30921 research outputs found
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Understanding the epigenetic role of PRMT1/H4R3me2a in cancer cells
No full textProtein arginine methyltransferase 1 (PRMT1) is a major type I arginine methyltransferase that catalyzes the formation of monomethyl and asymmetric dimethylarginine. It was first identified to asymmetrically methylate histone H4 at the third arginine residue, forming the H4R3me2a histone mark. H4R3me2a is an active mark associated with the active regions of the genome. H4R3me2a stimulates the activity of lysine acetyltransferases such as CBP/p300, which catalyzes the acetylation of H3K27, a mark of active enhancers, super-enhancers, and promoters. There are a few studies on the genomic location of H4R3me2a, but none in human cells. In this study, we analyzed chromatin immunoprecipitation sequencing data to understand the genomic location of H4R3me2a in the human breast cancer cell line MCF7. Consistent with previous findings in avian cells, MCF7 H4R3me2a is present in intronic and intergenic regions. Nucleosomes with H4R3me2a and H3K27ac are next to nucleosome-free regions at super-enhancers, enhancers, and promoter regions of expressed genes. Genes critical for breast cancer have broad domains of nucleosomes with H4R3me2a, H3K27ac, and H3K4me3. With known interactions between PRMT1 and CBP/p300, we found a strong correlation between H4R3me2a and H3K27ac in MCF7 cells. The correlation studies were extended to confirm the co-existence of H4R3me2a and H3K27ac in the same mononucleosome of leukemic cells (K562 and MOLM-13). This study also demonstrates the coexistence of H4R3me2a with other enhancer marks, including H2BK12ac, H4K5ac, and H4K8ac, suggesting a synergistic role in transcriptional regulation.
The study also characterizes the rate of removal of H4R3me2a compared to other methylation marks using a global methyltransferase inhibitor called Adenosine dialdehyde (AdOX). H3K4me3 is removed faster, with their levels declining in 13 hours, while H3K36me3 and H4R3me2a showed a difference in 48 hours. Other methylation marks like H3K27me3, H3K9me2, and H3K9me3 showed no difference with AdOX treatment within the tested timeframe (13-48 hours).
This study provides a foundation for understanding the genomic landscape of H4R3me2a in human cells for the first time. It establishes the possible association between the writers and their respective histone marks. AdOX-based studies in leukemic cells provide a framework for understanding the dynamics of histone methylation marks, thereby aiding in developing better therapeutic strategies.February 202
Nutrient sources for organic production: soil biological and agronomic responses
No full textThis study was divided into two chapters that evaluated various organic soil amendments as alternative Phosphorus (P) sources under field and greenhouse conditions. The first chapter was a field study that evaluated the effect of a long-term P mitigation strategy on P sufficiency and arbuscular mycorrhizal fungal (AMF) infection in flax (Linum usitatissimum) grown in a long-term field study in Manitoba. The two main objectives of the study were to test if manure addition improved plant performance in terms of P tissue concentration, AMF, and biomass and whether the changes in AMF were related to the plant’s P uptake. Flax was planted after wheat (Triticum aestivum) in a 4-year – alfalfa (Medicago sativa) – alfalfa – wheat rotation under three treatments: organic manured (ORG M), organic non-manured (ORG NM), and conventional (CONV). Under wet soil conditions, adding manure to the organic plots increased biomass by 33%. Manure did not have a significant effect on flax P tissue concentration under both dry and wet soil conditions and neither did it improve flax P sufficiency; ORG NM treatment presented 8% more P tissue concentration than the ORG M. AMF abundance was not significantly different in organic manured and non-manured treatment under wet soil conditions. The second chapter investigated various organic soil amendments as alternative P sources under greenhouse conditions. The general aim of the study was to test the performance of different organic soil amendments from multiple sources including livestock, insects, and food waste to expose farmers to more diverse options for their organic soil nutrients. Novel manures (rabbit and black soldier fly) were compared with traditional amendments on soybean (Glycine max L.) grown in low P soil in greenhouse experiments. Ground rabbit manure (GRM) had higher biomass and tissue P concentration than composted beef manure, anaerobic digestate, and monoammonium phosphate but similar to insect frass. GRM and insect frass demonstrated advantages in P supply associated with higher AMF.October 202
Mental health systems and policy in Ghana: a systematic review and meta-analyses
No full textBackground: This systematic review aims to critically evaluate the landscape of mental health systems and policies in Ghana, focusing on identifying strengths, weaknesses, and opportunities for improvement within the existing framework.
Objectives: The main objective of this review is to examine the current state of mental health systems and policies in Ghana, highlighting areas for enhancement and providing recommendations for future interventions and policy changes.
