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Exploring the Relationship Between Crop Rotations, Crop Insurance, Market Prices, and Crop Yields: Evidence from Three Studies in Saskatchewan
No full textThe abstract of this item is unavailable due to an embargo
EXAMINING THE SOCIAL EXPERIENCE IN A VIRTUAL CULINARY NUTRITION EDUCATION INTERVENTION: THE COGNITIVE KITCHEN
No full textBackground: Evidence suggests preventing or delaying the onset of dementia could have a substantial impact on both direct and indirect costs of health care as well as individual burden. It is estimated around 40% of dementia cases could be prevented through the reduction of modifiable risk factors. Following a nutritious eating pattern is one strategy to reduce the risk of cognitive decline and dementia, but knowledge on how to encourage adoption of dietary patterns shown to support brain health is limited. Being socially active and engaging in cognitively stimulating activities are also recommended dementia risk-reduction behaviours. Cooking classes provide a unique setting where social contact can be integrated with continued education and practical application of nutrition-related dementia risk-reduction strategies (i.e., through food preparation). Interest in studying virtual cooking class delivery has recently increased, with some circumstances making remote attendance appealing (e.g., to reduce travel during inclement weather and illness outbreaks, potentially reduce program costs associated with space rental). Very little published literature captures the feasibility of virtual cooking class delivery in maintaining key program outcomes identified in conventional in-person classes—namely, social interaction. For a dementia risk-reduction-focused virtual intervention in particular, understanding strategies to enhance social engagement is valuable to maximize outcomes for participants. Aim: Examine older adult participants’ experience of the social component of a virtual culinary nutrition education intervention for dementia risk reduction. Methods: The Interpretive Description (ID) methodological approach was used to explore participants’ experiences from two separate but identical offerings of a pilot virtual Cognitive Kitchen program. Data sources for this qualitative study included session observation fieldnotes, end-of-program focus group discussions with each group, participant digital journal entries (45 submissions), and semi-structured individual interviews (n=15, comprised of 13 individual interviews and one shared interview). The two focus groups and 14 interview recordings were transcribed verbatim and analyzed with the other data. Thematic analysis led to the identification of four themes that capture what was learned about the social component of the virtual Cognitive Kitchen from participants’ experiences. Findings: The themes respond to the research objectives of this study by describing the function of social interactions in the program and facilitators and barriers to social engagement in the virtual setting. Social interactions were described to contribute to key program outcomes related to providing culinary and nutrition education and promoting engagement in cooking, as represented by the themes Supporting Learning and Encouraging Application. The theme Trade-offs: Advantages and Missed Connections presents both benefits and drawbacks of the virtual setting that were identified to impact the social component of the program. Lastly, recommendations for future offerings of the Cognitive Kitchen are presented in the theme Ingredients for Engagement. Conclusion: The social component of the virtual Cognitive Kitchen was valued by participants and contributed to the achievement of key program outcomes. Specifically, contributions from group members were described to enhance the educational content on nutrition and socialization-related dementia risk-reduction strategies. Additionally, the group setting provided accountability for many participants to engage in home cooking and social interactions appeared to function to promote cooking as an activity to support well-being. The findings also capture that some social experiences are unable to be replicated via web-based programs. As such, additional effort by facilitators is necessary to enhance social engagement among participants in virtual culinary nutrition education interventions
The Journey of a kêhtê-aya (elder): kiskisi sôhkisiwin, tâpôkêyimoh, sôhkitêhê, nâkatohkê: Memorize the Strength, Have Faith, Have a Strong Heart, Pay Attention
No full textI am from Onion Lake Cree Nation. I am a nêhiyaw-iskwêw (Cree woman). My first
language is nêhiyawêwin/Cree. I lived with my great-grandparents until I started residential
school in 1956.
My PhD research is based on my belief in healing, reconciling, and reclaiming Indigenous education to benefit students, families, and communities. There is a critical need to explore the role of Elders in schools. How are they used and positioned, by whom, and why?
How can the education system move away from inviting Elders to check box-type activities and progress to having Elders acknowledged as having integral and continuous roles in schools where their knowledge is central to shaping and informing the unfolding curriculum being lived out with children and families? These are the questions that you will find explored and discussed in the videos that comprise the core of this dissertation, focused on discussions of the commodification and changing role of Elders; cultural trauma; artivism and reparation; and healing, reconciling, and reclaiming Indigenous education for the benefit of students, families,
and communities.
