Medicine and Health Sciences Commons^™

Metabolic Correlates In Spinal Cord Compression Measured By Magnetic Resonance Spectroscopy In The Motor And Sensory Cortices, Sandy Goncalves

Electronic Thesis and Dissertation Repository

Surgical outcome for patients suffering from cervical myelopathy (CM) is unpredictable with varying motor and sensory symptom recovery. Previous in-vivo magnetic resonance spectroscopy (MRS) studies of patients surgically treated for CM have demonstrated decreased N-acetylaspartate (NAA)/creatine levels in the motor cortex indicating reduced neuronal function. The goal of this thesis was to determine whether absolute NAA changes in the motor and sensory cortices mirror the pattern of motor and sensory functional change observed in patients post surgical treatment.

MRS data were acquired on a 3.0 Tesla Siemens MRI along with clinical outcome measures at baseline, 6-weeks and 6-months post-surgery. …

Marine Population Connectivity: Range Boundaries And Climate Change, Rhiannon Leigh Rognstad

Theses and Dissertations

Population connectivity, particularly in open systems, is an important metric for understanding population-level processes on both ecological and evolutionary timescales. In coastal marine systems, adults are typically sedentary and dispersal occurs primarily during a larval stage when individuals are transported in ocean currents. Because coastal marine populations exist as networks of interconnected subpopulations, variation in the magnitude and extent of population connectivity can have profound effects on population dynamics and species distribution limits. Connectivity is a complex process, affected by a multitude of factors, including adult inputs and physical dispersal, which operate at multiple scales and may interact. This dissertation …

Mcp-1 In Colorectal Cancer: Benefits Of Exercise, Jamie Lee Mcclellan

Theses and Dissertations

The etiology of colon cancer is a complex phenomenon that involves both genetic and environmental factors. However, only about 20% have a familial basis with the largest fraction being attributed to environmental causes that can lead to chronic inflammation. Tumors associated macrophages drive the pro-inflammatory response in the tumor micro-environment and are associated with poor prognosis in certain cancers. Monocyte chemoattractant protein 1 (MCP-1) is thought to be the most important chemokine for recruitment of macrophages to the tumor microenvironment. In chapter 1, we examined the timing and magnitude of the intestinal inflammatory cytokine response in relation to tumorigenesis in …

Mouse Models Of Intervertebral Disc Development, Degeneration And Mechanical Loading, Matthew R. Mccann

Electronic Thesis and Dissertation Repository

Intervertebral disc (IVD) degeneration is a complex and multi-factorial process that is influenced by aging, genetic predispositions and environmental influences, such as altered mechanical loading. While recent studies have begun to characterize changes in the IVD associated with degeneration, the underlying etiology remains elusive. It is thought that the loss of notochord cells from the nucleus pulposus (NP) is one initiating factor contributing to the cascade of disc degeneration. However, questions remain about the function of notochord cells within the disc, including their capacity as tissue specific progenitor cells for the nucleus pulposus. We have demonstrated, with the use of …

Modulation Of The Cardiomyocyte Hypertrophic Responses To Endothelin-1 By Adipocytes, Suresh Chandra Bairwa

Electronic Thesis and Dissertation Repository

Leptin and adiponectin are the adipokines that are shown to exert pro-hypertrophic and anti-hypertrophic effects respectively, in cardiomyocytes. We sought to determine the direct interaction between the adipocytes and cardiomyocytes during endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy and determine the role of leptin and adiponectin.

The adipose tissue conditioned medium (ACM) inhibited the ET-1-induced hypertrophy in a concentration-dependent manner and this anti-hypertrophic effect was more potent or reversed in the presence of leptin receptor antagonist (LRA; 0.1 nM) or adiponectin receptor-1 antibody (ARA; 100 ng/mL), respectively. ACM from heart failure rats induced by coronary artery ligation or obese rats did not mitigate …

A Critical Analysis Of Infant Mortality In Kalamazoo County, Audrey Jensen

Honors Theses

The following is a review of the state of infant and fetal health in Kalamazoo County in the 21st century. Since infant health is a marker for the effectiveness of health care, this review will analyze the leading causes of infant mortality in Kalamazoo County. Statistical indicators show that Kalamazoo County falls below both state and national IMR averages. The leading causes of infant mortality in Kalamazoo are considered preventable infant deaths. Therefore, this review will make recommendations for the reduction of IMR through the improvement of preventative prenatal healthcare practices.

