HARVEST
University of Saskatchewan's Repository for Research, Scholarship, and Artistic Work
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The Wnt/β-catenin pathway is important for replication of SARS-CoV-2 and other pathogenic RNA viruses
(Nature, 2024) Xu, Zaikun; Elaish, Mohamed; Wong, Cheung Pang; Hassan, Bardes B.; Lopez-Orozco, Joaquin; Felix-Lopez, Alberto; Ogando, Natacha S.; Nagata, Les; Mahal, Lara K.; Kumar, Anil; Wilson, Joyce A.; Noyce, Ryan; Power, Christopher; Evans, David; Hobman, Tom C.
Understanding how viruses affect cellular pathways during infection may facilitate development of host cell-targeted therapeutics with broad-spectrum antiviral activity. The interferon (IFN) response is critical for reducing replication and pathogenesis of many viruses including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. Mounting evidence indicates that peroxisomes which are best known as metabolic organelles, function in the IFN response. Recently, we reported that the Wnt/β-catenin signaling pathway strongly suppresses peroxisome biogenesis. Here, we show that SARS-CoV-2 infection activates Wnt/β-catenin signaling and hypothesized that pharmacological inhibition of this pathway would result in increased peroxisome formation and enhanced IFN production. Indeed, Wnt/β-catenin signaling potently inhibits replication of SARS-CoV-2 and other pathogenic RNA viruses in vitro and reduces viral load, inflammation and clinical symptoms in a mouse model of COVID-19. As such, targeting this cellular pathway may have prophylactic and/or therapeutic value in reducing the disease burden caused by emerging viral pathogens.
California Serogroup Viruses in a Changing Canadian Arctic: A Review
(MDPI, 2023) Snyman, Jumari; Snyman, Louwrens Pieter; Buhler, Kayla; Villeneuve, Carol-Anne; Leighton, Patrick A.; Jenkins, Emily J.; Kumar, Anil
The Arctic is warming at four times the global rate, changing the diversity, activity and distribution of vectors and associated pathogens. While the Arctic is not often considered a hotbed of vector-borne diseases, Jamestown Canyon virus (JCV) and Snowshoe Hare virus (SSHV) are mosquito-borne zoonotic viruses of the California serogroup endemic to the Canadian North. The viruses are maintained by transovarial transmission in vectors and circulate among vertebrate hosts, both of which are not well characterized in Arctic regions. While most human infections are subclinical or mild, serious cases occur, and both JCV and SSHV have recently been identified as leading causes of arbovirus-associated neurological diseases in North America. Consequently, both viruses are currently recognised as neglected and emerging viruses of public health concern. This review aims to summarise previous findings in the region regarding the enzootic transmission cycle of both viruses. We identify key gaps and approaches needed to critically evaluate, detect, and model the effects of climate change on these uniquely northern viruses. Based on limited data, we predict that (1) these northern adapted viruses will increase their range northwards, but not lose range at their southern limits, (2) undergo more rapid amplification and amplified transmission in endemic regions for longer vector-biting seasons, (3) take advantage of northward shifts of hosts and vectors, and (4) increase bite rates following an increase in the availability of breeding sites, along with phenological synchrony between the reproduction cycle of theorized reservoirs (such as caribou calving) and mosquito emergence.
Reciprocal Effects of Fibroblast Growth Factor Receptor Signaling on Dengue Virus Replication and Virion Production
(Elsevier, 2019) Cortese, Mirko; Kumar, Anil; Matula, Petr; Kaderali, Lars; Scaturro, Pietro; Erfle, Holger; Acosta, Eliana Gisela; Buehler, Sandra; Ruggieri, Alessia; Chatel-Chaix, Laurent; Rohr, Karl; Bartenschlager, Ralf
Dengue virus (DENV) is a human arboviral pathogen accounting for 390 million infections every year. The available vaccine has limited efficacy, and DENV-specific drugs have not been generated. To better understand DENV-host cell interaction, we employed RNA interference-based screening of the human kinome and identified fibroblast growth factor receptor 4 (FGFR4) to control the DENV replication cycle. Pharmacological inhibition of FGFR exerts a reciprocal effect by reducing DENV RNA replication and promoting the production of infectious virus particles. Addressing the latter effect, we found that the FGFR signaling pathway modulates intracellular distribution of DENV particles in a PI3K-dependent manner. Upon FGFR inhibition, virions accumulate in the trans-Golgi network compartment, where they undergo enhanced maturation cleavage of the envelope protein precursor membrane (prM), rendering virus particles more infectious. This study reveals an unexpected reciprocal role of a cellular receptor tyrosine kinase regulating DENV RNA replication and the production of infectious virions.
