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Role Of Transient Receptor Potential Channels In Epithelial Morphogenesis In Chick Embryo, Trinity Q. Waddell Jul 2019

Role Of Transient Receptor Potential Channels In Epithelial Morphogenesis In Chick Embryo, Trinity Q. Waddell

Theses and Dissertations

Transient Receptor Potential channels (TRP) are a superfamily of cationic specific ionchannels that are regulated by various stimuli such as temperature, pH, mechanical stress, ligandsand ion concentration. The role of TRP channels in disease states such as autosomal dominantpolycystic kidney disease, cancer metastasis, and developmental defects lend credence to thebelief that they play an important part in epithelial morphogenesis events. The development ofsomites, neural tube closure and migration of neural crest cells to form things such as the faceand heart is a good developmental model for the aforementioned cellular processes. We haveshown that TRP channels can be found in the …


Crispr-Cas9 Transfection Optimization And Use In A Forward Genetic Screen To Identify Telomere Length Maintenance Genes, Kelsey Phillips Apr 2018

Crispr-Cas9 Transfection Optimization And Use In A Forward Genetic Screen To Identify Telomere Length Maintenance Genes, Kelsey Phillips

Theses and Dissertations

Mutations in the telomere length maintenance pathway can lead to a spectrum of diseases called telomere syndromes, however, the pathway is not fully understood and there may still be unknown components. We designed a forward genetic screen to identify new genes involved in telomere length maintenance. Of the top ranked genes, ZNF827, a zinc finger protein, is the most promising candidate gene. The possible discovery of a new component involved in telomere length maintenance increases our understanding of the pathway and opens new avenues of research. Recent advances in molecular biology techniques, such as the use of RNA-guided nuclease CRISPR …


Multi-Tissue Examination Of Exercise Or Metformin On The Consequences Of Doxorubicin Treatment, Amy Dee Mackay Apr 2018

Multi-Tissue Examination Of Exercise Or Metformin On The Consequences Of Doxorubicin Treatment, Amy Dee Mackay

Theses and Dissertations

Doxorubicin (DOX) is an effective chemotherapeutic treatment with lasting deleterious side effects in heart and skeletal muscle. As an increased percentage of patients live many years past their cancer treatments, addressing the long-term side effects of chemotherapy treatment becomes critical. In an attempt to prevent heart and skeletal muscle damage caused by DOX, two co-treatments, exercise (EX) or metformin (MET) were studied for their effectiveness in maintaining muscle function, mitochondrial respiration and iron regulation. DOX is known to bind with iron, contributing to oxidative damage resulting in cardiac and skeletal muscle toxicity. However, the degree to which the toxic side …


Pharmaceutical And Natural (Exercise) Mechanisms To Mitigate The Negative Impact Of Ptsd And Chronic Stress On Synaptic Plasticity And Memory, Roxanne M. Miller Nov 2017

Pharmaceutical And Natural (Exercise) Mechanisms To Mitigate The Negative Impact Of Ptsd And Chronic Stress On Synaptic Plasticity And Memory, Roxanne M. Miller

Theses and Dissertations

Synapses can be altered due to experiences in a process called synaptic plasticity, which causes memory formations. Synapses can be strengthened through methods known as long-term potentiation (LTP) or weakened through long-term depression (LTD). Stresses can cause changes by altering synapses through either LTP or LTD. Rats were used to study the effects of post-traumatic stress disorder (PTSD)-like symptoms and a prophylactic treatment using pharmaceuticals. The first model used was the single prolonged stress (SPS) with two weeks of chronic light, which was not as effective for causing changes in synaptic plasticity. The second model, seven days of social defeat …


Pharmaceutical And Natural (Exercise) Mechanisms To Mitigate The Negative Impact Of Ptsd And Chronic Stress On Synaptic Plasticity And Memory, Roxanne M. Miller Nov 2017

Pharmaceutical And Natural (Exercise) Mechanisms To Mitigate The Negative Impact Of Ptsd And Chronic Stress On Synaptic Plasticity And Memory, Roxanne M. Miller