The Relationship Of Plantar Sensation With Standing Balance And Gait Post-Stroke, Stephen Parsons

Electronic Thesis and Dissertation Repository

Gait and balance dysfunction after stroke limit independence and quality of life. Numerous contributing factors have been investigated but the role of sensation deficits has received little attention. This thesis investigated the relationship between plantar cutaneous sensation and 1) standing balance, 2) gait, and 3) use of vision to compensate for sensory loss with a secondary analysis of data from individuals with subacute stroke. Associations between standing balance, gait and sensation were investigated with Spearman correlations. Individuals classified as impaired or intact sensation were compared on gait and standing balance measures. This thesis found plantar sensation is related to standing …

Effect Of Dual Tasking On Walking Over Even And Uneven Surfaces In Functionally Independent Community Older Adults, Olajide L. Kolawole

Seton Hall University Dissertations and Theses (ETDs)

While several studies have reported a decrement in performance by older adults while walking and concurrently performing a dual task on even surfaces, to date the effects of dual tasking while walking on uneven surfaces commonly found in the community has received less attention. Thus, we sought to test the hypothesis that an incremental decrement in gait parameters will be observed, when walking on an uneven versus an even surface and furthermore, that this decrement would be dependent upon the concurrent performance of a secondary cognitive and/or motor task in functionally independent-living-community older adults.

Dynamic Gait Index assessed the subject’s …

Regulation Of Crfr1 And 5-Ht2ar By Pdz Domain-Containing Proteins Sap97 And Psd-95, Henry A. Dunn

Electronic Thesis and Dissertation Repository

Previous studies identified a crosstalk mechanism whereby CRFR1 sensitized 5-HT_2AR-mediated signaling via interactions with PDZ domain-containing proteins: a mechanism that may underlie stress-induced anxiety and depression. This prompted an investigation into uncovering which PDZ domain-containing proteins could regulate the crosstalk between these two receptors, and how they could be regulated individually. In the current studies, a subset of PDZ domain-containing proteins were identified that may interact with CRFR1 and 5-HT_2AR. The focus narrowed to two candidates previously implicated in psychiatric disease: SAP97 and PSD-95. We confirmed SAP97 and PSD-95 as interacting partners of CRFR1 in adult …

Longitudinal Quantitative Analysis Of Gait And Balance In Friedreich's Ataxia, Jeannie B. Stephenson

USF Tampa Graduate Theses and Dissertations

Friedreich's Ataxia (FA) is an autosomal-recessive, neurodegenerative disease characterized by progressive lower extremity muscle weakness and sensory loss, balance deficits, limb and gait ataxia, and dysarthria. FA is considered a sensory ataxia because the dorsal root ganglia and spinal cord dorsal columns are involved early in the disease, whereas the cerebellum is affected later. Balance deficits and gait ataxia are often evaluated clinically and in research using clinical rating scales. Recently, quantitative tools such as the Biodex Balance System SD and the GAITRite Walkway System have become available to objectively assess balance and gait, respectively. However, there are limited studies …

Synthesis And Characterization Of Methacrylated Hyaluronan-Based Hydrogels For Tissue Engineering, Keegan Bradley Compton

Theses and Dissertations (ETD)

Polymers have revolutionized the field of tissue engineering due to the countless possibilities of scaffolds that can be constructed from such a material. Through conjugation of other functional groups onto a polymer backbone, the mechanical properties of polymers can be controlled and has the ability to span a wide range of strengths, allowing for application in multiple tissue environments. One such polymer, hyaluronic acid (HA), is a natural polysaccharide found most abundantly in the extracellular matrix (ECM) of connective tissues with structural, lubricating, and wound healing functions in the human body; for this reason, HA has great potential for utilization …

Mapping The Spatial And Temporal Dynamics Of Sensorimotor Integration During The Perception And Performance Of Wallowing, Megan E. Cuellar

Theses and Dissertations (ETD)

Similar to other complex sequences of muscle activity, swallowing relies heavily upon ‘sensorimotor integration.’ It is well known that the premotor cortex and primary sensorimotor cortices provide critical sensorimotor contributions that help control the strength and timing of swallowing muscle effectors. However, the temporal dynamics of sensorimotor integration remains unclear, even when performed normally without neurological compromise. Recent advances in EEG analysis blind source separation techniques via independent component analysis offer a novel and exciting opportunity to measure cortical sensorimotor activity in realtime during swallowing, concurrently with muscle activity during swallow initiation. In the current study, mu components were identified, …

Downregulation Of Prdm16 Is Critical For Hoxb4-Mediated Benign Hsc Expansion In Vivo, Hui Yu

