Medical Sciences Commons^™

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 …

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 …

Craniodental Anatomy Of A New Late Cretaceous Multituberculate Mammal From Udan Sayr, Mongolia., Amir Subhash Sheth

Electronic Theses and Dissertations

Multituberculates were the longest-lived group of early mammals, with a nearly worldwide distribution, and a temporal range from the Middle Jurassic to the Late Eocene. Multituberculates are typically represented by isolated teeth and jaw fragments; however, several localities in Mongolia revealed abundant, well-preserved multituberculate skulls and partial skeletons from the Late Cretaceous. This study is centered on two specimens of a new multituberculate taxon from a locality in the Gobi desert, Udan Sayr. Included is a (1) bone-by-bone description of the cranial and mandibular elements, as well as the dental features of both specimens, PSS-MAE 141 (holotype) and PSS-MAE 142, …

Effects Of Passive Immobilization On Locomotor Recovery After Spinal Cord Injury In Adult Rats., Kelsey Lee Stipp

Electronic Theses and Dissertations

Background: Spontaneous locomotor recovery in spinal rats has been attributed to animals moving freely in-cage. Environmental enrichment has been shown to increase in-cage movement and functional recovery subsequently. Anxiety has been shown to decrease overnight activity in rats. Methods: Rats were double-housed in medium cages (MC) or single-housed in tiny sized cages (TC). Slotted dividers allowed for partial isolation in TC. Overnight activity was monitored bi-weekly. The open field test and BBB’s were taken weekly. Gait analysis was performed at weeks six and eight. Results: MC showed higher overnight activity and improved gait overtime. No differences were found in BBB …

Bdnf Maintains Adult Taste Innervation And Is Required For Taste Nerve Regeneration After Injury., Lingbin Meng

Electronic Theses and Dissertations

Brain derived neurotropic factor (BDNF) is required for the gustatory neuron survival,target innervation, and taste bud maintenance during development. However, whether BDNF has any function in the adult gustatory system in normal conditions or after nerve injury is unclear. To address these issues, I inducibly removed BDNF in all cells expressing BDNF in adult mice. In the experimental animals, Bdnf expression decreased to 5% of control mice in the lingual epithelium and geniculate ganglion (p< 0.01) at both two weeks and ten weeks after tamoxifen administration. I found no effect on taste bud morphology at four weeks following Bdnf gene deletion. However, ten weeks following Bdnf gene deletion, P2X3-positive and TUJ1-positive gustatory innervation to individual taste buds was reduced by nearly half (each with p < 0.01) and both taste bud volume and taste cell number decreased 30% (each with p< 0.01). These experiments demonstrate that BDNF is required for maintenance of normal levels of taste innervation and normal taste bud morphology in adulthood. In addition, taste cells expressing PLCß2 (phospholipase C ß2), a marker for taste cells that respond to sweet, bitter and umami, did not decrease after Bdnf gene deletion in the adult. Thus, the missing taste cells are of another type. This indicates that taste cell loss is not uniform across the various taste cell types, even if nearly all taste cell types receive the P2X3 and TUJ1 innervation. Since BDNF is required for initial innervation of the taste system and supports taste bud innervation and size in adulthood, it could also be required for nerve reinnervation after injury. To determine if Bdnf is still expressed following nerve section, the chorda tympani nerve (taste nerve) was sectioned and Bdnf level was detected with Real Time RT-PCR. Bdnf continued to be expressed at normal levels from two days to two months post-surgery in both geniculate ganglion and tongue epithelium. Therefore, BDNF could be involved with chorda tympani regeneration. To determine if this was the case, the Bdnf gene was deleted in adult inducible transgenic mice (under the control of a Ubiquitin promoter) two weeks before chorda tympani nerve section. Taste bud number was reduced by half in all genotypes at two weeks post-surgery (p < 0.01). For the remaining taste buds, gustatory innervation was nearly gone with only a little innervation from the trigeminal nerve remaining in the taste bud (p < 0.01). Taste bud volume (p < 0.01) and taste cell number (p< 0.01) were reduced by half for both control and experimental genotypes. Eight weeks post-surgery, taste bud number recovered in mice without Bdnf gene deletion, but did not recover in mice following Bdnf gene deletion (p < 0.01). Gustatory nerve innervation returned in 70% of the taste buds in control mice (p< 0.01). For those reinnervated taste buds, both taste bud volume and taste cell number increased to normal levels. However, in mice lacking the Bdnf gene, gustatory fibers only reinnervated 7.8% of the taste buds (p < 0.01); for most uninnervated taste buds, both taste bud volume and taste cell number remained small. These experiments demonstrate that BDNF is crucial for promoting regeneration of gustatory nerve fibers in adulthood. Following gustatory nerve section, considerable adult plasticity has been observed on the contralateral side including enlarged taste buds with more cells (Guagliardo and Hill, 2007). To determine if this anatomical change was associated with alter Bdnf expression. I examined Bdnf level in the geniculate ganglion and tongue epithelium on the contralateral side following chorda tympani nerve section. Results showed Bdnf expression increased two fold at two weeks post-surgery in geniculate ganglion on the contralateral side (p < 0.05), indicating BDNF may involve with the observed plastic changes. To determine if the increase in taste bud size was associated with increased innervation and/or regulated by BDNF, the Bdnf gene was then deleted in inducible knockout mice before nerve surgery, and taste bud size and amount of innervation were measured on the contralateral side. The results showed taste bud volume, taste cell number and a marker for nerve fibers all increased on the contralateral side in mice without Bdnf gene deletion at eight weeks post-surgery. This indicates that larger taste buds could be supported by increased TUJ1 positive fibers from trigeminal nerve. In addition, in mice lacking Bdnf, taste bud volume, taste cell number and innervation did not increase on the contralateral side after surgery, which indicates that Bdnf may contribute to larger taste buds on the contralateral side following nerve section by supporting increased innervation to the larger taste buds.