Theses and Dissertations

Synapses can be altered due to experiences in a process called synaptic plasticity, which causes memory formations. Synapses can be strengthened through methods known as long-term potentiation (LTP) or weakened through long-term depression (LTD). Stresses can cause changes by altering synapses through either LTP or LTD. Rats were used to study the effects of post-traumatic stress disorder (PTSD)-like symptoms and a prophylactic treatment using pharmaceuticals. The first model used was the single prolonged stress (SPS) with two weeks of chronic light, which was not as effective for causing changes in synaptic plasticity. The second model, seven days of social defeat …


Mri T2 Signal Changes Indicate Tau Pathophysiology In A Murine Alzheimer's Disease Model, Rajan Deep Adhikari Aug 2017

Mri T2 Signal Changes Indicate Tau Pathophysiology In A Murine Alzheimer's Disease Model, Rajan Deep Adhikari

Theses and Dissertations

Pathogenesis, diagnosis and treatment, the essential domains in medical practice, seem helpless to address Alzheimer's disease (AD). With a huge mortality rate, it is looming and threatening the socioeconomic barrier. Despite many different studies, the pathogenesis of AD remains inconclusive. However, growing numbers of studies suggest oxidative stress to contribute to the initiation and progression of AD. We propose an iron hypothesis: iron mediated oxidative damage by reactive oxygen species (ROS), which induces protective roles of amyloid beta and hyper-phosphorylated tau (HP-tau) to sequester iron and limit the disease. We propose to study such mechanism using transgenic mice models for …


Modulation Of Synaptic Plasticity: Endocannabinoids And Novel G-Protein Coupled Receptors Expression And Translational Effects In Interneurons, Katrina M. Hurst Jul 2017

Modulation Of Synaptic Plasticity: Endocannabinoids And Novel G-Protein Coupled Receptors Expression And Translational Effects In Interneurons, Katrina M. Hurst

Theses and Dissertations

Learning and memory are important processes that occur in the brain. The brain is comprised of neurons that make connections with each other known as synapses. Synaptic plasticity is widely believed to be the physiologic mechanism by which learning and memory occur. Synapses can either be strengthened through a process known as long-term potentiation (LTP) or weakened through long-term depression (LTD). The area of the brain that is most studied for its role in learning and memory is the hippocampus, which has been shown to be involved in memory consolidation. The detection of endocannabinoids and their receptors has opened a …


Insulin And Ketones: Their Roles In Brain Mitochondrial Function, Sheryl Teresa Carr May 2017

Insulin And Ketones: Their Roles In Brain Mitochondrial Function, Sheryl Teresa Carr

Theses and Dissertations

The prevalence of both Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is increasing worldwide, and the trends are unfortunately expected to continue. AD has recently been tied with mitochondrial dysfunction and insulin resistance, creating a mechanistic tie between AD and T2DM. Unfortunately, insulin resistance is often increased with aging and therefore, all individuals are at risk of brain mitochondrial dysfunction. Without proper mitochondrial function, the brain will degenerate, causing impaired cognitive function and reduced quality of life. The purpose of this study is two-fold: first, to understand the role of ceramides in insulin-induced brain mitochondrial dysfunction, and; second, …


Chemogenetic Stimulation Of Electrically Coupled Midbrain Gaba Neurons In Alcohol Reward And Dependence, Stephanie Suzette Pistorius May 2017

Chemogenetic Stimulation Of Electrically Coupled Midbrain Gaba Neurons In Alcohol Reward And Dependence, Stephanie Suzette Pistorius

Theses and Dissertations

The prevailing view is that enhancement of dopamine (DA) transmission in the mesolimbic system leads to the rewarding properties of alcohol. The mesolimbic DA system, which plays an important role in regulating reward and addiction, consists of DA neurons in the midbrain ventral tegmental area (VTA) that innervate the nucleus accumbens (NAc). It is believed that VTA DA neurons are inhibited by local gamma-aminobutyric acid (GABA) interneurons that express connexin-36 (Cx36) gap junctions (GJs). We have previously demonstrated that blocking Cx36 GJs suppresses electrical coupling between VTA GABA neurons and reduces ethanol intoxication and consumption suggesting that electrical coupling between …


