VictorJuiz/thesis huggingface dataset:
Characterization of MATR3 Drosophila and Human Cell Models to Identify Genetic Modifiers of MATR3 Toxicity
Keywords: Amyotrophic Lateral Sclerosis
genetic screen
Matrin 3
Multisystem Proteinopathy
RNA binding protein

Multisystem proteinopathy (MSP) is a degenerative disorder combining amyotrophic lateral sclerosis, frontotemporal dementia, inclusion body myopathy and Paget’s disease of bone. Many MSP genes including Matrin3 (MATR3) encode RNA binding proteins, highlighting the role of RNA metabolism in MSP. Over a dozen mutations in MATR3 have been identified, but the mechanisms of MATR3 pathogenesis remain unknown. To investigate MATR3-associated MSP, we developed a Drosophila model expressing wildtype or mutant MATR3 in indirect flight muscles, which exhibits an abnormal wing position and muscle degeneration. We simultaneously developed human neuronal cell lines stably expressing MATR3. In both fly and human cell models, wildtype and mutant MATR3 are localized in the nucleus. However, MATR3 S85C and F115C are less soluble than wildtype MATR3. A candidate genetic screen identified enhancers of mutant MATR3 toxicity and implicated cytoskeletal dysfunction in MATR3 pathogenesis. Together, this work may shed light on the mechanisms underlying MATR3-associated MSP.
Direct Nerve Electrical Stimulation and Local FK506 Drug Delivery to Enhance Axon Regeneration in Nerve Gap Reconstruction
Keywords: Electrical stimulation
FK506
Local drug delivery
Nerve graft
Nerve regeneration
Tacrolimus

Functional recovery after peripheral nerve injuries is rarely complete, particularly with severe nerve injuries resulting in gap defects. Although nerve autografts are the gold standard for nerve gap reconstruction, they have inherent disadvantages such as limited quantity, donor site morbidity, and variable outcomes. Strategies to improve axon regeneration through nerve autografts or nerve substitutes have important implications for patients with devastating nerve gap defect injuries. In this thesis, we investigate two emerging bioengineering strategies. In Experiment 1, we demonstrate that low frequency, direct nerve electrical stimulation at the time of nerve gap reconstruction improves axon regeneration through nerve autografts. In Experiment 2, we demonstrate that a local FK506 (tacrolimus) drug delivery system enhances axon regeneration through fresh nerve allografts, a nerve substitute. Our results suggest that both electrical stimulation and local FK506 drug delivery may be clinically translatable strategies to improve peripheral nerve regeneration for patients with nerve gap defects.
Diabetes-Induced Impairments in Robo Signalling Augment Glomerular Angiogenesis
Keywords: Diabetes
Diabetic Nephropathy
Robo Signaling
Vascular Biology
VEGF

Diabetic glomerular angiogenesis represents an early form of diabetic kidney injury driven by VEGF. Robo1 and Robo4 are cell surface receptors that can regulate VEGF-mediated endothelial angiogenic activity. We have shown previously that glomerular endothelial Robo4 expression is downregulated with high glucose exposure, whereas Robo1 expression is unchanged and that Robo1 is essential for VEGF-induced angiogenic activity. In this thesis I aim to determine whether alterations in Robo2 and Robo4 levels regulate VEGF-induced glomerular angiogenesis in high glucose and diabetes. Robo4 deficiency was associated with augmented migration in vitro while Robo2 did not change with high glucose or diabetes exposure. Robo4 KO mice exhibited increased PECAM-1 density, glomerular capillary length, and creatinine clearance after 5 weeks of STZ-induced diabetes. Our observations suggest that diabetic glomerular angiogenesis is driven by enhanced glomerular endothelial VEGF responsiveness promoted by a shift in Robo signalling, favouring more pro-angiogenic Robo1, and less anti-angiogenic Robo4 activity.
Adverse Event Detection in Laparoscopic Videos
Keywords: bleeding detection
deep learning
laparoscopy
surgical adverse event detection
thermal injury detection

