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Theses/Dissertations

2015

Physiology

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Full-Text Articles in Life Sciences

Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity, Bryan K. Becker Dec 2015

Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity, Bryan K. Becker

Theses & Dissertations

Over activation of the sympathetic nervous system is prevalent in many forms of cardiovascular disease such as chronic heart failure (CHF) and hypertension. Although increased neuronal renin-angiotensin system activity in presympathetic neurons has been well implicated in mediating this sympatho-excitation, many of the neuronal effects of angiotensin II (Ang II) signaling remain poorly understood. One particular mechanism of Ang II-mediated increases in presympathetic neuronal activity is through reductions in voltage-gated K+ currents. Another pathway that has profound effects on neuronal K+ currents and that has been previously implicated in Ang II-signaling is brain-derived neurotrophic factor (BDNF) activity through its receptor ...


Systematic Dissection Of Roles For Chromatin Regulators In Dynamics Of Transcriptional Response To Stress In Yeast: A Dissertation, Hsiuyi V. Chen Dec 2015

Systematic Dissection Of Roles For Chromatin Regulators In Dynamics Of Transcriptional Response To Stress In Yeast: A Dissertation, Hsiuyi V. Chen

GSBS Dissertations and Theses

The following work demonstrates that chromatin regulators play far more pronounced roles in dynamic gene expression than they do in steady-state. Histone modifications have been associated with transcription activity. However, previous analyses of gene expression in mutants affecting histone modifications show limited alteration. I systematically dissected the effects of 83 histone mutants and 119 gene deletion mutants on gene induction/repression in response to diamide stress in yeast. Importantly, I observed far more changes in gene induction/repression than changes in steady-state gene expression. The extensive dynamic gene expression profile of histone mutants and gene deletion mutants also allowed me ...


Cardioprotective Role Of The Cholinergic System, Mouhamed Dakroub Dec 2015

Cardioprotective Role Of The Cholinergic System, Mouhamed Dakroub

Electronic Thesis and Dissertation Repository

The process of aging is an irreversible continuum experienced by all individuals. A large number of physiological transformations occur to the cardiovascular system as one ages. These changes result in increased risk of developing cardiovascular diseases, many of which are frequently seen in geriatric populations. While the exact mechanisms of age-related cardiac dysfunction have not been established, abnormal cholinergic dysfunction has been implicated in the pathology of other age related diseases; therefore, we have hypothesized that age induced cholinergic dysfunction is detrimental to cardiac function and health. This study seeks to identify whether increased cholinergic signaling, either by transgenic overexpression ...


Autophagy And Its Potential Role In Stress And Feed Efficiency Using Avian Lines, Alissa Laura Piekarski Dec 2015

Autophagy And Its Potential Role In Stress And Feed Efficiency Using Avian Lines, Alissa Laura Piekarski

Theses and Dissertations

Autophagy is a highly conserved cellular mechanism that is responsible for the degradation and recycling of damaged organelles. Recently, autophagy has been involved in critical roles during overall development of the organism and degradation of damaged cellular components. This pathway has witnessed dramatic growth in the last few years and has been extensively studied in yeast and mammals, however, there is a paucity of information in avian (non-mammalian) species. First, we characterized genes involved in the autophagy pathway in male and female Jungle Fowl to determine gender and tissue specific differences. Secondly, tissue and genotype differences in Japanese quail selected ...


Cardiovascular Regulation And Effects Of Respiratory Motor Training In Patients With Chronic Spinal Cord Injury., Bonnie Legg Ditterline Dec 2015

Cardiovascular Regulation And Effects Of Respiratory Motor Training In Patients With Chronic Spinal Cord Injury., Bonnie Legg Ditterline

Electronic Theses and Dissertations

This dissertation attempts to discover the mechanisms between cardiovascular and respiratory motor control post spinal cord injury (SCI): in normal, non-injured (NI) persons, cardiovascular regulation is dependent upon respiration, but there is nothing that suggests the mechanism for this relationship post-SCI. Thus we hoped to evaluate various aspects of cardiovascular regulation to further illustrate how this relationship is changed or unchanged by SCI. Chapter I describes the anatomy and physiology of the spine, respiratory system, and cardiovascular system in a NI person, and then describes how the function of these systems is changed by SCI. In addition, we describe therapies ...


