VictorJuiz/thesis huggingface dataset:
Biogenesis and Maturation of Asbestos-containing Phagosomes in Macrophages

Exposure to asbestos has been linked to the development of many diseases. Fibres are inhaled and circumvent the ciliated airways, depositing in the alveoli where they become targets for removal via phagocytosis. The fibre pathogenicity structure: activity paradigm states that fibres exceeding 15 Îźm are problematic for removal, purportedly causing frustrated phagocytosis. However, the cellular mechanisms involved in this process are not well understood. Our results demonstrate that the fibre length internalized by macrophages surpasses this threshold length, and that the time required for uptake is length-dependent. Following phagosome formation, maturation progresses to different stages based on the cell type. In all cells, however, asbestos-containing phagosomes fail to acidify, suggesting a defect in maturation that may contribute to pathogenicity. Altogether, our results indicate that length is not the primary factor in asbestos-induced toxicity and suggest that surface chemistry may contribute to a greater extent to the development of asbestos-related diseases.

Keywords: Asbestos
Filamentous morphology
Phagocytosis
Phagosomal maturation
Advisor: Terebiznik, Mauricio R
A Flexure-guided Piezo Drill for Penetrating the Zona Pellucida of Mammalian Oocytes

Opening of the outer membrane, zona pellucida, of an oocyte is an important procedure in clinical in vitro fertilization. Piezo drills use piezo-actuated vibrations on a glass micropipette to effectively penetrate the zona pellucida. However, this technology has not seen wide-spread clinical adoption due to the damage caused to the oocyte by large lateral vibration of the micropipette tip induced by the axial pulses. This thesis describes a new piezo drill device which uses a flexure guidance mechanism to control the micropipetteâ s motion during zona pellucida penetration. By designing the system with careful consideration of the micropipetteâ s dynamics, the in-air lateral vibration of the micropipette tip is reduced to less than 500 nm, a 20 times decrease of that reported in current literature. Its effectiveness in zona pellucida penetration was quantitatively evaluated using mouse oocytes which are notorious for being the most difficult to penetrate compared to other mammalian oocytes.

Advisor: Sun, Yu
Trafficking Dynamics in Arabidopsis Pollen-stigma Interactions

Reproduction in the Brassicaceae family depends on self-recognition, where cross-compatible pollen is distinguished from self-incompatible pollen prior to acceptance by the stigma. The stigma only gives compatible pollen the resources required for hydration and germination of a pollen tube for fertilization. These resources are sequestered away from self-incompatible pollen, inhibiting inbreeding. Many questions remain surrounding the specific signalling events that govern this self-recognition system. This research investigates how resource delivery to self-incompatible pollen is prevented in Arabidopsis. Topics explored include the localization of Sec5a, an exocyst complex member that delivers secretory vesicles to compatible pollen; the localization of ARC1, an E3 ubiquitin ligase which prevents the exocyst from delivering resources; and autophagyâ s degradation of the sequestered resources.

Keywords: Reproduction
Self-Incompatibility
Signalling
Advisor: Goring, Daphne
Investigating the Effect of scyllo-Inositol Treatment on the Brain in a Mouse Model of Alzheimer's Disease

scyllo-Inositol is a potential therapeutic for the treatment of agitation and aggression in patients with Alzheimer's disease. scyllo-Inositol reduces aggregation of beta-amyloid peptide, reduces amyloid plaques, and reduces myo-inositol concentration in the brain. The change in gene expression in the brain of TgCRND8 mice after scyllo-inositol treatment has not been previously investigated. I hypothesized that scyllo-inositol treatment would cause changes in expression of genes involved in neurodegenerative diseases and neuropsychiatric disorders. Affymetrix gene expression microarrays were used to analyze changes in the hippocampus and cerebral cortex of TgCRND8 mice as well as in non-transgenic littermates after 30 days of scyllo-inositol treatment. Analysis of the data with the Database for Annotation, Visualization and Integrated Discovery and Ingenuity Pathways Analysis program showed gene expression changes in synaptic function, calcium, dopamine receptor, glutamate receptor, and myo-inositol signalling pathways. In light of these results, I concluded that my hypothesis was correct.