The Examination of Commercial Wearable Devices for Children and Youth Who Use Manual Wheelchairs
(2025-12-17) Pearman, Katrina; Fuller, Daniel; McIlduff, Cari; Gustafson, Paul; Smith, Kirsten; Muhajarine, Nazeem
Background: Children and youth experiencing disability are less likely to be physically active compared to their peers. Commercial wearable devices include brands such as Apple Watch and Fitbit are increasingly targeted to children and youth. Unfortunately, the promise of individual and population level measurement of physical activity (PA) for children and youth in manual wheelchairs using commercial wearable devices has not been realized.
Purpose: To examine the pre-existing research on the validity of commercial wearable device’s push count detection for children and youth who use manual wheelchairs and explore the experiences these children and youth have with commercial wearable devices, as well as gaining insights from their parents on their experience.
Methods: This is a mixed-methods research design study. First, a secondary quantitative
analysis of two systematic reviews was conducted to analysis the data on the push count validity of commercial wearable devices for children and youth. Second, interviews with youth who use manual wheelchairs, and their parents were conducted to examine their experiences with the commercial wearable devices.
Results: The secondary quantitative analysis found no research on the validity of commercial wearable devices’ push count detection in children and youth who use manual wheelchairs. The themes that emerged from the interviews were: youth friendly, interest, tracking health metrics, concerns, and suggestions for designing devices.
Conclusion: More research is needed to make commercial wearable devices accessible for all children and youth. If this is done hopefully it can motivate children and youth who use manual wheelchairs to engage in more physical activity and this can result in better physical, mental, and social outcomes.
An Investigation of Seed Longevity and Antioxidant Changes of Conserved Barley Germplasm
(2025-12-17) Godakanda, Rasanwada Wijesundara; Bai, Yuguang; Fu , Yong-Bi; Bai, Yuguang; Tar’an, Bunyamin; Bueckert, Rosalind; Qiu, Xiao
Seed longevity is crucial for the sustainable ex situ conservation of germplasm in genebanks, yet its reliable assessment remains a significant challenge. This research was conducted to predict the longevity of a diverse barley (Hordeum vulgare L.) germplasm collection comprising cultivated and wild types preserved in long-term storage (LTS) at Plant Gene Resources of Canada (PGRC) for 5 to 37 years, and to study the changes in antioxidant levels during storage. In this study, a quadratic random intercept model was applied to viability data to predict longevity as a flexible modelling approach. Seedling lengths, variation in viability and lengths were analyzed in parallel with the viability model as a novel approach to longevity prediction. To account for intra-specific variation, modelling was also performed within several biological subcategories. Additionally, temporal dynamics of antioxidant parameters—total phenolic content (TPC), DPPH radical scavenging assay and total antioxidant capacity by FRAP assay—were evaluated for a subset of covered barley. Barley germplasm remained viable for nearly four decades in the PGRC base collection, suggesting that the first monitoring test could potentially be deferred until at least 35 years after storage. Distinct patterns of viability loss were observed among covered cultivars, hulless barley and covered wild barley, although the latter two groups were underrepresented. Models based on radicle length and on variability in viability (tCVV) and radicle length (tCVRL), aligned with the viability-based curve for all barley. However, for all covered barley and covered breeding lines, radicle length declined faster than viability, suggesting its potential use as an early indicator of viability loss. Together, these alternative modelling approaches reinforce the longevity estimates derived from the viability model. Changes in antioxidant parameters did not consistently reflect the observed patterns of viability loss across three covered barley germplasm types, although antioxidant parameters were highly correlated with each other (r > 0.7; p > 0.001). Interestingly, covered wild barley showed the highest TPC, DPPH and FRAP activities relative to cultivated and breeding barley groups, which increased with prolonged storage—except for notably low values in the intermediate group. Collectively, this study revealed characteristic patterns of viability loss and differences in antioxidant dynamics among barley subgroups under LTS at PGRC, suggesting that defining longevity parameters at the intra-specific levels may improve the management of seed collections in genebanks.