As a methodological approach, I followed the teachings shared by my mother, who is
central to this work. What I did, and how and when I did it, was led by following protocol,
prayer/prayer songs, and the offering of tobacco; it guided every aspect of my journey. My daily
work began with smudging and prayers, the tobacco led me to invite thought leaders for the four
conversations, it inspired my bookwork, and it guided my thought processes and decision
making throughout my doctoral journey. Each conversation began with smudging, prayer/prayer
song, and the offering of protocol to the thought leaders so that our conversation would unfold in
a good way, with open eyes, ears, minds, and hearts.
From January through December 2022, I spent one year in the field as an Elder/kêhtê-
aya. I kept a journal of my Elder/Knowledge/Keeper requests and recorded my research to prepare
for the commitment and my experience. This fieldwork was integral to planning and preparing
for four video conversations with invited thought leaders. To fully understand the work asked of
Elders it was necessary for me to immerse myself in the work of an Elder/Knowledge Keeper. I
made a commitment to accept up to three protocol requests per week. Topics were varied from
sharing opening prayers and comments, presenting on residential school history or treaties, and
sitting on cultural advisory committees.
To prompt each conversation, I created a bookwork arising out of the conceptualization
that became the focus. A bookwork is a non-book that relies on the viewer’s interaction with the
object to make meaning. Each installation is a narrative that tells a story. Artists’ books, or bookworks, first emerged in the 1960s and 1970s as an expression of social and political activism, a way to “talk back” to mass production and mass media. Creating the bookworks required extensive research on the focus topic, including consulting with artists, art professors, curators and visiting art exhibits. Each bookwork took six months to a year to complete.
My video dissertation is a compilation of 10 videos: my introduction to the research
journey, the four core conversations with thought leaders conducted in a talking circle format,
each with a separate video introduction by me, and a culminating video that shares my research
reflections. The videos have an accompanying transcript, in which I included the spoken Cree
and I translated the Cree language into English. My doctoral work also includes an eleventh
video which captures the gallery show I arranged and hosted at AKA Gallery in the Saskatoon
community to profile the four bookworks and showcase the video dissertation.
In summary, the videos, the transcripts, the bookworks, and the gallery show are all
integral pieces to my doctoral dissertation. Further, I have included a glossary of terms to
accompany the viewing/reading of the videos and transcripts, and a bibliography for those
individuals who want to pursue aspects of this work more deeply or for purposes that move
forward their own work and thinking
REGULATION OF NUCLEAR RIG-I MEDIATED INTERFERON SIGNALING BY DUSP11 DURING INFLUENZA A VIRUS INFECTION
No full textInfluenza A virus (IAV) poses a continuous public health threat owing to its ability of frequent antigenic drift and shift. Seasonal flu outbreaks and periodic pandemics cause significant morbidity and mortality, imposing substantial global economic burden. During the course of evolution, mammals have developed cellular defense mechanisms to combat pathogens, with the innate immune system serving as the first line of defense. The swift response of innate immunity against the invading pathogen triggers an effective antiviral response, while priming specific adaptive immunity. Recognition of IAV by the innate immune system involves various pattern recognition receptors (PRRs), notably the retinoic acid-inducible gene I (RIG-I), which plays a crucial role in initiating the type I interferon (IFN) response against IAV. RIG-I has previously been characterized as a cytoplasmic viral RNA sensor that recognizes short double-stranded RNA harboring a 5’-PPP/PP moiety. Despite having a single-stranded RNA genome, RIG-I detects IAV via its, double-stranded, 5’-PPP bearing panhandle structure, created by partial complementarity of the genomic RNA extremities.
Notably, IAV replicates in the nucleus, raising the question of how the cytoplasmic RNA sensor RIG-I detects a nuclear-replicating virus. To unravel this mystery, Liu et al. investigated the spatiotemporal dynamics of IAV detection by RIG-I and identified a nuclear-resident fraction of RIG-I responsible for sensing IAV replication within the nucleus. The nuclear RIG-I (nRIG-I) -mediated IAV sensing initiates an antiviral IFN signaling in a mitochondrial antiviral signaling protein (MAVS) dependent manner. These findings have redefined the paradigm of RNA sensing for nuclear-replicating viruses, unveiling a previously unknown subcellular context for RIG-I-like receptor sensing. However, the precise mechanisms governing the regulation of nRIG-I signaling during IAV infection have remained elusive until now.
