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Theses and Dissertations

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Articles 151 - 180 of 224

Full-Text Articles in Cell and Developmental Biology

Targeting Of Receptors For Advanced Glycation End-Products (Rage) Diminishes Acute Secondhand Smoke-Induced Inflammation In Mice, Tyler Thomas Wood Jul 2014

Targeting Of Receptors For Advanced Glycation End-Products (Rage) Diminishes Acute Secondhand Smoke-Induced Inflammation In Mice, Tyler Thomas Wood

Theses and Dissertations

The receptor for advanced glycation end-products (RAGE) has increasingly been demonstrated to be an important modulator of inflammation in cases of pulmonary disease. Published reports involving tobacco smoke exposure have demonstrated increased expression of RAGE, its participation in pro-inflammatory signaling and its role in irreversible pulmonary remodeling. The current research evaluated for the first time the in vivo effects of short-term tobacco smoke exposure in RAGE null and control mice compared to identical animals exposed to room air only. Quantitative real time PCR, immunoblotting, and immunohistochemistry revealed elevated RAGE expression in controls after four weeks of exposure and an anticipated …

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Expression Of Osteoarthritis Biomarkers In Temporomandibular Joints Of Mice With And Without Receptor For Advanced Glycation End Products (Rage), Elizabeth Murayama Chavez Matias Jun 2014

Expression Of Osteoarthritis Biomarkers In Temporomandibular Joints Of Mice With And Without Receptor For Advanced Glycation End Products (Rage), Elizabeth Murayama Chavez Matias

Theses and Dissertations

This thesis will be organized into three chapters discussing the mechanism underlying the onset and progression of osteoarthritis (OA) in the temporomandibular joint (TMJ). Understanding the mechanism of OA development in the TMJ helps in understanding how OA progresses and how to treat this disease. The goal of this investigation is to examine the process of cartilage degeneration and OA biomarker expression in the TMJ to understand their role in TMJ OA onset and development.Chapter one covers mechanisms that are altered in TMJ OA during disease progression. Using animal models with different stressors such as mechanical disturbances, direct injury, and …

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Rapid Adaptation Of Dopamine D2 Receptor Responses In The Brain And Blood Following Acute Ethanol, Ryan J. Folsom Jun 2014

Rapid Adaptation Of Dopamine D2 Receptor Responses In The Brain And Blood Following Acute Ethanol, Ryan J. Folsom

Theses and Dissertations

Dopamine (DA) D2 receptor expression parallels DA levels in the brain and these autoreceptors have been shown to be modulated by long-term ethanol exposure. We have previously demonstrated that ventral tegmental area (VTA) GABA neurons also express D2 autoreceptors (D2R), and that DA and D2R agonists markedly enhance the excitability of VTA GABA neurons, opposite to their well-known auto-receptor inhibition of DA neurons. Most importantly, D2R antagonists block ethanol inhibition of VTA GABA neurons and D2R expression in VTA GABA neurons down-regulates with chronic ethanol, as others have shown for whole VTA D2R expression. The aim of this study was …

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Examination Of Anabolic Signaling And Muscle Growth With Caffeine Treatment In Overloaded Hindlimb Muscle And Electrically Stimulated Muscle Lacking Liver Kinase B1, Timothy Michael Moore Jun 2014

Examination Of Anabolic Signaling And Muscle Growth With Caffeine Treatment In Overloaded Hindlimb Muscle And Electrically Stimulated Muscle Lacking Liver Kinase B1, Timothy Michael Moore

Theses and Dissertations

Skeletal muscle has the ability to increase in size (hypertrophy) after resistance is placed upon it. This hypertrophy is marked by significant upregulation of the mammalian target of rapamycin (mTOR) and its downstream targets. The upstream kinases, protein kinase B (also known as Akt) and AMP-activated protein kinase (AMPK), are two of the many regulators of the mTOR pathway. Recent studies suggest that the widely consumed neuroactive compound caffeine could potentially inhibit mTOR by acting through Akt and/or AMPK. The purpose of this thesis was to: 1) determine if caffeine can inhibit the mTOR pathway and ultimately attenuate skeletal muscle …

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Localization And Functional Analysis Of Dictyostelium Discoideum Gtpases, Rabs And Rab2, Katherine V. Maringer May 2014

