (2016). The Role of Intracellular Calcium Signaling in Regulating Transepithelial Ion Transport by the Malpighian Tubules of Rhodnius prolixus. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/7519
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hassan, Noman 1990-. “The Role of Intracellular Calcium Signaling in Regulating Transepithelial Ion Transport by the Malpighian Tubules of Rhodnius prolixus.” 2016. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/7519.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hassan, Noman 1990-. “The Role of Intracellular Calcium Signaling in Regulating Transepithelial Ion Transport by the Malpighian Tubules of Rhodnius prolixus.” 2016. Web. 03 Mar 2021.
Vancouver:
Hassan N1. The Role of Intracellular Calcium Signaling in Regulating Transepithelial Ion Transport by the Malpighian Tubules of Rhodnius prolixus. [Internet] [Thesis]. University of Saskatchewan; 2016. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/7519.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hassan N1. The Role of Intracellular Calcium Signaling in Regulating Transepithelial Ion Transport by the Malpighian Tubules of Rhodnius prolixus. [Thesis]. University of Saskatchewan; 2016. Available from: http://hdl.handle.net/10388/7519
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Saskatchewan
6.
Roebuck, Andrew J.
Modulation of the endocannabinoid system in Genetic Absence Epilepsy Rats from Strasbourg: New avenues for treatment of absence seizures and behavioural comorbidities.
Degree: 2021, University of Saskatchewan
URL: http://hdl.handle.net/10388/13204
► Current treatments for Absence Epilepsy (AE) are insufficient and do not adequately manage seizures and comorbidities in most patients. With the recent legalization of cannabis…
(more)
▼ Current treatments for Absence Epilepsy (AE) are insufficient and do not adequately manage seizures and comorbidities in most patients. With the recent legalization of cannabis in Canada, interest in its use for the treatment of epilepsy has increased. However, no studies have assessed cannabis in AE, and only limited preclinical evidence is available. Using Genetic Absence Epilepsy Rats from Strasbourg (GAERS), this thesis examines how cannabis-based medicines may be used to treat seizures and behavioural comorbidities relevant to AE. In Chapter 2, touchscreen chambers were used to identify visual learning and flexibility impairments in GAERS. These findings provide evidence of cognitive impairment, suggesting GAERS may be used to model this comorbidity. In Chapter 3, we tested the effects of plant-derived phytocannabinoids on seizures in GAERS. Injected Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent in cannabis, increased the number of seizure events as measured by increased spike-and slow wave discharges (SWDs) recorded through electroencephalogram (EEG). In contrast, cannabidiol (CBD) produced a moderate decrease in SWDs. As cannabis is usually smoked, we used a novel smoke exposure protocol to subject animals to high-THC and high-CBD cannabis smoke. Consistent with the injection data, high-THC smoke increased SWDs whereas high-CBD smoke had no effect. These findings are the first to demonstrate a seizure modulating effect of THC and CBD in a rat model of AE. Chapter 4 characterized the endocannabinoid system (ECS) in GAERS and investigated whether type 1 cannabinoid receptor (CB1R) positive allosteric modulators (PAMs) may be effective in reducing SWDs. Sex-specific and regional alterations in the ECS were identified which may contribute to seizure propagation and behavioural comorbidities in GAERS. These experiments also demonstrated that the CB1R PAMs GAT211 and GAT229 reduce SWDs in GAERS without producing adverse behavioural effects observed following THC exposure. In Chapter 5, GAT211 was tested to determine whether it could also reverse behavioural impairments observed in GAERS. This experiment used a battery assessing anxiety-like behaviour and social impairment as these deficits have previously been shown to respond to antiepileptic drug treatment. These data provided some evidence to suggest a potential therapeutic effect of GAT211, but future experiments will be required to confirm these results. Overall, these data identify additional comorbidities, and demonstrate seizure modulating effects of several cannabinoids. The seizure reducing effects of CBD, GAT211, and GAT229 highlight the potential use of cannabinoids in GAERS as a promising area for continued preclinical research in AE.
Advisors/Committee Members: Howland, John G, Mulligan, Sean, Campanucci, Veronica, Laprairie, Robert B, Ianowski, Juan.
Subjects/Keywords: Cannabis; epilepsy; seizures; cannabidiol
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APA ·
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APA (6th Edition):
Roebuck, A. J. (2021). Modulation of the endocannabinoid system in Genetic Absence Epilepsy Rats from Strasbourg: New avenues for treatment of absence seizures and behavioural comorbidities. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/13204
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Roebuck, Andrew J. “Modulation of the endocannabinoid system in Genetic Absence Epilepsy Rats from Strasbourg: New avenues for treatment of absence seizures and behavioural comorbidities.” 2021. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/13204.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Roebuck, Andrew J. “Modulation of the endocannabinoid system in Genetic Absence Epilepsy Rats from Strasbourg: New avenues for treatment of absence seizures and behavioural comorbidities.” 2021. Web. 03 Mar 2021.
