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Theses and Dissertations

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Full-Text Articles in Life Sciences

Genetic Analysis Of Ribosome Stalling And Rescue, Douglas Ray Tanner May 2009

Genetic Analysis Of Ribosome Stalling And Rescue, Douglas Ray Tanner

Theses and Dissertations

In eubacteria, ribosome stalling on broken messenger RNA transcripts can lead to cell death. The trans-translation quality control mechanism rescues many of these stalled ribosomes. In this process, tmRNA enters stalled ribosomes by mimicking a transfer RNA, accepting the stalled nascent peptide. The ribosome then releases the broken mRNA and resumes translation on a coding region within tmRNA itself. Translation of tmRNA marks the nascent peptide for destruction by the addition of a short proteolysis tag and the ribosome is released at a stop codon within the tmRNA open reading frame. An intriguing aspect of trans-translation is that …


Lactate Threshold: The Comparison Of Running On A Land Treadmill Versus Head-Out Water Immersion Treadmill Running, Stephanie Alyce Jones May 2009

Lactate Threshold: The Comparison Of Running On A Land Treadmill Versus Head-Out Water Immersion Treadmill Running, Stephanie Alyce Jones

Theses and Dissertations

Introduction. Exercise and head-out water immersion (HOI) have consistently reported an increase in central blood volume associated with the cephalad shift in blood volume. This causes an increase in left ventricular end diastolic volume and greater stroke volume during exercise compared to exercise in air at similar metabolic costs. In contrast, the metabolic response, specifically, blood lactate accumulation during exercise combined with HOI has yielded varying results depending on the mode of exercise. At present it appears that during exercise at similar metabolic costs, cycle ergometry exercise augments plasma lactate over treadmill running while HOI reduces the plasma lactate response …


Synthesis And Evaluation Of Stimulatory Properties Of Glycolipids For Natural Killer T Cells, Xiangtian Long May 2009

Synthesis And Evaluation Of Stimulatory Properties Of Glycolipids For Natural Killer T Cells, Xiangtian Long

Theses and Dissertations

Natural killer T cells (NKT cells) are a subset of T cells. They regulate a wide range of diseases including infection, tumor growth, and autoimmune diseases, through recognizing glycolipid antigens in the context of CD1d. An understanding of the scope of glycolipid antigens would facilitate use of this cell type in controlling immune responses. Till today, a lysosomal glycolipid, isoglobotrihexosylceramide (iGb3), is the only natural glycolipid that has been found to be recognized by both human and mouse NKT cells. To elucidate the molecular basis of this specific recognition, iGb3 variants were designed and prepared: i) replacement of the C26 …


Predator And Abiotic Effects On Hatching Phenotype And Survival Of Arboreal Frog Eggs With Implications For Phytoplankton, Jessica Hite May 2009

Predator And Abiotic Effects On Hatching Phenotype And Survival Of Arboreal Frog Eggs With Implications For Phytoplankton, Jessica Hite

Theses and Dissertations

Historically studies have focused on either the terrestrial or aquatic environments independently. However, these systems are inherently linked through numerous pathways including organisms with complex life cycles. Both abiotic factors and predators of these organisms can influence connections by changing the number of prey moving across habitat boundaries and by changing the phenotype of prey. When the focal organisms are primary consumers, these effects may have important implications for ecosystem processes. My study investigated how terrestrial predators and abiotic factors affect the number and phenotype of herbivorous tadpole inputs into a tropical forest pond. I found that predators and abiotic …


The Small Molecule Bcl-2 Inhibitor Ha14-1 Potentiates The Lethality Of A Regimen Combining Mek1/2 And Chk1 Inhibitors In Multiple Myeloma Cells, Leena Youssefian May 2009

The Small Molecule Bcl-2 Inhibitor Ha14-1 Potentiates The Lethality Of A Regimen Combining Mek1/2 And Chk1 Inhibitors In Multiple Myeloma Cells, Leena Youssefian