Localization And Functional Analysis Of Dictyostelium Discoideum Gtpases, Rabs And Rab2, Katherine V. Maringer

Theses and Dissertations

Dictyostelium discoideum is a simple eukaryotic amoeba that has proven useful in studying various aspects of endosomal and lysosomal membrane trafficking, as well as development. The Rab family of small molecular weight GTPases has been implemented in several cellular processes to include various vesicle trafficking roles, cell-cell signaling, and development. This study focuses on the localization and function of two Dictyostelium GTPases, RabS, and Rab2 which we hypothesized to both localize to the Golgi, and the contractile vacuole system. Expression of GFP-tagged DdRab2, and DdRabS proteins revealed similar localization to ER-Golgi membranes as well as the contractile vacuole system. Microscopic …

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Characterization Of Secondhand Smoke (Shs) And Materno-Fetal Interactions In Receptors For Advanced Glycation End-Products (Rage)-Targeted Mice, Duane Ray Winden May 2014

Characterization Of Secondhand Smoke (Shs) And Materno-Fetal Interactions In Receptors For Advanced Glycation End-Products (Rage)-Targeted Mice, Duane Ray Winden

Theses and Dissertations

Receptors for advanced glycation end-products (RAGE) are pattern recognition receptors of the immunoglobulin superfamily highly expressed in the lung. Likely functions include the modulation of pulmonary inflammation during disease. However, the contributions of RAGE in the developing lung in cases where secondhand smoke (SHS) exposure occurs are unknown. In order to test the hypothesis that RAGE misexpression adversely affects lung morphogenesis, we exposed gestating dams to a controlled dose of SHS during the last four critical days of in utero lung morphogenesis. We discovered that both maternal and fetal lungs respond to SHS by up-regulating RAGE. Exposed fetuses were markedly …

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Synaptic Plasticity In Gabaergic Inhibition Of Vta Neurons, Jennifer Kei Mabey May 2014

Synaptic Plasticity In Gabaergic Inhibition Of Vta Neurons, Jennifer Kei Mabey

Theses and Dissertations

Past research has demonstrated that the motivational effects of opiates causes a change in ventral tegmental area (VTA) γ-amino butyric acid (GABA) subtype A receptor [GABA(A)R] complexes in opiate-dependent animals, which switch from a GABA-induced hyperpolarization of VTA GABA neurons to a GABA-induced depolarization. Previously shown in naïve animals, superfusion of ethanol (IC50 = 30 mM) and the GABA(A)R agonist muscimol (IC50 = 100 nM) decreased VTA GABA neuron firing rate in a dose-dependent manner. The aim of this study was to evaluate VTA GABA neuron excitability, GABA synaptic transmission to VTA GABA neurons, and a potential switch in GABA(A)R …

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Role Of Α6 Nachrs In Ethanol Modulation Of Vta Neurons, Samuel Injae Shin Mar 2014

Role Of Α6 Nachrs In Ethanol Modulation Of Vta Neurons, Samuel Injae Shin

Theses and Dissertations

The prevailing view is that enhancement of dopamine (DA) transmission in the mesolimbic system leads to the rewarding properties of alcohol and nicotine (NIC). The mesolimbic DA system consists of DA neurons in the midbrain ventral tegmental area (VTA) that innervate the nucleus accumbens (NAc). DA neurotransmission is regulated by inhibitory VTA GABA neurons, whose excitability is a net effect of glutamate (GLU) and GABA neurotransmission that are modulated by NIC cholinergic receptors (nAChRs) on afferent terminals. We have previously demonstrated that VTA GABA neurons are excited by low-dose ethanol but are inhibited by moderate to high-dose ethanol, and they …

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Different Expression Of Placental Pyruvate Kinase M2 In Normal, Preeclamptic, And Intrauterine Growth Restriction Pregnancies, Brigham L. Bahr Mar 2014

Different Expression Of Placental Pyruvate Kinase M2 In Normal, Preeclamptic, And Intrauterine Growth Restriction Pregnancies, Brigham L. Bahr

Theses and Dissertations

This thesis will be organized into two chapters discussing the placental expression of two proteins, pyruvate kinase M2 (PKM2) and heat shock protein 27 (HSP 27), in human placentas. Understanding the mechanisms of placental metabolism in healthy and diseased placentas helps us understand how placenta disorders occur and how we can treat these disorders. The goal is to investigate these proteins to gain an understanding of their roles in placental disorders and help decrease maternal and fetal mortality rates. Chapter one covers the background of pyruvate kinase M2 (PKM2) in cancer and embryonic tissues, and the expression of PKM2 in …