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 ...


Brain Injury And Inflammation And Placental Inflammation In Response To Repetitive Umbilical Cord Occlusions In The Near Term Ovine Fetus, Alex Xu Nov 2015

Brain Injury And Inflammation And Placental Inflammation In Response To Repetitive Umbilical Cord Occlusions In The Near Term Ovine Fetus, Alex Xu

Electronic Thesis and Dissertation Repository

We hypothesized that repetitive umbilical cord occlusions (UCOs) leading to severe acidemia will stimulate a placental and fetal inflammatory response associated with brain injury, which will be exacerbated by chronic hypoxemia and low-grade infection. Chronically instrumented fetal sheep served as controls or underwent repetitive UCOs for up to 4 hours or until fetal arterial pH was2saturation pre-UCOs of >55% and


Dexamethasone Regulates Gene Expression Induced By The Mechanosensitive P2x7 Receptor In Osteoblasts, Meena Na Nov 2015

Dexamethasone Regulates Gene Expression Induced By The Mechanosensitive P2x7 Receptor In Osteoblasts, Meena Na

Electronic Thesis and Dissertation Repository

Orthodontic tooth movement involves activation of osteoblasts and osteoclasts in response to mechanical forces. Extracellular nucleotides, released in response to mechanical stimuli, signal through P2 receptors in osteoblasts. P2X7 receptors are ATP-gated cation channels implicated in mechanotransduction in bone. Corticosteroids such as dexamethasone exhibit anti-inflammatory effects and their chronic use has been linked to serious side-effects such as osteoporosis. We investigated gene expression following P2X7 receptor activation with benzoylbenzoyl-ATP (P2X7 receptor agonist) in osteoblast precursor cells in the presence or absence of dexamethasone. We hypothesized that dexamethasone inhibits the ability of ATP to stimulate the expression of anabolic (bone forming ...


Hepatic Nutrient And Hormonal Regulation Of The Pancreatic-Derived Factor (Pander) Promoter, Whitney Ratliff Nov 2015

Hepatic Nutrient And Hormonal Regulation Of The Pancreatic-Derived Factor (Pander) Promoter, Whitney Ratliff

Graduate Theses and Dissertations

PANcreatic-DERived factor (PANDER, FAM3B) has been shown to regulate glycemic levels via interactions with both pancreatic islets and the liver. Although PANDER is predominantly expressed from the endocrine pancreas, recent work has provided sufficient evidence that the liver may also be an additional tissue source of PANDER production. At physiological levels, PANDER is capable of disrupting insulin signaling and promoting increased hepatic glucose production. As shown in some animal models, strong expression of PANDER, induced by viral delivery within the liver, induces hepatic steatosis. However, no studies to date have explicitly characterized the transcriptional regulation of PANDER from the liver ...


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 ...


Roles Of Protein Arginine Methyltransferase 7 And Jumonji Domain-Containing Protein 6 In Adipocyte Differentiation: A Dissertation, Yu-Jie Hu Oct 2015

Roles Of Protein Arginine Methyltransferase 7 And Jumonji Domain-Containing Protein 6 In Adipocyte Differentiation: A Dissertation, Yu-Jie Hu

GSBS Dissertations and Theses

Regulation of gene expression comprises a wide range of mechanisms that control the abundance of gene products in response to environmental and developmental changes. These biological processes can be modulated by posttranslational modifications including arginine methylation. Among the enzymes that catalyze the methylation, protein arginine methyltransferase 7 (PRMT7) is known to modify histones to repress gene expression. Jumonji domain-containing protein 6 (JMJD6) is a putative arginine demethylase that potentially antagonize PRMT7. However, the biological significance of these enzymes is not well understood. This thesis summarizes the investigation of both PRMT7 and JMJD6 in cell culture models for adipocyte differentiation. The ...


