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Acquired Bracket Pellicle Modulation Via Exposure To Histatin 3, Niklas W. Neilson Dec 2018

Acquired Bracket Pellicle Modulation Via Exposure To Histatin 3, Niklas W. Neilson

Electronic Thesis and Dissertation Repository

Objectives: To investigate the effect of histatin 3 on the protein pellicle formation on the orthodontic bracket surface.

Methods: Our study consisted of 4 sample groups. A sample of human parotid saliva without histatin functioned as a control group. Other groups were immersed with or without histatin 3 and human parotid saliva. Each group was incubated for 2 hours in their respective substrate at 37°C. The acquired pellicle from each group was harvested, then analyzed with SDS-PAGE and LC-ESI-MS/MS.

Results: Thirty-nine proteins were identified in the control group, 18 were identified in group 2, and 21 were identified in group …


Normalizing Masculinity: Explaining Processes, Factors, And Contexts That Influence How Rural Male Farmers Seek Health Information In Southwest Ontario, Bradley C. Hiebert Dec 2018

Normalizing Masculinity: Explaining Processes, Factors, And Contexts That Influence How Rural Male Farmers Seek Health Information In Southwest Ontario, Bradley C. Hiebert

Electronic Thesis and Dissertation Repository

Disproportionately high mortality and morbidity rates experienced by rural men are often related to the high prevalence of rural male farmers (RMFs) who are consistently exposed to chemicals, animal waste, and dust, or injured or killed while working. This dissertation aimed to explain processes by which RMFs seek health information (HI), and how these processes are influenced by rural social, cultural, political, and geographical factors.

Three studies were conducted as part of this dissertation. The first study was a literature review that explored the relationship between rural men’s health, health information seeking (HIS) theory, and masculinity theory. The second study …


Virtual Reality Simulation Of Glenoid Reaming Procedure, Mohammadreza Faieghi Dec 2018

Virtual Reality Simulation Of Glenoid Reaming Procedure, Mohammadreza Faieghi

Electronic Thesis and Dissertation Repository

Glenoid reaming is a bone machining operation in Total Shoulder Arthroplasty (TSA) in which the glenoid bone is resurfaced to make intimate contact with implant undersurface. While this step is crucial for the longevity of TSA, many surgeons find it technically challenging. With the recent advances in Virtual Reality (VR) simulations, it has become possible to realistically replicate complicated operations without any need for patients or cadavers, and at the same time, provide quantitative feedback to improve surgeons' psycho-motor skills. In light of these advantages, the current thesis intends to develop tools and methods required for construction of a VR …


Effect Of Bacterial Superantigens On The Magnitude And Breadth Of Influenza-Specific Cd8+ T Cell Responses, Courtney Meilleur Dec 2018

Effect Of Bacterial Superantigens On The Magnitude And Breadth Of Influenza-Specific Cd8+ T Cell Responses, Courtney Meilleur

Electronic Thesis and Dissertation Repository

Severe cases of influenza A virus (IAV) infection are often complicated by concomitant bacterial pneumonia or sepsis. Many bacterial species are capable of producing potent immunomodulators called superantigens (SAgs), which have the potential to interfere with cell-based antiviral immune mechanisms. I asked what effects bacterial SAgs have on both the magnitude and the breadth of antiviral CD8+ T cell (TCD8+) responses. Surprisingly, administration of SAgs to mice shortly before or after vaccination with IAV increased the number of primary TCD8+ responding to select IAV-derived epitopes. T cell receptor staining of these SAg-augmented populations revealed expression of …


Investigating The Use Of M-Health For Learning And Clinical Training By Medical Students In Ghana, Abdul M. Sulley Dec 2018

Investigating The Use Of M-Health For Learning And Clinical Training By Medical Students In Ghana, Abdul M. Sulley