Vancouver:
Roebuck AJ. Modulation of the endocannabinoid system in Genetic Absence Epilepsy Rats from Strasbourg: New avenues for treatment of absence seizures and behavioural comorbidities. [Internet] [Thesis]. University of Saskatchewan; 2021. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/13204.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Roebuck AJ. Modulation of the endocannabinoid system in Genetic Absence Epilepsy Rats from Strasbourg: New avenues for treatment of absence seizures and behavioural comorbidities. [Thesis]. University of Saskatchewan; 2021. Available from: http://hdl.handle.net/10388/13204
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
7.
Mishra, Manish 1980-.
Effects of heme oxygenase system on inflammation, oxidative stress, insulin signaling and tissue injury in liver, heart, kidney and pancreas in obese, diabetic and hypertensive rats.
Degree: 2017, University of Saskatchewan
URL: http://hdl.handle.net/10388/8249
► Tissue injury and metabolic dysfunction are salient features of obesity, diabetes, and hypertension. Inflammation and oxidative stress are considered key players behind this altered tissue…
(more)
▼ Tissue injury and metabolic dysfunction are salient features of obesity, diabetes, and hypertension. Inflammation and oxidative stress are considered key players behind this altered tissue homeostasis that drastically affect several vital organs including liver, heart, kidney and pancreas resulting in the development of hepatic steatosis, cardiomyopathy, nephropathy, pancreatic insulitis and abnormal glucose metabolism. Despite significant advancement in pharmaceutical interventions, the desired efficacy to manage these conditions is still lacking. In these situations, cytoprotective and functional attributes of the heme oxygenase (HO) system can be used as an alternative management tool. Although, the HO system is cytoprotective, its role in tissue injury and dysfunction in obesity, diabetes, and hypertension is not completely clear. To explore the importance of upregulating HO in these conditions, HO is induced through hemin in the rat models of obesity, diabetes and hypertension. My thesis work show that HO upregulation reduced the inflammation and oxidative stress-induced tissue injury in liver, heart, kidney, and pancreas through reduction of proinflammatory M1 macrophage marker (ED1) expression, cytokines (TNF-α, IL-1β, IL-6), oxidative-markers (8-isoprostane, ET-1) and profibrotic/extracellular matrix proteins (TGF-β, collagen-IV, fibronectin) and enhancement of the anti-inflammatory M2-macrophage markers (ED2, CD206, CD36, CD14), adiponectin and total-antioxidant capacity. HO upregulation improved glucose metabolism through potentiation of insulin signalling components (IRS-1, IRS-2, PI3K, GLUT4), reduced hyperglycemia, and enhanced several markers implicated in pancreatic repair and/or regeneration (c-Kit, Sca-1, Oct3/4, Pax2, β-catenin, Islet-1, Nkx6.1 and GLUT2). Collectively, the data from my thesis suggested the multifaceted cytoprotective mechanisms of the HO system against increasing tissue injury and metabolic dysfunction during obesity, diabetes and hypertension. Thus, HO upregulation through hemin may be part of therapeutic management strategies against tissue injury and metabolic dysfunction in obesity, diabetes and hypertension in the future.
Advisors/Committee Members: Prasad, Kailash, Lee, Paul, Hiebert, Linda, Ianowski, Juan.
Subjects/Keywords: Diabetes; hypertension; obesity; tissue injury; insulin signaling
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APA (6th Edition):
Mishra, M. 1. (2017). Effects of heme oxygenase system on inflammation, oxidative stress, insulin signaling and tissue injury in liver, heart, kidney and pancreas in obese, diabetic and hypertensive rats. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/8249
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Mishra, Manish 1980-. “Effects of heme oxygenase system on inflammation, oxidative stress, insulin signaling and tissue injury in liver, heart, kidney and pancreas in obese, diabetic and hypertensive rats.” 2017. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/8249.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Mishra, Manish 1980-. “Effects of heme oxygenase system on inflammation, oxidative stress, insulin signaling and tissue injury in liver, heart, kidney and pancreas in obese, diabetic and hypertensive rats.” 2017. Web. 03 Mar 2021.
Vancouver:
Mishra M1. Effects of heme oxygenase system on inflammation, oxidative stress, insulin signaling and tissue injury in liver, heart, kidney and pancreas in obese, diabetic and hypertensive rats. [Internet] [Thesis]. University of Saskatchewan; 2017. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/8249.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Mishra M1. Effects of heme oxygenase system on inflammation, oxidative stress, insulin signaling and tissue injury in liver, heart, kidney and pancreas in obese, diabetic and hypertensive rats. [Thesis]. University of Saskatchewan; 2017. Available from: http://hdl.handle.net/10388/8249
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
8.
Anderson, Michael David 1995-.
THE EFFECTS OF DEGRADING PERINEURONAL NETS IN THE MEDIAL PREFRONTAL AND POSTERIOR PARIETAL CORTICES ON THE SPATIAL WORKING MEMORY OF RATS.