Keywords: aggression
agitation
Alzheimer
neuropsychiatric
scyllo-inositol
Advisor: McLaurin, JoAnne
Identification of Ploidy Maintenance Genes in Saccharomyces cerevisiae

In eukaryotes, ploidy maintenance is very important for ensuring genome stability and proper cellular function. Mistakes in the spindle checkpoint, spindle pole body (SPB) duplication and insertion, interaction between the kinetochore and microtubules, and cytokinesis failure can all lead to an increase in ploidy. In this thesis, I described the identification of 64 non-essential genes whose deletion results in ploidy increase in Saccharomyces cerevisiae, suggesting their roles in ploidy maintenance pathways. Within the increase-in-ploidy mutants, 13 diploidized through mating-type switching, while the remaining mutants increased their ploidy through different types of DNA segregation defects. Moreover, 39 mutants formed stable diploids and 3 mutants formed stable tetraploids. Fluorescence microscopy revealed that the ploidy increase in tetraploidized mutants was mainly caused by SPB attachment failure during mitosis. Together, these findings reveal new pathways involved in ploidy maintenance and contribute to defining a complete set of genes responsible for the regulation of ploidy.

Advisor: Brown, Grant W
Transient Receptor Potential Melastatin 2 (TRPM2) Channel Plays a Role in Neonatal Hypoxic-ischemic Brain Injury

Recent advances in stroke research have identified non-glutamate mechanisms associated with ischemic neuronal death in adults. Among the molecules involved in non-glutamate mechanisms, transient receptor potential melastatin 2 (TRPM2), a calcium-permeable non-selective cation channel, is reported to mediate brain damage following ischemic insults in adult mice. However, the role of TRPM2 channels in neonatal hypoxic-ischemic brain injury remains unknown. Here, we propose that TRPM2-null mice (TRPM2+/- and TRPM2-/-) reduces neonatal hypoxic-ischemic brain injury in postnatal 7-day-old mice. We report that the infarct volumes are significantly smaller and behavioral outcomes are improved in neonatal TRPM2+/- and TRPM2-/- mice compared to wild type mice. Next, we found that TRPM2-null mice down-regulated GSK-3β activity following HI. We subsequently tested the role of GSK-3β in neonatal HI brain injury using the pharmacological blocker TDZD-8. We showed that GSK-3β activity is involved in apoptotic neuronal cell death that could link the Akt/GSK-3β/caspase-3 pathway.

Advisor: Sun, Hong-Shuo
Enrichment and Analysis of Proteasome Storage Granules

Ubiquitin-proteasome system (UPS) is a conserved eukaryotic pathway essential for the turn-over of short-lived or unwanted proteins, through the coordination of substrate ubiquitylation, and subsequent degradation by proteasomes. Proteasomes are complexes predominantly located in the nucleus of mitotic eukaryotic cells. However, upon entry into quiescence, cultured yeast cells sequester proteasomes into stable cytoplasmic bodies named proteasome storage granules (PSGs), which dissociate rapidly upon growth resumption. Our group seeks to understand the functional significance and dynamic nature behind proteasome sequestration. Through systems biology approaches, our group has previously identified 21 genes spanning several functional groups to be involved in PSG formation. In this thesis, I complemented our systems biology findings through affinity purification and enrichment of PSG from chemically-fixed yeast cells, and subsequent biochemical and proteomic analyses. I showed that PSG primarily constitutes proteasomal proteins, and implicated free mono-ubiquitin as an organization factor in PSG. Further structural analysis of PSGs is underway using ubiquitin probes.

Keywords: enrichment
proteasome
PSG
quiescence
ubiquitin
yeast
Advisor: Enenkel, Cordula
The Development of Positive Symptoms in Young Adults with Schizotypal Traits: A Cognitive Model

Objective: We sought to determine what cognitive mechanisms contribute to the development of positive symptomatology in schizophrenia. We hypothesized that the constellation of schizotypal traits would be a risk factor for the presentation of subsyndromal positive symptomatology. In order for subsyndromal positive symptomatology to be present, however, fantasy proneness and an externalizing bias must also be present and automatic thoughts must be externalized. Method: Undergraduate students (N = 215) completed self-report measures to assess schizotypal traits, externalizing bias, fantasy proneness, and automatic thoughts, with subsyndromal positive symptomatology as the outcome variable. Self-esteem and depressive symptom measures were included as covariates. Results: Schizotypal traits, fantasy proneness, and depressive symptoms were significantly related to subsyndromal positive symptomatology, explaining 39.7% of the variance. Conclusions: An externalizing bias may not be associated with subsyndromal positive symptomatology, possibly because the mechanism underlying positive symptoms differs depending on the severity of the symptoms.