Building a Novel Two-Port Element for Lumped Modeling of Integrated Microfluidic Circuits
(2025-12-17) Ezegwui, Chidum Chukwuka; Zhang, Chris; Zhang, Lifeng; Chen, Li
Understanding the underlying principles of operation in relatively new fields, such as microfluidics, is crucial for developing new technology within that field. To this end, this study presents a novel two-port circuit element for microfluidic devices with flexible structures surrounded by fluid, which complements the method reported by Oh, Lee, Ahn, and Furlani (2012) for devices with only rigid members. This two-port element is developed for devices known as Integrated Microfluidic Circuits (IMCs), which operate autonomously using a flexible membrane as a control mechanism and a power source as the sole external input. Applying the Two-Port Lumped Element Method, the IMCs of Mosadegh et al. (2010) and Furtado (2021) were modeled to verify the accuracy of the proposed method, demonstrating the accuracies of 80.0% and 88.2% for the prediction of the membrane deflection for the two IMCs, respectively. These results demonstrate the usefulness of the two-port model as a tool in the preliminarily design of IMC switching systems. This method provides a standardized tool for napkin considerations during the conceptual design phase. The proposed method can be applied across various configurations of IMCs, as long as they have a flexible membrane and operate in the fluid domain.
Changes in the cryosphere and impacts on water
(United Nations Educational, Scientific and Cultural Organization (UNESCO), 2025) Johnson, Zoë; DeBeer, Chris; Schuster Wallace, Corinne; Pomeroy, John; Muhammad, Sher; Wrona, Fred; Black, Kerry; Wangchuk, Sonam ; Pradhananga, Dhiraj; Wrona, Fred
Mountain regions span a wide range of elevations. In this chapter, ‘high mountains’ are defined as mountains where snow and ice play an important role in global freshwater provisioning (Viviroli et al., 2020; IPCC, 2023) and the local or regional hydrological cycle. Although the two are related, hydroclimate – as opposed to elevation – is a more relevant categorical basis for understanding impending changes in the mountain cryosphere and the consequences for water. Often called ‘water towers’, high mountains receive greater amounts of precipitation than lower-lying areas and are responsible for generating large amounts of runoff and streamflow (Immerzeel et al., 2020; Viviroli et al., 2020). Much of this precipitation occurs as snowfall, which is stored as seasonal snowpacks and glacial ice during cold periods and then released as meltwater during warmer periods.
It is often stated that about 2 billion people depend on mountains – and therefore on contributions from the melting cryosphere – for their freshwater supply. This is a number derived from the estimate that 2 billion people live in drainage basins that originate in mountains (Immerzeel et al., 2020; Viviroli et al., 2020). Nevertheless, the relative importance and contributions of melting snow, ice and frozen ground
to downstream water resources availability and quality are often poorly understood and mischaracterized (Gascoin, 2024). Generalizations such as “Himalayan glaciers alone provide water to 1.4 billion people” (Milner et al., 2017, p. 9771) or “Glaciers are crucial sources of life on Earth as they provide vital water resources to half of humanity for domestic use, agriculture and hydropower” (UNESCO/IUCN, 2022, p. 3)
can leave the inaccurate impression that, without glaciers, billions of people will be without water (Gascoin, 2024).
Glaciers play an important role in freshwater provisioning, but they do so with far more nuance and regional variation than the above claims suggest. It must be recognized that multiple other hydroclimatic processes are also involved in freshwater systems. In fact, in most high mountain areas, the seasonal snowpack, rather than glaciers, is the primary source of runoff (Barnett et al., 2005). Climate change is radically affecting all components of the mountain cryosphere. Therefore, the complexities of such impacts need to be explicitly examined and addressed.
This chapter describes why high mountains are hydrologically significant and how the mountain cryosphere is changing. Global warming is amplified at most high elevations, and is reducing snow accumulation and snow cover duration, accelerating glacier mass loss and retreat, causing permafrost (permanently frozen ground) thaw, and advancing the timing and sometimes the rate of snow and ice melt, with high spatial and temporal variability (Pepin et al., 2022; IPCC, 2023). The previously predictable timing of warm season melt is being replaced by more variable rainfall-dominated runoff regimes, with complex downstream effects. The potential impacts of these changes on freshwater systems and the occurrence of extreme events (including droughts, floods, landslides and more) are discussed below, along with implications for downstream ecosystems and communities.