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The Effects Of Aging On Skeletal Muscle Ampk Activation And An Analysis Of Chronic Aicar Treatment On The Aging Phenotype, Shalene E. Hardman Mar 2014

The Effects Of Aging On Skeletal Muscle Ampk Activation And An Analysis Of Chronic Aicar Treatment On The Aging Phenotype, Shalene E. Hardman

Theses and Dissertations

AMP-activated protein kinase (AMPK), a metabolic regulator, acts in opposition to many of the effects of aging and may provide insights into the development of sarcopenia. However, the effect of aging on AMPK activation is unclear. The purpose of this dissertation was to: 1) clarify the controversy concerning the activation of AMPK in response to endurance-like exercise in aged skeletal muscle; 2) address mechanisms for the age-associated alterations in AMPK activation; and 3) address the known benefits of chronic AICAR treatment in aged skeletal muscle. First, to clarify the effect of age on AMPK activation, young adult (YA) (8 mo.) …

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Endocannabinoid Biosynthetic Enzyme Mrna: Patterns Of Expression In Hippocampus And Ventral Tegmental Area And Effects On Synaptic Plasticity, Collin Brutch Merrill Mar 2014

Endocannabinoid Biosynthetic Enzyme Mrna: Patterns Of Expression In Hippocampus And Ventral Tegmental Area And Effects On Synaptic Plasticity, Collin Brutch Merrill

Theses and Dissertations

Endocannabinoids (eCBs) are lipophilic signals that are produced by postsynaptic neurons in an activity-dependent manner, and signal in a retrograde fashion to modulate neurotransmitter release. As such, eCBs are highly involved in synaptic plasticity, a process that strengthens or weakens synapses. eCB-mediated synaptic plasticity is involved in many brain processes including learning, short-term memory, and adaptive reward, which are processed in the hippocampus and ventral tegmental area (VTA), respectively. However, the expression of eCB biosynthetic enzyme mRNA within hippocampal and VTA neurons, as well as the relationship between these mRNA species and the occurrence of synaptic plasticity, remains unclear. The …

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Inhibition Of Pim And Axl Kinases As Potential Treatments For A Variety Of Hematological Malignancies And Solid Tumors, Kent James Carpenter Feb 2014

Inhibition Of Pim And Axl Kinases As Potential Treatments For A Variety Of Hematological Malignancies And Solid Tumors, Kent James Carpenter

Theses and Dissertations

This thesis is divided into three chapters. In each case, the goal is to achieve inhibition of a growth kinase (PIM or AXL) and subsequent arrest of cell growth and induction of apoptosis (in vitro cell culture models) or decrease in tumor volume (in vivo xenograft studies). Chapter one and chapter two discuss inhibition of proviral integration site for Moloneymurine leukemia virus (PIM) kinases. The three PIM kinases, PIM-1, PIM-2, and PIM-3, are a subfamily of serine/threonine kinases that are known to be involved in signaling pathways as downstream effectors of signal transducer and activator of transcription-5 (STAT5) signaling and …

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The Effect Of Lactic Acid On Mast Cell Function, Andrew J. Spence Jan 2014

The Effect Of Lactic Acid On Mast Cell Function, Andrew J. Spence

Theses and Dissertations

This study shows for the first time the effect that L-(+)-lactic acid has on mast cell activation. Lactic acid is a byproduct of anaerobic glycolysis and is associated with inflammatory environments such as wounds, tumors and, asthma. In this study, pre-treatment with lactic acid altered cytokine production by bone marrow-derived mast cells (BMMC). Specifically, lactic acid enhanced cytokine secretion following IgE cross-linking, but decreased IL-33 mediated cytokine production. These effects were altered by genetic background, since C57BL/6 mast cells demonstrated the aforementioned result, but lactic acid had no effect on IgE-mediated cytokine production in 129/SvJ mast cells. The affected cytokines …

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Sildenafil And Celecoxib Interact To Kill Breast Cancer Cells, Brittany Binion Jan 2014