Extracellular Ubiquitin: Role In Cardiac Myocyte Apoptosis And Myocardial Remodeling, Christopher Ray Daniels

Electronic Theses and Dissertations

Activation of sympathetic nervous system is a key component of myocardial remodeling that generally occurs following ischemia/reperfusion (I/R) injury and myocardial infarction. It induces cardiac myocyte apoptosis and myocardial fibrosis, leading to myocardial dysfunction. Intracellular ubiquitin (UB) regulates protein turnover by the UB-proteosome pathway. The biological functions of extracellular UB in the heart remain largely unexplored. Previously, our lab has shown that β-adrenergic receptor (β-AR) stimulation increases extracellular UB levels, and extracellular UB inhibits β-AR-stimulated apoptosis in adult rat ventricular myocytes (ARVMs). This study explores the role of extracellular UB in myocyte apoptosis, fibroblast phenotype and function, and myocardial remodeling …

Novel Therapeutic Approaches For Ischemic Heart And Brain Injury: Modulation Of Toll-Like Receptor-Mediated Signaling Pathways And Pi3k/Akt Signaling, Chen Lu

Electronic Theses and Dissertations

Innate immune and inflammatory responses contribute to myocardial and cerebral ischemia/reperfusion (I/R) injury. Toll-like receptors (TLRs) play a critical role in the induction of innate immune and inflammatory responses via activation of nuclear factor kappa B (NF-κB). We have shown that activation of NF-κB contributes to myocardial and cerebral I/R injury. Indeed, inhibition of TLR4-mediated NF-κB activation significantly decreased myocardial and cerebral I/R injury via activation of PI3K/Akt signaling. PI3K/Akt signaling is an important pathway in regulating cellular survival and inflammatory responses. Therefore, an important question is how to differentially modulate PI3K/Akt signaling and TLR/NF-κB-mediated signaling pathway during I/R injury? …

Identification Of A Treatment-Resistant, Ketamine-Sensitive Genetic Line In The Chick Anxiety-Depression Model, Stephen Walter White

Electronic Theses and Dissertations

Approximately 60% of Major Depressive Disorder (MDD) patients do not respond to FDA-approved antidepressants. Introducing effective pharmacotherapies for this treatment-resistant population is hindered by the lack of pre-clinical screening assays that accurately model the clinical features of TRD. The purpose of this research was to screen representatives of different classes FDA-approved antidepressants and one novel antidepressant in two genetic lines of domestic fowl chicks that have previously been identified as stress-vulnerable and stress-resilient in the chick anxiety depression model. Separate groups of socially raised Black Australorp (stress-vulnerable) and Production Red (stress-resilient) chicks were administered the tricyclic antidepressant imipramine (0-20 mg/kg), …