Insulin And Ketones: Their Roles In Brain Mitochondrial Function, Sheryl Teresa Carr May 2017

Insulin And Ketones: Their Roles In Brain Mitochondrial Function, Sheryl Teresa Carr

Theses and Dissertations

The prevalence of both Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is increasing worldwide, and the trends are unfortunately expected to continue. AD has recently been tied with mitochondrial dysfunction and insulin resistance, creating a mechanistic tie between AD and T2DM. Unfortunately, insulin resistance is often increased with aging and therefore, all individuals are at risk of brain mitochondrial dysfunction. Without proper mitochondrial function, the brain will degenerate, causing impaired cognitive function and reduced quality of life. The purpose of this study is two-fold: first, to understand the role of ceramides in insulin-induced brain mitochondrial dysfunction, and; second, …


Chemogenetic Stimulation Of Electrically Coupled Midbrain Gaba Neurons In Alcohol Reward And Dependence, Stephanie Suzette Pistorius May 2017

Chemogenetic Stimulation Of Electrically Coupled Midbrain Gaba Neurons In Alcohol Reward And Dependence, Stephanie Suzette Pistorius

Theses and Dissertations

The prevailing view is that enhancement of dopamine (DA) transmission in the mesolimbic system leads to the rewarding properties of alcohol. The mesolimbic DA system, which plays an important role in regulating reward and addiction, consists of DA neurons in the midbrain ventral tegmental area (VTA) that innervate the nucleus accumbens (NAc). It is believed that VTA DA neurons are inhibited by local gamma-aminobutyric acid (GABA) interneurons that express connexin-36 (Cx36) gap junctions (GJs). We have previously demonstrated that blocking Cx36 GJs suppresses electrical coupling between VTA GABA neurons and reduces ethanol intoxication and consumption suggesting that electrical coupling between …


Lkb1 Regulation Of High-Fat Diet-Induced Adaptation In Mouse Skeletal Muscle, Ting Chen Mar 2017

Lkb1 Regulation Of High-Fat Diet-Induced Adaptation In Mouse Skeletal Muscle, Ting Chen

Theses and Dissertations

Ad libitum high-fat diet (HFD)-induced obesity leads to insulin resistance in skeletal muscle, altered gene expression, and altered growth signaling, all of which contributes to pathological changes in metabolism. Liver kinase B1 (LKB1) is an important metabolism regulator. The purpose of this dissertation was to understand how knocking out LKB1 influences HFD induced adaptations in mouse skeletal muscle. To do so, control and skeletal muscle LKB1 knock-out (LKB1-KO) mice were put on either standard diet (STD) or HFD for 1 week or 14 weeks, or put on the HFD for 14 weeks and then switched to STD for 1 week …


Alterations In Tight Junctional Proteins And Their Effects On Pulmonary Inflammation, Joshua B. Lewis Mar 2017

Alterations In Tight Junctional Proteins And Their Effects On Pulmonary Inflammation, Joshua B. Lewis

Theses and Dissertations

The lungs represent one of the earliest interfaces for pathogens and noxious stimuli to interact with the body. As such, careful maintenance of the permeability barrier is vital in providing homeostasis within the lung. Essential to maintaining this barrier is the tight junction, which primarily acts as a paracellular seal and regulator of ionic transport, but also contributes to establishing cell polarity, cell-to-cell integrity, and regulating cell proliferation and differentiation. The loss of these tight junctions has been documented to result in alterations in inflammation, and ultimately the development of many respiratory disorders such as COPD, Asthma, ARDS, and pulmonary …


The Effects Of L-Cysteine On Alzheimer's Disease Pathology In Apoe2, Apoe3, And Apoe4 Homozygous Mice, Stephen Gerard Cieslak Dec 2016