Sildenafil And Celecoxib Interact To Kill Breast Cancer Cells, Brittany Binion

Theses and Dissertations

Breast cancer is the second most commonly diagnosed cancer among American women and is responsible for the second highest number of cancer-related deaths. Targeted therapeutic agents sildenafil, a phosphodiesterase type 5 inhibitor, and celecoxib, a cyclooxygenase-2 inhibitor, have been used individually in conjunction with other chemotherapeutic agents to enhance cell killing in a variety of cancers. Sildenafil when combined with traditional chemotherapeutic drugs, such as the taxanes and anthracyclines, or celecoxib combined with traditional hormone therapies have been used to increase cytotoxicity and cell killing. The data presented here demonstrates that the novel combination of sildenafil and celecoxib work together …

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Isolation And Characterization Of Multipotent Lung Stem Cells From P53 Mutant Mice Models, Venkat Sundar Gadepalli Jan 2014

Isolation And Characterization Of Multipotent Lung Stem Cells From P53 Mutant Mice Models, Venkat Sundar Gadepalli

Theses and Dissertations

Recent advances in understanding lung biology have shown evidence for the existence of resident lung stem cells. Independent studies in identifying and characterizing these somatic lung stem cells have shown the potential role of these cells in lung repair and regeneration. Understanding the functional characteristics of these tissue resident stem/progenitor cells has gained much importance with increasing evidence of cancer stem cells, cells in a tumor tissue with stem cell characteristics. Lung cancer is most commonly characterized by loss of p53 function which results in uncontrolled cell divisions. Incidence of p53 point mutations is highest in lung cancer, with a …

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The Osh Family Of Proteins And Their Role In Caloric Restriction-Mediated Lifespan Extension In The Budding Yeast Saccharomyces Cerevisiae, William Douglas Craft Dec 2013

The Osh Family Of Proteins And Their Role In Caloric Restriction-Mediated Lifespan Extension In The Budding Yeast Saccharomyces Cerevisiae, William Douglas Craft

Theses and Dissertations

Oxysterol-binding protein homolouges (OSH) have been implicated in mediating non-vesicular sterol transport. Caloric restriction (CR) down-regulates sterol synthesis in a variety of organisms, including the budding yeast Saccharomyces cerevisiae. OSH6, when up-regulated, extends replicative lifespan. In contrast, OSH5 up-regulation shortens replicative lifespan. In this thesis I obtained evidence to show that the deletion of OSH5 extends replicative lifespan in normal media. Deletion of OSH5 in the presence of caloric restriction blocks the lifespan-extending properties of the CR media. My data demonstrate that the total cellular sterol levels of the longevity mutants are indistinguishable from that of wild type. This suggests …

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Involvement Of Ampk And Ap-1 Biochemical Pathways In Il-6 Regulation Of Steroidogenic Enzymes In The Adrenal Cortex, Matharage Shenali De Silva Dec 2013

Involvement Of Ampk And Ap-1 Biochemical Pathways In Il-6 Regulation Of Steroidogenic Enzymes In The Adrenal Cortex, Matharage Shenali De Silva

Theses and Dissertations

The adrenal cortex is a crucial endocrine gland in the mammalian stress response. In chronic inflammatory stress, cortisol is elevated whereas adrenal androgens are decreased. Furthermore, ACTH levels have poor correlation with the plasma cortisol in these conditions, thus suggesting that other factors are driving the stress response during chronic inflammatory stress. Interleukin-6 (IL-6), a cytokine which is released during chronic inflammatory stress, is assumed to be one such factor. Thus the biochemical pathways by which IL-6 increases cortisol release from the zona fasciculata (ZF), and decreases adrenal androgen release from the zona reticularis (ZR) were investigated. Since IL-6 activates …

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Fgf4 Induced Wnt5a Gradient In The Limb Bud Mediates Mesenchymal Cell Directed Migration And Division, John C. Allen Dec 2013

Fgf4 Induced Wnt5a Gradient In The Limb Bud Mediates Mesenchymal Cell Directed Migration And Division, John C. Allen

Theses and Dissertations

The AER has a vital role in directing embryonic limb development. Several models have been developed that attempt to explain how the AER directs limb development, but none of them are fully supported by existing data. I provide evidence that FGFs secreted from the AER induce a gradient of Wnt5a. I also demonstrate that limb mesenchyme grows toward increasing concentrations of Wnt5a. We hypothesize that the changing shape of the AER is critical for patterning the limb along the proximal to distal axis. To better understand the pathway through which Wnt5a elicits its effects, we have performed various genetic studies. …

