Life Sciences Commons^™

Investigation Of Chitosan-Based Hydrogels As A Cell Delivery Platform For Adipose-Derived Stem/Stromal Cell Transplantation To Promote Angiogenesis In Ischemic Tissues, Jobanpreet Singh Dhillon

Electronic Thesis and Dissertation Repository

Stem cell transplantation is under investigation to stimulate angiogenesis in patients with peripheral artery disease. To develop a cell-delivery platform that enhances cell retention and function post-transplantation, the response of human adipose-derived stem/stromal cells (ASCs) encapsulated within N-methacrylate glycol chitosan (MGC) hydrogels with or without integrin-binding RGD or IKVAV motifs was explored. ASC viability was enhanced in the MGC and MGC-RGD hydrogels relative to the MGC-IKVAV group under hypoxic (2% O­₂) culture conditions, with cell spreading and higher metabolic activity noted in MGC-RGD at 14 days. Analysis of angiogenic gene expression revealed similar patterns between all hydrogel …

Hsp90 And Its Co-Chaperones Modify Tdp-43 Localization, Aggregation, And Toxicity, Lilian T. Lin

Electronic Thesis and Dissertation Repository

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with protein misfolding and protein aggregation. In particular, the TAR DNA-binding protein (TDP-43) is often found in the pathological inclusions in neurons of ALS patient brains and spinal cords. This phenomenon is known as TDP-43 proteinopathy, the mislocalization of TDP-43 from the cell nucleus and the formation of aggregates in the cytoplasm. Numerous mutations in the gene encoding TDP-43 have also been linked to familial cases of ALS (fALS) and cause TDP-43 proteinopathy. This study attempts to decipher how the molecular chaperone Hsp90 and its co-chaperones, Aha1, Sti1, and Cdc37, modulate …

Ang1 Treatment Reduces Muscle Pathology And Prevents A Decline In Perfusion In Dmd Mice, Kelly M. Gutpell, Nikola Tasevski, Boaz Wong, William Thomas Hrinivich, Feng Su, Lise Desjardins, Ting-Yim Lee, Lisa Marie Hoffman

Anatomy and Cell Biology Publications

Vascular endothelial growth factor (VEGF) and other pro-angiogenic growth factors have been investigated to enhance muscle tissue perfusion and repair in Duchenne muscular dystrophy (DMD). Current understanding is limited by a lack of functional data following in vivo delivery of these growth factors. We previously used dynamic contrast-enhanced computed tomography to monitor disease progression in murine models of DMD, but no study to date has utilized this imaging technique to assess vascular therapy in a preclinical model of DMD. In the current study, we locally delivered VEGF and ANG1 alone or in combination to dystrophic hind limb skeletal muscle. Using …

Superantigen Responsive T Cells Are Required For Nasopharyngeal Infection By Streptococcus Pyogenes, Joseph J. Zeppa

Electronic Thesis and Dissertation Repository

Streptococcus pyogenes is a human-specific pathogen that is responsible for serious morbidity and mortality worldwide despite being susceptible to common antibiotics. Furthermore, there is currently no licensed vaccine available against this organism. Previous research from our laboratory implicated a critical role for SAgs in a transgenic mouse model of acute nasopharyngeal infection by S. pyogenes. Herein, we are able to detect SAg production in vivo and establish that anti-SAg antibodies generated by either passive immunization or active vaccination with a MHC II-binding interface SAg toxoid reduces S. pyogenes nasopharyngeal burden. We were also able to demonstrate that this organism …

Discovery And Validation Of Information Theory-Based Transcription Factor And Cofactor Binding Site Motifs., Ruipeng Lu, Eliseos J Mucaki, Peter K Rogan

Biochemistry Publications

Data from ChIP-seq experiments can derive the genome-wide binding specificities of transcription factors (TFs) and other regulatory proteins. We analyzed 765 ENCODE ChIP-seq peak datasets of 207 human TFs with a novel motif discovery pipeline based on recursive, thresholded entropy minimization. This approach, while obviating the need to compensate for skewed nucleotide composition, distinguishes true binding motifs from noise, quantifies the strengths of individual binding sites based on computed affinity and detects adjacent cofactor binding sites that coordinate with the targets of primary, immunoprecipitated TFs. We obtained contiguous and bipartite information theory-based position weight matrices (iPWMs) for 93 sequence-specific TFs, …