Degree: 2019, University of Saskatchewan
URL: http://hdl.handle.net/10388/12299
► Perineuronal nets (PNNs) are specialized extracellular matrix structures that surround subsets of neurons in the central nervous system (CNS). They help in maintaining a stable…
(more)
▼ Perineuronal nets (PNNs) are specialized extracellular matrix structures that surround subsets of neurons in the central nervous system (CNS). They help in maintaining a stable excitatory-inhibitory balance in the brain, and the adult loss of PNNs can lead to a period of increased synaptic plasticity. Furthermore, the loss of PNNs can affect cortical networks and influence learning, memory, and cognition. The aim of this thesis was to test the effect that degrading PNNs in the medial prefrontal (mPFC) and posterior parietal (PPC) cortices had on spatial working memory (WM). To do this, the spatial WM of Long-Evans rats was measured using the trial unique, delayed nonmatching-to-location (TUNL) task in touchscreen-equipped operant conditioning chambers. Rats were trained in this task and then assigned to either a penicillinase (PEN) control or chondroitinase ABC (ChABC) treatment. ChABC is an enzyme that compromises the structure of PNNs by degrading one of their major components: chondroitin sulfate proteoglycans (CSPGs). Surgeries were performed to infuse these enzymes into the medial prefrontal cortex (mPFC) in a first set of rats and into the posterior parietal cortex (PPC) in a second set of rats. All rats were trained under a standard 6 s delay and then tested under 4 conditions: a 6 s delay, a variable 2 s or 6 s delay, a 2 s delay with a 1s inter-trial interval (interference condition), and a 20 s delay. Rats that received mPFC ChABC infusions initially performed better than controls in the 20 s delay condition, but did not perform any differently in any of the other three conditions. Rats that received PPC ChABC infusions did not perform significantly differently from controls in any condition. Immunohistochemical analysis confirmed that CSPGs were degraded in both cortical regions. This suggests that PNNs in the mPFC are involved in learning a novel delay in a spatial WM task, but that they are not essential for general spatial WM function. Furthermore, it appears that PNNs in the PPC are not involved in spatial WM. Ultimately, these findings contribute to a growing body of literature that explores how cortical PNNs are involved in cognition.
Advisors/Committee Members: Howland, John G, Baillie, Landon, Ianowski, Juan, Borowsky, Ron.
Subjects/Keywords: perineuronal nets; Chondroitinase ABC; medial prefrontal cortex; posterior parietal cortex
…University of Saskatchewan
GD30.7, Health Sciences Building 107 Wiggins Rd
Saskatoon, SK, Canada… …John
G. Howland1,*
1
Department of Anatomy, Physiology and Pharmacology University of… …Saskatchewan,
Saskatoon, SK, Canada, S7N 5E5
2
Department of Psychiatry, University of Alberta…
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APA (6th Edition):
Anderson, M. D. 1. (2019). THE EFFECTS OF DEGRADING PERINEURONAL NETS IN THE MEDIAL PREFRONTAL AND POSTERIOR PARIETAL CORTICES ON THE SPATIAL WORKING MEMORY OF RATS. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/12299
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Anderson, Michael David 1995-. “THE EFFECTS OF DEGRADING PERINEURONAL NETS IN THE MEDIAL PREFRONTAL AND POSTERIOR PARIETAL CORTICES ON THE SPATIAL WORKING MEMORY OF RATS.” 2019. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/12299.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Anderson, Michael David 1995-. “THE EFFECTS OF DEGRADING PERINEURONAL NETS IN THE MEDIAL PREFRONTAL AND POSTERIOR PARIETAL CORTICES ON THE SPATIAL WORKING MEMORY OF RATS.” 2019. Web. 03 Mar 2021.
Vancouver:
Anderson MD1. THE EFFECTS OF DEGRADING PERINEURONAL NETS IN THE MEDIAL PREFRONTAL AND POSTERIOR PARIETAL CORTICES ON THE SPATIAL WORKING MEMORY OF RATS. [Internet] [Thesis]. University of Saskatchewan; 2019. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/12299.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Anderson MD1. THE EFFECTS OF DEGRADING PERINEURONAL NETS IN THE MEDIAL PREFRONTAL AND POSTERIOR PARIETAL CORTICES ON THE SPATIAL WORKING MEMORY OF RATS. [Thesis]. University of Saskatchewan; 2019. Available from: http://hdl.handle.net/10388/12299
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
9.
Rostampour, Nasim 1988-.
Linking new genes to an odontogenesis TP63-mediated gene regulatory network that is peripheral to jaw morphogenesis.
Degree: 2018, University of Saskatchewan
URL: http://hdl.handle.net/10388/8453
► Despite that teeth and jawbones can develop and evolve independently of each other, the genetic processes that independently regulate cranial and dental morphogenesis remain unclear.…
(more)
▼ Despite that teeth and jawbones can develop and evolve independently of each other, the
genetic processes that independently regulate cranial and dental morphogenesis remain unclear.
Previous microarray screens indicated that a TP63-mediated gene regulatory network is integral
to odontogenesis but peripheral to jaw morphogenesis.
Here, I characterized the expression of four genes flagged by our lab’s previous
microarray screens, comparing embryonic wild-type and TP63-null (TP63-/-) mutant mouse
mandible prominences. I hypothesized that in the normal dental epithelium, TP63 up-regulates
Fermt1 and Pltp and down-regulates Cbln1 and Krt8.
I validated the expression domains of these genes in TP63-/- mutant and wild-type mice
using RNA in-situ hybridization on paraffin tissue sections at two stages, E11.5, just after
odontogenesis begins, and at E13.5, just after odontogenesis arrests in the TP63-/- mutant.