Electronic Thesis and Dissertation Repository

There is a challenge with healthcare access in most developing countries. With the high rate of mobile technology penetration in these countries, there is a strong belief that mobile technology can help address this and other health system and education challenges. This study investigated how clinical year medical students in Ghana used m-health and with what outcomes. This was a mixed-methods study to assess what technologies students used, what the impact of use was, what enablers and barriers they encountered, what factors explained m-health adoption and what the attitudes of students, staff and faculty members were towards m-health use. The …


Applications Of Ct Perfusion-Based Triaging And Prognostication In Acute Ischemic Stroke, Eric A. Wright Dec 2018

Applications Of Ct Perfusion-Based Triaging And Prognostication In Acute Ischemic Stroke, Eric A. Wright

Electronic Thesis and Dissertation Repository

CT Perfusion (CTP) is a minimally invasive imaging technique that aids acute ischemic stroke (AIS) triage and prognostication by determining tissue viability based on hemodynamic parameters. The goals of this research are to determine: 1) CTP thresholds for estimation of infarct and penumbra volume, 2) how CTP scan duration impacts infarct and penumbra volume estimates, and 3) reliability of CTP for predicting functional outcomes following intra-arterial therapy (IAT).

Chapter 2 introduced an experimental study for determining ischemia-time dependent thresholds for brain infarction using multimodal imaging in a porcine stroke model that is easier to implement than previous large animal stroke …


The Role Of Tbx3 In Early Breast Cancer Progression, Milica Krstic Dec 2018

The Role Of Tbx3 In Early Breast Cancer Progression, Milica Krstic

Electronic Thesis and Dissertation Repository

TBX3 is a transcriptional regulator involved in embryonic development and in tumorigenesis of several cancer types. There are two isoforms of TBX3 (TBX3iso1 and TBX3iso2) with different DNA binding domains. The large-scale functional roles of TBX3iso1 and TBX3iso2 were characterized in a breast cancer context. Both TBX3 isoforms induced invasiveness and an epithelial-to-mesenchymal (EMT) phenotype. Coupling data from genome-wide ChIP-array and RNA-Seq studies provided a novel list of genes regulated by each isoform. Both TBX3 isoforms regulate expression of several EMT-related genes, including SLUG and TWIST1. Importantly, TBX3 is a direct regulator of SLUG, and SLUG expression is required for …


Diagnostic Ultrasound In The Measurement Of Cortical Bone Thickness In Porcine Mandibular Specimens, Diego Diaz Guerrero Nov 2018

Diagnostic Ultrasound In The Measurement Of Cortical Bone Thickness In Porcine Mandibular Specimens, Diego Diaz Guerrero

Electronic Thesis and Dissertation Repository

Introduction: Ultrasound (US) is a safe, non-invasive diagnostic method that has been used in various capacities in medicine and dentistry. Periodontal bone loss, bony dehiscence, and gingival recession have been reported as potential risks of orthodontic treatment in patients who have decreased buccal/labial bone thickness. US has the potential to aid in the diagnosis of patients at risk for these possible complications of orthodontic treatment. Purpose: To validate the use of a novel US device in the measurement of buccal cortical bone (BCB) thickness over roots in porcine mandibles. Materials and Methods: Jaw and cortical bone models were constructed and …


Medial Geniculate Projections To Auditory And Visual Cortex In Hearing And Deaf Cats, Benjamin Trachtenberg Nov 2018

Medial Geniculate Projections To Auditory And Visual Cortex In Hearing And Deaf Cats, Benjamin Trachtenberg

Electronic Thesis and Dissertation Repository

Following early-onset deafness, studies have demonstrated crossmodal plasticity, throughout “deaf” auditory cortex. Crossmodally reorganized auditory cortex shows increased dendritic spine density, which suggests increased numbers of axon terminals. I examined projections from the medial geniculate body (MGB) of hearing and early-deaf cats in order to reveal the distribution of synaptic boutons in the cortex, originating from MGB neurons. Anterograde fluorescent dextran tracers were deposited bilaterally in the MGB in order to label cortical axon terminals. Deafness resulted in axon terminal increases in visual cortex, and conservation of auditory axon terminal distribution. Visual areas PLLS and area 18 received increased projections …