Cost-Effectiveness Of Cerebrospinal Biomarkers For The Diagnosis Of Alzheimer's Disease, Spencer A. W. Lee, Luciano A. Sposato, Vladimir Hachinski, Lauren E. Cipriano

Anatomy and Cell Biology Publications

Background: Accurate and timely diagnosis of Alzheimer's disease (AD) is important for prompt initiation of treatment in patients with AD and to avoid inappropriate treatment of patients with false-positive diagnoses. Methods: Using a Markov model, we estimated the lifetime costs and quality-adjusted life-years (QALYs) of cerebrospinal fluid biomarker analysis in a cohort of patients referred to a neurologist or memory clinic with suspected AD who remained without a definitive diagnosis of AD or another condition after neuroimaging. Parametric values were estimated from previous health economic models and the medical literature. Extensive deterministic and probabilistic sensitivity analyses were performed to evaluate …

P31. Assessing The Long Term Effects Of Perceived Predation Risk On The Avian Brain, Lauren E. Witterick

Western Research Forum

Predators affect prey populations not only through direct killing, but also through the perception of predation risk. Responding to predator threats is critical for prey survival, however perceived predation risk can have lasting effects ranging from individual changes in neurobiology up to the population level. My research focuses on the lasting effects of predator ‘fear’ on the avian brain. I will be using auditory playbacks to manipulate predation risk in black-capped chickadees (Poecile atricapillus) in acoustic isolation and brown-headed cowbirds (Molothrus ater) in large outdoor aviaries. Lasting behavioural changes have been found in black-capped chickadees one week after …

P08. Unravelling Organelle Genome Evolution Architecture Using Rna-Sequencing Data, Matheus Sanita Lima, David Roy Smith

Western Research Forum

Background: Mitochondria genomes vary from 11 Mb to 6 kb, while plastids can vary from 1 Mb to 30 kb. Non-coding DNA accounts for most of this size variation, but the mechanistic and evolutionary reasons for that are still unknown. Next generation sequencing has generated unprecedented amounts of genomic and transcriptomic data that can be used for organelle genome evolution studies. However, most of these data is used only for the study of cell nucleus. Therefore, I decided to use these untapped data source to investigate the transcription of organelle genomes in plastid-bearing protists.

Methods: I mapped the transcriptomes over …

P17. P3b Event-Related Potentials Show Changes In Varsity Football Players Due To Accumulated Sub-Concussive Head Impacts, Jeffrey S. Brooks, James W. Thompson, James P. Dickey

Western Research Forum

BACKGROUND: Concussion has been a focus in football at all levels of participation. However, there is a growing appreciation that repetitive sub-concussive impacts may have more significant effects on overall neurological health than the isolated diagnosed concussions that have been the focus of recent research. The purpose of this study was to evaluate the relationship between the number of head impacts that players experience throughout the season and their P300 evoked potential.

METHODS: Canadian university football players (n=45) were separated into three groups based on player mass and position/skill (small-skilled, big-skilled and big-unskilled). Groups were separated into low and high …

P24. The Birds And The Beats: Perception Of A Beat In An Avian Model, Brendon Samuels

Western Research Forum

Background: Beat perception is a complex cognitive skill that enables humans to “feel” the beat in music, and is an essential component of synchronization of behavior and dance. The mechanisms in the human brain that facilitate beat perception are not entirely understood, and have only been studied thus far using non-invasive techniques. Some animals, such as songbirds, also seem to be able to detect a beat in rhythms, though this has never been formally tested independent of motor synchronization.

Methods: An operant experiment is used to assess if European starlings, a type of songbird, are capable of categorizing …

P32. Altered Sensory Processing In Response To Novel Dreadd-Induced Inactivation Of Gaba In Pedunculopontine Tegmental Nucleus, Niveen Fulcher

Western Research Forum

Niveen Fulcher¹, Cleusa De Oliveira², & Susanne Schmid^1,2

¹Schulich School of Medicine & Dentistry, University of Western Ontario

²Anatomy and Cell Biology, University of Western Ontario

Altered sensory processing in response to novel DREADD-induced inactivation of GABA in pedunculopontine tegmental nucleus

Background: Sensory processing deficits are associated with certain psychiatric illnesses, such as schizophrenia and autism spectrum disorder (ASD). Sensory filtering and sensorimotor gating are evolutionarily conserved preattentive responses that filter and block redundant sensory stimuli that would otherwise overwhelm our brains. To date, underlying mechanisms of these deficits are undefined. Prepulse …