Theses and Dissertations

Previously, we have found that the co-administration of MEK1/2 inhibitors and Chk1 inhibitors synergistically induce multiple myeloma cell apoptosis through upregulation of the BH3-only pro-apoptotic protein Bim. However, these apoptotic events were largely blocked by the characteristic over-expression of Bcl-2 of Bcl-xL in multiple myeloma cells. HA14-1, a small molecule Bcl-2 inhibitor, may therefore circumvent this resistance to apoptosis by blocking Bcl-2 and Bcl-xL anti-apoptotic protein actions. In our project, we hypothesize that the co-administration of HA14-1 with MEK/Chk1 inhibitors will enhance apoptosis in multiple myeloma (MM) cells. To test this hypothesis, we exposed MM cells U266 and RPMI8226, or …


Tacrolimus Is Not Neuroprotective Against Bilirubin Induced Auditory Impairment, Lori Walker Apr 2009

Tacrolimus Is Not Neuroprotective Against Bilirubin Induced Auditory Impairment, Lori Walker

Theses and Dissertations

In newborns, unconjugated bilirubin (UCB) is not readily excreted, and when bilirubin levels exceed the serum albumin binding capacity, pathological levels of UCB exist. Hyperbilirubinemia may lead to auditory damage and ultimately cause a hearing disorder called auditory neuropathy/dys-synchrony, characterized by absent or abnormal brainstem auditory evoked potentials (BAEPs) with evidence of normal inner ear function assessed by either otoacoustic emissions or cochlear microphonic responses. Phototherapy and double volume exchange transfusion are used as treatment methods for neonatal hyperbilirubinemia. Spontaneously jaundiced Gunn rat pups given sulfadimethoxine to displace bilirubin from serum albumin develop bilirubin encephalopathy and have abnormal BAEPs comparable …


The Second Generation Proteasome Inhibitor Carfilzomib Interacts Synergistically With Hdac Inhibitors In Diffuse Large B-Cell Lymphoma Cells Through Multiple Mechanisms And Circumvents Bortezomib Resistance, Dmitry Lembersky Apr 2009

The Second Generation Proteasome Inhibitor Carfilzomib Interacts Synergistically With Hdac Inhibitors In Diffuse Large B-Cell Lymphoma Cells Through Multiple Mechanisms And Circumvents Bortezomib Resistance, Dmitry Lembersky

Theses and Dissertations

Mechanisms underlying the interactions between the proteasome inhibitor carfilzomib and HDAC inhibitors were examined in both germinal center (GC) and activated B-cell (ABC) subtypes of human diffuse large B-cell lymphoma (DLBCL). Simultaneous exposure to minimally toxic concentrations of carfilzomib and HDAC inhibitor vorinostat resulted in the release of mitochondrial pro-apoptotic proteins SMAC and cytochrome c, pro-apoptotic caspase activation, and synergistic induction in apoptosis in both ABC and GC DLBCL subtypes. These events were associated with a marked increase in the stress kinase JNK, ROS generation, G2-M cell cycle arrest, as well as induction of DNA damage. Genetic knockdown of JNK …


Role Of The Porphyromonas Gingivalis Ecf Sigma Factor, Sigh, In Oxidative Stress Response, Sara Sarrafee Apr 2009

Role Of The Porphyromonas Gingivalis Ecf Sigma Factor, Sigh, In Oxidative Stress Response, Sara Sarrafee

Theses and Dissertations

Periodontal disease affects a majority of the US population. Porphyromonas gingivalis is the major etiological agent for development and progression of the disease. P. gingivalis is a hemin-dependent, obligate anaerobe that is found predominantly in periodontal pockets in infected patients. So for, little is known regarding the mechanisms which allow P. gingivalis to survive and sustain itself in the oral cavity. To better understand the adaptive mechanisms of the bacterium to the varying conditions in the oral cavity, regulatory mechanisms must be characterized. Sigma factors (σ) are responsible for initiating transcription by guiding RNA polymerase binding to specific DNA promoter …


Understanding Evolutionary Relationships In The Angiosperm Order Apiales Based On Analyses Of Organellar Dna Sequences And Nuclear Gene Duplications, Antoine Nicolas Apr 2009