Multi-Scale Peripheral Vasculopathy With Metabolic Syndrome, Kent Lemaster Nov 2018

Multi-Scale Peripheral Vasculopathy With Metabolic Syndrome, Kent Lemaster

Electronic Thesis and Dissertation Repository

The combination of cardiovascular and metabolic risk factors including obesity, dyslipidemia, hypertension, and insulin resistance, in combination with a prothrombotic and proinflammatory state, is a condition termed Metabolic Syndrome (METS). Twenty percent of the adult population is afflicted with METS which increases the risk of type-2 diabetes mellitus and cardiovascular disease. Further, the presence of peripheral vascular disease (PVD) is tightly coupled with METS which is a perfusion-demand mismatch of blood supply to active skeletal muscle resulting in painful claudication and a late-stage potential for amputation. The underlying contributors of METS associated micro-vasculopathies in the skeletal muscle, their impact on …


Effect Of Clear Aligner Therapy On Masticatory Muscle Tenderness And Orthodontic Pain, Johnny Tran Nov 2018

Effect Of Clear Aligner Therapy On Masticatory Muscle Tenderness And Orthodontic Pain, Johnny Tran

Electronic Thesis and Dissertation Repository

Introduction: Patients undergoing orthodontic clear aligner therapy (CAT) may experience discomfort in their teeth and jaws, and often present with visible wear on their aligners. This multi-site prospective clinical study aimed to analyze tooth pain and masticatory muscle tenderness in patients subjected to CAT with Invisalign©.

Methods: Twenty-seven healthy adults undergoing treatment with Invisalign© were recruited from three university-based orthodontic clinics. Tooth pain and muscle tenderness were reported on visual analog scales in pain diaries prior to, and after starting CAT. Pressure pain thresholds (PPT) measured using pressure algometers were used to assess somatosensory changes in trigeminal and extra-trigeminal locations. …


Promoting Healthy Beverage Consumption Habits Among Elementary School Children: Evaluating The Healthy Kids Community Challenge 'Water Does Wonders' Interventions In London, Ontario, Bridget R. Irwin Nov 2018

Promoting Healthy Beverage Consumption Habits Among Elementary School Children: Evaluating The Healthy Kids Community Challenge 'Water Does Wonders' Interventions In London, Ontario, Bridget R. Irwin

Electronic Thesis and Dissertation Repository

Childhood obesity is a major public health concern and has been attributed to poor diet, among other factors. Sugar-sweetened beverage (SSB) consumption, in particular, has been linked to excess weight gain in childhood, while water consumption is a protective factor. Taking advantage of the Water Does Wonders theme of the Healthy Kids Community Challenge, an initiative by the provincial government to promote water consumption, this thesis uses pre-post surveys of children aged 8-14 years to examine (a) the association between knowledge and beverage consumption habits, and (b) the effectiveness of a school- based education and environment intervention to reduce SSB …


Limbic System Involvement In Absence Seizures, Rukham Ajaz Oct 2018

Limbic System Involvement In Absence Seizures, Rukham Ajaz

Electronic Thesis and Dissertation Repository

Absence epilepsy is characterized by brief spells of absent stare and spike wave discharges (SWDs), generally believed to be generated by a thalamocortical network. Our lab showed that hippocampal neuronal firings were synchronous with SWDs in a gamma butyrolactone (GBL) model of absence epilepsy in rats (Arcaro et al., 2016). We hypothesize that, in a GBL model of absence seizures, 30-400 Hz oscillations in the spontaneous local field potentials (LFPs) in the hippocampus and other parts of limbic system (amygdala and nucleus accumbens) are phase modulated by SWDs, and this modulation is mediated through nucleus reuniens of midline thalamus (RE). …


Lung-Derived Selectins Interact With Cd44 And Enhance The Migration Of Breast Cancer Cells, Sami U. Khan Oct 2018