This study presents a revelation that centers on the role of RNA triphosphatase dual specificity phosphatase 11 (DUSP11) in the negative regulation of nRIG-I-mediated IFN production, promoting IAV infection. DUSP11 belongs to a subfamily of protein tyrosine phosphatases known for dephosphorylating serine/threonine/tyrosine residues on protein substrates. Interestingly, DUSP11 lacks the N-terminal domain that typically confers specificity for protein substrates; instead, it exhibits a strong affinity for 5’-PPP/PP bearing RNA, dephosphorylating them to 5’ monophosphate. Crucially, some of the host transcripts, especially those transcribed by RNA polymerase III, are tri-phosphorylated at the 5’end and possess complex secondary structures enabling them to activate PRRs such as RIG-I. DUSP11's catalytic action on these triphosphorylated transcripts prevents an aberrant inflammatory response in the absence of genuine pathogenic stimuli. However, 5′-PPP RNAs are a characteristic feature of viral RNA genomes, prompting the viruses to exploit DUSP11 catalytic activity to modify their RNA and evading detection by the innate immune system.
In this study, we show that IAV infection orchestrates the recruitment of DUSP11 into the nucleus, where it exerts its influence on viral RNA. Specifically, DUSP11 acts as an editor of viral RNA by removing 5’-terminal diphosphates. This strategic editing process enables the viral RNA to evade detection by nRIG-I, effectively preventing its activation and the subsequent initiation of an IFN response. The mechanism driving the nuclear translocation of DUSP11 appears to hinge on its interaction with the viral nucleoprotein, the interaction probably mediated by specific amino acid residues, Y99 and Y100 in DUSP11, and, P477 and F479 in NP. Mutant DUSP11s (Y99A/Y100A) are unable to translocate to nucleus upon IAV infection, whereas, IAVs carrying mutant NP (P477A/F479A) are unable to recruit DUSP11 into the nucleus, provoke higher levels of IFN production and exhibit attenuation in replication. Interestingly, this attenuation can be rescued by the introduction of nuclear-targeted DUSP11.
Collectively, these findings reveal an ingenious compartmentalization strategy employed by IAV to evade recognition by nRIG-I, thereby evading the host's immune response. This not only adds a new layer of complexity to our understanding of host-virus interactions during IAV infection but also underscores the crucial role of DUSP11 in shaping the outcome of this battle. Targeting DUSP11 could hold promise as a novel approach to bolster the host's defenses against IAV and potentially other viruses employing similar evasion tactics
IMMUNOHISTOCHEMISTRY AS A TOOL FOR MECHANISTIC STUDIES OF RADIOIMMUNOTHERAPY OF OSTEOSARCOMA
No full textOsteosarcoma (OS), characterised by the direct formation of immature bone or osteoid tissue by
tumor cells, is a primary malignant bone cancer affecting humans and canines. This study explores
the potential of Targeted Radionuclide Therapy (TRT), specifically Radioimmunotherapy (RIT),
as a novel treatment approach for OS. RIT utilises antibody molecules to deliver radiation to tumor
cells, with promising applications in treating metastatic disorders. Notably, the cation-independent
mannose-6-phosphate/insulin-like growth factor-2 receptor (IGF2R) has been identified as a viable
therapeutic target for RIT in OS due to its high expression in tumor cells.
To investigate the impact of RIT on the OS tumor microenvironment (TME), we conducted
Immunohistochemistry (IHC) analyses. The results revealed a reduction in IGF2R-positive cells,
OS stem cells, and pro-tumorigenic M2 macrophages following RIT. Notably, RIT showed diverse
effects on natural killer (NK) cells and M1 macrophages. Specifically, RIT employed two
radioisotopes with different decay schemes: the alpha-emitting Actinium-225 (225Ac) and the betaemitting
Lutetium-177 (177Lu). The alpha-emitting 225Ac led to a decrease in NK cell numbers; at
the same time, the beta-emitting 177Lu increased NK cell populations, potentially indicating a
stimulating effect. Likewise, the increase in M1 macrophages numbers in Gracie (canine OS cell
line) and the decrease in M1 macrophages numbers in OS33 (human OS cell line) post-RIT
suggests the highly dynamic and variable behaviour of TME.