Understanding Evolutionary Relationships In The Angiosperm Order Apiales Based On Analyses Of Organellar Dna Sequences And Nuclear Gene Duplications, Antoine Nicolas

Theses and Dissertations

I studied evolutionary history in the angiosperm order Apiales, with a special emphasis on interactions between form, time, and space. Four broad categories of problems were addressed: interfamilial relationships in Apiales, the assignment of genera traditionally assigned to the Apiaceae subfamily Hydrocotyloideae, the estimation of divergence times of the major clades, and the reconstruction of the biogeographic history of Apiales. We used molecular markers with different evolutionary properties and rates derived from the plastid (trnD-trnT and rpl16), nuclear (RPB2), and mitochondrial (nad1 intron 2) genomes, from more than 250 species representing all major clades in the order. The nuclear RPB2 …


The Role Of Brca1 In Dna Double-Strand Break Repair, Seth Dever Apr 2009

The Role Of Brca1 In Dna Double-Strand Break Repair, Seth Dever

Theses and Dissertations

Mutations in the breast cancer susceptibility 1 (BRCA1) gene are linked to breast as well as ovarian cancers. However, most cancer-causing mutations within the BRCA1 gene have been found in the N’ and C’ terminal regions of the BRCA1 protein, both believed to be important for DNA double-strand break (DSB) repair. The BRCA1 C’ terminal (BRCT) repeats have been implicated in phospho-serine protein binding whereas the N’ terminal RING domain interacts with the BARD1 protein to form a hetero-dimeric complex with E3 ubiquitin ligase activity. The BRCA1 BRCT domain binds CtIP, BACH1, and RAP80, all of which have been directly …


Scribble As A Possible Binding Partner For The Map Kinases Erk2 And Erk6, William Allen Apr 2009

Scribble As A Possible Binding Partner For The Map Kinases Erk2 And Erk6, William Allen

Theses and Dissertations

We worked on finding a new kinase regulator to develop basic data to be used for cancer prevention. Our work found a link between three previously unrelated proteins involved in cancer, ERK2 and ERK6 and Scribble. The MAP kinase cascade is involved in cell proliferation, which is highly deregulated in cancer. Through the screening of ERK6 associating molecules, we found the cell polarity, and cell cycle related molecule Scribble. Furthermore, we found that Scribble was a dual-specific kinase regulator. We clearly demonstrated that these ERKs interact with Scribble through the LRR and the PDZ domains of Scribble. We hypothesize that …


Influence Of Salinity Variations On The Desorption And Lability Of Soil Organic Carbon Associated With Tidal Freshwater Marshes, Lindsey Michelle Koren Apr 2009

Influence Of Salinity Variations On The Desorption And Lability Of Soil Organic Carbon Associated With Tidal Freshwater Marshes, Lindsey Michelle Koren

Theses and Dissertations

Tidal freshwater marshes (TFMs) are unique ecosystems that bridge the gap between terrestrial and aquatic ecosystems and are important in the sequestration of soil organic carbon. With the ever changing global climate, TFMs are left vulnerable to downstream effects of rising sea level and salt water intrusion due to increases in flooding by saline waters. These changes often act over large spatial and temporal scales resulting in significant impacts to local and regional environments. This multidisciplinary study assessed the amount and lability of desorbed organic carbon in tidal freshwater marsh soils from the Waccamaw River Marsh, South Carolina and Sweet …


Role Of Hepatic Cholesterol Ester Hydrolase (Ceh) In Hydrolyzing Cholesterol Esters (Ce) Delivered Via Sr-Bi (Scavenger Receptor Class B Type I) And Sr-Bii, Saurabh Bajpai Apr 2009

Role Of Hepatic Cholesterol Ester Hydrolase (Ceh) In Hydrolyzing Cholesterol Esters (Ce) Delivered Via Sr-Bi (Scavenger Receptor Class B Type I) And Sr-Bii, Saurabh Bajpai