My in situ results validated our lab’s previous microarray screens. My work revealed that Fermt1
is expressed in wild-type oral epithelium and dental epithelium, and that Pltp is expressed in
dental epithelium. Compared to wild-type littermates, in TP63-/- mice, Fermt1 and Pltp
expression intensity in the dental epithelium was decreased. Cbln1 was not expressed in wildtype
dental epithelium, although it expressed intensely in the dental epithelium of TP63-/-
littermates. Krt8 was expressed in the dental epithelium of both wild-type and TP63-/- embryos,
with increased intensity in the TP63-/- mice. In sum, my results largely supported my hypothesis.
As such, I propose that Fermt1, Pltp, Cbln1, and Krt8 belong to a TP63-mediated gene
regulatory network and co-regulate odontogenesis by mediating cell adhesion, cell signaling, and
epithelial-mesenchymal interactions at early stages of tooth development.
Advisors/Committee Members: Boughner, Julia, Krone, Patrick, Eames, Brian, Ianowski, Juan.
Subjects/Keywords: Odontogenesis; TP63; Gene regulatory network
…the Health Sciences Building at the University of Saskatchewan. This care
included breeding… …accordance with University of Saskatchewan animal use protocol # 20110008.
Immediately after…
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APA ·
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Export
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APA (6th Edition):
Rostampour, N. 1. (2018). Linking new genes to an odontogenesis TP63-mediated gene regulatory network that is peripheral to jaw morphogenesis. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/8453
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Rostampour, Nasim 1988-. “Linking new genes to an odontogenesis TP63-mediated gene regulatory network that is peripheral to jaw morphogenesis.” 2018. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/8453.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Rostampour, Nasim 1988-. “Linking new genes to an odontogenesis TP63-mediated gene regulatory network that is peripheral to jaw morphogenesis.” 2018. Web. 03 Mar 2021.
Vancouver:
Rostampour N1. Linking new genes to an odontogenesis TP63-mediated gene regulatory network that is peripheral to jaw morphogenesis. [Internet] [Thesis]. University of Saskatchewan; 2018. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/8453.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Rostampour N1. Linking new genes to an odontogenesis TP63-mediated gene regulatory network that is peripheral to jaw morphogenesis. [Thesis]. University of Saskatchewan; 2018. Available from: http://hdl.handle.net/10388/8453
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
10.
Gioino, Paula.
THE ROLE OF CALCIUM IN THE MALPIGHIAN TUBULES OF THE KISSING BUG Rhodnius prolixus.
Degree: 2013, University of Saskatchewan
URL: http://hdl.handle.net/10388/ETD-2013-12-1334
► Stimulation of urine production by the Malpighian (renal) tubules in Rhodnius prolixus is regulated by at least two diuretic hormones, CRF-related peptide and serotonin, that…
(more)
▼ Stimulation of urine production by the Malpighian (renal) tubules in Rhodnius prolixus is regulated by at least two diuretic hormones, CRF-related peptide and serotonin, that have traditionally been believed to function through the activation of cAMP-mediated intracellular second messenger pathways. In this study I demonstrate that serotonin stimulation triggered, in addition to cAMP, intracellular Ca2+ waves in the Malpighian tubule cells of R. prolixus. Treatment with the intracellular Ca2+ chelator BAPTA-AM blocked the intracellular Ca2+ waves and reduced serotonin-stimulated fluid secretion by 75%. This suggests a role for intracellular Ca2+ signaling in the excretory system of R. prolixus. Serotonin stimulated Malpighian tubules (MTs) exposed to Ca2+-free saline plus BAPTA-AM secreted an abnormal fluid, showing: increased K+ concentration, reduced Na+ concentration and lower pH. These results along with measurement of transepithelial potential (TEP) suggest that the basolateral Na+:K+:2Cl- cotransporter (NKCC) activity is reduced in tubule cells treated with BAPTA-AM, suggesting that Ca2+ is required to modulate the activity of the basolateral NKCC.
Treatment with the non-hydrolysable cell-permeable cAMP analog, 8Br-cAMP, produced fluid with the same K+ and Na+ concentration and at the same secretion rate as serotonin-stimulated tubules. In addition, 8Br-cAMP triggered intracellular Ca2+ oscillations similar to those obtained with serotonin. 8Br-cAMP-stimulated tubules treated with BAPTA-AM decreased their fluid secretion by about 40% and increased Na+ concentration, similar to the effect observed on serotonin-stimulated tubules. Therefore, I conclude that the intracellular Ca2+ waves triggered by serotonin are mediated by cAMP.
The role of inositol-3-phospate (InsP3) in Ca2+ release was tested by treating the tubules with the InsP3 receptor blocker xestospongin. The treatment decreased fluid secretion rate as well as the amplitude of Ca2+ waves in serotonin-stimulated tubules. These results suggest that serotonin activates the production of InsP3 and, most likely, diacylglycerol (DAG). Thus, I decided to test whether the protein kinase C (PKC) may be involved in serotonin-stimulated secretion.