The Effects Of L-Cysteine On Alzheimer's Disease Pathology In Apoe2, Apoe3, And Apoe4 Homozygous Mice, Stephen Gerard Cieslak

Theses and Dissertations

The APOE gene is of profound importance regarding the onset of Alzheimer's disease (AD). From the small physical differences among the protein products of the isoforms of this gene arises a profound difference in their physiologies. For example, the APOE2 isoform confers resistance to AD, the APOE3 isoform confers neutral susceptibility to AD, and the APOE4 isoform confers proneness to AD. L-cysteine is an amino acid that has several anti-AD properties, among which are its ability to sequester iron and form glutathione – a powerful antioxidant – and therefore may be a promising potential dietary supplement for ameliorating AD …


Endocannabinoid-Mediated Synaptic Plasticity In The Ventral Tegmental Area And Hippocampus, Lindsey Nicole Friend Dec 2016

Endocannabinoid-Mediated Synaptic Plasticity In The Ventral Tegmental Area And Hippocampus, Lindsey Nicole Friend

Theses and Dissertations

Synaptic plasticity is the process whereby connections between neurons can be altered in an experience dependent manner. For example, drugs of abuse alter plasticity in the ventral tegmental area (VTA) of the midbrain. A large amount of research has been applied to uncovering the mechanism whereby synapses on the reward signaling dopamine cells is altered, however, less is known regarding the VTA inhibitory GABA neurons. Our objective was to examine the ability of GABA neurons to exhibit plasticity, and determine how drugs of abuse could influence it. Here we report a novel type of plasticity of excitatory neurotransmission onto VTA …


A Semi-Automated Algorithm For Segmenting The Hippocampus In Patient And Control Populations, Nathan Mckay Muncy Jun 2016

A Semi-Automated Algorithm For Segmenting The Hippocampus In Patient And Control Populations, Nathan Mckay Muncy

Theses and Dissertations

Calculating hippocampal volume from Magnetic Resonance (MR) images is an essential task in many studies of neurocognition in healthy and diseased populations. The `gold standard' method involves hand tracing, which is accurate but laborious, requiring expertly trained researchers and significant amounts of time. As such, segmenting large datasets with the standard method is impractical. Current automated pipelines are inaccurate at hippocampal demarcation and volumetry. We developed a semi-automated hippocampal segmentation pipeline based on the Advanced Normalization Tools (ANTs) suite of programs to segment the hippocampus. We applied the semi-automated segmentation pipeline to 70 participant scans (26 female) from groups that …


Glutamate And Gaba Receptor-Mediated Plasticity In The Mesolimbic Dopamine System By Alcohol, Ashley Cerise Nelson Jun 2016

Glutamate And Gaba Receptor-Mediated Plasticity In The Mesolimbic Dopamine System By Alcohol, Ashley Cerise Nelson

Theses and Dissertations

Alcoholism is a devastating chronic relapsing disorder with significant costs to individuals and society. The mesolimbic dopamine (DA) system plays an important role in regulating reward and addiction. GABA neurons located in the ventral tegmental area (VTA) regulate VTA DA neuron activity, and are a relevant target for alcohol in the brain. VTA GABA neurons exhibit marked hyperexcitability during withdrawal from ethanol. Past research has demonstrated that the motivational effects of opiates cause a change in VTA GABA(A) receptors in opiate-dependent animals, which switch from a GABA-induced hyperpolarization of GABA neurons to a GABA-induced depolarization. The focus of this study …


An Evaluation Of The Influences Of Extra-Hippocampal Processes On Pattern Separation, Malia L. Anderson Apr 2016

An Evaluation Of The Influences Of Extra-Hippocampal Processes On Pattern Separation, Malia L. Anderson