Lung-Derived Selectins Interact With Cd44 And Enhance The Migration Of Breast Cancer Cells, Sami U. Khan

Electronic Thesis and Dissertation Repository

The lung is among the deadliest sites of breast cancer metastasis. Previous work from our laboratory demonstrated that aggressive CD44-expressing breast cancer cells preferentially metastasize to the lung in vivo, and observed the presence of multiple CD44-interacting proteins in the lung including E-, L- and P-selectin. We hypothesized that lung-derived selectins promote breast cancer migration and/or growth via interactions with CD44. Using an ex vivo model of the soluble lung-microenvironment, we demonstrate that lung-derived selectins enhance in vitro migration but not proliferation of breast cancer cells. Co-immunoprecipitation experiments reveal that CD44 expressed by breast cancer cells in vitro interacts …


Understanding The Impact Of Hiv-1 Genetic Diversity On The Function Of Nef And Its Role In Serinc5 Antagonism, Aaron Leslie Johnson Aug 2018

Understanding The Impact Of Hiv-1 Genetic Diversity On The Function Of Nef And Its Role In Serinc5 Antagonism, Aaron Leslie Johnson

Electronic Thesis and Dissertation Repository

HIV-1 Nef is a key pathogenic protein, allowing HIV-1 to evade the host immune system by downregulating MHC-I and CD4. Furthermore, it was recently discovered that Nef counteracts the host factor SERINC5 to increase HIV-1 infectivity, but the mechanistic details of the Nef:SERINC5 interaction still need to be explored. Throughout this dissertation, I will explore the hypothesis that the genetic diversity that defines HIV-1 has a pronounced effect on the HIV-1 protein Nef, altering its function between and within group M subtypes. To address this hypothesis I investigated how MHC-I and CD4 downregulation differ among all non-recombinant group M subtypes. …


Elucidating The Importance Of Hope And Its Potential Lewis Glycosylation In Helicobacter Pylori, Keertika Yogendirarajah Aug 2018

Elucidating The Importance Of Hope And Its Potential Lewis Glycosylation In Helicobacter Pylori, Keertika Yogendirarajah

Electronic Thesis and Dissertation Repository

Helicobacter pylori colonizes 50% of the world’s population, whereby glycoproteins and Lewis Y-containing lipopolysaccharides contribute to its pathogenesis. We investigated whether the HopE porin is glycosylated, if the glycan is Lewis Y, and if this is mediated by the putative oligosaccharide transferase HP0946 or the O-antigen ligase WaaL. Western blotting was performed on outer membranes with anti-HopE antibodies, anti-Lewis Y antibodies and fucose-binding BambL lectin to ascertain HopE glycosylation. We discovered that HopE is likely glycosylated by a non-Lewis Y fucose-containing glycan and neither HP0946 nor WaaL are the transferase. Additionally, we investigated HopE’s role in antibiotic susceptibility via Etest …


Impact Of Feeding Tube Status On Health Outcomes For Individuals With Oropharyngeal Cancer, Nedeljko Jovanovic Aug 2018

Impact Of Feeding Tube Status On Health Outcomes For Individuals With Oropharyngeal Cancer, Nedeljko Jovanovic

Electronic Thesis and Dissertation Repository

Abstract

This study investigated differences in outcomes related to health, swallowing, and quality of life (QoL) for individuals with oropharyngeal squamous cell carcinoma (OPSCC) receiving either radiotherapy (RT) alone, or concomitant chemoradiotherapy (CRT). Differences were assessed based on whether patients received a feeding tube (FT group) or not (NFT group). Measures including the Functional Oral Intake Scale (FOIS), Performance Status Scale for Head and Neck Cancer (PSS-HN), M.D. Anderson Dysphagia Inventory (MDADI), and weight were collected for 126 individuals at baseline, and at 3, 6, and 12 months post-treatment. Data were analyzed to identify potential prognostic differences between the groups, …