Human errors are one of the main causes of surgical adverse events. These events are reported by physicians which is an error-prone process. An automatic surgical adverse event detection system can reduce biases in the reports, provide quick feedback to surgeons, and help guide postoperative care. Few studies have developed such a system for laparoscopic procedures -- a major type of minimally-invasive procedure that has 15 million cases each year. We developed a deep learning system that can automatically detect two major surgical adverse events: bleeding and thermal injury. The system consists of a module that reduces camera motion in a scene, a module that extracts spatial-temporal features from videos, and a final module that takes into account the full temporal resolution of a procedure and makes predictions. This system significantly outperforms the prior state-of-the-art architectures developed for action recognition and adverse event detection in laparoscopic videos.
The Investigation of ABA Transport in Arabidopsis thaliana and Brassica napus
Keywords: ABA transport
Abscisic acid
Arabidopsis thaliana
Brassica napus
Positron emission tomography

Abscisic acid (ABA) is a phytohormone that plays a major role in plant responses to biotic and abiotic stresses. Increases in ABA levels have been reported in conditions such as drought, high salinity, and low temperature. Although the movement of ABA within plants has been documented, its migration pattern is still debatable. Recent application of Positron Emission Tomography (PET) on plants using radioactive tracers has provided a potential new method of studying ABA migration within plants. In order to study the localization pattern of 3’-18F-ABA in planta, I performed histochemical analyses of β-glucuronidase (GUS) expression in GUS reporter lines, and report that the radioactive tracer, 3’-F-ABA, has similar bioactivity to ABA. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) -based phytochemical analyses of 3’-F-ABA- or ABA-treated Arabidopsis thaliana and Brassica napus plants also showed a bi-directional distribution towards the reproductive organs and to the roots, suggesting a phloem mediated transport of ABA under non-stressed conditions.
Skipping a Beat: Development and Characterization of a 3D in vitro Model of Human Cardiac Arrhythmia
Keywords: 3D Model
Arrhythmia
Cardiac lipotoxicity
Heart-on-a-chip
Human Cardiac Stem Cells
Metabolic Dysfunction

Introduction: Cardiac arrhythmias impact ≥350,000 Canadians result in ≥40,000 deaths annually. High-fat diets promote heart failure and arrhythmias. Studying arrhythmias in living patients and animals has practical ethical constraints. Furthermore, 2D in vitro models do not recapitulate the human heart environment. A 3D in vitro model would address these limitations. Aim: Develop characterize a robust 3D acquired arrhythmia model. Methods: Three-dimensional microtissues consisted of hiPSC-derived cardiomyocytes and fibroblasts. Arrhythmia was induced by high fatty acid supplemented media. Electrophysiology, contractile force, beating frequency, pharmacological electrical cardioversion, and differential gene expression were assessed. Results: Arrhythmias developed within 5 days; more complex electrophysiological phenotypes were observed towards day 5. Arrhythmogenesis significantly reduced contractile force and elevated beating frequency and pathogenic gene expression was evident. Pharmacological and electrical interventions effectively cardioverted arrhythmic tissues. Conclusion: This robust 3D in vitro arrhythmia model can serve as a fundamental investigative tool for understanding arrhythmias developing novel therapies.
Effect of Maternal Vitamin D Supplementation on Nasal Pneumococcal Carriage in Infants in Dhaka, Bangladesh
Keywords: Bangladesh
Carriage
Infants
Pneumoccocus
Vitamin D

Nasopharyngeal carriage of Streptococcus pneumoniae (pneumococcus) is a necessary antecedent to invasive pneumococcal disease. In vitro studies have shown that vitamin D (VD) is an immunomodulator that promotes specific responses against pneumococcus. This study investigated whether these in-vitro effects translate into the public health context by examining whether VD supplementation during pregnancy and lactation, versus placebo, had an effect on the risk of pneumococcal acquisition, dynamics and density (pneumococcal carriage) in infants in Dhaka, Bangladesh. In this sub-study of the Maternal Vitamin D Supplementation for Infant Growth Trial, we found no significant effect of VD supplementation on pneumococcal carriage. However, parental education, season and number of siblings in the household were associated with carriage. Contrary to our hypothesis, there was no protective effect of prenatal and postpartum VD supplementation against infant pneumococcal carriage and therefore cannot be recommended at this time for the prevention of pneumococcal carriage in early infancy.
Investigating the Colorimetric Response of Surfactant Capped Gold Nanoparticles
Keywords: Colorimetric
Gold Nanoparticles
Nanoparticles
Surfactant

