Open Access. Powered by Scholars. Published by Universities.®
- Institution
- Keyword
-
- AMPK (11)
- RAGE (7)
- Apoptosis (5)
- GABA (5)
- LKB1 (5)
-
- Lung (5)
- Mitochondria (5)
- VTA (5)
- AMPKK (4)
- Development (4)
- Ethanol (4)
- Metabolism (4)
- Pax3 (4)
- Wnt5a (4)
- AER (3)
- Behavior (3)
- Ceramide (3)
- DAX-1 (3)
- Interleukin-6 (3)
- Laurdan (3)
- Rat (3)
- Ror2 (3)
- Skeletal muscle (3)
- StAR (3)
- Wnt (3)
- AICAR (2)
- AMP-activated protein kinase (2)
- Adrenal (2)
- Amantadine (2)
- CREB (2)
Articles 1 - 30 of 85
Full-Text Articles in Physiology
Role Of Transient Receptor Potential Channels In Epithelial Morphogenesis In Chick Embryo, Trinity Q. Waddell
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 …
Deciphering The Consequences Of Yolk Testosterone Metabolism In Birds, Nicole A. Campbell
Deciphering The Consequences Of Yolk Testosterone Metabolism In Birds, Nicole A. Campbell
Theses and Dissertations
Maternal steroids transferred to eggs can elicit permanent effects on various aspects of offspring phenotype. Although, testosterone was thought to be a key mediator of maternal effects in birds, we now know that vertebrate embryos actively regulate their exposure to maternal testosterone through steroid metabolism, suggesting testosterone metabolites may elicit the observed phenotypic effects. To address the role steroid metabolism plays in mediating yolk testosterone effects, we used European starling (Sturnus vulgaris) eggs to characterize the timing of testosterone metabolism and determine whether etiocholanolone, a prominent testosterone metabolite in avian embryos, is capable of influencing early embryonic development. Tritiated testosterone …
An Evaluation Of Induced Shear Stress On Endothelial Cellular Adhesion Molecules, Edward B. Crabb
An Evaluation Of Induced Shear Stress On Endothelial Cellular Adhesion Molecules, Edward B. Crabb
Theses and Dissertations
The pathophysiology of atherosclerotic cardiovascular disease (CVD) is highlighted by vascular dysfunction and low-grade vascular inflammation. Furthermore, the site-specific distribution of atherosclerosis throughout the arterial vasculature is primarily determined by local hemodynamic force. Therefore, this dissertation outlines three experiments designed to investigate the role of acute mental and physical (i.e., aerobic exercise), and vascular wall shear stress (SS) on the inflammatory aspects of atherosclerosis. Chapter 2 examines the effect of acute laboratory-induced mental stress on intracellular pro-inflammatory signaling pathways in peripheral blood mononuclear cells. Chapter 3 investigates the impact of acute laboratory-induced mental stress and maximal aerobic exercise on the …
Impact Of Aerobic Exercise On Monocyte Subset Receptor Expression And Macrophage Polarization, Anson M. Blanks
Impact Of Aerobic Exercise On Monocyte Subset Receptor Expression And Macrophage Polarization, Anson M. Blanks
Theses and Dissertations
Atherosclerotic cardiovascular disease (CVD) is hallmarked by inflammatory immune activation, particularly by the induction of a response by monocytes. Classical (CD14++CD16-) are anti-inflammatory mediators under homeostatic conditions, while intermediate (CD14++CD16+) and non-classical (CD14LowCD16++) monocytes promote inflammation following activation. Monocyte activation and functionality is dependent upon receptor expression and ligand production by a variety of cells, including monocytes. Alterations in the expression of surface receptors often have a direct impact upon monocyte function, such as the increased pro-inflammatory cytokine production in response to activation that accompanies elevated CD14 expression …
Deletion Of Cardiac Mir-17-92 Cluster Increases Ischemia/ Reperfusion Injury Via Pten Upregulation, Meeta B. Prakash
Deletion Of Cardiac Mir-17-92 Cluster Increases Ischemia/ Reperfusion Injury Via Pten Upregulation, Meeta B. Prakash
Theses and Dissertations
The miR-17- 92 cluster is necessary for cell proliferation and development of the cardiovascular system. Deletion of this cluster leads to death in neonatal mice. The role of this cluster still needs to be defined following ischemia and reperfusion. Methods and Results: Adult male mice were injected with Tamoxifen- was to induce inducible cardiac-specific miR-17- 92-deficient (miR-17- 92-def: MCM:TG:miR-17- 92 flox/flox ) and wild type (WT: MCM:NTG:miR-17-92 flox/flox ) mice were subjected to 30 minutes of myocardial ischemia via left anterior descending coronary artery ligation followed by reperfusion for 24 hours. Post I/R survival (48%) and ejection fraction were reduced, …