Health Professional Students' Understanding Of Oral Health In Traumatic Brain Injury, Samira Omar Aug 2018

Health Professional Students' Understanding Of Oral Health In Traumatic Brain Injury, Samira Omar

Electronic Thesis and Dissertation Repository

Oral health is a significant consideration in recovery following severe traumatic brain injury (TBI) as it is associated with overall health. Health-care providers play an essential role in rehabilitation following TBI. Thus, using qualitative descriptive research and focus groups, this thesis examined the experiences and perceptions of eight final-year health-professional students in nursing, occupational therapy, and speech-language pathology with respect to oral health in TBI. Results suggest that health-professional students lack a deep understanding of i) what constitutes oral health, ii) common oral health challenges that may be faced by persons with TBI, and iii) optimal oral care in persons …


Identification And Characterization Of Hiv-1 Antagonists To The Antiviral Protein, Herc5, Divjyot S. Kochar Jul 2018

Identification And Characterization Of Hiv-1 Antagonists To The Antiviral Protein, Herc5, Divjyot S. Kochar

Electronic Thesis and Dissertation Repository

Interferons that trigger the release of innate antiviral proteins are a vital immune defense mechanism against viruses such as HIV-1. HERC5, an interferon stimulated protein inhibits HIV-1 replication through two independent mechanisms: inhibiting export of HIV-1 RNA through the Rev-dependent pathway and blocking an early step in the assembly of the virion. HERC5 is an antiviral protein yet individuals infected with HIV fail to control the infection. This can be due to viral antagonist mechanisms which counteract the function of restriction factors. Using a viral particle release assay, I discovered HIV-1 Env and Vpu can function as potential antagonists to …


Design, Development, Manufacturing And Biomechanical Testing Of Stand-Alone Cage For Posterior Lumbar Interbody Fusion, Fahad Alhelal Jun 2018

Design, Development, Manufacturing And Biomechanical Testing Of Stand-Alone Cage For Posterior Lumbar Interbody Fusion, Fahad Alhelal

Electronic Thesis and Dissertation Repository

Introduction: The most common method of spinal fusion includes pedicle screws instrumentation, either with or without interbody cage fusion. This thesis aimed to develop and test a novel stand-alone intervertebral device that eliminates the need for pedicle screws and rods.

Method: The stand-alone cage was designed in collaboration with spinal surgeons and engineers using computer assisting drawings, and manufactured in titanium by 3D printing. Biomechanical testing comparing the stand-alone cage with standard posterior lumbar interbody fusion (PLIF) in sawbones (n=6) and cadavers (n=8).

Result: Compared to PLIF, the stand-alone cage demonstrated no significant difference in range of flexion, lateral bend …


Methods For The Investigation Of Microvascular Control Of Oxygen Distribution, Richard Sove Jun 2018

Methods For The Investigation Of Microvascular Control Of Oxygen Distribution, Richard Sove

Electronic Thesis and Dissertation Repository

The purpose of this thesis was to develop tools for studying oxygen-dependent regulation of red blood cell (RBC) flow distribution in the microcirculation. At the microvascular level, arterioles dictate the distribution of oxygen (O2) carrying RBCs to downstream capillaries, a process which needs to be tightly regulated and coupled to O2 off loading from capillaries to the tissue. To investigate potential regulatory mechanisms, an O2 exchange platform was developed to manipulate the RBC hemoglobin O2 saturation (SO2) at the muscle surface while limiting the changes in SO2 to only a single capillary …


The Development Of A Temporomandibular Force Simulator To Study Craniofacial Strain In-Vitro, Kenneth Kc Ip Jun 2018

The Development Of A Temporomandibular Force Simulator To Study Craniofacial Strain In-Vitro, Kenneth Kc Ip