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Endocannabinoid-Dependent Long-Term Depression Of Ventral Tegmental Area Gaba Neurons, Jared Mark Weed Dec 2013

Endocannabinoid-Dependent Long-Term Depression Of Ventral Tegmental Area Gaba Neurons, Jared Mark Weed

Theses and Dissertations

GABA neurons in the ventral tegmental area of the midbrain are important components in the brain's reward circuit. Long term changes in this circuit occur through the process of synaptic plasticity. It has been shown that high frequency stimulation, as well as treatment with endocannabinoids, can cause GABA neurons in the ventral tegmental area to undergo long term depression, a form of synaptic plasticity that decreases excitability of cells. The present study elaborates on the mechanism whereby high frequency stimulation can result in long term depression of ventral tegmental area GABA neurons. Using the whole cell patch clamp technique in …

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Beta-Amyloid Inhibition Of Alpha 7 Nicotinic Acetylcholine Receptors And Factors That Potentially Influence The Aî²/Nachr Interaction, Christopher L. Jacobsen Jul 2013

Beta-Amyloid Inhibition Of Alpha 7 Nicotinic Acetylcholine Receptors And Factors That Potentially Influence The Aî²/Nachr Interaction, Christopher L. Jacobsen

Theses and Dissertations

Alzheimer's disease (AD) is a neurodegenerative disorder that manifests in the form of deficiencies in cognitive processes such as memory and learning. The pathological features of AD include hyperphosphorylated tau proteins that form neurofibrillary tangles as well as senile plaques composed primarily of the peptide β-amyloid (Aβ). When present in high concentrations in the brain, Aβ inhibits certain subtypes of neuronal nicotinic acetylcholine receptors (nAChRs) in the hippocampus. The effects of Aβ in the hippocampus have proven to be neurotoxic, resulting in reduced functionality of nAChRs and the subsequent death of neurons in the cholinergic pathway. The early stages of …

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Susceptibility Of Apoptotic Cells To Hydrolysis By Spla2: Molecular Basis And Mechanisms Defined, Elizabeth Gibbons Jul 2013

Susceptibility Of Apoptotic Cells To Hydrolysis By Spla2: Molecular Basis And Mechanisms Defined, Elizabeth Gibbons

Theses and Dissertations

Secretory phospholipase A2 hydrolyzes phospholipids at a lipid-water interface, resulting in pro-inflammatory products being released from cell membranes. Healthy cells are resistant to cleavage by this enzyme, but apoptotic cells become susceptible to its activity. Only bilayers with certain characteristics are able to be hydrolyzed. Most recently, studies in this lab have emphasized the idea that the biophysical state of the bilayer (in terms of lipid order, spacing, and fluidity) is relevant in determining the probability of one phospholipid escaping the membrane to be hydrolyzed. Prior to this study, it had been shown that apoptotic cells undergo biophysical alterations that …

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A Model For Sensory Neuron Development By Fgf And Notch: A Multifactorial Approach, Jacob Eugene Voelkel Jun 2013

A Model For Sensory Neuron Development By Fgf And Notch: A Multifactorial Approach, Jacob Eugene Voelkel

Theses and Dissertations

The ophthalmic trigeminal placode (opV) exclusively gives rise to sensory neurons. A number of signaling pathways including Wnt, PDGF, FGF, and Notch are all involved in the progression of an undifferentiated cell in the opV placode to a proneural cell in the condensing opV ganglion. However, the regulatory relationships between these signal transduction pathways are still unknown. To determine if FGF activation acts to modulate Notch signaling in the sensory neurogenesis pathway, a novel multifactorial approach was employed: FGF signaling was inhibited in individual cells and globally with simultaneous inactivation of Notch signaling in chick embryos to investigate if FGF …

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Long-Term Depression Of Excitatory Inputs To Gabaergic Neurons In The Ventral Tegmental Area, Philip J. Sandoval Dec 2012

Long-Term Depression Of Excitatory Inputs To Gabaergic Neurons In The Ventral Tegmental Area, Philip J. Sandoval