Host And Bacterial Determinants Of Staphylococcus Aureus Nasal Colonization In Humans, Gowrishankar Muthukrishnan

Electronic Theses and Dissertations

Staphylococcus aureus (SA), an opportunistic pathogen colonizing the anterior nares in approximately 30% of the human population, causes severe hospital-associated and community-acquired infections. SA nasal carriage plays a critical role in the pathogenesis of staphylococcal infections and SA eradication from the nares has proven to be effective in reducing endogenous infections. To understand SA nasal colonization and its relation with consequent disease, assessment of nasal carriage dynamics among a diverse population and determining factors responsible for SA nasal carriage have become major imperatives. Here, we report on an extensive longitudinal monitoring of SA nasal carriage in 109 healthy individuals over …

Preparation, Characterization, And Delivery Of Antibodies Binding To A Model Oncogenic Rna, Human Initiator Trna, Jennifer Archer

Electronic Theses and Dissertations

Non-coding RNAs (ncRNAs) account for a higher percent of the genome than coding mRNAs, and are implicated in human disease such as cancer, neurological, cardiac and many others. While the majority of ncRNAs involved in disease were originally attributed to a class of RNAs called micro RNAs (miRNAs) with a small size of only about 19 -24 base pairs, emerging research has now demonstrated a class of long non-coding RNAs (lncRNAs) that have a size of over 200 base pairs to be responsible for gene regulation and other functional roles and have also found to contribute to pathogenesis in humans. …

The Role Of Lim Kinase 1 And Its Substrates In Cell Cycle Progression, Lisa Ritchey

Electronic Theses and Dissertations

LIM Kinase 1 (LIMK1), a modulator of actin and microtubule dynamics, has been shown to be involved in cell cycle progression. In this study we examine the role of LIMK1 in G1 phase and mitosis. We found ectopic expression of LIMK1 resulted in altered expression of p27Kip1, the G1 phase Cyclin D1/Cdk4 inhibitor. Overexpression of LIMK1 resulted in lower levels of p27Kip1 and p27Kip1-pY88 (inactive p27Kip1). Knockdown of LIMK1 resulted in elevated levels of p27Kip1 and p27Kip1-pY88. Together, these results suggest LIMK1 regulates progression of G1 phase through modulation of p27Kip1 expression. LIMK1 is involved in the mitotic process through …

Retention Strategies For Medical Technologists: Addressing The Shortages And Vacancies In The Clinical Laboratory, Kathy S. Small

Electronic Theses and Dissertations

It is important to have well-trained and qualified laboratory professionals. Seventy percent of patient care is based on decisions made from laboratory results, yet there is a growing shortage of medical technologists. Although some baby boomers are delaying retirement, worsening of the shortage crisis is inevitable. Retention of medical technologists has become more important than recruitment. The purpose of this study was to identify and evaluate innovative retention strategies used by clinical laboratory managers throughout the United States.

A significant finding of this study was the lack of qualified medical technologists entering the ranks of laboratory managers. This study identified …

Systemic Leptin Modulates The Expression Of E-Cadherin, Β-Catenin In The Ovary Of Dietary-Induced Obese Infertile Rats, Olufunke A. Sokan

Electronic Theses and Dissertations

One of the numerous complications of obesity is infertility. Leptin has been shown to reverse infertility; however, exact mechanism is poorly understood. Recent evidence indicates Ecadherin/ β-catenin complex, which is a structural constituent of adherens junction, is expressed in the rat ovary during folliculogenesis. We hypothesized that systemic leptin modulates the expression of E-cadherin and β-catenin in dietary-induced obese infertile rats to reverse infertility. Female Sprague-Dawley rats were fed either regular chow diet (RCD) (n=6) or high fat diet (HFD) (n=14). Oestrus cycles were monitored daily until their cycles became irregular. 100 ug/ml of leptin was given intraperitoneally to HFD-fed …

Bioengineering The Expression Of Active Recombinant Human Cathepsin G, Enteropeptidase, Neutrophil Elastase, And C-Reactive Protein In Yeast, Eliot T. Smith