Gold nanoparticles are popular colorimetric agents. The colour of a gold nanoparticle solution is dependent on the nanoparticle size, shape, etc. The colorimetric response of gold nanoparticles stems from their aggregation in different conditions and exposure to analyte(s) they have been programmed to react to. This work uses surfactants/polymers as nanoparticle capping agents for two distinctly different types of nanoparticles. Each surfactant/polymer might be used as a capping agent for one or both type of nanoparticles under investigation. The nanoparticles display a number of different colours, colour intensities, and timed responses to particular testing media. The behaviour of each differently capped nanoparticle sample is investigated separately, two-surfactant systems are explored in terms of enhanced stability, and a few nanoparticle mixtures are examined for the development of a wearable time sensing device.
Museums and Human-nature Relationships in Japan: A Case Study Analysis of Echigo-Tsumari Art Field
Keywords: art festivals
contemporary art
Japanese culture
museums
nature
regional development

Echigo-Tsumari Art Field (ETAF) presents an expanded type of museum overlooked in the museological literature. Embarking from ETAF’s own assertions—that “all of satoyama is an art museum” and that “human beings are part of nature”—I conduct an autoethnography and content analysis on materials gathered during participation in the 2018 Echigo-Tsumari Art Triennale. I demonstrate how ETAF enacts and interprets heritage in mediating between state and grassroots interests. ETAF’s practice of regionalism—its adoption of the satoyama concept of encultured nature, mapping and thematization—results in both normative and strategically diversified representations of collective identity. ETAF’s narrative draws from a selective history to depict historically marginalized agricultural lifeways, becoming an expressive metaphor for ongoing regional regeneration. When placed within salient socio-historical contexts, these findings illustrate how ETAF both departs from and leverages traditional top-down museological approaches towards social cohesion, pointing to the mediating potential of cultural institutions in declining communities.
Functional Contributions of TGFB2 Signaling to Metanephric Progenitors and Stromal Cells
Keywords: Hedgehog
Stroma
Transformation Growth Factor Beta
Ureteropelvic Junction Obstruction

Recent analyses using spatial and temporal targeted genetic deletions of Hh signaling components revealed lineage-specific requirements within the metanephric progenitor pool and their stromal derivatives. Stage-specific activation of Hedgehog signaling through a Ptch1-deficiency in metanephric progenitors leads to intrinsic ureteropelvic junction (UPJ) obstruction and hydronephrosis in mice. Ptch1-deficient metanephric progenitors give rise to ectopically located stromal cells which occlude the presumptive ureteropelvic junction and block proper urinary outflow. Preliminary evidence implicates transformation growth factor beta 2 (TGFB2) as a downstream effector of Hedgehog signaling. Here, we show that, while TGFB signaling is dispensable within the metanephric progenitors during normal kidney development, it acts downstream of Hh signaling to contribute to the pathogenesis of UPJ obstruction. A lack of TGFB signaling in a Ptch1-deficient background partially rescues the frequency and severity of hydronephrosis. Further, single-cell RNA sequencing investigates novel targets of Hedgehog-TGFB signaling in the stromal and nephrogenic lineages.
Sleep-dependent Consolidation Enhances Naturalistic Episodic Memory Recall
Keywords: consolidation
episodic memory
item memory
naturalistic design
sequence memory
sleep

Compared to wakefulness, sleep can enhance episodic memory through consolidation. Yet, sleep may not boost all aspects of memory given that it has been shown to favour memory for spatiotemporal over item details. Previous work has tested memory for lab-based stimuli in one experimental session, making it unclear whether these findings generalize to memory for real-life events over a longer period of time. To address this question, we assessed participants’ memory after they experienced the same staged event with online recognition memory tests across four timepoints. Participants made true/ false judgments about the items and sequences they encountered during the event, allowing us to dissociate between these two memory measures. These data suggest that sleep, relative to wakefulness, confers a widespread – but short-lived –mnemonic advantage since both elements of episodic memory were equally retained. This investigation yields insights into the mnemonic benefit of sleep-dependent consolidation for our real-world experiences.
Characterizing the Basis of Strigolactone Perception by HYPOSENSITIVE TO LIGHT/KARRIKIN INSENSITIVE 2
Keywords: hormone receptor
karrikin
strigolactone
synthetic biology