The PKC inhibitors chelerythrine and bisindolylmaleimide (BIM) decreased secretion fluid rate in serotonin-stimulated tubules by 50% and 70%, respectively. Fluid secreted by tubules treated with BIM showed no differences in K+ and Na+ concentrations compared to controls, however both ion fluxes decreased. The evidence suggests that PKC is involved in serotonin stimulated secretion; the mechanism is still not understood.
Taken together, the results suggest that cAMP, Ca2+ and PLC-PKC pathway are involved in serotonin stimulated secretion. However cAMP stimulation is enough for maximal secretion rate. Therefore PLC-PKC must act downstream of cAMP. Based on those results we hypothesize that serotonin binds a GPCR, increasing cAMP by activation of an adenylate cyclase (AC). Subsequently, cAMP is somehow able to activate…
Advisors/Committee Members: Ianowski, Juan P., Bekar, Lane K., West, Nigel, Desautels, Michel.
Subjects/Keywords: Malpighian tubules; Chagas; Rhodnuis prolixus; Calcium oscillations; NKCC
…maintained at 25–26°C and
~60% relative humidity in the Department of Physiology, University of… …Saskatchewan.
Experiments were carried out at room temperature (20–23°C). Nymphal stages…
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APA ·
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Manager
APA (6th Edition):
Gioino, P. (2013). THE ROLE OF CALCIUM IN THE MALPIGHIAN TUBULES OF THE KISSING BUG Rhodnius prolixus. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/ETD-2013-12-1334
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Gioino, Paula. “THE ROLE OF CALCIUM IN THE MALPIGHIAN TUBULES OF THE KISSING BUG Rhodnius prolixus.” 2013. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/ETD-2013-12-1334.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Gioino, Paula. “THE ROLE OF CALCIUM IN THE MALPIGHIAN TUBULES OF THE KISSING BUG Rhodnius prolixus.” 2013. Web. 03 Mar 2021.
Vancouver:
Gioino P. THE ROLE OF CALCIUM IN THE MALPIGHIAN TUBULES OF THE KISSING BUG Rhodnius prolixus. [Internet] [Thesis]. University of Saskatchewan; 2013. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/ETD-2013-12-1334.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Gioino P. THE ROLE OF CALCIUM IN THE MALPIGHIAN TUBULES OF THE KISSING BUG Rhodnius prolixus. [Thesis]. University of Saskatchewan; 2013. Available from: http://hdl.handle.net/10388/ETD-2013-12-1334
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
11.
Martinson, Mercedes 1982-.
Bent Laue X-ray Beam Expander.
Degree: 2017, University of Saskatchewan
URL: http://hdl.handle.net/10388/7739
► Synchrotron imaging beamlines around the world all suffer from a similar limitation, namely a beam that is smaller in the vertical direction than the horizontal.…
(more)
▼ Synchrotron imaging beamlines around the world all suffer from a similar limitation, namely a beam that is smaller in the vertical direction than the horizontal. This can produce a beam that is so small in the vertical direction that some imaging applications are limited or even impossible. At the BioMedical Imaging and Therapy (BMIT) beamline facility at the Canadian Light Source (CLS), the vertical beam sizes on the Bend Magnet (BM) and Insertion Device (ID) beamlines are 7 mm and 11 mm, respectively. This limited vertical beam size results in several limitations. Micro-computed-tomography experiments requiring multiple rotations to produce a full three-dimensional representation of the sample result in longer scan times and possible reconstruction errors due to misalignment between rotations. Similarly, projection images requiring vertical scans to cover the entire two dimensional field of view extend acquisition times and lead to potential stitching errors between exposures. Dynamic phase-based imaging (i.e. movies), which are being used for some of the most cutting edge biomedical imaging research taking place worldwide, is virtually impossible with samples larger than the vertical beam size.
This problem has been solved at other synchrotrons by building very long beamlines and allowing the beam to naturally diverge to a larger field of view, however this was not possible for BMIT due to budgetary and geographical limitations. In order to vertically expand the beam, a bent Laue double crystal monochromator was used in a non-dispersive divergent geometry to ultimately produce a beam expansion of 12× the incident height. Improvements were made to the system to preserve the quality of transverse coherence in the beam, allowing phase-based imaging techniques to be performed with a larger field of view. This was achieved by carefully matching the geometric and single-ray focal points in the so-called “magic condition.”
The quality of the expanded beam was compared to that produced by the beamline’s standard flat Bragg double crystal monochromator and was found to differ in divergence by less than 10% between the two monochromator systems. Further testing was done to evaluate the criticality of matching the two focal types, and to determine at least a minimum energy range over which the system could be used reliably. These tests showed that the system is much more flexible than previously believed, with energy ranges of at least ±5 keV producing images wherein the vertical and horizontal edge width differ by less than 1%, indicating that the expander does not adversely affect the beam in the diffraction plane. Despite the improvement to the diffraction and focus characteristics of the system, there was an ongoing issue with areas of missing intensity in the beam. The hypothesis that this was caused by imperfect bending of the second crystal has been confirmed using diffraction and mechanical measurement techniques.
Advisors/Committee Members: Chapman, Dean, Babyn, Paul, Tanaka, Kaori, Ianowski, Juan, Chang, Gap Soo, Pywell, Rob.