P02. Production Of A Protein Subunit Vaccine For Mannheimia Haemolytica In Lettuce Chloroplasts, Coby K. Martin

Western Research Forum

The cattle industry worldwide is ravaged by bovine respiratory disease (BRD), a bacterial disease caused by Mannheimia haemolytica. We have designed a chimeric protein subunit vaccine against M. haemolytica based on recent evidence demonstrating the protective potential of antigens against a virulence factor, leukotoxin, in addition to a surface lipoprotein. Plant-based production of this protein vaccine provides a safe and inexpensive alternative to traditional production methods. Plant-base production also supports the use of an edible vaccine that will deliver antigens to pharyngeal tissues to provide local immunization against M. haemolytica to prior to its progression into the lungs. Chloroplasts …

P18. Backstroke Start Performance: The Impact Of Using The Omega Backstroke Ledge, Gordon E. Barkwell, James P. Dickey

Western Research Forum

Background: FINA recently approved use of the “backstroke ledge” (Omega OBL2) to improve backstroke start performance in competition, but its performance has not been thoroughly evaluated. The purpose of this study was to compare starts performed on a flat wall to those performed with the OBL2, and to identify factors that contribute to better start performance. Methods: Ten elite backstroke swimmers performed three flat-wall and three OBL2 starts. Horizontal impulse, vertical impulse, takeoff velocity and takeoff angle were calculated from the force plate data. Entry distance, time to 10 m and start of hip and knee extension were recorded using …

P23. Elucidation Of The Signaling Pathway Of Mertk, Kyle Taruc

Western Research Forum

Background

Mer Tyrosine Kinase (MERTK) is a receptor which mediates efferocytosis – removal of apoptotic cells by phagocytes such as macrophages. MERTK plays a critical role in homeostasis, with mutations in MERTK associated with the development and progression of atherosclerosis, the buildup of cholesterol-laden plaque in the sub-arterial space. Indeed, one MERTK allele is associated with 66% (heterozygous) to 75% (homozygous) protection from atherosclerosis, while other alleles and SNP’s pre-dispose to atherosclerosis and autoimmunity. Complications resulting from atherosclerosis, including heart attack and stroke, are currently the second leading cause of mortality in Canada. Despite the importance of MERTK in atherosclerosis …

P27. Acute Impact Of An Extremely Low Frequency Magnetic Stimulus On Human Neurophysiological Function - Magnetophosphene Perception, Cadence M. Baker

Western Research Forum

Background: Magnetophosphenes are classified as colourless, flickering lights that are perceived with closed eyes in the dark, and upon exposure to a magnetic field (MF). Uncertainties exist involving the MF threshold for magnetophosphene perception.

Methods: Forty subjects will be enrolled in this experiment aiming to provide a frequency-response curve of magnetophosphene perception under MF exposure. Subjects will sit in a whole head MF exposure device wearing a 64-channel MRI-compatible EEG cap. Subjects will be exposed to a MF with a frequency of 5-300 Hz, in the form of an increasing flux density ramp (increasing magnetic field flux density from 0-100 …

P35. Investigating The Effect Of Maternal Immune Activation On Sensory Filtering, Social Behaviour And Attention, Faraj Haddad

Western Research Forum

Background

Altered brain development is associated with many neuropsychiatric disorders like Autism Spectrum Disorder (ASD) and schizophrenia. Environmental insults can interfere with neurodevelopment, and a prominent example is maternal infection during pregnancy. Epidemiological studies show that children born to mothers who were infected during pregnancy display a higher risk of developing ASD and schizophrenia, and this effect is mainly due to the maternal immune response. Polyinosinic-polycytidilic acid (Poly I:C) is a double stranded RNA molecule that mimics viral markers and elicits an immune response. When injected in pregnant rodents, this model produces offspring that exhibit core symptoms of ASD and …

P30. Optimizing Current Steering In Deep Brain Stimulation For Treating Parkinsonian Axial Motor Symptoms, Daphne Hui

Western Research Forum

Background: The proposed study will investigate deep brain stimulation (DBS), of the subthalamic nucleus (STN) to improve gait dysfunctions in advanced Parkinson’s Disease (PD). DBS requires implantation of electrodes into the brain that contain contacts where current traverses to stimulate neurons. Imprecise electrode implantations are inherent in surgical implantation; thus, contributing to the elusiveness of DBS on gait.