Theses and Dissertations

Reduction of cholesterol ester (CE) from lipid burden lesion-associated macrophage foam cells has been shown to reduce plaque volumes. Hydrolysis of CE to free cholesterol (FC) in macrophages is an essential step for removal of CE from the macrophage and its transport to the liver by high density lipoprotein (HDL) for further metabolism. Since CE must again be hydrolyzed into FC in the liver catalyzing this hydrolysis, it becomes imperative to find the identity of these enzymes. In this study the role of key enzyme in catalyzing the hydrolysis of CE to FC, neutral cholesterol ester hydrolase (CEH) was evaluated. …


The Effects Of Cold Water Immersion On Fractioned Response Time, Patricia Jean Romney Apr 2009

The Effects Of Cold Water Immersion On Fractioned Response Time, Patricia Jean Romney

Theses and Dissertations

Objectives: Quantify the effects of cold water immersion of the ankle on fractioned response time of the dominant lower limb. Design and Setting: A 2x2x5x5 crossover design with repeated measures on time and treatment directed data collection. The independent variables were gender, treatment, time (pretreatment, and post 15 seconds, 3 minutes 6 minutes and 9 minutes) and trial (5 trials for each time group). Response time (Tresp), reaction time (Treac), trial and surface temperature were measurement variables. Subjects: Thirty-six subjects, 18 females and 18 males were recruited from a physically active volunteer college student population. Measurements: Fractioned response time was …


Consequences Of Shrub Encroachment: Linking Changes In Canopy Structure To Shifts In The Resource Environment, Steven Brantley Apr 2009

Consequences Of Shrub Encroachment: Linking Changes In Canopy Structure To Shifts In The Resource Environment, Steven Brantley

Theses and Dissertations

Shrub expansion in herbaceous ecosystems is emerging as an important ecological response to global change, especially in mesic systems where increases in canopy biomass are greatest. Two consequences of woody encroachment are increases in belowground resources, such as carbon and nitrogen, and reductions in above-ground resources such as light, which affect diversity, community trajectory, and ecosystem function. My objective was to determine how expansion of the nitrogen-fixing shrub Morella cerifera affected the resource environment across a chronosequence of shrub expansion on a Virginia barrier island. I quantified changes in carbon (C) and nitrogen (N) cycling, canopy structure and understory light …


The Presence Of Amphibian Ranavirus In Virginia Warm Water Fish Hatchery Ponds, Elizabeth Nelson Apr 2009

The Presence Of Amphibian Ranavirus In Virginia Warm Water Fish Hatchery Ponds, Elizabeth Nelson

Theses and Dissertations

Amphibian declines have been occurring world wide over the past several decades. Infectious disease and environmental changes have been implicated as the causative agents in these declines. Fish stocking from hatcheries provides a unique opportunity for organisms, including infectious diseases, to travel over long distances. Ranavirus was previously found in two ponds at Harrison Lake National Fish Hatchery in Charles City County, Virginia. Therefore, the primary objective of this study was to determine if ranavirus is present in tadpoles from four warm water fish hatcheries in Virginia. A secondary objective of this study was to determine if there are relationships …


Body Composition And Carotid Artery Intima-Media Thickness In 12 To 17-Year-Old Adolescents, Jennifer J. Willis Apr 2009

Body Composition And Carotid Artery Intima-Media Thickness In 12 To 17-Year-Old Adolescents, Jennifer J. Willis

Theses and Dissertations

Background and Purpose—There is controversy in the literature regarding the relationship between intima-media thickness (IMT) and body composition among adolescents. This study investigated the relationship between body fat percentage and IMT, while controlling for height, weight, age, blood pressure, cholesterol, glucose, triglycerides and VO2max in 12 to 17-year-old children.
Methods—111 children (mean age = 14.33 years) participated in this study. Body fat percentage was assessed using dual energy x-ray absorptiometry (DXA). A B-mode, high-resolution ultrasonograph was used to measure the IMT of the right and left common carotid arteries (CCA). Fasting blood tests were performed to obtain blood …