Dopamine Effects Of Stimulant And Non-Stimulant Drugs Used In The Treatment Of Attention Deficit Hyperactivity Disorder, Preeti Chalwadi
Dopamine Effects Of Stimulant And Non-Stimulant Drugs Used In The Treatment Of Attention Deficit Hyperactivity Disorder, Preeti Chalwadi
Theses and Dissertations
Attention deficit hyperactivity disorder (ADHD) is thought to be associated with dysfunction of ascending catecholamine neuronal systems, particularly dopamine (DA) and norepinephrine (NE). Dysfunction of these catecholamine neurons innervating the prefrontal cortex is hypothesized to underlie impaired executive functions. Dysfunction of the DA neurons innervating the striatum is additionally hypothesized to underlie deficits in motivation and reinforcement learning. However, mechanisms of action of therapeutic drugs used for treating ADHD have mainly focused on catecholamines in the prefrontal cortex and have not adequately addressed the role played by DA signaling in the striatum. Stimulants such as Adderall® and Ritalin® are chemically …
The Role Of Hypoxia On Pyruvate Kinase M2, Mammalian Target Of Rapamycin, Mitochondrial Function, And Cell Invasion In The Trophoblast, Rebecca Lutz Kimball
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 …
Third Ventricle Width As A Metric For Fast And Efficient Detection Of Atrophy In Traumatic Brain Injury, Christopher Scott Finuf
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
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 …
Differential Receptors For Advanced Glycation End-Products (Rage) Expression In Preeclampsia, Intrauterine Growth Restriction And Gestational Diabetes, Kristen Lena Alexander
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
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
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 …
The Role Of Receptors For Advanced Glycation End-Products (Rage) And Ceramide In Cardiovascular Disease, Michael Bruce Nelson
The Role Of Receptors For Advanced Glycation End-Products (Rage) And Ceramide In Cardiovascular Disease, Michael Bruce Nelson
Theses and Dissertations
Type 2 diabetes and cigarette smoke exposure are associated with an increased risk of cardiovascular complications. The role of advanced glycation end-products (AGEs) is already well-established in numerous comorbidities including cardiomyopathy. Given the role of AGEs and their receptor, RAGE, in activating inflammatory pathways, we sought to determine whether ceramides could be a mediator of RAGE-induced altered heart mitochondrial function. Using an in vitro model, we treated H9C2 cardiomyocytes with carboxy-methyl lysine-BSA, followed by mitochondrial respiration assessment. We found that mitochondrial respiration was significantly impaired in AGE-treated cells, but not when co-treated with myriocin, an inhibitor of de novo …
The Biology Of Claudin 6 (Cldn6) In The Developing Mouse Lung, Felix Ruben Jimenez Rondan
The Biology Of Claudin 6 (Cldn6) In The Developing Mouse Lung, Felix Ruben Jimenez Rondan
Theses and Dissertations
The tight junctions (TJ), which are located in the apical region between epithelial and endothelial cells, regulate the paracellular diffusion of ions and small molecules and play an important role in maintaining cell polarity, cell-cell integrity, and permeability. In the lung, epithelial cells are attached by TJ structures. They provide a permeable barrier and cell communication. The loss of barrier integrity, which is maintained by the expression of claudins (Cldn), results in cellular permibilization and leads to paracellular diffusion of solutes and harmful molecules. There are 27 known Cldn homologous members in mice and human. Cldn6 is mostly expressed in …
Alcohol Modulation Of Dopamine Release, Nathan Dan Schilaty
Alcohol Modulation Of Dopamine Release, Nathan Dan Schilaty
Theses and Dissertations
The mesolimbic dopamine (DA) system projects from the ventral tegmental area (VTA) to structures associated with the limbic system, primarily the nucleus accumbens (NAc). This system has been implicated in the rewarding effects of drugs of abuse. Many drugs of abuse act in the VTA, the NAc, or both. Dopamine neurons in the VTA that project to the NAc, and the GABA neurons that inhibit DA neurons locally in the VTA or project to the NAc, play an important role in mediating addiction to various drugs of abuse, in particular alcohol. There is a growing body of evidence of co-dependence …