Electronic Thesis and Dissertation Repository

An in-vitro musculoskeletal loading simulator was developed to replicate the internal forces of mastication, and then employed in a comparison of clinically relevant facial fracture repairs. Muscle forces are simulated by pneumatic pistons via 3D printed mounts that are reverse-engineered from CT scan to match muscle attachment sites, which are adhered to bone in order to simulate native stress distributions. Bite force and bone strain pattern of the craniofacial structure under load were measured using a force sensor and strain gauges respectively. In a series of five fresh-frozen cadaveric heads, it was found that strain patterns of the craniofacial structure …


The Indigenous Determinants Of Health As Predictors For Diabetes And Unmet Health Needs Among Urban Indigenous People: A Respondent-Driven Sampling Study In Toronto, Ontario, Stephanie Rachael Mcconkey Jun 2018

The Indigenous Determinants Of Health As Predictors For Diabetes And Unmet Health Needs Among Urban Indigenous People: A Respondent-Driven Sampling Study In Toronto, Ontario, Stephanie Rachael Mcconkey

Electronic Thesis and Dissertation Repository

National statistics commonly present Indigenous peoples as a falsely homogenous group of people experiencing disproportionate ill health when compared to non-Indigenous peoples. There are significant gaps in statistical information regarding the health services access barriers experienced by Indigenous people that disrupts the quality of care they receive or prevents them from accessing care altogether. Our Health Counts Toronto is a community-based study that employed respondent-driven sampling (RDS) methodologies to sample 917 urban Indigenous adults. Prevalence estimates and prevalence ratios were calculated using RDS-II weights and adjusting for clustering by shared recruiter in SAS 9.4 and SAS-callable SUDAAN 11.0 software. This …


Investigating The Pathogenesis Of Staphylococcus Aureus In Periprosthetic Joint Infections, Santiago L. Iglesias Jun 2018

Investigating The Pathogenesis Of Staphylococcus Aureus In Periprosthetic Joint Infections, Santiago L. Iglesias

Electronic Thesis and Dissertation Repository

The most challenging complication after total joint replacement is the periprosthetic joint infection (PJI). Staphylococcus aureus is a commensal bacterium and a human pathogen. It is responsible for more than half of the PJI. We demonstrated that synovial fluid has antimicrobial properties against S. aureus and the iron restriction is one of the mechanisms used for the host to prevent bacterial growth, and is even able to increase killing of S. aureus. We have shown a clear role of transferrin as a restrictive factor in synovial fluid that functions by iron starving the bacteria and sensitizing them to killing …


The ‘Meanings’ And ‘Enactments’ Of Science And Technology: Ant-Mobilities’ Analysis Of Two Cases, Farrukh Chishtie Apr 2018

The ‘Meanings’ And ‘Enactments’ Of Science And Technology: Ant-Mobilities’ Analysis Of Two Cases, Farrukh Chishtie

Electronic Thesis and Dissertation Repository

In this work I study two cases involving practices of science and technology in the backdrop of related and recent curricular reforms in both settings. The first case study is based on the 2005 South Asian earthquake in Muzaffarabad, Pakistan which led to massive losses including large scale injuries and disabilities. This led to reforms at many levels ranging from disaster management to action plans on disability, including educational reforms in rehabilitation sciences. Local efforts to deal with this disaster led to innovative approaches such as the formation of a Community Based Rehabilitation (CBR) model by a local NGO, which …


Quality Of Antenatal Care And Its Relationship With Women’S Intended Use Of Their Anc Facility For Delivery: A National Cross-Sectional Study In Kenya, Jisoo Kim Apr 2018

Quality Of Antenatal Care And Its Relationship With Women’S Intended Use Of Their Anc Facility For Delivery: A National Cross-Sectional Study In Kenya, Jisoo Kim

Electronic Thesis and Dissertation Repository

Maternal deaths have been one of the leading causes of deaths in sub-Saharan Africa. Delivering at an institution can prevent the majority of maternal deaths in developing countries. A national cross-sectional survey of Kenya was used to determine if the quality of antenatal care (ANC) provided to women is associated with their intention to deliver at the same facility. Multilevel mixed-effects logistic regression was used to examine this relationship. Quality of ANC variables assessed in this study were not significantly associated with women’s intention to deliver at the same facility. Mothers preferred to deliver at hospitals, rather than clinics/dispensaries. ANC …