Age-Related Changes In The Neuronal Architecture Of Caenorhabditis Elegans: A Dissertation, Anagha Khandekar Oct 2015

Age-Related Changes In The Neuronal Architecture Of Caenorhabditis Elegans: A Dissertation, Anagha Khandekar

GSBS Dissertations and Theses

Though symptoms such as loss of vision, decline in cognition and memory are evident during aging, the underlying processes that affect neuronal function during aging are not well understood. Unlike changes in other tissues and organs, age-related changes in the nervous system affect the overall physical, mental as well as social state of human beings. To start elucidating the molecular mechanisms underlying normal age-dependent brain decline, we have characterized structural neuronal changes occurring during Caenorhabditis elegans aging. Our analysis reveals distinct neuronal alterations that arise with age and that the types of changes and their age of onset are neuronal-type ...


Regulation Of Metabolism By Hepatic Oxphos: A Dissertation, Thomas E. Akie Oct 2015

Regulation Of Metabolism By Hepatic Oxphos: A Dissertation, Thomas E. Akie

GSBS Dissertations and Theses

Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent issue in the modern world, predisposing patients to serious pathology such as cirrhosis and hepatocellular carcinoma. Mitochondrial dysfunction, and in particular, diminished hepatic oxidative phosphorylation (OXPHOS) capacity, have been observed in NAFLD livers, which may participate in NAFLD pathogenesis.

To examine the role of OXPHOS in NAFLD, we generated a model of enhanced hepatic OXPHOS using mice with liver-specific transgenic expression of LRPPRC, a protein which activates mitochondrial transcription and augments OXPHOS capacity. When challenged with high-fat feeding, mice with enhanced hepatic OXPHOS were protected from the development of liver steatosis ...


Kinematics And Hydrodynamics Of Cephalopod Turning Performance In Routine Swimming And Predatory Attacks, Rachel A. Jastrebsky Oct 2015

Kinematics And Hydrodynamics Of Cephalopod Turning Performance In Routine Swimming And Predatory Attacks, Rachel A. Jastrebsky

Biological Sciences Theses & Dissertations

Steady rectilinear swimming has received considerable attention in aquatic animal locomotion studies. Unsteady swimming movements, however, represent a large portion of many aquatic animals’ locomotive repertoire and have not been examined extensively. This study incorporates kinematic analyses of routine turning performance of brief squid Lolliguncula brevis and dwarf cuttlefish Sepia bandensis (Chapter 2), 3D velocimetry techniques to examine hydrodynamic turning performance of L. brevis (Chapter 3) and kinematic analyses of turning performance of L. brevis during predatory attacks on shrimp and fish prey (Chapter 4).

Both L. brevis and S. bandensis demonstrated high maneuverability, having the lowest measures of length-specific ...


Effects Of Supplemental Hydration On Physiology And Behavior Of Northern Pacific Rattlesnakes (Crotalus Oreganus Oreganus), Griffin D. Capehart Oct 2015

Effects Of Supplemental Hydration On Physiology And Behavior Of Northern Pacific Rattlesnakes (Crotalus Oreganus Oreganus), Griffin D. Capehart

Master's Theses and Project Reports

Hydration is a critical element for many physiological processes in vertebrates, such as protein production, innate immunity, and behavioral processes such as daily activity and thermoregulation. Few studies have directly assessed the effect of hydration on these animals in nature. While it seems intuitive that drought is stressful to animals, studies examining drought are typically observational and fail to assess how the hydration state of these animals influences their physiology and behavior. We tested for an effect of hydration on several physiological and behavioral parameters in Northern Pacific rattlesnakes (Crotalus oreganus oreganus) by experimentally manipulating hydration levels in the field ...


The Inconstancy Of Bodies: Yvonne Meier's Works, 1985 ' 2012, Lindsey Ann Drury Sep 2015

The Inconstancy Of Bodies: Yvonne Meier's Works, 1985 ' 2012, Lindsey Ann Drury

All Dissertations, Theses, and Capstone Projects

What is ability? And conversely, what is disability? This research on the dancer and choreographer Yvonne Meier theorizes that her more than 30-year career has challenged the oft perceived polarities between function and dysfunction, utility and futility through the physical actions of dance performances. As she developed as a dancer and choreographer, Meier engaged in forms of movement training that pledged to expand her ability by unearthing the hidden causes and effects of actions. And yet, she created works which foregrounded the very gaps in knowledge between acts, their intentions, and effects. The fundamental disability expressed through Meier's works ...