Electronic Theses and Dissertations

The yeasts Pichia pastoris and Kluyveromyces lactis were used to express several recombinant human proteins for further biochemical characterization. Two substitution variants of recombinant human enteropeptidase light chain (rhEPL) were engineered to modify the extended substrate specificity of this serine protease. Both were secreted as active enzymes in excess of 1.7 mg/L in P. pastoris fermentation broth. The substitution variant rhEPL R96Q showed significantly reduced specificities for the preferred substrate sequences DDDDK and DDDDR; however, the rhEPL Y174R variant displayed improved specificities for these substrate sequences relative to all other reported variants of this enzyme. The neutrophil serine proteases human …

Regulating Rsma Expression In Pseudomonas Aeruginosa, Sean D. Stacey

Electronic Theses and Dissertations

Pseudomonas aeruginosa, a Gram-negative bacillus, commonly infects immunocompromised individuals and uses a variety of virulence factors to persist in these hosts. The posttranscriptional regulator, RsmA, plays a role in the expression of many virulence factors in P. aeruginosa. RsmA up regulates virulence factors used in colonizing hosts. However, regulation of rsmA is not well elucidated. Transposon mutagenesis was performed on P. aeruginosa containing a transcriptional rsmA-lacZ fusion to answer this question. Mutants were screened via β-galactosidase assay and transposon insertions identified via arbitrary PCR. A probable MFS transporter, we named mtpX, was one significant transposon mutant identified. …

The Involvement Of Beta-Catenin In The Inflammatory Response Leading To Autoimmune Diabetes Development., Arin Lee Zirnheld

Electronic Theses and Dissertations

We identified and characterized a novel defect in β-catenin expression in bone marrow derived dendritic cells (BMDC) from NOD mice, a model for human Type I diabetes. This protein is expressed at high levels throughout the lifespan of the mouse and correlates with increased pro-inflammatory cytokine production by the BMDC and IFNγ induction by T cells cocultured with the BMDC. These defects, including a similar pattern of pro-inflammatory cytokine production, are also observed in human monocytederived DC from diabetic patients. After exploring several potential mechanisms involved in the accumulation of β-catenin in NOD BMDC, we found that β-catenin is phosphorylated …

A Neurophysiological Examination Of Stress Control In Martial Artists, Jack Pemment

Electronic Theses and Dissertations

The philosophies behind many martial arts often claim that by practicing martial arts individuals can gain better control over stress. We tested this idea by using controlled physical stressors to elicit an acute stress response from martial artists (n=15) and non-martial artists (n=18). To measure the extent of the stress response, we looked at changes in heart rate, respiratory sinus arrhythmia, and galvanic skin level. These three measures explore both parasympathetic and sympathetic responses, and changes in these variables continue to be explored in studies of stress and reactive aggression. In addition to our physical stressors we also exposed individuals …

Il-1Β Amplification Of Nitric Oxide Production And Its Inhibitory Effects On Glucose Induced Early Growth Response-1 Expression In Ins-1 Cells, Ada Young

Electronic Theses and Dissertations

The pathophysiology of cytokines released by infiltrating white blood cells upon pancreatic beta cells is not fully understood. Early growth response gene-1 (Egr-1) expression is specifically and transiently up regulated in pancreatic beta cells in response to glucose. We hypothesized that interleukin-1 beta (IL-1▀) induction of nitric oxide alters glucose induced Egr-1 transcription levels. Egr-1 levels were assessed via western blot, nitric oxide was measured with a Griess Reagent kit and insulin levels via ELISA. Glucose induced both insulin and Egr-1 production in INS-1 cells. IL-1▀ dose dependently increased nitric oxide production over time and significantly attenuated glucose induced Egr-1 …

Effects Of Burn Injury On Biological Ethanol And Ethyl Glucuronide Concentrations, Trista Haupt Wright

Electronic Theses and Dissertations

Alcohol is the most abused drug in the United States and most frequently performed assay in forensic laboratories. Alcohol is routinely present in biological specimens from fatal residential fires and forensic toxicologists must interpret if these individuals are impaired by determination of their blood alcohol concentrations on post-incineration blood collected at autopsy. There is no known data available to confirm or refute blood alcohol concentrations and impairment in fire-related deaths. Ethyl glucuronide (EtG), a non-volatile minor ethanol metabolite, may provide a better biomarker for ethanol consumption prior to burn injury. The literature does not address the possibility that ethanol or …