Generation Of Macrophage Chemotactic Factors By Spla2, Andria Chambers Apr 2009

Generation Of Macrophage Chemotactic Factors By Spla2, Andria Chambers

Theses and Dissertations

Removal of apoptotic cells by macrophages is required in order to prevent autoimmune responses. Previous studies have reported that group IIA secretory phospholipase A2 (sPLA2) preferentially binds to apoptotic cells and induces a chemotactic factor which promotes the migration of macrophages to apoptotic cells. Based on these observations, we hypothesized that the pool of sPLA2 trapped on apoptotic cells produces chemoattractant lipids that recruit macrophages to phagocytose the apoptotic cells. To test this hypothesis, Jurkat cells were cultured under normal conditions and induced to undergo early apoptosis through treatment with D,L-threo-dihydrosphingosine. Live and early apoptotic cells were incubated with catalytically …


The Role Of Connexin-36 Gap Junctions In Alcohol Intoxication And Reward, Kathryn Diane Bradley Apr 2009

The Role Of Connexin-36 Gap Junctions In Alcohol Intoxication And Reward, Kathryn Diane Bradley

Theses and Dissertations

The purpose of this thesis project was to examine the function of connexin-36 (Cx36) gap junctions (GJs) in producing alcohol's intoxicating and rewarding effects. GABA neurons are thought to inhibit dopamine (DA) neurotransmission in the mesocorticolimbic system, which originates in the midbrain ventral tegmental area (VTA) and projects to limbic structures such as the nucleus accumbens (NAcc). The mesolimbic DA system is believed to be the neural substrate of alcohol intoxication and addiction (Tepper, Paladini, & Celada, 1998). Alcohol suppresses the firing rate of GABA neurons in the VTA (Gallegos, Criado, Lee, Henriksen, & Steffensen, 1999) and presumably disinhibits DA …


Synthesis Of 2,4,5-Triaminocyclohexane Carboxylic Acid As A Novel 2-Deoxystreptamine Mimetic, Sarah Elizabeth Roberts Apr 2009

Synthesis Of 2,4,5-Triaminocyclohexane Carboxylic Acid As A Novel 2-Deoxystreptamine Mimetic, Sarah Elizabeth Roberts

Theses and Dissertations

RNAs have become increasingly recognized as possible drug targets due to their involvement in important biochemical functions, as well as their unique but well-defined structures. Recently published crystal structures depict the binding of a series of aminoglycosides- or more specifically- 2-deoxystretamine (2-DOS), the most preserved central scaffold of aminoglycosides, to a conserved 5'-GU-3'region on their target RNAs. A novel unnatural γ-amino acid, 1, has been synthesized using 2-deoxystreptamine as a template through structure-based rational design. The unnatural amino acid has been designed to replace a glycosidic linkage with an amide bond, which may limit the promiscuous binding characteristics of aminoglycosides …


Factors Affecting Dissolved Oxygen Metabolism In Coastal Plain Streams Of Virginia, Julie Frank Apr 2009

Factors Affecting Dissolved Oxygen Metabolism In Coastal Plain Streams Of Virginia, Julie Frank

Theses and Dissertations

I investigated seasonal and inter-site variation in factors influencing diel dissolved oxygen (DO) metabolism at four streams in the Virginia Coastal Plain. Data were collected monthly from January to August 2008 to characterize DO metabolism (diel DO amplitude, production, respiration), incident solar radiation (PAR), dissolved nutrients, fine benthic materials (mass, C:N, Chlα) and hydrology (discharge, water transit time, transient storage). Reach-scale metabolism estimates were determined using the one-station diurnal DO technique and transit time and transient storage were determined by conservative tracer additions. Incident solar radiation was the primary determinant of DO metabolism as streams experiencing higher light levels (Herring …


Development Of An Exercise Test To Predict Vo2max In Children And Adolescents, Nathan E. Black Apr 2009

Development Of An Exercise Test To Predict Vo2max In Children And Adolescents, Nathan E. Black