Keywords: psychosis
schizophrenia
schizotypy
subsyndromal positive symptoms
Advisor: Zakzanis, Konstantine K
Type I Interferon Responses Drive Intrahepatic T cells to Promote Metabolic Syndrome

Obesity-related insulin resistance is driven by low-grade chronic inflammation of metabolic tissues mediated by innate and adaptive immunity. During obesity, the liver undergoes steatosis, leading to non-alcoholic fatty liver disease that is associated with hepatic insulin resistance and systemic glucose dysregulation. The immunological factors supporting these processes are poorly understood. We found that the liver accumulates pathogenic CD8+ T cell subsets which control hepatic insulin sensitivity and gluconeogenesis during diet-induced obesity. Accumulation and activation of these cells are supported by type I interferon (IFN-I) responses in the liver. Livers from obese mice upregulate critical interferon regulatory factors (IRFs) and interferon stimulatory genes (ISGs), while IFNaR1-/- mice, or CD8-specific IFNaR1-/- chimeric mice are protected from disease. IFNaR1 inhibitors improve metabolic parameters in mice, while CD8+ T cells, IFN-I IRFs and ISG expression correlate with fatty liver disease activity in human patients. IFN-I responses govern intrahepatic T cell pathogenicity during metabolic disease.

Keywords: Adaptive Immunity
Immunology
Insulin Resistance
Metabolic Syndrome
Non-alcoholic Fatty Liver Disease
Obesity
Advisor: Winer, Daniel
Upper Small Intestinal Protein Sensing in the Regulation of Glucose Homeostasis

High-protein diets improve glucose control in both healthy and type 2 diabetic individuals. Given that upper intestinal lipids trigger a pre-absorptive, gut-brain-liver neuronal axis to suppress glucose production (GP), it is urgent to assess the potential glucoregulatory capacity of intestinal protein sensing. We here demonstrate that in healthy rodents in vivo, upper small intestinal infusion of protein hydrolysate improved intravenous glucose tolerance. This was due at least in part to insulin-independent effects on the liver, given that the same infusion suppressed hepatic GP during a basalinsulin euglycemic clamp. Co-infusion of tetracaine reversed the ability of protein to improve glucose tolerance, indicating that a neuronal network is initiated at the level of the gut to regulate glucose homeostasis. Collectively, these findings show for the first time that pre-absorptive protein sensing in the upper small intestine improves glucose tolerance by triggering a neuronal network to lower GP.

Keywords: Amino Acids
Diabetes
Glucose Production
Nutrients
Obesity
Protein
Advisor: Lam, Tony KT
Defects in sialylation cause glomerular injury

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by hemolytic anemia, thrombocytopenia, and renal impairment. Complement dysregulation is associated with most cases, especially deficiency in the regulator complement factor H (CFH). Recessive mutations resulting in loss of the sialyltransferase activity of ST3GAL1 were identified in three siblings with aHUS with normal systemic complement laboratory indices. To test whether ST3GAL1 deficiency causes complement activation by reducing available CFH binding sites, complement deposition was assessed by flow cytometry on endothelial cells with decreased sialic acid content. Treatment with neuraminidase, which cleaves sialic acids, and genetic knockout of ST3GAL1 did not cause complement activation. Global blockade of sialyltransferases, which previously caused kidney failure in mice, did not induce a phenotype in rats. Glycoproteins lacking sialic acid residues in ST3GAL1 knockout endothelial cells were isolated and identified using a pull-down approach followed by mass spectrometry, providing targets for future study.

Keywords: atypical hemolytic uremic syndrome
endothelial biology
Advisor: Lemaire, Mathieu
The Informational Body: A Sociomedical Theory of Disability and the Ethics of the Brain-Machine Interface (BMI)

Cybernetic and bionic technologies hold great emancipatory potential for people with disabilities. Yet, scientists and disability scholars are polarized in their views on developing biotechnologies. Different discourses converge upon the brain machine interface—a link between the central nervous system and an external device—that augments sensory information and mobility for people with disabilities. This study combines philosophical, cultural studies, and social sciences methods to examine perceptions of these technologies held by people with physical, mobility disabilities and those of the researchers who develop them. Participants with acquired disabilities were more open to brain-machine technologies than those with congenital disabilities; scientists focused on patient “quality of life” and the ethics surrounding biotechnologies. I propose a “sociomedical” theory of disability that reconciles opposed medical and social models through an “informational body heuristic” that delineates the disabled body as a functionally-impaired cybernetic system. Ideological reconciliation would facilitate access to biotechnologies, thus improving the quality of life for people with disabilities.