Prelamin A Influences A Program Of Gene Expression In Regulation Of Cell Cycle Control, Christina N. Bridges

Electronic Theses and Dissertations

The A-type lamins are intermediate filament proteins that constitute a major part of the eukaryotic nuclear lamina—a tough, polymerized, mesh lining of the inner nuclear membrane, providing shape and structural integrity to the nucleus. Lamin A (LA) filaments also permeate the nucleoplasm, providing additional structural support, but also scaffolding numerous tethered molecules to stabilize, organize, and facilitate molecular interactions to accomplish critical functions of cellular metabolism. Over the past 2 decades, much attention has been focused on roles of LA in maintenance of nuclear structural integrity. Only since the late 1990s have scientists discovered the devastating effects of LA gene …

Stem Cell Biology And Strategies For Therapeutic Development In Degenerative Diseases And Cancer, Angel A. Alvarez

Electronic Theses and Dissertations

Stem cell biology is an exciting field that will lead to significant advancements in science and medicine. We hypothesize that inducing the expression of stem cell genes, using the embryonic stem cell gene nanog, will reprogram cells and dedifferentiate human mesenchymal stem cells into pluripotent stem cells capable of neural differentiation. The aims of initial studies are as follows: Aim 1: Demonstrate that forced expression of the embryonic stem cell gene nanog induces changes in human mesenchymal stem cells to an embryonic stem cell-like phenotype. Aim 2: Demonstrate that induced expression of nanog up-regulates the expression of multiple embryonic stem …

Distinct Domains Of Bax Are Involved In Mitochondrial Bioenergetics And Apoptosis, Ge Zhang

Electronic Theses and Dissertations

Apoptosis is essential for cellular homeostasis and is also a pathologic feature of various diseases. The balance between Bcl-2 family proteins determines whether a cell will live or die. Bax, a member of the BCL-2 family proteins, is a pro-apoptotic protein that exists in both a soluble, cytoplasmic form and a membrane-bound form. Upon apoptotic stimuli, Bax undergoes a conformational change and translocates to the mitochondria, initiating apoptotic events. However, little is known about whether Bax is involved in the regulation of mitochondrial function under non-apoptotic conditions, and how Bax binds to mitochondria to exert its activity. Here, we investigate …

Avian Cerebellum Specialization In Relation To Acrobatic Courtship Displays In Manakins (Pipridae), Steven Ray Wilkening

Electronic Theses and Dissertations

The courtship displays of male manakins (Pipridae) involve an array of acrobatic and postural elements. Previously it was found that species with elaborate displays exhibit specializations in motor planning and coordination areas of the brain. Several studies have suggested a relationship between cerebellum (Cb) morphology and distinct motor-related functions for the anterior Cb (somatosensory, flying, hopping/walking), posterior Cb (vision, audition, flying, hopping/walking), and vestibular Cb (flying, hopping/walking, vestibular). The anterior, posterior and vestibular Cb as well as basic morphological features of the Cb were measured and tested for a relationship with courtship display complexity in manakins. I compared Cb morphology …

Role Of Membrane Lipids In Modulating Protein Structure & Function, Ray Supriyo

Electronic Theses and Dissertations

A-B family of toxins consists of plant toxins such as ricin and bacterial toxins such as cholera. The A subunit is the enzymatic domain and the B subunit is the receptor binding domain. Commonly, these toxins bind to the target cell plasma membrane receptors through their B subunit followed by endocytosis and a transport to the endoplasmic reticulum (ER). Inside the ER, the A subunit dissociates from the rest of the toxin, unfolds and triggers the ER quality control mechanism of ER-associated degradation (ERAD). Most ERAD substrates are purged out of the ER into the cytosol for proteasomal degradation. However, …

Hybrid Adult Neuron Culture Systems For Use In Pharmacological Testing, Darin Keay Edwards

Electronic Theses and Dissertations

Neuronal culture systems have many applications, such as basic research into neuronal structure, function, and connectivity as well as research into diseases, conditions, and injuries affecting the brain and its components. In vitro dissociated neuronal systems have typically been derived from embryonic brain tissue, most commonly from the hippocampus of E18 rats. This practice has been motivated by difficulties in supporting regeneration, functional recovery and long-term survival of adult neurons in vitro. The overall focus of this dissertation research was to develop a dissociated neuronal culture system from human and animal adult brain tissue, one more functionally and developmentally correlative …