The Role Of Ceramides In Mediating Endotoxin-Induced Mitochondrial Disruption, Melissa Ellen Hansen
The Role Of Ceramides In Mediating Endotoxin-Induced Mitochondrial Disruption, Melissa Ellen Hansen
Theses and Dissertations
Ceramides are sphingolipids that serve as important second messengers in an increasing number of stress-induced pathways. Ceramide has long been known to affect the mitochondria, altering both morphology and physiology. Lipopolysaccharide (LPS) is a prevalent circulating inflammatory agent in obesity, potentially mediating some of the pathologies associated with weight gain. Given previous findings of TLR4-mediated ceramide accrual and ceramide-mediated mitochondrial disruption, we questioned whether ceramide is necessary for LPS-induced mitochondrial disruption. We found that LPS treatment increased gene transcript levels of ceramide synthesis enzymes and mitochondrial fission proteins and increased ceramide content in cultured myotubes and in mouse tissue. Mitochondrial …
Extent Of Cysteine Modification Of Snap-25 In Vitro, Alex Mcgregor Dabell
Extent Of Cysteine Modification Of Snap-25 In Vitro, Alex Mcgregor Dabell
Theses and Dissertations
Exocytosis, the fusion of a vesicle to a cellular membrane, involves a protein named SNAP-25. This protein, containing two alpha helices connected with a linker region, is localized to the cell membrane via palmitic acids attached to the cysteine residues of its linker region in a process called palmitoylation. Are cysteine residues of the SNAP-25 linker region palmitoylated in an ordered manner and to a particular extent? The answer to this question may give insight into the regulated nature of exocytosis. While it is generally accepted that SNAP-25 must be palmitoylated in order to perform its exocytotic functions, the details …
Targeting Of Receptors For Advanced Glycation End-Products (Rage) Diminishes Acute Secondhand Smoke-Induced Inflammation In Mice, Tyler Thomas Wood
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 …
Expression Of Osteoarthritis Biomarkers In Temporomandibular Joints Of Mice With And Without Receptor For Advanced Glycation End Products (Rage), Elizabeth Murayama Chavez Matias
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 …
Rapid Adaptation Of Dopamine D2 Receptor Responses In The Brain And Blood Following Acute Ethanol, Ryan J. Folsom
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 …
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
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 …
Characterization Of Secondhand Smoke (Shs) And Materno-Fetal Interactions In Receptors For Advanced Glycation End-Products (Rage)-Targeted Mice, Duane Ray Winden
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 …
Synaptic Plasticity In Gabaergic Inhibition Of Vta Neurons, Jennifer Kei Mabey
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 …
Role Of Α6 Nachrs In Ethanol Modulation Of Vta Neurons, Samuel Injae Shin
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 …
Different Expression Of Placental Pyruvate Kinase M2 In Normal, Preeclamptic, And Intrauterine Growth Restriction Pregnancies, Brigham L. Bahr
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 …
The Effects Of Aging On Skeletal Muscle Ampk Activation And An Analysis Of Chronic Aicar Treatment On The Aging Phenotype, Shalene E. Hardman
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.) …
Endocannabinoid Biosynthetic Enzyme Mrna: Patterns Of Expression In Hippocampus And Ventral Tegmental Area And Effects On Synaptic Plasticity, Collin Brutch Merrill
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 …
Inhibition Of Pim And Axl Kinases As Potential Treatments For A Variety Of Hematological Malignancies And Solid Tumors, Kent James Carpenter
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 …
Fgf4 Induced Wnt5a Gradient In The Limb Bud Mediates Mesenchymal Cell Directed Migration And Division, John C. Allen
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. …
Endocannabinoid-Dependent Long-Term Depression Of Ventral Tegmental Area Gaba Neurons, Jared Mark Weed
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 …