Subjects/Keywords: bent laue; beam expander; double crystal monochromator; biomedical imaging
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APA (6th Edition):
Martinson, M. 1. (2017). Bent Laue X-ray Beam Expander. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/7739
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Martinson, Mercedes 1982-. “Bent Laue X-ray Beam Expander.” 2017. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/7739.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Martinson, Mercedes 1982-. “Bent Laue X-ray Beam Expander.” 2017. Web. 03 Mar 2021.
Vancouver:
Martinson M1. Bent Laue X-ray Beam Expander. [Internet] [Thesis]. University of Saskatchewan; 2017. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/7739.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Martinson M1. Bent Laue X-ray Beam Expander. [Thesis]. University of Saskatchewan; 2017. Available from: http://hdl.handle.net/10388/7739
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
12.
Grishchenko, Nikolay.
Abnormal Na+ transport by distal airway surface epithelia in cystic fibrosis swine.
Degree: 2018, University of Saskatchewan
URL: http://hdl.handle.net/10388/11300
► Abstract One of the most prevalent hypotheses pertaining to the sequence of events that lead to cystic fibrosis (CF) airway disease is that in normal…
(more)
▼ Abstract
One of the most prevalent hypotheses pertaining to the sequence of events that lead to cystic fibrosis (CF) airway disease is that in normal airway epithelia the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) anion channel inhibits the activity of the Epithelial Na+ Channel (ENaC). In CF patients, where CFTR is mutated, the inhibition of ENaC is lost. Consequently, ENaC becomes hyperactive, resulting in fluid depletion from the airway, collapse of the mucociliary apparatus, and impaired clearance of microbes, which initiates a cycle of infection and inflammation that may eventually result in respiratory failure. This hypothesis has recently been challenged by reports suggesting that animal models of CF do not exhibit hyperactive ENaC, and that the cilia in their airway appear normally functioning. This constitutes a paradigm shift in CF with serious consequences for current and future CF treatments. However, there is evidence that ENaC hyperactivity in CF may depend on the stimulation of airway epithelia by secretagogues. Thus, using a self-referencing ion selective microelectrode technique with unparalleled spatial resolution, we tested the Na+ transport properties of the surface epithelia in the distal airway (~2mm) of CFTR- \- swine after stimulation of intracellular cAMP or Ca2+ signaling pathways. We show that the epithelial cells located at the folds of the distal airway are capable of both secreting and reabsorbing Na+, and are sensitive to CFTR and ENaC inhibition with CFTRinh172 and amiloride, suggesting that both ENaC and CFTR are expressed at the folds. Most importantly, using the response to amiloride as an assay for ENaC activity, we detected hyperactive ENaC in forskolin-stimulated CFTR-/- airways. This indicates that CFTR-/- swine airways do indeed suffer from hyperactive ENaC after increased intracellular cAMP, thus potentially collapsing the PCL at those sites.
Advisors/Committee Members: Ianowski, Juan Dr., Campanucci, Veronica Dr., Lee, Paul Dr., Cayabyab, Francisco Dr..
Subjects/Keywords: CF; ion transport
…Swine Centre, University of Saskatchewan). The CFTR-/- and wild-type lungs were dissected… …I). All procedures
were approved by the Animal Care Committee of the University of… …Saskatchewan.
2.1.1. Tissue preparation
Blocks of tissue (3 cm3) were excised from the…
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APA ·
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Manager
APA (6th Edition):
Grishchenko, N. (2018). Abnormal Na+ transport by distal airway surface epithelia in cystic fibrosis swine. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/11300
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Grishchenko, Nikolay. “Abnormal Na+ transport by distal airway surface epithelia in cystic fibrosis swine.” 2018. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/11300.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Grishchenko, Nikolay. “Abnormal Na+ transport by distal airway surface epithelia in cystic fibrosis swine.” 2018. Web. 03 Mar 2021.
Vancouver:
Grishchenko N. Abnormal Na+ transport by distal airway surface epithelia in cystic fibrosis swine. [Internet] [Thesis]. University of Saskatchewan; 2018. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/11300.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Grishchenko N. Abnormal Na+ transport by distal airway surface epithelia in cystic fibrosis swine. [Thesis]. University of Saskatchewan; 2018. Available from: http://hdl.handle.net/10388/11300
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
13.
Luan, Xiao Jie 1987-.
Effect of Bacteria on Airway Submucosal Glands Liquid Secretion in Swine.
Degree: 2018, University of Saskatchewan
URL: http://hdl.handle.net/10388/8348
► Cystic fibrosis (CF) is a genetic disorder caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. Currently,…
(more)
▼ Cystic fibrosis (CF) is a genetic disorder caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. Currently, more than 4,100 Canadians have CF. The major cause of CF morbidity and mortality is airway disease, for which there is no cure.