The Role Of Perineuronal Nets In Regulating Barrel Cortex Physiology, Philip Chu Sep 2015

The Role Of Perineuronal Nets In Regulating Barrel Cortex Physiology, Philip Chu

All Dissertations, Theses, and Capstone Projects

The ability of the brain to adapt to changing environmental conditions is regulated by genetic and environmental factors. One component of the brain extracellular matrix, a scaffold of proteins and proteoglycans, tightly ensheaths the soma and proximal processes of neurons. These Perineuronal nets (PNNs) play protective and structural roles in the brain, but also regulate plasticity and behavior. Their developmental expression is highly attenuated following sensory deprivation, or pharmacological silencing of neuronal activity. Thus, PNNs contribute to the activity dependent regulation of plasticity in the brain. Although PNNs are relatively ubiquitous in the neocortex, little is known about the degree ...


Diet-Responsive Gene Networks Rewire Metabolism In The Nematode Caenorhabditis Elegans To Provide Robustness Against Vitamin B12 Deficiency: A Dissertation, Emma Watson Sep 2015

Diet-Responsive Gene Networks Rewire Metabolism In The Nematode Caenorhabditis Elegans To Provide Robustness Against Vitamin B12 Deficiency: A Dissertation, Emma Watson

GSBS Dissertations and Theses

Maintaining cellular homeostasis is a complex task, which involves monitoring energy states and essential nutrients, regulating metabolic fluxes to accommodate energy and biomass needs, and preventing buildup of potentially toxic metabolic intermediates and byproducts. Measures aimed at maintaining a healthy cellular economy inherently depend on the composition of nutrients available to the organism through its diet. We sought to delineate links between dietary composition, metabolic gene regulation, and physiological responses in the model organism C. elegans.

As a soil-dwelling bacterivore, C. elegans encounters diverse bacterial diets. Compared to a diet of E. coli OP50, a diet of Comamonas aquatica accelerates ...


Degrees Of Damage: Quantifying Male Vs. Female Exercise-Induced Muscle Damage Through Magnetization Transfer Ratios, Nicholai Michael Clausius Crawford Sep 2015

Degrees Of Damage: Quantifying Male Vs. Female Exercise-Induced Muscle Damage Through Magnetization Transfer Ratios, Nicholai Michael Clausius Crawford

Electronic Thesis and Dissertation Repository

No direct, quantitative, and non-invasive markers presently exist to assess exercise-induced muscle damage (EIMD). However, magnetization transfer ratios (MTR), an emerging measurement quantified via magnetic resonance imagery, provide more direct indication of muscle integrity following EIMD. This study compares and correlates the temporal pattern of the MTR to alternative indirect markers of EIMD in male vs. female populations, and subsequently establishes whether there are sex differences in biochemical activity during recovery. The antioxidant properties of estrogen hypothetically minimize muscle trauma, maintain membrane stability, and limit swelling resulting in heightened tissue integrity and resilience to EIMD. Six males and three females ...


Exploring The Role Of Fus Mutants From Stress Granule Incorporation To Nucleopathy In Amyotrophic Lateral Sclerosis: A Dissertation, Hae Kyung Ko Sep 2015

Exploring The Role Of Fus Mutants From Stress Granule Incorporation To Nucleopathy In Amyotrophic Lateral Sclerosis: A Dissertation, Hae Kyung Ko

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by preferential motor neuron death in the brain and spinal cord. The rapid disease progression results in death due to respiratory failure, typically within 3-5 years after disease onset. While ~90% of cases occur sporadically, remaining 10% of ALS cases show familial inheritance, and the number of genes linked to ALS has increased dramatically over the past decade.

FUS/TLS (Fused in Sarcoma/ Translocated to liposarcoma) is a nucleic acid binding protein that may regulate several cellular functions, including RNA splicing, transcription, DNA damage repair and microRNA biogenesis. More than ...