This research underscores the potential of RIT in modulating the TME and offers new insights into
its efficacy against OS. Understanding the intricate relationship between RIT, the choice of a
radioisotope, and TME is essential for refining treatment strategies and harnessing the immune
system's capabilities. This study paves the way for more personalised and effective therapeutic
approaches, which could benefit patients facing this challenging cancer
Developing and Applying a Yeast Model of Hutchinson-Gilford Progeria Syndrome
No full textThe human premature aging disorder Hutchinson-Gilford progeria syndrome can, by virtue of its single molecular cause, be introduced to other living systems which allows for a more controlled and nuanced study of the disease. We have applied this philosophy to the study of aging in yeast (Saccharomyces cerevisiae) and generated a model system of premature aging which captures several of the major molecular phenotypes of Hutchinson-Gilford progeria syndrome. Our system is based on a galactose inducible pYES plasmid vector system that is readily maintained in yeast under selection and that expresses the disease-causing progerin protein N terminally tagged with EGFP. We successfully applied the yeast model of progeria towards exploring interactions and influences between core cellular processes and the severity of the Hutchinson-Gilford rapid aging phenotype. This initially involved inducing Hutchinson-Gilford progeria syndrome in mutant yeast strains with single non-essential gene deletions and screening for phenotype severity. This screening further reinforced confidence in our yeast model of progeria by implicating several processes, including those of genomic stability and mitochondrial function and organization, which were previously known to be influenced by Hutchinson-Gilford type premature aging. As such, we proceeded to apply the yeast model of progeria towards the study of the syndrome. Deletions of individual subunits of the Chromatin Assembly Factor 1 replication-dependent histone assembly complex were found to apparently reduce the fitness-impairment effect of progerin expression in yeast and so represented promising ground for in-depth assessment. Our work suggests that activity of Chromatin Assembly Factor 1 influences the severity of the Hutchinson-Gilford rapid aging phenotype and represents a promising target for future studies
The Rainbow Bike Experiences of School for Parents Whose Children Have Needs: A Narrative Inquiry into Whose Knowledge Counts
No full textHaving chosen narrative inquiry as my research methodology, I sat for hours in my first
narrative inquiry class wondering how I was going to tell my story. I observed countless examples
of rich narratives. They all spoke to me in different ways, but I still did not know how to begin.
Finally, the metaphor of the rainbow bike crashed into my head, just as it crashed so long ago as a
little girl. I decided to use the rainbow bike metaphor to conceptualize and tell my story of
experience and as an entry into this narrative inquiry. As a child, my rainbow bike was a place of
escape from pain and hurt. As a narrative inquirer in the field, I continued to ride my rainbow bike
when I needed help to carry the heaviness of the stories my research participants shared and I
needed to escape to places of safety and comfort to unpack those stories. As I engaged in analysis
and interpretation of my field text, my rainbow bike carried me to places of discovery and joy.
Now, as I conclude this narrative inquiry, I park my rainbow bike for some much needed rest.
It was through writing my own narrative beginnings that I learned how to portray the lived
experiences and stories of my research participants: three pairs of parent partners who have a child
with needs, the term I use to step away from the language and labelling of ‘special needs’ that
‘others’ children and their families. Parents with children with needs often find themselves pushed
to the margins at their children’s schools, seen to be lesser than other parents, seen to be less
knowing. My purpose in inquiring into their lived experiences was to foreground the parent
knowledge they hold, individually as parents and together as parent partners, that can be used
alongside teachers’ knowledge to inform their children’s schooling experiences.
Attentive to the three-dimensional space of this narrative inquiry, I captured participants’
stories as they unfolded over time, moving between earlier moments, present realities, and
imagined future possibilities. I was drawn to their innermost thoughts and feelings as we engaged
in conversations in the social space of our living rooms. Through the sharing of our stories, we
journeyed to childhood homes, communities, and schools. This narrative inquiry has been a long
and in-depth rainbow bike ride, backward and forward, inward and outward, visiting many places
during the sharing of stories of our lives.