Keywords: brain-machine interface
disability
ethics
heuristics
information
sociomedical
Advisor: Gibson, Twyla
The Spatial and Temporal Variability of Greenhouse Gas Fluxes within an Urban Bay-mouth Bar Coastal Marsh that has undergone Sediment Restoration

Wetlands contribute to carbon cycling through integrated aerobic and anaerobic redox processes within their ecosystem. Despite overwhelming support that climate and land use changes threaten to alter greenhouse gas (GHG) status, both coastal marsh wetlands and the effects of dredging restoration are understudied. To address this, a field experiment was conducted to monitor GHG fluxes through ebullition, diffusion, and plant-assisted transport in Rattray Marsh (Mississauga, Ontario, Canada). This research aims to answer two questions: (i) What is the spatial variation and temporal variability of GHG fluxes across inorganic sediment exposure? and (ii) What are the driving factors for GHG fluxes? The experiment results reveal that (i) Elevated diffusive and ebullitive fluxes were observed at restored locations; (ii) GHG fluxes are seasonally driven; and (iii) GHG driving factors are highly variable. This suggests that the removal of inorganic sediment through dredging results in an elevated emission of GHG to the atmosphere.

Keywords: Diffusion
Ebullition
Freshwater Mineral Wetland
Greenhouse Gas
Plant assisted transport
Restoration
Advisor: He, Yuhong
Lehnherr, Igor
Motion Compensation using Principal Component Analysis and Projection onto Dipole Fields for Abdominal Magnetic Resonance Thermometry

High-intensity focused ultrasound is a non-invasive heat-based therapy, which is often guided by magnetic resonance (MR) thermometry. MR thermometry provides accurate temperature measurement at the target and in surrounding tissue. This is critical to ensure that sufficient thermal dose is achieved and to monitor for collateral damage. Unfortunately, MR thermometry is severely compromised by motion and susceptibility artifacts that are caused by respiration (periodic motion) and peristalsis (aperiodic motion). A hybrid method has been designed to correct these artifacts using principal component analysis as a multi-baseline method, and projection onto dipole fields as a near-referenceless approach. In vivo measurements in porcine and human kidneys, achieved a temperature stability and precision of 0.85 째C and 1.00 째C, respectively, without the need for any user-interaction or supplementary tracking tools. This is about twice as accurate as the leading hybrid method, which scored 1.97 째C and 2.22 째C, respectively, on the same data.

Keywords: High-Intensity Focused Ultrasound
Magnetic Resonance Thermometry
Motion compensation
MRI
Advisor: Drake, James M
Waspe, Adam C
The Potential Effect of Alpha-Linolenic Acid on Prostate Specific Antigen

The objectives were to investigate the effect of alpha-linolenic acid (ALA) on prostate specific antigen (PSA) through two studies: 1) Determine the effect of ALA-enriched diet on PSA levels and serum ALA concentrations, through a secondary analysis of a randomized controlled trial in type 2 diabetes patients. 2) Determine the effect of ALA on prostate cancer cell growth and PSA production. Results: 1) ALA supplementation resulted in a reduction of 0.43 ng/ml on PSA (P=0.014). 2) ALA-enriched diet increased percentage composition of ALA in total lipids, phospholipids, free fatty acids and triglycerides (P

Keywords: ALA
Alpha-Linolenic Acid
prostate
prostate cancer
Prostate Specific Antigen
PSA
Advisor: Jenkins, David JA
The Effect of Legumes on Blood Pressure

Our objective was to assess the effect on blood pressure (BP) of legumes through a secondary analysis of a 6-month randomized controlled trial (RCT), and a systematic review and meta-analysis of RCTs. In the first study, diastolic BP (DBP) was significantly lower on a low-glycemic index (GI) diet which included legume recommendations, versus a high-cereal fibre diet. Furthermore, total legume intake was associated with lower systolic BP (SBP), DBP, and mean arterial pressure (MAP) in baseline-adjusted analyses. When subgrouping legumes by type, effects were stronger and more robust for pulses versus non-pulse legumes. Significance was lost after adjustment for legume characteristics. Meta-analysis of 44 trials (n=2319) found legume diets significantly lowered SBP and DBP versus control diets. Strongest effects were in hypertensive study populations. Results of these studies suggest that legume consumption lowers BP.