Theses and Dissertations

Long-term declarative memory depends on pattern separation, which reduces the degree of overlap between similar representations, to maintain memory specificity, and on pattern completion, which occurs when a degraded cue is used to retrieve a previously stored memory. Previous studies aimed at evaluating the underlying neuronal substrates of these computational processes have used a mnemonic discrimination paradigm and fMRI to focus on the hippocampus, to the exclusion of cortical processing. We aim to investigate the influences extra-hippocampal processes have on pattern separation in the following two studies. Study 1. Computational models of pattern completion suggest it occurs cortically and results …


A Neuroimaging Investigation Of The Effects Of Age And Sleep On Pattern Separation, Christopher Robert Doxey Mar 2016

A Neuroimaging Investigation Of The Effects Of Age And Sleep On Pattern Separation, Christopher Robert Doxey

Theses and Dissertations

Effective memory representations must be specific to prevent interference between episodes that may overlap in terms of place, time, or items present. Pattern separation, a computational process performed by the hippocampus overcomes this interference by establishing non-overlapping memory representations. This project explores pattern separation and how it is impacted by age and sleep. Experiment 1. Structures of the medial temporal lobe (MTL) are known to be involved in declarative memory processes. However, little is known about how age-related changes in MTL structures, white matter integrity, and functional connectivity affect pattern separation processes in the MTL. In the present study, we …


Rab8 Mediates Trpv4 Vesicle Trafficking To The Plasma Membrane In Hgf-Stimulated Mdck Cells, Hillary Jean Haws Mar 2016

Rab8 Mediates Trpv4 Vesicle Trafficking To The Plasma Membrane In Hgf-Stimulated Mdck Cells, Hillary Jean Haws

Theses and Dissertations

Epithelial to mesenchymal transition (EMT) is a process whereby epithelial cells, which act collectively through robust cell–cell interactions, take on mesenchymal characteristics, breaking cell–cell junctions to become solitary, invasive and motile. Our previous results show that a transient increase in calcium influxes through TRP channels at the plasma membrane is required for hepatocyte growth factor (HGF)– stimulated EMT. Since this transient increase requires an intact microtubule cytoskeleton, we propose that HGF stimulation results in the mobilization of calcium channels to the plasma membrane from an intracellular compartment via microtubule–dependent vesicle trafficking. Through immunofluorescence, we show that prior to HGF treatment, …


The Role Of Hypoxia On Pyruvate Kinase M2, Mammalian Target Of Rapamycin, Mitochondrial Function, And Cell Invasion In The Trophoblast, Rebecca Lutz Kimball Mar 2016

The Role Of Hypoxia On Pyruvate Kinase M2, Mammalian Target Of Rapamycin, Mitochondrial Function, And Cell Invasion In The Trophoblast, Rebecca Lutz Kimball

Theses and Dissertations

This thesis will be organized into two chapters discussing the role of hypoxia in the human placenta. The goal of this thesis is to characterize pyruvate kinase M2, mammalian target of rapamycin, mitochondrial function, and cell invasion in hypoxic conditions in the trophoblast. Understanding the mechanisms of placental metabolism can lead to further treatments for placental diseases. Chapter one covers the background of intrauterine growth restriction, hypoxia, placental metabolism, and pyruvate kinase M2 (PKM2). Little is currently understood about the role of the mitochondria in placental diseases. Expression of PKM2, trophoblast cell invasion, and mitochondrial function is shown to be …


Identification And Characterization Of Serum Biomarkers Associated With Breast Cancer Progression, Adhari Abdullah Alzaabi Mar 2016

Identification And Characterization Of Serum Biomarkers Associated With Breast Cancer Progression, Adhari Abdullah Alzaabi

Theses and Dissertations

Despite the recognized advances in the treatment of breast cancer, it still accounts for 15% of all cancer-related deaths. 90% of breast cancer deaths are due to unpredicted metastasis. There is neither successful treatment for metastatic patients nor a specific test to predict or detect secondary lesions. Patients with primary tumor will be either over-treated with cytotoxic side effects or under-treated and risk recurrence. This necessitates the need for personalized treatment, which is hard to offer for such heterogeneous disease. Obstacles in treating breast cancer metastasis are mainly due to the gaps exist in the understanding of the molecular mechanism …