Discovery And Optimization Of Novel Small-Molecular Inhibitors Suppressing Stat3-Dependent Tumor Process, Xiaolei Zhang

Electronic Theses and Dissertations

With the critical role of aberrantly active Signal Transducer and Activator of Transcription (Stat) 3 protein in many human cancers, selective small-molecule inhibitors targeting the dimerization event which is required for stat3 activation, would be valuable as therapeutic agents. And the inhibitors will be useful chemical probes to clarify the complex biological functions of Stat3. By computational and structural analyses of the interaction between Stat3 and the lead dimerization disruptor, S3I-201, we have designed a diverse set of analogs. One of the most active analogs, S3I-201.1066 is derived to contain a cyclo-hexyl benzyl moiety on the amide nitrogen, which increases …

Genetic And Physiological Contribution Of Adrenergic Cells In Heart Development, Kingsley Osuala

Electronic Theses and Dissertations

The adrenergic hormones norepinephrine (NE) and epinephrine (EPI) are essential for cardiovascular development as embryos lacking NE/EPI begin to die abruptly between embryonic days 10.5 and 11.5 due to apparent cardiac failure. The objective of this research aims to elucidate the mechanism of the embryonic fatality observed in the NE/EPI deficient mouse model. Here we utilized the dopamine β- hydroxylase knockout (Dbh-/-) mouse model, which lacks the gene and subsequent enzyme necessary for the conversion of dopamine to norepinephrine. Embryonic mouse hearts were extracted from Dbh+/+ (control) and Dbh-/- (experimental model) mice for mRNA transcript expression profiling. These studies were …

Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass

Electronic Theses and Dissertations

Transplanted embryonic stem (ES) cells following myocardial infarction (MI) contribute to limited cardiac repair and regeneration with improved function. Therefore novel strategies are still needed to enhance the efficacy by which ES cells differentiate into cardiac cell types and inhibit adverse remodeling in the infarcted myocardium. Our studies evaluate whether genetic manipulation of transplanted ES cells employing miR- 1, a pro-cardiac microRNA, and TIMP-1, an anti-apoptotic and anti-fibrotic protein, will enhance cardiac myocyte differentiation, inhibit native cardiac apoptosis, and reduce fibrosis in the infarcted myocardium. Furthermore, we assess levels of associated pro- (caspase-3, PTEN) and anti-(Akt) apoptotic proteins as well …

Translocation Of The Cholera Toxin A1 Subunit From The Endoplasmic Reticulum To The Cytosol, Michael Prentice Taylor

Electronic Theses and Dissertations

AB-type protein toxins such as cholera toxin (CT) consist of a catalytic A subunit and a cell-binding B subunit. CT proceeds through the secretory pathway in reverse, termed retrograde trafficking, and is delivered to the endoplasmic reticulum (ER). In order for the catalytic A1 subunit to become active it must separate from the rest of the holotoxin, and this dissociation event occurs in the ER lumen. CTA1 assumes an unfolded conformation upon dissociation from the holotoxin and is recognized by ERassociated degradation (ERAD), a quality control system that recognizes and exports misfolded proteins to the cytosol for degradation by the …

Glial Differentiation Of Human Umbilical Stem Cells In 2d And 3d Environments, Hedvika Davis

Electronic Theses and Dissertations

During differentiation stem cells are exposed to a range of microenvironmental chemical and physical cues. In this study, human multipotent progenitor cells (hMLPCs) were differentiated from umbilical cord into oligodendrocytes and astrocytes. Chemical cues were represented by a novel defined differentiation medium containing the neurotransmitter norepinephrine (NE). In traditional 2 dimensional (2D) conditions, the hMLPCs differentiated into oligodendrocyte precursors, but did not progress further. However, in a constructed 3 dimensional (3D) environment, the hMLPCs differentiated into committed oligodendrocytes that expressed MBP. When co-cultured with rat embryonic hippocampal neurons (EHNs), hMLPCs developed in astrocytes or oligodendrocytes, based on presence of growth …