As stories were lived and told, I understood more deeply how parent knowledge is held and
used, either individually, exercised as a form of roving leadership within their partnership, or co-
constructed to create new shared knowledge for both parents. It became clear that if parent
knowledge is used alongside teacher knowledge, it is possible to dramatically transform the current
hierarchy of schools, creating teaching and learning centres in which parents have a place and
voice.
It is my hope that the lived experiences of the parents in my inquiry have been educative
for themselves and will be for other parents on a similar journey, for educators who will “walk
alongside” the parents as their children with needs enter schools and school systems, and for
schools and school systems in which some parents and families find themselves in the margins of
the school landscape
EXPLORING TEACHER RECRUITMENT AND RETENTION POLICIES, PRACTICES, AND PERSPECTIVES IN SASKATCHEWAN AND WEST VIRGINIA A DESCRIPTIVE STUDY
No full textThis descriptive study explored and compared what recruitment and retention policies and practices school divisions in Saskatchewan, Canada and West Virginia, United States used to staff their schools and whether or not, and to what degree, institutional isomorphic forces influenced those policies and practices. Survey data from 21 Saskatchewan and 19 West Virginia school divisions and semi-structured interview data from five self-identified survey respondents was collected. Descriptive and inferential statistical techniques and simple qualitative descriptive techniques were used to analyze the data.
This study corroborated the suggestion in the literature that school divisions have similar staffing administrative functions, regardless of their location in Saskatchewan or West Virginia; and further that the policies and practices used to recruit and retain teachers are comparable. By extension, school divisions generally have administrative functions, such as staffing, that may be described and compared aculturally. The data supports this assertion. Further, the study also found that institutional isomorphic (coercive, mimetic, and normative) forces affected policies and practices related to recruitment and retention of teachers. All respondents indicated at least some effect on policies and practices by each isomorphic force. The data showed the effect of coercive influencing forces indicates that the Saskatchewan school divisions have a greater degree of autonomy and self-governance than their counterparts in West Virginia.
Further, significant findings from the survey data in this study indicated recruiting and retention in rural/remote school divisions was more difficult than non-rural/remote school divisions; recruiting and retention were more difficult for school divisions in West Virginia than school divisions in Saskatchewan. Additionally, the data indicated recruiting and retention challenges and issues in West Virginia were more often related to financial factors compared to Saskatchewan school divisions where non-financial factors were more of an issue.
Analysis indicated statistically significant differences between West Virginia and Saskatchewan school divisions around challenges they face when recruiting teachers. These challenges included low/uncompetitive salaries (p=.000), certification requirements (p=.000), degree requirements (p=.002), and uncompetitive benefits (p=.002). Likewise, statistically significant differences between West Virginia and Saskatchewan were also revealed regarding the challenges school divisions face when retaining teachers. The challenges that affected teacher retention were low/uncompetitive salaries, certification requirements, degree requirements, closer proximity to higher paying divisions, and uncompetitive benefits. West Virginia had much more difficulty and faced greater barriers in recruiting and retaining teachers than Saskatchewan. When looking at specific recruitment and retention strategies, West Virginia schools were more likely to rely on assisting teachers in obtaining full license/certification as a strategy than divisions in Saskatchewan, which is likely related to the use of alternative certification practices and provisionally licensed staff in West Virginia.
This study illustrated recruitment and retention policies and practices overall are similar among school divisions in Saskatchewan and West Virginia. However, although both school divisions face similar challenges, the West Virginia school divisions were affected more by financial factors, while the Saskatchewan school divisions were affected more by non-financial factors
NUCLEAR FACTOR ERYTHROID 2 RELATED FACTOR-1 (NRF1) MEDIATES CELASTROL-INDUCED GENE REGULATION, DEPENDING ON ITS HETERODIMERIC INTERACTIONS
No full textOxidative stress has been recognized as critical in human aging and the progression of
many chronic diseases, including cancer. Cells undergo oxidative stress when the overproduction
of reactive oxygen species (ROS) within the cell outweighs its antioxidant defenses. As a defense
mechanism, a series of cytoprotective genes is initiated and regulated by various transcription
factors in order to minimize oxidative damage to the cell. NF-E2-related factor 1 (NRF1) is a
Cap'N'Collar (CNC) transcription factor family member that plays a major role in regulating genes
involved in defense against cell stress and damage. For example, NRF1 is a vital regulator of
antioxidant and proteasome genes to counteract ROS and impaired protein homeostasis. Upon
stress caused by impaired protein turnover, NRF1 undergoes endoplasmic reticulum to nuclear
translocation and binds antioxidant response elements (ARE) located in close proximity to stress
defense genes throughout the genome. The result is altered transcription of the associated gene.