Theses and Dissertations

The purpose of this study was to evaluate the use of nonexercise (N-EX) data, specifically, the Perceived Functional Ability (PFA) and Physical Activity Rating (PA-R) questionnaires, with the treadmill walk-jog-run protocol to estimate VO2max in 12 to 17 year old boys and girls. Ninety-one participants (49 males and 42 females) took part in this study. Data were collected via PFA and PA-R questionnaires, a walk-jog-run submaximal treadmill test, and a maximal graded exercise test (GXT). Data collected included gender, age, height, weight, PFA and PA-R scores, heart rate (HR), treadmill speed, maximal treadmill grade, respiratory exchange ratio (RER), rating of …


Molecular Systematics Of Spiny Pocket Mice (Subfamily Heteromyinae) Inferred From Mitochondrial And Nuclear Sequence Data, Melina Crystal Williamson Apr 2009

Molecular Systematics Of Spiny Pocket Mice (Subfamily Heteromyinae) Inferred From Mitochondrial And Nuclear Sequence Data, Melina Crystal Williamson

Theses and Dissertations

This study aims to determine species-level relationships within the genus Heteromys, as well as generic-level relationships among members of the subfamily Heteromyinae using a phylogenetic framework. Molecular sequence data were generated from two mitochondrial genes (cytochrome b and cytochrome oxidase I) and three nuclear gene segments (β-fibrinogen, engrailed protein II, and myosin heavy chain II), and analyzed under maximum parsimony, maximum likelihood, and Bayesian optimality criteria to infer relationships. Chapter 1 focuses on the phylogenetic and taxonomic implications for Heteromys from the analyses of sequence data. Phylogenies also provided a framework for delimiting species boundaries within the wide-ranging Heteromys desmarestianus …


Matrix Metalloproteinase Expression In Models Of Parkinson's Disease, Justin Mcclain Apr 2009

Matrix Metalloproteinase Expression In Models Of Parkinson's Disease, Justin Mcclain

Theses and Dissertations

Parkinson’s disease (PD) is a devastating neurodegenerative disorder characterized by progressive loss of dopaminergic neurons located in the substantia nigra. Accumulating evidence indicates that microglia-driven neuroinflammation contributes significantly to chronic neurodegeneration in PD. The matrix metalloproteinases (MMPs) play an important role in several neuroinflammatory paradigms; however, their relationship to dopaminergic neurodegeneration in PD remains relatively unexplored. To address this, the temporal relationship between MMP-2, MMP-3, MMP-9, and MMP-13 expression and dopaminergic neurodegeneration was compared in the 6-hydroxydopamine (6-OHDA) and lipopolysaccharide (LPS) models of PD. In dopaminergic SH-SY5Y cells, 6-OHDA treatment significantly increased MMP-13 mRNA expression; however, examination of 6-OHDA-lesioned rats …


Coupling Of Autotrophic And Heterotrophic Plankton Food Web Components In The Tidal-Freshwater James River, Usa, Matthew Beckwith Apr 2009

Coupling Of Autotrophic And Heterotrophic Plankton Food Web Components In The Tidal-Freshwater James River, Usa, Matthew Beckwith

Theses and Dissertations

Empirical studies have shown that algal- and detrital-based food web components are coupled in many pelagic systems as algal carbon enhances bacterioplankton production and growth efficiencies. Such phyto-bacterioplankton coupling impacts carbon flow through plankton food webs, yet the extent of coupling is poorly understood in systems receiving large amounts of allochthonous carbon. To investigate this issue, bacterioplankton abundance (BA) and community composition were compared to chlorophyll a concentrations and phytoplankton production in the tidal-freshwater James River (VA). BA averaged 107 cells mL-1 and was significantly related to chlorophyll a, phytoplankton production, and DOC concentrations. Analysis of DOC quality using fluorescence …


Identification Of Binding Partners Of A Novel P. Falciparum Exported Protein, Monica Zapata Apr 2009

Identification Of Binding Partners Of A Novel P. Falciparum Exported Protein, Monica Zapata