Theses and Dissertations

Dopamine cells within the ventral tegmental area of the brain are involved in motivation and reward. Drugs of abuse target these dopamine cells altering their activity and plasticity resulting in addiction. While dopamine cell activity is primarily involved in addiction, the GABA neurons in the VTA have also been shown to have an indirect role. By decreasing the activity of the inhibitory GABA inputs onto dopamine neurons abusive drugs can indirectly increase dopamine cell activity resulting in addictive behaviors. However, although GABA neurons are important in the perception of reward, much less is known about how the excitatory inputs to …

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Regulation Of Sensory Neurogenesis In The Trigeminal Placode: Notch Pathway Genes, Pax3 Isoforms, And Wnt Ligands, Jason Samuel Adams Nov 2012

Regulation Of Sensory Neurogenesis In The Trigeminal Placode: Notch Pathway Genes, Pax3 Isoforms, And Wnt Ligands, Jason Samuel Adams

Theses and Dissertations

This dissertation is divided into three chapters, each discussing the study of different regulatory molecules involved in sensory neurogenesis occurring in the trigeminal placode. Chapter one is a spatiotemporal description of Notch pathway genes in chick opV placode by stage-specific expression analysis, showing expression of many Notch pathway genes and effectors in the opV placode. Notch pathway gene expression is primarily confined to the ectoderm with highest expression of these genes at the beginning stages of peak neuronal differentiation. This information preceded studies of the functional roles that Notch signaling has in the opV placode and how it may affect …

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Membrane Properties Involved In Calcium-Stimulated Microparticle Release From The Plasma Membranes Of S49 Lymphoma Cells, Lauryl Elizabeth Campbell Aug 2012

Membrane Properties Involved In Calcium-Stimulated Microparticle Release From The Plasma Membranes Of S49 Lymphoma Cells, Lauryl Elizabeth Campbell

Theses and Dissertations

The mechanism of microparticle shedding from the plasma membrane of calcium-loaded cells has been investigated in erythrocytes and platelets. Recent studies have revealed the physiological and clinical importance of microparticle release from nucleated cells such as lymphocytes and endothelium. The experiments of this study were designed to address whether simple mechanisms discovered in platelets and erythrocytes also apply to the more complex nucleated cells. Four such mechanisms were addressed: potassium efflux, transbilayer phosphatidylserine migration, cytoskeleton degradation, and membrane lipid order. The rate and amount of microparticle release in the presence of a calcium ionophore, ionomycin, was assayed by light scatter …

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Tissue Specific Porcupine Deletion Reveals A Novel Role For Ectodermal Wnts In Musculotendon Development, Aaron P. Smith Jul 2012

Tissue Specific Porcupine Deletion Reveals A Novel Role For Ectodermal Wnts In Musculotendon Development, Aaron P. Smith

Theses and Dissertations

The Wnt family of secreted proteins consists of 19 family members (in the mouse) and is known to signal through multiple pathways that regulate crucial processes in the development of almost all tissues. Dissecting the roles of individual Wnts has been hampered due to functional redundancy that exists between family members. We made use of a conditional allele of the acyltransferase, Porcupine (Porcn), that is required for the secretion of all Wnt ligands, and the Msx2Cre deleter to eliminate the secretion of all Wnt ligands from the ventral limb ectoderm, ventral abdominal ectoderm, and urogenital ectoderm. Phenotypically the …

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The Pro-Inflammatory Contributions Of Receptors For Advanced Glycation End-Products (Rage) In Alveolar Macrophages Following Cigarette Smoke Exposure, Adam Benjamin Robinson Jun 2012

The Pro-Inflammatory Contributions Of Receptors For Advanced Glycation End-Products (Rage) In Alveolar Macrophages Following Cigarette Smoke Exposure, Adam Benjamin Robinson

Theses and Dissertations

Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors of the immunoglobin family expressed by epithelium and macrophages. RAGE expression increases following ligand binding and when diverse cells are exposed to a variety of insults including cigarette smoke extract (CSE). The current research sought to characterize the pro-inflammatory contributions of RAGE expressed by alveolar macrophages (AMs) following CSE exposure. Acute exposure of mice to CSE via nasal instillation revealed diminished bronchoalveolar lavage (BAL) cellularity and fewer AMs in RAGE null mice compared to controls. Primary AMs were obtained from BAL, exposed to CSE in vitro, and RNA, DNA, …