Forward Chemical Genetics Drug Screen Yields Novel Proteases And Proteolytic Inhibitors Of Hgf–Induced Epithelial–Mesenchymal Transition, Jeffrey Thomas Schuler Mar 2016

Forward Chemical Genetics Drug Screen Yields Novel Proteases And Proteolytic Inhibitors Of Hgf–Induced Epithelial–Mesenchymal Transition, Jeffrey Thomas Schuler

Theses and Dissertations

Hepatocyte Growth Factor (HGF)–induced Epithelial–Mesenchymal Transition (EMT) is a complex cellular pathway that causes epithelial cell scattering by breaking cell–cell contacts, eliminating apical–basal polarity, and replacing epithelial markers and characteristics with mesenchymal markers. Early EMT events include a brief period of cell spreading, followed by cell compaction and cell–cell contact breaks. A forward chemical genetics drug screen of 50,000 unique compounds measuring HGF–induced cell scattering identified 26 novel EMT inhibitors, including 2 proteolytic inhibitors. Here, we show that B5500–4, one of the EMT inhibitors from the screen, blocks HGF–induced EMT by a predicted blocking of the protease furin, in addition …


Calcium Signaling And Ca2+/Calmodulin-Dependent Kinase Ii Activity In Epithelial To Mesenchymal Transition, Melissa Ann Mcneil Dec 2015

Calcium Signaling And Ca2+/Calmodulin-Dependent Kinase Ii Activity In Epithelial To Mesenchymal Transition, Melissa Ann Mcneil

Theses and Dissertations

Epithelial to mesenchymal transition (EMT) is an important process in embryonic development, tissue repair, inflammation, and cancer. During EMT, epithelial cells disassemble cell-cell adhesions, lose apicobasal polarity, and initiate migratory and invasive processes that allow individual cells to colonize distant sites. It is the means by which non-invasive tumors progress into malignant, metastatic carcinomas. In vitro, EMT occurs in two steps. First, cells spread out, increasing in surface area and pushing the colony borders out. Then cells contract, pulling away from neighboring cells and rupturing cell-cell junctions, resulting in individual highly migratory cells. Recent discoveries indicate that calcium signaling is …


Third Ventricle Width As A Metric For Fast And Efficient Detection Of Atrophy In Traumatic Brain Injury, Christopher Scott Finuf Dec 2015

Third Ventricle Width As A Metric For Fast And Efficient Detection Of Atrophy In Traumatic Brain Injury, Christopher Scott Finuf

Theses and Dissertations

In an average year more than 1.7 million people will experience a traumatic brain injury (TBI) in the United States. It is known that atrophy occurs across a spectrum for TBI patients, ranging from mild to severe. Current conventional magnetic resonance imaging (MRI) methods are inconsistent in detecting this atrophy on the milder end of the spectrum. Also more contemporary imaging tools, although efficient, are too time consuming for clinical applicability. It is for these reasons that a quick and efficient measurement for detecting this atrophy is needed by clinicians. The measuring of third ventricle width had the potential to …


The Anatomy Of Porcine And Human Larynges: Structural Analysis And High Resolution Magnetic Resonance Imaging Of The Recurrent Laryngeal Nerve, Nena Lundgreen Mason Nov 2015

The Anatomy Of Porcine And Human Larynges: Structural Analysis And High Resolution Magnetic Resonance Imaging Of The Recurrent Laryngeal Nerve, Nena Lundgreen Mason

Theses and Dissertations

The recurrent laryngeal nerve (RLN) innervates all the intrinsic muscles of the larynx that are responsible for human vocalization and language. The RLN runs along the tracheoesophageal groove bilaterally and is often accidentally damaged or transected during head and neck surgical procedures. RLN palsy and vocal cord paralysis are the most common and serious post op complications of thyroid surgeries. Patients who suffer from RLN injury can develop unilateral or bilateral vocal fold paralysis (BVFP). Theoretically, selective reinnervation of the posterior cricoarytenoid muscle would be the best treatment for BVFP. The phrenic nerve has been shown in several studies to …