The HYPOSENSITIVE TO LIGHT/KARRIKIN INSENSITIVE 2 (HTL/KAI2) α/β hydrolases likely play a critical role in the life cycle of parasitic plants of the genus Striga. Several of these hydrolases serve as receptors for strigolactones (SLs), a class of compounds exuded by the roots of some plants, including many economically significant crops. Upon perception of minute levels of SLs, Striga seeds germinate and parasitize the nearby host, often leading to massive losses in crop yields in affected regions. We have produced a series of mutant variants of the Arabidopsis thaliana homolog of HTL/KAI2, which is only weakly responsive to SL. By substituting certain key amino acids in the protein’s active site, we have created a receptor conferring increased Arabidopsis germination under inhibitory conditions in the presence of SL. Additional study of this mutant receptor may offer insight into the biochemical basis of Striga’s SL sensitivity.
Towards Humanizing Online Discourse - Exploring Linguistic and Emotional Tones in Online Learning
Keywords: Affective learning
Emotions
Online learner
Online learning

Online learning has seen tremendous growth over the last few years, but there is limited research in understanding the role of tones in an online learning environment. The goal of this thesis is to explore the presence of both emotional and linguistic tones in threaded discourse to understand their role in online conversations. This study presents evidence of the presence of emotions in online discussions using a sequential mixed-methods design by analyzing text using machine learning techniques based on the theory of psycholinguistics to predict both linguistic and emotional tones in discourse. It further explores participants’ experiences and insights using semi-structured interviews with learners and instructors. The analysis uncovered significant differences in tone across different courses, users and notes. This research is a first step to acknowledge, identify and understand tones in text written by the user; thereby humanizing text discourse online.
Investigation of a Potential Slam-dependent Secreted Protein in Vibrio harveyi
Keywords: hemophore
secretion
Slam
Vibrio harveyi

Vibrio harveyi is a Gram-negative bacterium predominantly existing in marine environments. It has a wide host range infecting various marine animals. A Slam-containing gene cluster was identified in V. harveyi. Slam and Slam substrates are bacterial proteins usually associated with bacterial virulence. My project was to determine the Slam-dependency, structure and ligand of a V. harveyi Slam substrate named PUF1. In this study, I successfully reconstituted Slam- dependent secretion of PUF1 in E.coli cells. Using X-ray crystallography, I determined the structure of PUF1, illustrating it has a comparable tertiary structure to those of previously identified Slam substrates consisting of a b-handle domain and a b-barrel domain. The structure of PUF1 and spectroscopic analysis disclosed the role of PUF1 as hemophore. Interestingly, unlike previously identified Slam substrates that are surface lipoproteins, PUF1 is not attached to the cell surface. Rather, PUF1 is a secreted protein reporting a new type of Slam substrate.
Development and Evaluation of a Prototype Camera System for Intraoperative Video Recording of Open Surgery
Keywords: camera technology
computer vision
innovation
machine learning
open surgery
surgical video

Intraoperative video enables better surgical training, continued performance enhancement and quality improvement initiatives; however, there exists a lack of technology to reliably and routinely capture high-quality video of open surgical procedures. Using the limitations of previously identified capture systems as innovation targets, we developed a prototype camera system and benchmarked it against existing capture technology using objective and subjective evaluation frameworks. In a simulated OR environment, there was less movement of the prototype camera measured by a physical sensor, and algorithmic video analysis demonstrated more stable, sharper, higher contrast images but with more surgical field obstruction. In the real OR environment, surgeons rated the usability of the prototype more favourably for ‘weight’ and ‘would recommend to a colleague’, and rated the video product higher for ‘camera stability’ but lower for ‘unobstructed view of the surgical field’. This work demonstrates a novel and effective method for intraoperative video capture of open surgery.
Human Milk-based Protein Concentrate Supports Growth of Weanling Rats
Keywords: donor human milk
human milk protein
preclinical assessment
rat bioassay
very low birth weight infant