While this general concept has been established, the mechanism by which NRF1 is processed,
selected for nuclear translocation rather than degradation, and the role of post-translational
modifications is not understood. Moreover, previous studies show NRF1 must form a heterodimer
with other transcription factors such as small musculoaponeurotic fibrosarcoma oncogene
homolog (MAF) proteins to bind AREs and regulate gene transcription. The mechanism
underlying NRF1 heterodimer formation and ARE binding and whether distinct heterodimers
regulate distinct genes is unclear. I hypothesize NRF1 regulates proteasome and oxidative stress
defense via specific heterodimer interactions.
In this thesis, I describe our identification of the nutraceutical celastrol as a stimulant for
NRF1’s transcriptional activity. For centuries, celastrol has been used to treat inflammatory and
chronic diseases and more recently found to influence a multitude of stress pathways and suppress
chymotrypsin-like activity of the proteasome. I then proceeded to use celastrol to investigate my
hypothesis. Using cultured Hep3B cells, I show celastrol elicits dose-dependent inhibition of the
proteasome and this increases the level of a cleaved NRF1 protein product known to regulate
transcription. Using clustered regularly interspaced short palindromic repeats (CRISPR)/cas9
based technology to produce NRF1 loss-of-function cells, I show celastrol induces transcription
of proteasome and oxidative stress defense genes in an NRF1-dependent manner. Likewise,
quantitative polymerase chain reaction measurement of immunoprecipitated chromatin revealed
that NRF1 binds to AREs in stress defense genes GCLC, GCLM, HO1, NQO1A in a manner that
corresponds with transcription regulatory profiles. Moreover, ablation of NRF1 heterodimers
MAFG, MAFK, or MAFF resulted in refractory responses to celastrol that partially and nonredundantly
matched NRF1 deficiency.
Collectively, results of my research support a model whereby NRF1 heterodimerization
with MAFK regulates one gene sub-set or program, whereas heterodimerization with MAFG or
MAFF regulates another one. In other words, specific heterodimeric interactions coordinately
stimulate or repress the transcription of a group of target genes
Nucleation Simulation Studies of Propane Vapour Condensation
No full textMolecular dynamics (MD) simulations are used to study the nucleation kinetics of propane condensation. Using the TAMie potential for propane, equilibrium MD simulations are performed first to calculate the pressure-volume equation of state for the model in the metastable region over a range of temperatures. The resulting data shows good agreement with the predictions of the Peng equation of state (EOS), which makes the Peng EOS suitable to calculate the theoretical predictions of the binodal and spinodal.
The nucleation behaviour, including the rate, free energy barrier, Zeldovich factor, and critical cluster size calculations, are obtained using the mean first passage time (MFPT) method over a range of decreasing temperatures that approach the calculated mean field spinodal, at a fixed system volume. As the temperature decreases, the barrier decreases and the sigmoidal MFPT behaviour associated with classical nucleation crosses over to a linear, growth-dominated regime. The MFPT calculations are compared with the classical nucleation theory (CNT), which shows that all the CNT critical sizes are smaller than those calculated from simulation. The nucleation rate and nucleation lag times are also obtained using the survival probability (SP) method. The nucleation rate calculated using the MFPT, CNT and the SP methods are all in very good agreement.
The effect of the initial cluster distribution on the measured nucleation rate is also examined by selecting two ensembles of starting configurations from T = 800K and T = 340K. There is no distinguishable difference in the nucleation rates obtained using the different initial conditions. However, the nucleation lag times obtained from T=340K initial condition are consistently smaller.
We also compared the results obtained from two commonly used cluster criteria, the Stillinger criterion and the Frenkel criterion. No significant difference in nucleation rates is detected given the statistics obtained in this study