Multi-Stress Proteomics: The Global Protein Response To Multiple Environmental Stressors In The Porcelain Crab Petrolisthes Cinctipes, Michael A. Garland Sep 2015

Multi-Stress Proteomics: The Global Protein Response To Multiple Environmental Stressors In The Porcelain Crab Petrolisthes Cinctipes, Michael A. Garland

Master's Theses and Project Reports

Global climate change is increasing the number of hot days along the California coast as well as increasing the incidence of off-shore upwelling events that lower the pH of intertidal seawater; thus, intertidal organisms are experiencing an increase in more than one stress simultaneously. This study seeks to characterize the global protein response of the eurythermal porcelain crab Petrolisthes cinctipes to changes in thermal, pH, and tidal regime treatments, either combined or individually. The first experiment examined temperature stress alone and sought to determine the effect of chronic temperature acclimation on the acute heat shock response. We compared the proteomic ...


Engineered Cx26 Variant Established Functional Heterotypic Cx26/Cx43 And Cx26/Cx40 Gap Junction Channels, Levent Berk Karademir Aug 2015

Engineered Cx26 Variant Established Functional Heterotypic Cx26/Cx43 And Cx26/Cx40 Gap Junction Channels, Levent Berk Karademir

Electronic Thesis and Dissertation Repository

Two hexameric connexin hemichannels dock together to from a whole gap junction (GJ) channel. The mechanisms of docking specificity in forming homotypic and heterotypic GJ channels are not fully clear. To reveal the key differences between Cx26 and Cx43 (or Cx40) in their docking residues, we aligned and analyzed ten well studied connexin sequences. Five of them are docking compatible with Cx26 and the rest (including Cx43 and Cx40) are not. According to Cx26 crystal structure at the docking interface, we identified two putative docking residues on the second extracellular domain (E2) that are well conserved within docking compatible connexins ...


Examination Of The Non-Linear V̇O2p Response To Exercise: Non-Invasive Evidence Of Linear Systems Control Using V̇O2p Kinetic Analyses, Daniel A. Keir Aug 2015

Examination Of The Non-Linear V̇O2p Response To Exercise: Non-Invasive Evidence Of Linear Systems Control Using V̇O2p Kinetic Analyses, Daniel A. Keir

Electronic Thesis and Dissertation Repository

The pulmonary O2 uptake (V̇O2p) response to exercise has been characterized by exponential kinetics that remain constant regardless of the exercise protocol used to force the change in V̇O2p (kinetics are invariant). A system that responds in this way is classified as “dynamically linear”, implying that a first-order rate reaction controls V̇O2 at the muscle level (V̇O2m). However, slowed V̇O2p kinetics when initiating exercise from raised baseline intensities challenges this notion. The purpose of this thesis was to characterize the rate (τV̇O2p) and magnitude (gain) of adjustment ...


Molecular Mechanisms Underlying The Contralateral Repeated Bout Effect (Crbe) In Human Skeletal Muscle, Ling Xin Aug 2015

Molecular Mechanisms Underlying The Contralateral Repeated Bout Effect (Crbe) In Human Skeletal Muscle, Ling Xin

Doctoral Dissertations

Eccentric (muscle lengthening) exercise induces temporary muscle damage that can lead to long-term muscle adaptation, a process known as the repeated bout effect where subsequent exercise results in less damage. The existence of a contralateral repeated bout effect (CRBE) has been controversial. The primary goals of this study were to: 1) validate the existence of the CRBE; and 2) define the underlying molecular mechanisms.

Thirty-six young men performed 100 maximal eccentric actions of the knee extensors using one leg (bout 1) and repeated the exercise with the contralateral leg five weeks later (bout 2). Vastus lateralis muscle biopsies were ...


Role Of Rgs2 In Cellular Stress, Chang-Hui Wang Aug 2015

Role Of Rgs2 In Cellular Stress, Chang-Hui Wang

Electronic Thesis and Dissertation Repository

Stresses from the external environment can disrupt cellular processes and result in damaging effects, such as the misfolding of proteins, which have been linked to several diseases. Regulator of G protein signalling 2 (RGS2) is upregulated by several forms of stress and can inhibit protein synthesis, an established response to stress typically achieved via the phosphorylation of the initiation factor, eIF2, to conserve energy and resources. Under reduced translation, some factors are selectively expressed via alternative translation mechanisms and these factors consequently may promote apoptosis. The molecular mechanisms mediating such opposing responses to stress are not well understood. Here, we ...