Theses and Dissertations (ETD)

Overexpression of HOXB4 in hematopoietic stem cells (HSCs) leads to increased self-renewal without causing hematopoietic malignancies in transplanted mice. The molecular basis of HOXB4-mediated benign HSC expansion in vivo is not well understood. To gain further insight into the molecular events underlying HOXB4-mediated HSC expansion, we analyzed gene expression changes at multiple time points in Lin-Sca1+c-kit+ (LSK) cells from mice transplanted with bone marrow (BM) cells transduced with a MSCV-HOXB4-ires-YFP vector. A distinct HOXB4 transcriptional program was reproducibly induced and stabilized by 12 weeks after transplant. Dynamic expression changes were observed in genes critical for HSC self- renewal as well …

Effect Of Nedd4 Haploinsufficiency On Insulin Sensitivity, Adiposity And Neuronal Behaviors, Jingjing Li

Theses and Dissertations (ETD)

The neural precursor cell expressed developmentally down-regulated gene 4 (NEDD4) is a HECT-type E3 ubiquitin ligase that has received broad attention in recent years. Many of its reported substrates are active players in metabolism, implying a potential role of NEDD4 itself in metabolic regulation. Since homozygous Nedd4 deletion leads to embryonic or perinatal lethality, we investigated the function of NEDD4 in metabolic regulation in vivo, using Nedd4- haploinsufficient mice in a high fat diet-induced obesity (HFDIO) model.

Our studies show that Nedd4-haploinsufficient mice fed a normal diet (ND) exhibited decreased body weight in both genders and proportionally reduced tissue mass …

Novel Insights Into The Role Of The Smoothened Cysteine Rich Domain In Hedgehog Signalling, Rajashree Rana

Theses and Dissertations (ETD)

The Hedgehog (Hh) signal transduction pathway functions as one of the key developmental pathways and deranged Hh signalling is associated with numerous cancer and tumor conditions. The Smoothened (Smo) G protein coupled receptor (GPCR) functions as the signal transducer of the Hh pathway and is the most attractive drug target of the pathway. The structure of the Smo receptor includes seven membrane spanning domains, extracellular and intracellular loops connecting the membranous domains and the extracellular cysteine rich domain (CRD). The extracellular CRD of the Smo receptor is homologous to the Frizzled (FzD) CRD. The FzD CRD interacts with the physiological …

Effects Of Fatty Acid Structure On Endothelial Cell Expression Of Connexin43, Albert E. Sowers Iii

Masters Theses

The epidemic of obesity-related metabolic and cardiovascular diseases is linked to elevated fatty acids (FA). Epidemiological data argue that trans FA contribute to the development and progression of these disease processes. Previous work suggests the similarity in structure between saturated and trans FA may stimulate inflammation through trans FA interactions with toll-like receptor 4 (TLR4). To evaluate the impact of trans FA on cardiovascular health, the response of endothelial cells to trans FA was evaluated. Specifically, responses to the 18-carbon trans FA elaidic acid (EA) were compared to the same length cis FA oleic acid (OA). Endothelial cells were exposed …

The Nutrient Intake Of Homeless Women Of Grand Rapids, Michigan, Emily D. Popma-Metsaars

Masters Theses

Background Homeless individuals comprise about 1% of the American population with 1/3 of this particular population being women. And despite the potential for hunger, the homeless population has a similar prevalence of overweight/obese as other Americans. The Heartside neighborhood of Grand Rapids is a very low-income area of the city, inhabited by the poor and homeless. The Food Access in Michigan Project is studying the relationship between food insecurity and food environments in Michigan.

Objectives The purpose of this study was to determine the characteristics of the diet of homeless women in Heartside. This study examined the level of food …

Arsenic Targets Neural Plate Border Specifier Cells In P19 Cells, Christopher Mccoy

All Theses

Epidemiological studies have shown that arsenic exposure during early embryogenesis can cause reduced weight gain and neurological deficits later on in life. In addition, in vitro and in vivo studies have indicated that arsenic suppresses neurogenesis and myogenesis. The exact mechanism of how arsenic causes these undesired developmental outcomes is poorly understood, however both skeletal muscle and sensory neuron development require the Wnt/β-catenin signaling pathway to initiate the specific differentiation of precursor cells. We were interested in determining the target cell population of arsenic and its metabolites. Arsenic's metabolites were of interest because they have been shown to be more …

Nprl2/Tusc4 Functions As A Tumor Suppressor By Regulating Brca1’S Stability Via The E3 Ubiquitination Pathway, Yang Peng