This study explores the feasibility of using donor human milk to produce a protein concentrate and evaluates whether its use can support normal growth in weanling rats. A human milk-based protein (HMP) concentrate was produced from defatted milk, followed by membrane filtration and high hydrostatic pressure (HHP) processing. Thirty rats were randomized and fed AIN-93G diets containing casein, the HMP concentrate, or a bovine whey protein isolate for four weeks. No significant differences in body weight, feed consumption, fat mass, or plasma amino acid profiles were observed between rats fed the HMP concentrate and those fed the control diet. Full cecum weights were higher in rats fed the HMP concentrate (mean difference, 5.6; 95%CI, 4.5-6.7 g; p
The Effect of Prolonged Nitrate Administration on Ocular Disease Phenotypes in a Transgenic Rat Model of Chronic Hypertension
Keywords: age-related macular degeneration
confocal scanning laser ophthalmoscope
hypertension
hypertensive retinopathy
nitric oxide
organic nitrates

Nitrate-based vasodilators (NBVs), a source of nitric oxide, are used to treat multiple cardiovascular diseases, including hypertension. However, epidemiological studies suggest that chronic nitrate intake (from NBVs/dietary nitrates) is a risk factor for retinal diseases, including age-related macular degeneration (AMD). Additionally, we previously demonstrated that combining NBVs with oxidative stress increased outer retinal atrophy in a rat model of dry AMD. We therefore hypothesized that prolonged administration of isosorbide dinitrate (ISDN), a NBV, may reduce hypertension, but aggravate ocular disease phenotypes in the (mREN2)27 transgenic rat model of chronic hypertension. Using in vivo ophthalmic imaging and systolic blood pressure (SBP) measurements, we established the (mREN2)27 model to mimic features of retinovascular disease in patients. In summary, following a five-week treatment period, ISDN did not reduce SBP compared to hypertensive (mREN2)27 rodents but exacerbated ocular disease phenotypes in male (mREN2)27 rats. Investigations into the role of nitrates and inflammation are ongoing.
FOXO1: A Novel Metabolic Target in the Reversal of Radiation Fibrosis
Keywords: Fibrosis
Metabolism
Radiotherapy

Radiation fibrosis (RF) is a long-term consequence of cancer radiotherapy with complex pathophysiology leading to tissue dysfunction and patient morbidity. Our laboratory has demonstrated that suppression of fatty acid oxidation (FAO) is a predominant alteration in RF, and that adipose-derived stromal cell (ADSC) transplantation restores metabolism while reducing fibrosis severity. We hypothesized that epigenetic regulation of metabolism may be central to RF pathogenesis and treatment. Genome-wide methylation profiling of ADSC-treated fibrotic murine tissue revealed that hypermethylation of FOXO1 binding sites may be therapeutically favourable. Pharmacological inhibition of FOXO1 restored the expression of FAO genes, decreased fibrotic protein expression, and reduced murine skin fibrosis severity. Moreover, a convergence of the FOXO1 and prostaglandin E2 pathways was identified as a novel mechanism through which FOXO1 may regulate RF. This work will lead to a deeper understanding of RF pathogenesis while proceeding toward a novel therapeutic strategy for the treatment of this condition.
Characterizing Trends in the Dietary Patterns of Canadians: Evidence from Two Cycles of the Canadian Community Health Survey—Nutrition
Keywords: Canadian Community Health Survey
CCHS
dietary patterns
obesity

Healthy dietary patterns have been associated with reduced risk of non-communicable diseases. The overall goals of this thesis were to examine adherence to healthy dietary patterns using nationally-representative Canadian data and to determine the association between these trends and obesity among Canadian adults. In the first study, the likelihood of being obese was compared between samples from the Canadian Community Health Survey-Nutrition (CCHS) 2004 and CCHS 2015; results suggested that Canadian adults who did not adhere to a healthy dietary pattern had over 2x greater odds of obesity than those who did adhere. In the second study, an energy-dense, low-fiber and high fat dietary pattern was identified in CCHS 2015; results suggest key foods to focus on in policy which contribute to an “obesogenic” dietary pattern. The findings presented in this thesis highlight the importance of examining healthy dietary patterns and their association with health outcomes among the Canadian population.