Contribution Of Enterococcus Faecalis To Urinary Tract Infection, Samantha Ann Whiteside Mar 2018

Contribution Of Enterococcus Faecalis To Urinary Tract Infection, Samantha Ann Whiteside

Electronic Thesis and Dissertation Repository

The purpose of this thesis was to increase understanding of enterococcal UTI, in particular, the response of Enterococcus to antibiotic prophylaxis in vitro and in vivo and enterococcal communication with the bladder.

We studied the in vitro effects of trimethoprim-sulfamethoxazole (TMP/SMX) and nitrofurantoin, two of the antibiotic treatments used most commonly in the management of both urinary tract infection (UTI) and recurrent UTI (RUTI), on Enterococcus faecalis attachment to urothelial cells. In doing so, we documented nitrofurantoin-induced increases in bacterial attachment at growth inhibitory concentrations of nitrofurantoin, but not TMP/SMX. This increased virulence did not correlate with increased expression of …


Kallikrein-Related Peptidases Are Dysregulated In Pleomorphic Adenoma, Matthew D. Morrison Feb 2018

Kallikrein-Related Peptidases Are Dysregulated In Pleomorphic Adenoma, Matthew D. Morrison

Electronic Thesis and Dissertation Repository

Objectives: Pleomorphic adenoma (PA) is the most common benign salivary gland tumor. Kallikrein-related peptidases (KLKs) have been identified as biomarkers in many human tumors and may influence tumor behavior. We investigated KLK1-15 messenger ribonucleic acid (mRNA) and proteins in PA specimens to determine a KLK expression profile for this tumor.

Methods: Fresh frozen PA tissue specimens (n = 26) and matched controls were subjected to RT-qPCR to detect KLK1-15 mRNA. Expression of KLK1, KLK12, KLK13 and KLK8 proteins were then evaluated via immunostaining techniques. Statistical analyses were performed with the level of significance set at P < .05.

Results: We observed downregulation …


Examining The Role Of Ganglioside Homeostasis In Neurodegeneration And Aging Using Maldi Imaging Mass Spectrometry, Sarah Caughlin Feb 2018

Examining The Role Of Ganglioside Homeostasis In Neurodegeneration And Aging Using Maldi Imaging Mass Spectrometry, Sarah Caughlin

Electronic Thesis and Dissertation Repository

Gangliosides are a family of membrane lipids enriched in the central nervous system (CNS) that play an important role in cell signaling processes on the membrane. Alterations in the homeostatic distribution of the a-series family of gangliosides has been observed in both pre-clinical models and human patients with neurodegenerative diseases and injuries, such as Alzheimer’s disease (AD) and strokes. Ganglioside dysregulation has been implicated as an important mechanisms driving pathology in the aging brain, yet there is little information on where and when these lipid changes occur as well as the role of dysregulation during neurodegeneration. Matrix-Assisted Laser Desorption/Ionization (MALDI) …


Functional And Structural Mimicry Of A-Kinase Anchoring Proteins By Human Adenovirus E1a, Cason R. King Feb 2018

Functional And Structural Mimicry Of A-Kinase Anchoring Proteins By Human Adenovirus E1a, Cason R. King

Electronic Thesis and Dissertation Repository

As an obligate intracellular parasite, human adenovirus (HAdV) must utilize host factors for survival and replication. Early during infection, its multifunctional E1A protein interacts with an impressive range of cellular target proteins to exert control over the cellular environment. Through these virus-host interactions, E1A massively reprograms both viral and cellular transcription to activate the other HAdV genes, downregulate the host’s immune response, and induce the cell cycle. Consequently, E1A converts the infected cell into a compliant state more amenable for HAdV replication, resulting from its numerous protein-protein interactions. I sought to examine E1A’s interaction with cellular protein kinase A (PKA), …