The events leading from CFTR gene mutation to CF airway disease are not fully understood, and there is controversy regarding the primary defect responsible for CF airway disease pathogenesis. Newborn CFTRΔF508/ΔF508 and CFTR-/- swine show no sign of infection and inflammation in the lung but suffer from defective bacteria eradication caused by abnormal innate immune system. The cornerstone of the airway’s innate immune defense is mucociliary clearance, which relies on the normal regulation of airway surface liquid (ASL), which covers the airway epithelium. It has been hypothesized that abnormal ASL is the primary defect that leads to the failure of the airway innate immune defense in CF. Evidence show that the airway submucosal gland functions abnormally in both CF patients and in animal models of CF. This is not surprising since airway submucosal glands normally express CFTR. However, the function of the gland in health and disease is not fully understood. The response of airway submucosal gland to inhaled bacteria has never been tested and its ion transport properties have not been fully described.
Our objective is to investigate the effect of inhaled bacteria on airway submucosal gland secretion, and to study and compare the function of different segments of airway submucosal gland in wild-type and CF airway. Knowledge generated by this thesis would help better understand CF airway pathophysiology and may contribute to improving treatment methods.
Advisors/Committee Members: Ianowski, Juan P., Chapman, Dean, Fisher, Thomas E., Lee, Paul, Aulakh, Gurpreet K..
Subjects/Keywords: Cystic fibrosis; Airway surface liquid; Submucosal gland; Pseudomonas aeruginosa; Synchrotron imaging
…Prairie Swine Centre, University of Saskatchewan. The tracheas were dissected within 15-30… …the University of Saskatchewan.
The experimental hutch was located 25.5 meters away from the… …isolate P. aeruginosa generously
provided by Dr. Gordon at the University of Saskatchewan (…
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APA (6th Edition):
Luan, X. J. 1. (2018). Effect of Bacteria on Airway Submucosal Glands Liquid Secretion in Swine. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/8348
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Luan, Xiao Jie 1987-. “Effect of Bacteria on Airway Submucosal Glands Liquid Secretion in Swine.” 2018. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/8348.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Luan, Xiao Jie 1987-. “Effect of Bacteria on Airway Submucosal Glands Liquid Secretion in Swine.” 2018. Web. 03 Mar 2021.
Vancouver:
Luan XJ1. Effect of Bacteria on Airway Submucosal Glands Liquid Secretion in Swine. [Internet] [Thesis]. University of Saskatchewan; 2018. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/8348.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Luan XJ1. Effect of Bacteria on Airway Submucosal Glands Liquid Secretion in Swine. [Thesis]. University of Saskatchewan; 2018. Available from: http://hdl.handle.net/10388/8348
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
14.
G Baskaran, Manoj Nair 1984-.
RAGE-DEPENDENT SENSITIZATION OF THORACIC SENSORY NEURONS DURING INFLAMMATORY CONDITIONS.
Degree: 2016, University of Saskatchewan
URL: http://hdl.handle.net/10388/7630
► Various airway inflammatory diseases progress as a result of chronic inflammation, specifically neurogenic inflammation. One factor known to be involved in this is RAGE. This…
(more)
▼ Various airway inflammatory diseases progress as a result of chronic inflammation, specifically neurogenic inflammation. One factor known to be involved in this is RAGE. This work has established RAGE as a key mediator in LPS-induced sensitization of afferent thoracic dorsal root ganglia neurons of the upper airway in mice. This was demonstrated from electrophysiological data showing the failure of LPS to potentiate capsaicin-evoked TRPV1 currents and increase action potential generation in RAGE KO relative to wild-type thoracic neurons. Mass spectrometry analysis for protein identification represents a step forward in biochemistry, allowing to obtain a global picture of the proteins expressed in a cell, including isoforms, post-translational modifications and downstream signalling pathways.
Advisors/Committee Members: Campanucci, Veronica, Ianowski, Juan, Mulligan, Sean, Chlan-Fourney, Jennifer, Cayabyab, Francisco.
Subjects/Keywords: RAGE; RAGE isoforms; RAGE KO; thoracic dorsal root ganglia; LPS; airway inflammatory disease; neurogenic inflammation; sensory neuron sensitization
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APA ·
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MLA ·
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APA (6th Edition):
G Baskaran, M. N. 1. (2016). RAGE-DEPENDENT SENSITIZATION OF THORACIC SENSORY NEURONS DURING INFLAMMATORY CONDITIONS. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/7630
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
G Baskaran, Manoj Nair 1984-. “RAGE-DEPENDENT SENSITIZATION OF THORACIC SENSORY NEURONS DURING INFLAMMATORY CONDITIONS.” 2016. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/7630.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
G Baskaran, Manoj Nair 1984-. “RAGE-DEPENDENT SENSITIZATION OF THORACIC SENSORY NEURONS DURING INFLAMMATORY CONDITIONS.” 2016. Web. 03 Mar 2021.
Vancouver:
G Baskaran MN1. RAGE-DEPENDENT SENSITIZATION OF THORACIC SENSORY NEURONS DURING INFLAMMATORY CONDITIONS. [Internet] [Thesis]. University of Saskatchewan; 2016. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/7630.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
G Baskaran MN1. RAGE-DEPENDENT SENSITIZATION OF THORACIC SENSORY NEURONS DURING INFLAMMATORY CONDITIONS. [Thesis]. University of Saskatchewan; 2016. Available from: http://hdl.handle.net/10388/7630
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
15.
Blais, Christianne M 1993-.