Dissertations & Theses (Open Access)

Expression of the tumor suppressor protein BRCA1 is frequently lost in breast cancer patients, and the loss of its expression is associated with disruption of various critical functions in cells and cancer development. In the present study, we demonstrate through microarray analysis that cells with tumor suppressor candidate 4 (NPRL2/TUSC4) knockdown show critical changes to cell cycle, cell death pathways and a global impact on cancer development. More importantly, we observed a clear cluster pattern of NPRL2/TUSC4-knockdown gene profiles with established homologous recombination (HR) repair defect signature. Additionally, NPRL2/TUSC4 protein physically interacts with the E3 ligase HERC2 and prevents ubiquitin …

The Role Of Mcl-1 In The Heart: Gateway From Life To Death, Xi Wang

Theses and Dissertations (ETD)

MCL-1 is an essential BCL-2 family member that promotes the survival of multiple cellular lineages, but its role in cardiac muscle has remained unclear. Here, we have demonstrated that cardiac-specific ablation of Mcl-1 results in a rapidly fatal, dilated cardiomyopathy preceded by loss of myofibrils and cardiac contractility, abnormal mitochondria ultrastructure, defective mitochondrial respiration, and impaired autophagy. Genetic ablation of both pro-apoptotic effectors (Bax and Bak) could largely rescue the lethality and impaired cardiac function induced by Mcl-1 deletion. However, Mcl-1-, Bax-, and Bak-deficient hearts still revealed mitochondrial ultrastructural abnormalities and displayed deficient mitochondrial respiration, and are hypersensitive to chronic …

Measuring The Role Of Inhibition In Auditory Discrimination In Mice, Tazima Nur

Graduate Theses and Dissertations

Understanding how inhibitory neurons affect sensory information processing in the cerebral cortex is an ongoing goal of both neuroscience and statistical physics research. In this master's thesis research project, an experimental system has been designed and built for studying how auditory dynamic range depends on inhibitory neurons, based on observations of mouse behavior. In this thesis, firstly, the topic of inhibition and information processing has been introduced. Then two papers related to inhibition and dynamic range has been reviewed in detail. One of the papers is an experimental work that analyzes the affect of inhibition on dynamic range. The other …

Mrp4-Dependent Regulation Of Fibroblast Migration, Chandrima Sinha

Theses and Dissertations (ETD)

Roles of cyclic nucleotides and cyclic nucleotide-dependent signaling molecules in regulating several signaling pathways including cell migration have long been known. However, the new and revolutionary concept is that it is not just the absence or presence of cyclic nucleotides, but a highly coordinated balance between these molecules regulates cell migration. Multi-drug resistance protein 4 (MRP4), is a member of the large family of ATP binding cassette (ABC) transporter proteins, that localizes to the plasma membrane and functions as a nucleotide efflux transporter and thus plays a pivotal role in the regulation of intracellular cyclic nucleotide dynamics. In our study …

Autoimmune Susceptibility Imposed By Public Tcrβ Chains, Yunqian Zhao

Theses and Dissertations (ETD)

The major histocompatibility complex (MHC) is the strongest genetic risk factor for autoimmunity. It acts together with a corresponding TCR repertoire, yet, considering the extent of the repertoire's diversity, how this imposes disease susceptibility on a population is not well understood. We address the hypothesis that shared or public TCR, those present in most individuals, modulate autoimmune risk. High resolution analyses of autoimmune encephalomyelitis-associated T-cell receptor β chain (TCRβ) showed preferential utilization of public TCR sequences, implicating them in pathogenesis. Disease-associated public TCRβ, when transgenically expressed in association with endogenously rearranged T-cell receptor α chain (TCRα), could further endow unprimed …

Genetic And Chemical Dissection Of Bloodbrain Barrier Development In Zebrafish, Robyn Anne Umans

Theses and Dissertations (ETD)

The blood-brain barrier (BBB) maintains a homeostatic environment as well as prohibits the entrance of xenobiotics into the brain. Because of these qualities, drug delivery is a fundamental challenge for the treatment of many diseases of the central nervous system (CNS). Along with limiting the access of therapeutics into the brain, the BBB is also impaired in CNS pathologies. Understanding the molecular cues that are essential for healthy BBB development and integrity may reveal targets for drug delivery leading to decreased progression or possible treatment of many detrimental CNS diseases. While the central features of the BBB have been accepted, …