Hmgb1 And Ceramides: Potential Mediators Of Cigarette Smoke-Induced Metabolic Dysfunction, Mikayla Orton Thatcher Jun 2015

Hmgb1 And Ceramides: Potential Mediators Of Cigarette Smoke-Induced Metabolic Dysfunction, Mikayla Orton Thatcher

Theses and Dissertations

While cigarette smoking is a common-knowledge way to stay lean, it has long been known as a risk factor for diabetes and obesity. Here we establish that smoking causes fat gain and metabolic disruption in mice, effects which are exacerbated by a high-fat, high-sugar diet. We found that smoke exposure increases levels of ceramide—the lipid responsible for diet-induced insulin resistance—and that blocking ceramide production with the pharmacological inhibitor myriocin restored insulin sensitivity, stopped weight gain, and rescued mitochondrial respiration in vivo and in vitro.We also sought to assess the impact of the RAGE ligand HMGB1 on skeletal muscle metabolism. We …


Differential Receptors For Advanced Glycation End-Products (Rage) Expression In Preeclampsia, Intrauterine Growth Restriction And Gestational Diabetes, Kristen Lena Alexander Jun 2015

Differential Receptors For Advanced Glycation End-Products (Rage) Expression In Preeclampsia, Intrauterine Growth Restriction And Gestational Diabetes, Kristen Lena Alexander

Theses and Dissertations

Preeclampsia (PE), intrauterine growth restriction (IUGR) and gestational diabetes (GDM) increase the risk of maternal and fetal morbidity and mortality. The roles of Advanced Glycation End-products (AGEs) are already well documented concerning inflammation, hypoxia and oxidative stress. AGEs bind to its receptor, Receptor for Advanced Glycation End-products (RAGE), and activate an inflammatory pathway. This pathway alters the efficacy of invasive trophoblast cells and in the placenta and can result in placental dysfunction. We hypothesized that the placental dysfunction found in PE, IUGR, and GDM resulted from an over activation of the RAGE-mediated inflammatory pathway. Using human placental samples, we found …


The Effects Of Inhibiting Wnt Secretion And Activity On Cranial And Neural Development, Julie Louise Hulet Jun 2015

The Effects Of Inhibiting Wnt Secretion And Activity On Cranial And Neural Development, Julie Louise Hulet

Theses and Dissertations

Wnt signaling has been shown to have several roles in the development of sensory neurons, particularly in the ophthalmic portion of the trigeminal nerve. Many of these studies have relied on the conclusion that Wnt is necessary but not sufficient for the induction and maintenance of the neural precursor cells that develop in the ophthalmic placode. Wnt had been inhibited in the ophthalmic placode using a dominant negative t-cell factor (TCF) and resulted in the loss of Pax3 expression (indicative of undifferentiated placode cells) in all targeted cells, suggesting a loss of specification/commitment of these cells to the sensory neuron …


Cigarette Smoke Increases Cardiomyocyte Ceramide Accumulation And Inhibits Mitochondrial Respiration, Trevor Stanley Tippetts Jun 2015

Cigarette Smoke Increases Cardiomyocyte Ceramide Accumulation And Inhibits Mitochondrial Respiration, Trevor Stanley Tippetts

Theses and Dissertations

Cigarette smoking is a common and lethal worldwide habit, with considerable mortality stemming from its deleterious effects on heart function. While current theories posit altered blood lipids and fibrinogen metabolism as likely mediators, none have explored the role of the sphingolipid ceramide in exacerbating heart function with smoke exposure. Ceramide production is a consequence of cigarette smoke in the lung, and considering ceramide's harmful effects on mitochondrial function, we sought to elucidate the role of ceramide in mediating smoke-induced altered heart mitochondrial respiration. Lung cells were exposed to cigarette smoke extract and heart cells were exposed to the lung-cell conditioned …