BRONCHOPROTECTION PROVIDED BY LONG-ACTING MUSCARINIC ANTAGONISTS AND ULTRA LONG-ACTING β2 AGONISTS AGAINST METHACHOLINE-INDUCED BRONCHOCONSTRICTION IN MILD ASTHMATICS.
Degree: 2017, University of Saskatchewan
URL: http://hdl.handle.net/10388/8034
► Background: Although asthma treatments are extensively studied for their physiological effects in animal models and their safety and efficacy in humans, their effects on standard…
(more)
▼ Background: Although asthma treatments are extensively studied for their physiological effects in animal models and their safety and efficacy in humans, their effects on standard testing methods and their physiological benefits in asthmatics are often unknown. The result is a gap in knowledge on newer therapies such as long-acting muscarinic antagonists (LAMAs) and ultra- long acting β2 agonists (uLABAs); standardization guidelines for methacholine challenge testing (MCT), a common research and clinical technique, remain uninformed as to an appropriate abstinence period from these drug classes prior to testing. In addition, the mechanisms through which these drugs improve airway hyperresponsiveness, an important factor in asthma, remain unknown. These mechanisms can be elucidated through methacholine dose-response curves, which illustrate airway hyperresponsiveness in terms of airway sensitivity (position), reactivity (slope), and maximal airway narrowing response.
Methods: Two single dose, double blind, double dummy, randomized clinical trials were performed; the first crossover study examined the duration and degree of bronchoprotection provided by two LAMAs, tiotropium and glycopyrronium, against methacholine-induced bronchoconstriction in mild asthmatics; the second study had a three-way crossover design for investigating the effects of glycopyrronium (LAMA) and indacaterol (uLABA), alone and in combination, on the methacholine dose-response curve of mild asthmatics. The first study entailed baseline MCT, treatment administration, and repeat MCT at 1, 24, 48, 72, 96, and 168 hours for each treatment, while the second study used a similar protocol but only followed participants for 48 hours.
Results: The first study found that the two LAMAs provided clinically significant and sustained bronchoprotection for up to seven days, with the maximal degree of protection (16-fold increase in methacholine tolerance) provided at one hour post-treatment. The second study revealed that glycopyrronium and combination glycopyrronium/indacaterol each significantly reduced airway sensitivity and reactivity. The combination therapy also significantly reduced the maximal airway narrowing response to methacholine. Indacaterol alone only produced a mild and short- lived reduction in airway sensitivity.
Conclusion: LAMAs should be abstained from for at least seven days prior to undergoing MCT to ensure test accuracy. The LAMA glycopyrronium and the combination glycopyrronium/indacaterol both show promising results in terms of improvements in airway sensitivity, reactivity, and maximal response characteristics of airway hyperresponsiveness and following further experimentation may become standard therapies for the treatment of poorly controlled asthma.
Advisors/Committee Members: Cockcroft, Donald W, Davis, Beth E, Lee, Paul, Ianowski, Juan, McKay, Gordon.
Subjects/Keywords: methacholine challenge; long-acting muscarinic antagonist; ultra long-acting beta-2 agonist; methacholine dose-response curve
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APA ·
Chicago ·
MLA ·
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CSE |
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to Zotero / EndNote / Reference
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APA (6th Edition):
Blais, C. M. 1. (2017). BRONCHOPROTECTION PROVIDED BY LONG-ACTING MUSCARINIC ANTAGONISTS AND ULTRA LONG-ACTING β2 AGONISTS AGAINST METHACHOLINE-INDUCED BRONCHOCONSTRICTION IN MILD ASTHMATICS. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/8034
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Blais, Christianne M 1993-. “BRONCHOPROTECTION PROVIDED BY LONG-ACTING MUSCARINIC ANTAGONISTS AND ULTRA LONG-ACTING β2 AGONISTS AGAINST METHACHOLINE-INDUCED BRONCHOCONSTRICTION IN MILD ASTHMATICS.” 2017. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/8034.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Blais, Christianne M 1993-. “BRONCHOPROTECTION PROVIDED BY LONG-ACTING MUSCARINIC ANTAGONISTS AND ULTRA LONG-ACTING β2 AGONISTS AGAINST METHACHOLINE-INDUCED BRONCHOCONSTRICTION IN MILD ASTHMATICS.” 2017. Web. 03 Mar 2021.
Vancouver:
Blais CM1. BRONCHOPROTECTION PROVIDED BY LONG-ACTING MUSCARINIC ANTAGONISTS AND ULTRA LONG-ACTING β2 AGONISTS AGAINST METHACHOLINE-INDUCED BRONCHOCONSTRICTION IN MILD ASTHMATICS. [Internet] [Thesis]. University of Saskatchewan; 2017. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/8034.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Blais CM1. BRONCHOPROTECTION PROVIDED BY LONG-ACTING MUSCARINIC ANTAGONISTS AND ULTRA LONG-ACTING β2 AGONISTS AGAINST METHACHOLINE-INDUCED BRONCHOCONSTRICTION IN MILD ASTHMATICS. [Thesis]. University of Saskatchewan; 2017. Available from: http://hdl.handle.net/10388/8034
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
. 
Open Access Theses and Dissertations