Methods: Studies and reports focusing on mental health systems and policies in Ghana, published in peer-reviewed journals, books, or grey literature between 2014 and 2024, were included in the review. Databases such as PubMed, PsycINFO, and Google Scholar were searched to identify relevant studies. The last search was conducted in January 2024. The risk of bias in the included studies was assessed using established criteria for quality assessment, considering factors such as study design, methodology, and reporting. The results were synthesized using a narrative approach, summarizing key findings and themes across the included studies to provide a comprehensive overview of mental health systems and policies in Ghana.
Results: A total of 43 studies were included in the review, encompassing a variety of study designs such as cross-sectional, ethnographic, and alternative methodologies. The studies provided insights into the strengths and challenges of mental health systems in Ghana. The synthesis of results highlighted key issues in mental health policy and practice in Ghana, emphasizing the need for integrated and evidence-based approaches to address gaps in service delivery and coordination.
Discussion: Limitations of the evidence included in the review includes study risk of bias, inconsistency in findings, and imprecision in data reporting. The findings of this review underscore the importance of addressing deficiencies in mental health systems and policies in Ghana to improve service delivery and promote better mental health outcomes. Recommendations for policy changes and interventions are provided to guide future efforts in this area.October 202
Exploring protein – ligand interactions: from mechanistic insight to inhibitor development
No full textBiological processes required for life can be understood by studying the underlying molecular
and chemical processes which give rise to these biological processes. Proteins are the primary
functional molecules of biological systems where they serve as catalysts, cell signaling
molecules, receptors and also serve structural and mechanical roles. In order to perform these
various functions, proteins must physically interact with other molecules referred to as ligands.
Therefore, developing a detailed understanding of protein – ligand interactions from a chemical
and molecular perspective improves the understanding of the biological processes which these
interactions give rise to. A detailed understanding of these protein ligand interactions also
enables the development of drugs capable of disrupting or modulating protein – ligand
interactions for the treatment of diseases. In other cases, the study of protein – ligand
interactions can be used to develop new and useful biotechnologies. Many techniques can be
useful for studying protein – ligand interactions including structural, computational, and
biophysical techniques. Of these, biophysical techniques often provide the greatest deal of
foundational insight into the nature of the protein – ligand interactions. In addition, a biophysical
characterization of a protein – ligand interaction is often a prerequisite for the development of
drugs and biotechnological applications for these protein- ligand interactions.
Three unique protein – ligand interaction systems are explored in this thesis, using a
combination of structural, computational, and biophysical techniques. In the first part of this
thesis the interaction between the Laminin N-terminal domain and Ca2+ is explored using a
combination of structural, computational, and biophysical techniques. From this approach, a
detailed understanding of the molecular basis and functional properties of the interaction
between the Laminin N-terminal domain and Ca2+ is developed. In the next part of this thesis,
the biophysical and enzymatic characterization of the SARS-CoV-2 Main protease is performed.
Guided by this biophysical and enzymatic characterization, an improved substrate for
high throughput screening is developed. The final part of this thesis performs a thorough
examination of the interaction between Netrin-1 and UNC5B including the requirement for a
heparin co-receptor. From this examination of the Nertrin-1 UNC5B interaction, peptide
inhibitors of the interaction are rationally designed. Together the work presented in this thesis
demonstrates the study of multiple aspects of protein - ligand interactions. It combines studies
aimed at gaining an understanding of molecular basis and functional properties of protein –
ligand interactions, developing methods to identify and test inhibitors of protein – ligand
interactions, and leveraging the gained understanding to rationally design inhibitors of protein-
ligand interactions.October 202
Counting what counts: assessing quality of life and its social determinants among nursing home residents with dementia
No full textBackground
Maximizing quality of life (QoL) is a major goal of care for people with dementia in nursing homes (NHs). Social determinants are critical for residents' QoL. However, similar to the United States and other countries, most Canadian NHs routinely monitor and publicly report quality of care, but not resident QoL and its social determinants. Therefore, we lack robust, quantitative studies evaluating the association of multiple intersecting social determinants with NH residents’ QoL. The goal of this study is to address this critical knowledge gap.
Methods
We will recruit a random sample of 80 NHs from 5 Canadian provinces (Alberta, British Columbia, Manitoba, Nova Scotia, Ontario). We will stratify facilities by urban/rural location, for-profit/not-for-profit ownership, and size (above/below median number of beds among urban versus rural facilities in each province). In video-based structured interviews with care staff, we will complete QoL assessments for each of ~ 4,320 residents, using the DEMQOL-CH, a validated, feasible tool for this purpose. We will also assess resident’s social determinants of QoL, using items from validated Canadian population surveys. Health and quality of care data will come from routinely collected Resident Assessment Instrument – Minimum Data Set 2.0 records. Knowledge users (health system decision makers, Alzheimer Societies, NH managers, care staff, people with dementia and their family/friend caregivers) have been involved in the design of this study, and we will partner with them throughout the study. We will share and discuss study findings with knowledge users in web-based summits with embedded focus groups. This will provide much needed data on knowledge users' interpretations, usefulness and intended use of data on NH residents’ QoL and its health and social determinants.