Knowledge- and capacity-building
(United Nations Educational, Scientific and Cultural Organization (UNESCO), 2025) Johnson, Zoë; DeBeer, Chris; Schuster Wallace, Corinne; Pomeroy, John; Muhammad, Sher; Wrona, Fred; Black, Kerry; Pradhananga, Dhiraj; McPhee, James
The hydrological fundamentals of high mountain regions need to be better understood to support decision-making. Priority policies are needed to: reduce gaps in the collection of hydrometeorological data in mountain regions; develop physically based, integrated atmosphere–cryosphere–hydrology–ecology–human models; expand training to allow for the integration of different knowledge types (e.g. biophysical data, socio-economic data, and Indigenous and local knowledge); and facilitate the participation of Indigenous Peoples and local communities (IPLCs) and women in knowledge-gathering processes.
Exploring Fairness and Opportunity in the Admissions Process of Canadian Dental Schools
(2025-12-17) Ardenghi, Diego Machado; Papagerakis, Petros; Liu, Juxin; Papagerakis, Silvana; Walker, Keith; Wallin, Dawn; Taghibiglou, Changiz; Leite, Maria Luisa; Paiva, Saul
Decades of evidence have demonstrated a lack of workforce diversity and sustaining disparities in dentistry. Underrepresented minority students may face challenges and implicit bias during the den-tal schools’ admission/selection process – which perpetuates the disparities. This dissertation want-ed to explore the fairness and opportunities for people who have been prevented from studying dentistry – more specifically, the link between Equity-Diversity-Inclusion (EDI) and the admission practices in dental schools. The literature has shown a growth in publications on equity measures during dental admission/selection processes, indicating a positive movement in this field. The ef-forts performed by dental schools to increase the representation of minorities in the profession have been made and become more internationalized and multifaceted recently. Some strategies to address both access and retention challenges included: prioritization of holistic approaches (during selection of candidates) and implementation of recruitment programs (which combine mentoring opportuni-ties and skills-based activities). Nevertheless, while these initiatives have demonstrated progress toward a more equitable dental workforce, sustained commitment and adaptation of strategies are essential to ensure lasting and meaningful change. The second and third parts of this dissertation focused on Canadian institutions’ admissions practices. Through a document analysis of dental schools’ websites (visual and written information), I noticed that the concept of EDI is connected to the admission process by showing prospective students that the university environment is welcom-ing, globalized, and that diverse students are embraced by the institution. But the websites’ commu-nication had several problems, including the poor choice of words and the lack of an equity defini-tion and equity information. At last, through semi-structured interviews, I interviewed the inter-viewers of the admission processes. Ten individuals who had acted as interviewers in dental schools’ admissions were vocal about the strengths and weaknesses in the process. Predominantly, participants criticized what they consider a defective process. The participants’ experiences revealed a tension between objectivity and holistic evaluation. This dissertation suggests adopting positive and alternative strategies, such as integrating equity-focused strategies for people involved in the admission process. These efforts require a combination of human, financial, and strategic resources.
Identification of Human Host Substrates of the SARS-CoV-2 Mpro and PLpro Using Subtiligase N-Terminomics
(American Chemical Society, 2023-04) Luo, Shu Y.; Moussa, Eman W.; Lopez-Orozco, Joaquin; Felix-Lopez, Alberto; Ishida, Ray; Fayad, Nawell; Gomez-Cardona, Erik; Wang, Henry; Wilson, Joyce A.; Kumar, Anil; Hobman, Tom C.; Julien, Olivier
The recent emergence of SARS-CoV-2 in the human population has caused a global pandemic. The virus encodes two proteases, Mpro and PLpro, that are thought to play key roles in the suppression of host protein synthesis and immune response evasion during infection. To identify the specific host cell substrates of these proteases, active recombinant SARS-CoV-2 Mpro and PLpro were added to A549 and Jurkat human cell lysates, and subtiligase-mediated N-terminomics was used to capture and enrich protease substrate fragments. The precise location of each cleavage site was identified using mass spectrometry. Here, we report the identification of over 200 human host proteins that are potential substrates for SARS-CoV-2 Mpro and PLpro and provide a global mapping of proteolysis for these two viral proteases in vitro. Modulating proteolysis of these substrates will increase our understanding of SARS-CoV-2 pathobiology and COVID-19.