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Characterization Of Altered Epithelial Cell Turnover And Differentiation In Embryonic Murine Lungs That Over-Express Receptors For Advanced Glycation End-Products (Rage), Jeffrey Alan Stogsdill May 2012

Characterization Of Altered Epithelial Cell Turnover And Differentiation In Embryonic Murine Lungs That Over-Express Receptors For Advanced Glycation End-Products (Rage), Jeffrey Alan Stogsdill

Theses and Dissertations

Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors highly expressed in the lung that modulate pulmonary inflammation during disease. However, the contributions of RAGE signaling are unknown during pulmonary organogenesis. In order to test the hypothesis that RAGE misexpression adversely affects lung morphogenesis, conditional transgenic mice were generated that over-express RAGE in alveolar type II cells of the lung. When RAGE is over-expressed throughout embryogenesis, severe lung hypoplasia ensues, culminating in perinatal lethality. Flow cytometry and immunohistochemistry employing cell-specific markers for various distal cell types demonstrated anomalies in key epithelial cell populations resulting from RAGE up-regulation through …

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Molecular Analysis And Localization Of A Novel Dictyostelium Discoideum Rab Protein, Rabs, Katherine V. Maringer Apr 2012

Molecular Analysis And Localization Of A Novel Dictyostelium Discoideum Rab Protein, Rabs, Katherine V. Maringer

Theses and Dissertations

Functional analysis and localization of the small GTPase RabS in the slime mold, Dictyostelium discoideum, was explored using cell lines that over-express a GFP tagged RabS protein. Based on homology to Rab1, Golgi association was explored. Immunofluoresence analysis of the intracellular localization of this GFP tagged protein revealed that this GFP-Rab had a partial co-localization with the contractile vacuole organelle system. Additionally, when the over-expressed RabS cell lines were exposed to selective biochemical inhibitors, the GFP-Tagged Rab localized with what can be assumed is the Golgi network. This dual localization of Golgi and CV may support a previously proposed connection …

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Iron Deficiency Causes A Shift In Amp-Activated Protein Kinase (Ampk) Catalytic Subunit Composition In Rat Skeletal Muscle, John Merrill Apr 2012

Iron Deficiency Causes A Shift In Amp-Activated Protein Kinase (Ampk) Catalytic Subunit Composition In Rat Skeletal Muscle, John Merrill

Theses and Dissertations

To determine effects of iron deficiency on AMPK activation and signaling, as well as the AMPKα subunit composition in skeletal muscle, rats were fed a control (C=50-58 mg/kg Fe) or iron deficient (ID=2-6 mg/kg Fe) diet for 6-8 wks. Their respective hematocrits were 47.5% ± 1.0 and 16.5% ± 0.6. Iron deficiency resulted in 28.3% greater muscle fatigue (p<0.01) in response to 10 min of stimulation (1 twitch/sec) and was associated with a greater reduction in phosphocreatine (C: Resting 24.1 ± 0.9 micromol/g, Stim 13.1 ± 1.5 micromol/g; ID: Resting 22.7 ± 1.0 micromol/g, Stim 3.2 ± 0.7 micromol/g; p<0.01) and ATP levels (C: Resting 5.89 ± 0.48 micromol/g, Stim 6.03 ± 0.35 micromol/g; ID: Resting 5.51 ± 0.20 micromol/g, Stim 4.19 ± 0.47 micromol/g; p<0.05). AMPK activation increased with stimulation in muscles of C and ID animals. A reduction in Cytochrome c and other iron-dependent mitochondrial proteins was observed in ID animals (p<0.01). The AMPK catalytic subunit (alpha) was also examined because both isoforms are known to play different roles in responding to energy challenges. In ID animals, AMPK alpha2 subunit protein content was reduced to 71.6% of C (p<0.05), however this did not result in a significant difference in resting AMPK alpha2 activity. AMPK alpha1 protein was unchanged, however an overall increase in AMPK alpha1 activity was observed (C: 0.91 pmol/mg/min; ID: 1.63 pmol/mg/min; p<0.05). Resting phospho Acetyl CoA Carboxylase (pACC) was unchanged. This study indicates that chronic iron deficiency causes a shift in the expression of AMPK alpha subunit composition and potentially altered sensitivity to cellular energy challenges.

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