Discussion
This large-scale, robust, quantitative study will address a major knowledge gap by assessing QoL and multiple intersecting social determinants of QoL among NH residents with dementia. We will also generate evidence on clusters of intersecting social determinants of QoL. This study will be a prerequisite for future studies to investigate in depth the mechanisms leading to QoL inequities in LTC, longitudinal studies to identify trajectories in QoL, and robust intervention studies aiming to reduce these inequities
Optimization of mycelium bio-foam packaging design through drop test simulations and environmental impact assessment
No full textThe escalating demand for packaging materials, driven by the changes in consumptions patterns and e-commerce, has placed immense pressure on the environment. Traditionally dominated by plastic materials, the packaging industry is struggling with the material's detrimental environmental impacts, including resource depletion and persistent waste. This research explores the potential of mycelium-based bio-foam (MBF) as a promising eco-friendly substitute of foam packaging such as expanded polystyrene (EPS). A comprehensive market analysis revealed a growing public consciousness regarding plastic pollution and a corresponding desire for sustainable packaging solutions. While the potential of MBF was recognized, concerns about weight, cost, and environmental performance emerged as key barriers to widespread adoption. To address these challenges, this study focused on optimizing MBF design and assessing its overall environmental profile.
Through finite element analysis (FEA) simulations of drop tests on a 32-inch flat-screen TV and a porcelain vase, the study evaluated the impact of MBF properties and design configurations on shock absorption performance. Results demonstrated MBF's ability to protect both products from damage under various impact scenarios. Optimization of MBF design parameters, such as thickness and configuration, proved crucial in achieving optimal protection while minimizing material usage.
To comprehensively assess the environmental implications, a life cycle assessment (LCA) was conducted comparing MBF to EPS foam packaging. While MBF exhibited higher transportation emissions due to its greater weight, the overall environmental impact was notably lower across the product lifecycle compared EPS. Factors such as biodegradability and reduced energy consumption during production contributed to MBF's superior environmental performance.
This research highlights the potential of MBF as an alternative to traditional polystyrene packaging. However, to fully realize its commercial viability, continued research and development are essential to address challenges related to weight optimization, cost reduction, and large-scale production. By investing in these areas, the packaging industry can accelerate the transition towards a more sustainable future.October 202
Functional roles of Arctic foxes in tundra ecosystems: ecosystem engineering, nutrient transport, and consumptive and non-consumptive effects on prey
No full textPredators are widely recognized for their irreplaceable roles in influencing the abundance and traits of lower trophic levels. Yet, predators also shape community interactions and ecological processes via localized pathways, irrespective of their influence on prey density or behavior. I synthesized empirical and theoretical research and identified pathways by which predators have indirect ecological effects confined to discrete patches. This synthesis revealed how predators indirectly affect other species via patches – ranging from mediating scavenger interactions to influencing parasite/disease transmission risk – and ultimately provides a more holistic view of predation in ecosystems. I then demonstrated how satellite imagery could resolve whether Arctic foxes create biogeochemical hotspots via their denning behavior. Using satellite imagery, I showed that Arctic fox dens have greater plant productivity and green-up faster than reference sites, supporting the hypothesis that Arctic foxes cause the unique vegetation on their dens by concentrating nutrients derived from prey remains there. I then assessed how predators influence the reproductive ecology of Canada geese. Birds presumably select nest sites in areas they perceive are safer, but few links between spatial patterns of risk and nest habitat selection or nesting success exist. By comparing habitat selection models fit to goose nest locations and fox movement locations, I showed predator activity strongly affects the spatial distribution and reproductive success of geese. However, these effects were mediated by the date nest incubation started, revealing how nesting phenology and predator activity interact to shape bird reproduction. Finally, I assessed how fox predation affects goose reproductive success from an ecosystem-level perspective. I showed winter environmental conditions influence the abundance and availability of main winter foods for Arctic foxes, which in turn showed a numerical response to these foods and ultimately had a negative effect on goose reproductive success. These results demonstrate apparent competition between rodents and geese, and establish a link between the marine and terrestrial environments via Arctic fox use of marine subsidies. Given the importance of climate in mediating these trophic relationships, I contextualize the results of this thesis within ongoing climate change and highlight the vulnerability of coastal tundra ecosystems in a warming Arctic.I and the research underlying this dissertation were supported financially by the Natural Sciences and Engineering Research Council of Canada, Natural Resources Canada Polar Continental Shelf Program, Environment and Climate Change Canada, the University of Manitoba, the CNSC, the American Museum of Natural History, National Geographic, the American Society of Mammalogists, and the Explorers Club.October 202
CASE STUDY INVESTIGATING DAILY FLUCTUATIONS IN CORE AND REGIONAL SKIN TEMPERATURES IN A PERSON WITH TETRAPLEGIA
No full textIntroduction: Spinal cord injury (SCI) directly affects to a person’s ability to regulate core temperature, increasing their risk for hypo- and hyperthermia. Cognitive performance is also affected when exposed to low ambient temperatures. Although anecdotal reports of hypo- and hyperthermia exist, there are significant gaps in understanding how frequently core temperature fluctuations daily, and how varied ambient temperatures and exercise affect core temperature. An abbreviated literature review was conducted to partially address these gaps.