Strengths And Weaknesses Of Hybrid Tpr Technology For Obtaining Structural And Mechanistic Insights Into Tpr Proteins, Shanshan Yu

Theses and Dissertations (ETD)

Tetratricopeptide (TPR) repeats are a 34-residue helix-turn-helix motif that when repeated pack into a superhelical structure. TPR domains are frequently found mediating protein-protein interactions, often through a central groove. One protein complex bearing numerous TPR repeats is the Anaphase Promoting Complex (APC). The anaphase-promoting complex (APC) is a multi-subunit complex, which orchestrates mitotic cell cycles. APC is an E3 ligase in the ubiquitin cascade, and directs the 26S proteosome degradation of cell-cycle regulators. Throughout mitotic progression, proteins that are key regulators of the cell cycle are assembled with polyubiquitin chains by APC.

One domain of the human APC is comprised …

Screening For Novel Inhibitors Of Αlpha-Ynuclein Seeded Nucleation-Dependent Aggregation And Toxicity As A Potential Therapeutic Strategy For Parkinson’S Disease, Mustafa Taleb Ardeh

Dissertations

α-Synuclein aggregation is the key pathogenic event in several important neurological disorders including Parkinson’s Disease, dementia with Lewy bodies and multiple system atrophy, giving rise to a distinct group of neurodegenerative diseases known as synucleinopathies. Although the molecular basis of α-syn toxicity has not been precisely elucidated, recent studies indicate that α-syn toxicity is mediated by a nucleation-dependent aggregation process. To elucidate the structural basis of α-synuclein mediated toxicity, we developed various methods to prepare different α-synuclein species of a defined size and morphology distribution, and we investigated their toxicity in different human dopaminergic cell lines. We observed that crude …

Modulation Of T Lymphocytes By Tumor-Released Survivin, Jessica Marie Jutzy

Loma Linda University Electronic Theses, Dissertations & Projects

The tumor microenvironment is an area of intense interaction between normal and malignant cells. Factors and cell types within this environment can play a crucial role in the progression or regression of the tumor. Of primary interest are tumor-infiltrating T lymphocytes, which have been shown to have a key role in modifying the dynamics of the tumor microenvironment to promote or prevent tumor growth. While there is much in vitro and in vivo evidence for a modification of the tumor infiltrating T cell population toward a pro-tumor environment, what induces these changes within the tumor microenvironment has remained elusive. Our …

The Effect Of Spinal Cord Injury On Vagal Afferents., April N. Herrity

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a significant public health concern that leaves patients with a multitude of life-long disabilities. Major complications of SCI apart from paralysis, include deficits in bladder and bowel function. Lower urinary tract dysfunction continues to remain a top priority issue affecting quality of life for this population. The majority of visceral organs receive a dual sensory innervation from both spinal nerves as well as the vagus nerve. Following SCI, the vagus nerve is a potential pathway through which information from regions below the level of a spinal injury can travel directly to the brainstem, bypassing the …

Development Of Models For The Study Of The Molecular Mechanisms Of Host Restriction And Adaptation Of Hantaviruses., Ryan Carroll Mcallister 1988-

Electronic Theses and Dissertations

Hantaviruses, family Bunyaviridae, are present throughout the globe in a variety of mouse, rat, mole, vole, shrew, or bat species. Hantaviruses persist for the lifetime of the animal reservoir, while causing no signs or symptoms of disease. Only the rodent-borne hantaviruses cause disease in humans. In contrast, a “spillover” infection of a hantavirus into a nonreservoir rodent species results in an asymptomatic acute infection. We and others in the field are interested in understanding the biology of these virus-host interactions and mechanisms that underlie these three very different outcomes. The second chapter of my thesis focused on probing the intrahost …

Ahr-Related Activities In A Creosote-Adapted Population Of Adult Atlantic Killifish, Fundulus Heteroclitus, Two Decades Post-Epa Superfund Status, Josephine Wojdylo

All Dissertations

Atlantic killifish, Fundulus heteroclitus, have adapted to, or at least developed a level of resistance to creosote-based polycyclic aromatic hydrocarbons (PAHs) found at the Atlantic Wood (AW) superfund site in the southern branch of the Elizabeth River, VA USA. Historically, 90+% of the mummichogs at this site have hepatic lesions of varying severity, and 30+% of these fish have tumors of various origin. Many xenobiotics, including select PAHs found at the Atlantic Wood site, are ligands for the aryl hydrocarbon receptor (AhR), which is a promiscuous ligand-dependent transcription factor involved in developmental regulation, environmental sensing, and induction of a suite …