Non-Invasive Determination Of Pre-Clinical Markers Of Cardiovascular Diseases In Low Birth Weight And Maternal Western Diet Guinea Pig Offspring Exposed To A Postnatal Western Diet, Jacky Chiu Aug 2015

Non-Invasive Determination Of Pre-Clinical Markers Of Cardiovascular Diseases In Low Birth Weight And Maternal Western Diet Guinea Pig Offspring Exposed To A Postnatal Western Diet, Jacky Chiu

Electronic Thesis and Dissertation Repository

Low birth weight (LBW), and maternal Western Diet (WD) consumption have both been independently implicated to increase the risk of developing cardiovascular diseases (CVDs) in later life. These fetal programmed risks are also believed to exacerbate the effects of a postnatal WD pattern. Therefore, resulting in the development of pre-clinical markers of CVDs, such as insulin resistance (IR), coronary circulation disruptions. This thesis aimed to elucidate the roles of sub-optimal in utero growth through placental insufficiency, or chronic maternal WD consumption, and postnatal WD consumption on the long-term programming of CVDs in a guinea pig model. Early pre-clinical markers of ...


Investigating The Effects Of Mutant Fus On Stress Response In Amyotrophic Lateral Sclerosis: A Thesis, Laura J. Kaushansky Aug 2015

Investigating The Effects Of Mutant Fus On Stress Response In Amyotrophic Lateral Sclerosis: A Thesis, Laura J. Kaushansky

GSBS Dissertations and Theses

During stress, eukaryotes regulate protein synthesis in part through formation of cytoplasmic, non-membrane-bound complexes called stress granules (SGs). SGs transiently store signaling proteins and stalled translational complexes in response to stress stimuli (e.g. oxidative insult, DNA damage, temperature shifts and ER dysfunction). The functional outcome of SGs is proper translational regulation and signaling, allowing cells to overcome stress.

The fatal motor neuron disease Amyotrophic Lateral Sclerosis (ALS) develops in an age-related manner and is marked by progressive neuronal death, with cytoplasmic protein aggregation, excitotoxicity and increased oxidative stress as major hallmarks. Fused in Sarcoma/Translocated in Liposarcoma (FUS) is ...


Fibulin-3 Promotes Triple Negative Breast Cancer Cell Invasion, Michelle M. Noonan Aug 2015

Fibulin-3 Promotes Triple Negative Breast Cancer Cell Invasion, Michelle M. Noonan

Electronic Thesis and Dissertation Repository

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer, and metastasis is a leading cause of mortality in these patients. Fibulin-3, a secreted extracellular matrix protein, has a pro-invasive role in other cancers. However, a role for fibulin-3 in TNBC invasion is unknown. We have previously shown that KISS1R signaling promotes TNBC cell invasion through EGFR and MMP-9 activity, via β-arrestin2. Thus, we hypothesized that KISS1R signaling promotes TNBC cell invasion via fibulin-3. Our clinical data suggests that plasma fibulin-3 levels are elevated in metastatic TNBC patients. Additionally, we found that invasive breast cancer cells have increased ...


Stability And Activity Of Naturally Occurring Rgs2 Variants, Patrick Stockwell Aug 2015

Stability And Activity Of Naturally Occurring Rgs2 Variants, Patrick Stockwell

Electronic Thesis and Dissertation Repository

Regulator of G protein signaling protein 2 (RGS2) attenuates G Protein-Coupled Receptor (GPCR) signaling by promoting the hydrolysis of GTP in the activated Gα subunit to GDP, thereby governing many physiological and pathophysiological signals. However, how RGS2 itself is regulated remains to be elucidated. In this study, our principal goal was to discover the molecular mechanisms controlling RGS2 degradation and if altered degradation affects Gα signaling. RGS2 has four initiation sites (at residues 1, 5, 16, and 33), resulting in the existence of four distinct N-terminal initiation site variants. Additionally, there are naturally occurring mutations in this region at residues ...