Objective: To determine the presence of circadian rhythm and the effects of environmental temperature and exercise on the regulation of core temperature in a person with cervical SCI.
Methods: An individual with cervical-level SCI had their core temperature continuously recorded over two seven-day periods during a warm (July) and a cold (November) season. Surface skin temperature and daily activity were also recorded in November. Daily minimum-maximum fluctuations were measured as well as periods of hypo- and hyperthermia.
Results: Daily core temperature fluctuated an average 2.36°C ± 1.4°C in November, and 1.89°C ± 0.8°C in July. The participant demonstrated 17 instances of sub-normal core temperature and 3 instances of hyperthermia in November. An additional 12 instances of sub-normal core temperature and 12 instances of hyperthermia were observed in July. These findings demonstrate the relatively high frequency and duration of sub-normal and hyperthermic core temperatures experienced by this person with cervical SCI, despite taking steps to maintain a comfortable core temperature.
Conclusion: These findings indicate temperature-related life quality of persons with cervical level SCI may be commonly and significantly impaired. This suggests the need to identify better means to monitor and pre-emptively regulate core temperatures in this population under different environmental conditions
Big data management and mining models and their applications
No full textThe world is dynamic, so are big data. The evolving challenges of managing big data volume, variety, veracity, validity, and velocity has resulted in several studies focusing on solving one or more of these perplexing issues. In this Ph.D. research, I focus on the evolving issues arising from big data variety, veracity, privacy, and accessibility. First, I design a conceptual model for capturing and storing variety of big data types including structured, semi-structured and unstructured data types and in addition, design a metadata collection framework for managing the big data in support of machine learning and open data FAIR principle of Findable, Accessibility, Interoperability and Re-usability such that the information about the data are available beyond the life cycle of the data. Second, I design hierarchical spatial-temporal model (HSTM) for managing individual record in big data in the aforementioned open data lake architecture with metadata collection framework. Third, I extend the HSTM and design the resulting hierarchical spatial-temporal privacy preserving model (HSTPPM) for preserving privacy of individual record in big data. Fourth, I extend and design applications of the HSTPPM to big data co-occurrence pattern mining and big data visualization.Mitacs: http://dx.doi.org/10.13039/501100004489
NSERC: https://doi.org/10.13039/501100000038October 202
Cerebral physiologic insult burden in acute traumatic neural injury: a Canadian High Resolution-TBI (CAHR-TBI) descriptive analysis
No full textBackground
Over the recent decades, continuous multi-modal monitoring of cerebral physiology has gained increasing interest for its potential to help minimize secondary brain injury following moderate-to-severe acute traumatic neural injury (also termed traumatic brain injury; TBI). Despite this heightened interest, there has yet to be a comprehensive evaluation of the effects of derangements in multimodal cerebral physiology on global cerebral physiologic insult burden. In this study, we offer a multi-center descriptive analysis of the associations between deranged cerebral physiology and cerebral physiologic insult burden.
Methods
Using data from the Canadian High-Resolution TBI (CAHR-TBI) Research Collaborative, a total of 369 complete patient datasets were acquired for the purposes of this study. For various cerebral physiologic metrics, patients were trichotomized into low, intermediate, and high cohorts based on mean values. Jonckheere–Terpstra testing was then used to assess for directional relationships between these cerebral physiologic metrics and various measures of cerebral physiologic insult burden. Contour plots were then created to illustrate the impact of preserved vs impaired cerebrovascular reactivity on these relationships.
Results
It was found that elevated intracranial pressure (ICP) was associated with more time spent with cerebral perfusion pressure (CPP) 20 or 22 mmHg and more time spent with impaired cerebrovascular reactivity. Elevated cerebrovascular reactivity indices were associated with more time spent with CPP 20 or 22 mmHg. Low brain tissue oxygenation (PbtO2) only demonstrated a significant association with more time spent with CPP < 60 mmHg. Low regional oxygen saturation (rSO2) failed to produce a statistically significant association with any particular measure of cerebral physiologic insult burden.
Conclusions
Mean ICP, CPP and, cerebrovascular reactivity values demonstrate statistically significant associations with global cerebral physiologic insult burden; however, it is uncertain whether measures of oxygen delivery provide any significant insight into such insult burden