Methods: The proposed investigation will divide current between two contacts to receive 0, 30, 50, 70, or 100% of current, to find the best combination to improve gait. Gait changes associated with fractional combinations will be visually assessed with clinical scales, and …

P34. The Effects Of Standing Desks On Classroom Performance Of University Students, Siobhan Smith

Western Research Forum

Background:

It is well established that there are many health risks associated with prolonged sedentary time.¹ Unfortunately, research conducted on university students is limited but yet they experience excessive periods of sitting time during class and while studying.

Methods:

Recently, we investigated the effect of sitting, dynamic sitting, and standing desks on classroom performance of university students.² Participants performed three 3-minute classroom simulations, one for each of the three desks. The order of the desks and simulations were randomized. Each of the simulations included a different typing and memory task.

Results:

Results showed no significant difference in the …

The Impact Of Various Predator Perceptions On Stress Response And Spatial Memory In Birds, Chlöe S. N. Carter

Western Research Forum

The Impact of Various Predator Perceptions on Stress Response and Spatial Memory in Birds

Background

This project will explore the impact of environmental stressors on the cognitive abilities of birds. Predator perception has been demonstrated to elicit a stress response by elevating stress hormones which can alter the behaviour of birds. The aim of this study is to observe if chronic stress from differently perceived threats of predation in an individual’s environment will lead to differences in the spatial memory abilities in two species of birds. I predict that chronic stress resulting from predator stimuli will impair the bird’s performance …

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …

The Effects Of Intrauterine Growth Restriction (Iugr) On The Pulmonary Surfactant And Lung Injury, Reza Khazaee

Western Research Forum

The Effects of Intrauterine Growth Restriction (IUGR) on the Pulmonary Surfactant and Lung Injury

Khazaee R¹, McCaig LA², Hardy D¹, Yamashita CM², Veldhuizen, RAW²

Department of Physiology and Pharmacology¹, Western University, London, ON, Canada. Lawson Health Research Institute², London, ON, Canada

Background: Acute respiratory distress syndrome (ARDS) is defined as severe lung dysfunction that occurs after an insult to the lung such as an infection. The lung dysfunction in ARDS is due to alterations to surfactant, a lipid-protein mixture coats the inside of the lung and …

Rapid Regulatory And Effector Immune Responses In Toxic Shock Syndrome, Peter Anthony Szabo

Electronic Thesis and Dissertation Repository

Toxic shock syndrome (TSS) is an acute, potentially fatal condition characterized by high-grade fever, hypotensive shock and systemic inflammation. It is caused by exposure to staphylococcal and streptococcal superantigens (SAgs), which can activate up to 50% of T cells resulting in a hyperinflammatory ‘cytokine storm’ within hours. This inflammatory cascade progresses to a life-threatening illness with alarming rapidity, and SAg-exposed individuals can develop multi-organ failure within hours of onset of symptoms. However, there are currently no available treatments that efficiently mitigate the cytokine storm, which drives TSS immunopathology. Therefore, identifying and understanding the critical components underlying this process should hold …

A Method For Independent Component Graph Analysis Of Resting-State Fmri, Demetrius Ribeiro De Paula, Erik Ziegler, Pubuditha M. Abeyasinghe, Tushar K. Das

Anatomy and Cell Biology Publications

Introduction: Independent component analysis (ICA) has been extensively used for reducing task-free BOLD fMRI recordings into spatial maps and their associated time-courses. The spatially identified independent components can be considered as intrinsic connectivity networks (ICNs) of non-contiguous regions. To date, the spatial patterns of the networks have been analyzed with techniques developed for volumetric data. Objective: Here, we detail a graph building technique that allows these ICNs to be analyzed with graph theory. Methods: First, ICA was performed at the single-subject level in 15 healthy volunteers using a 3T MRI scanner. The identification of nine networks was performed by a …

Eligibility For Minimally Invasive Coronary Artery Bypass Examination Of Epicardial Adipose Tissue Using Computed Tomography, Kate E. M. Dillon, Marjorie Johnson, Bob Kiaii

Anatomy and Cell Biology Publications

Objective: A variable that necessitates conversion to a conventional full-sternotomy coronary artery bypass procedure from a robotic-assisted endoscopic single-vessel small thoracotomy is the inability to visualize the left anterior descending coronary artery within the surrounding epicardial adipose tissue using the endoscopic camera. The purpose of this study was to determine whether anatomical properties of the epicardial adipose tissue examined using preoperative computed tomography (CT) images are able to predict and thus reduce the need for intraoperative conversion based on effective preoperative exclusion criteria. Methods: Retrospective analysis of patient preoperative CT angiography scans from both converted (n = 17) and successful …