Keywords: Blood pressure
Hypertension
Legumes
Pulses
Advisor: Jenkins, David JA
Optimal Discharge Control in Capacity-constrained Systems: A Dynamic Programming Approach

In this thesis, we study a stochastic discharge control problem with patient readmissions in a capacity-constrained hospital unit. The problem is formulated as a multi-stage dynamic program where the objective is to determine the optimal discharge policy so as to minimize the expected total number of patients in the system until it is emptied. In the one-bed unit case, we fully characterize the optimal policy as a two-threshold policy (TTP). In the multi-bed unit case, the problem is more challenging since the associated dynamic programming equations are not fully decomposable bed-by-bed. To this end, we propose a so-called Marginal Policy Iteration (MPI) algorithm, that decomposes the joint optimization problem into easier one-bed marginal optimization problems and establish convergence of this algorithm to the optimal policy.

Keywords: Dynamic programming
Healthcare management
Operation research
Stochastic control
Advisor: Kim, Michael J
The Fresh Prince Syndrome: Experiences of Urban Black Males in Educational Settings

This thesis examines how urban Black males shape and negotiate their identities and how they situate themselves within schooling experiences. I take a phenomenological approach and use principles of CART to explore and analyze the stories of six individuals who claim an urban Black identity, including myself. This study is distinct in that it examines how identity is fostered inside of schooling environments as well as how it undergoes transformation from high school to university. This study also closely examines identity of urban Black males who find themselves clinging to a hip-hop cultural allegiance and the implications that has on their schooling. These experiences of aesthetic representation, space, and peer relationships combine to extend a narrative regarding urban Black male experience in school while providing insight into how educational institutions can facilitate more productive and engaging learning environments.

Keywords: anti-racism
black masculinity
cultural studies
hip-hop
pop culture
Advisor: Dei, George S
Todorova, Miglena
Local Delivery System to Reduce Pain in a Model of Back Surgery

Lumbar disc herniation is a common cause for lower back pain and reason for spinal surgery. Inevitably, patients will feel acute post-operative pain following surgery, thus local analgesics are given to patients after the surgery to alleviate pain. Existing drug delivery methods are limited by large doses, quick clearance rate from the injury site, short pain-relief period and multiple injections. As a result, there is an unmet need for a local, controlled and sustained drug delivery system following spine surgery. We propose to investigate a novel biomaterial to prolong the delivery of drugs to the local injury site. The drug-loaded hydrogel was characterized in terms of its release profile (where different factors were considered to prolong the release of the drug), storage modulus and swelling ratio. Behavioural tests and a pharmacokinetic study were conducted to determine the effects of the drug-loaded hydrogel in vivo.

Keywords: Biomaterial
Drug Delivery
Pain
Advisor: Shoichet, Molly S
SFMBT2 Function in Chromatin Architecture Mediates Trophoblast Stem Cell Maintenance

The mammalian Polycomb Group gene Sfmbt2 is implicated in embryonic viability through the maintenance of the trophoblast stem (TS) cells and their contribution to development of the placenta. To elucidate the regulatory role SFMBT2 plays in TS cell maintenance, I performed ChIP-seq analyses against endogenous and FLAG-SFMBT2. Genome-wide SFMBT2 localization analyses revealed broad binding profiles suggesting SFMBT2 recruitment is more complex than its Drosophila counterpart dSfmbt. Analysis of SFMBT2 peaks revealed preferential localization to repetitive elements, specifically LINEs, major satellite sequences, and lncRNAs. A consistent pattern of histone and transcription factor accumulation across SFMBT2 peaks was observed. RNA-seq analysis of extraembryonic tissues of SFMBT2-null murine embryos revealed that 75% of differentially expressed genes were upregulated, as expected for loss of a transcriptional repressor. Collectively, the data suggests that SFMBT2 plays a complex regulatory role in mediating chromatin architecture which may contribute to the maintenance of stemness in TS cells.

Keywords: chromatin structure
LINEs
lncRNAs
Major Satellites
SFMBT2
Trophoblast
Advisor: Varmuza, Susannah