Theses and Dissertations

Plasmodium falciparum is the causative agent of the most severe form of malaria. This parasite drastically modifies its host cell, the erythrocyte, to create a hospitable environment for its growth and reproduction. In order for these modifications to occur, the parasite secretes proteins into the erythrocyte. While the secretion machinery is still unknown, many secreted proteins have been found to have a hydrophobic signal sequence and a novel host-targeting signal downstream of the hydrophobic sequence. A novel P. falciparum protein has been shown to be secreted from the parasitophorous vacuole, yet it lacks both a hydrophobic signal sequence and a …


Novel Mechanisms Regulating Cytokine-Induced Gene Expression In Astrocytes And Glioblastoma Cells, Lauren Bryan Apr 2009

Novel Mechanisms Regulating Cytokine-Induced Gene Expression In Astrocytes And Glioblastoma Cells, Lauren Bryan

Theses and Dissertations

Chronic inflammation in the brain results in the development of several CNS diseases, including Alzheimer’s and Parkinson’s diseases, multiple sclerosis, and tumors. IL-1, a pro-inflammatory cytokine released by activated microglia and astrocytes, instigates the expression of factors promoting the progression of these CNS disorders, including cytokines, chemokines, and components of matrix remodeling systems, such as the plasminogen activator system. IL-1 also increases the mRNA expression and activity of SphK, the enzyme that phosphorylates Sph to form S1P, a bio-active sphingolipid. This thesis demonstrates that IL-1 and S1P enhance the mRNA and protein expression of PAI-1 and uPAR, two key components …


Molecular Mechanisms For Regulation Of Gene Expression By Lysophosphatidic Acid In Ovarian Carcinoma Cells, Regina Oyesanya Apr 2009

Molecular Mechanisms For Regulation Of Gene Expression By Lysophosphatidic Acid In Ovarian Carcinoma Cells, Regina Oyesanya

Theses and Dissertations

Lysophosphatidic acid (LPA) is a potent bioactive phospholipid mediator that functions through multiple G protein couple receptors (GPCRs). LPA is elevated in ascites of ovarian cancer patients and is involved in growth, survival and metastasis of ovarian cancer cells. Gene promoter analyses revealed that some LPA-target genes share similar sets of binding sites for prominent transcription factors posing the possibility of a general mechanism for activation of their expression by LPA. Detailed investigation of the mechanisms of regulation of cyclooxygenase 2 (Cox-2), a paradigm of LPA-regulated genes, showed that LPA robustly upregulated the expression of Cox-2 in ovarian cancer cells …


The Role Of Mitogen-Activated Protein Kinases In The Regulation Of Plant Development, Erica Satterfield Apr 2009

The Role Of Mitogen-Activated Protein Kinases In The Regulation Of Plant Development, Erica Satterfield

Theses and Dissertations

Mitogen-activated protein kinases are part of an evolutionarily conserved protein phosphorylation cascade which serves essential regulatory functions in eukaryotic organisms. Although the role of MAPKs in the regulation of a plant’s response to environmental stress and plant defense has been well established, very little is known about their role in the regulation of plant developmental processes. In order to examine the role of MAPKs in plant growth and development, a strong mammalian MAPK phosphatase (MKP-1), which is known to inactivate MAPKs in plants, was introduced into tobacco plants. In tobacco plants, MKP-1 overexpression altered plant responses to the phytohormones, ethylene …


Role Of Molecular Chaperones In G Protein B5-Regulator Of G Protein Signaling Dimer Assembly And G Protein By Dimer Specificity, Alyson Cerny Howlett Apr 2009

Role Of Molecular Chaperones In G Protein B5-Regulator Of G Protein Signaling Dimer Assembly And G Protein By Dimer Specificity, Alyson Cerny Howlett

Theses and Dissertations

In order for G protein signaling to occur, the G protein heterotrimer must be assembled from its nascent polypeptides. The most difficult step in this process is the formation of the Gβγ dimer from the free subunits since both are unstable in the absence of the other. Recent studies have shown that phosducin-like protein (PhLP1) works as a co-chaperone with the cytosolic chaperonin complex (CCT) to fold Gβ and mediate its interaction with Gγ. However, these studies did not address questions concerning the scope of PhLP1 and CCT-mediated Gβγ assembly, which are important questions given that there are four Gβs …