The Effects Of Sex, Energy, And Environmental Conditions On The Movement Ecology Of Migratory Bats, Kristin A. Jonasson

Electronic Thesis and Dissertation Repository

Lack of knowledge about the behaviour of migratory species during the migratory period is a major barrier to conservation efforts. In this thesis I focus primarily on differences between the sexes of the bat Lasionycteris noctivagans, during spring migration. Females are pregnant during spring migration and this overlap between migration and reproduction may affect the time and energy management of females as compared to males. In Chapter 2 I examine spring migration phenology of bats at a stopover site. Females arrived earlier than males, likely to give their pups a long growing season. Fat stores appeared to reflect a …

The Effects Of Acetylenic Tricyclic Bis-(Cyano Enone) On Cell Migration, Eddie Chan

Electronic Thesis and Dissertation Repository

Although cancer survival rates have significantly improved over the past few decades, the improvements are primarily due to early diagnosis and inhibiting cancer growth. Limited progress has been made in the treatment of cancer metastasis, which contributes to 90% of cancer related deaths, and therapeutic agents targeting the various aspects of metastasis are lacking. One potential approach is to utilize small pharmacological compounds to inhibit tumour cell motility, as a strategy against tumour cell migration, invasion, and metastasis. The acetylenic tricyclic bis-(cyano enone), TBE-31, has been shown to be a promising chemopreventative compound. However, its effects on cell migration are …

Communicating Through A Brain-Computer Interface: Towards The Assessment Of Quality Of Life In Minimally Conscious And Covertly Aware Vegetative State Patients, Jasmine Tung

Electronic Thesis and Dissertation Repository

Neuroimaging has been utilized to establish communication, using a brain-computer interface, with select patients with severe brain injuries and profound communication impairments. Due to the severe injuries sustained by these patients, traditional techniques used to develop quality of life instruments cannot be used. The Aware Study used a novel approach to establish the key dimensions for assessing the quality of life of patients who can only communicate using this sophisticated technology. Consensus methodology was employed, with the assistance of a multidisciplinary panel of experts, to collectively decide which dimensions are essential for the inclusion in a quality of life instrument …

Cytosolic Acetyl-Coa Promotes Histone H3 Lysine 27 Acetylation In Arabidopsis, Chen Chen

Electronic Thesis and Dissertation Repository

Acetyl-coenzyme A (acetyl-CoA) serves as a central metabolite in energy metabolism and biosynthesis. High level of acetyl-CoA can fuel the tricarboxylic acid (TCA) cycle to generate energy and store excess energy in fatty acids. Meanwhile, it also provides acetyl groups for protein acetylation, which normally occurs at the lysine or arginine residues. Acetylation regulates protein functions largely due to the change of total charges. Acetylation of histones, for example, can lead to loss of the interaction between histone and DNA, thus relaxing chromatin structure and potentially promoting gene expression. However, whether and how acetyl-CoA regulates plant chromatin remains unexplored. Here, …

Thermal Biology Of Insect Immunity And Host-Microbe Interactions, Laura V. Ferguson

Electronic Thesis and Dissertation Repository

The influence of temperature on interactions with pathogenic or symbiotic microbes is a driving force behind the survival of insects under climate change. However, we know little of how insects physiologically respond to these pressures. In temperate climates, winter dominates the thermal landscape; thus, I am particularly interested in how cold interacts with insect responses to microbes. Here I explore the thermal biology of the insect immune system and the impacts of cold on host-microbe interactions. First, I demonstrate that acute exposure to cold activates selective components of immunity in Drosophila melanogaster, as a compensatory response to trade-offs or …

Quantitative Proteomic Characterization Of Cx-4945, A Clinical Stage Inhibitor Of Protein Kinase Ck2, Adam J. Rabalski

Electronic Thesis and Dissertation Repository

Protein phosphorylation is controlled by protein kinases, and represents a critical signaling mechanism involved in the regulation of fundamental biological processes. Furthermore, the aberrant regulation of kinase activity is implicated in diseases such as cancer and has resulted in efforts to target kinases therapeutically. Protein kinase CK2, although frequently considered constitutively active, has emerged as a clinical target on the basis of its altered expression in different types of human cancers and its regulatory participation in multiple biological processes. In fact, CX-4945, a small molecule ATP-competitive inhibitor of CK2 has advanced to clinical trial and has been widely used to …