Life Sciences Commons^™

The Role Of Secreted Phosphoprotein-24 In Osteoblast Differentiation And Matrix Mineralization, Samuel Ramage

Theses and Dissertations

Secreted Phosphoprotein-24 (Spp24) was initially isolated and characterized as a component of bovine cortical bone matrix. Subsequent characterization has shown it is multiply phosphorylated and homologous to cystatin and TGF-β receptor type II. Spp24 is a minor component of the serum fetuin mineral complex that binds calcium-phosphate minerals and prevents their deposition. The TGF-β receptor homology domain binds BMP-2 weakly in vitro and enhances BMP-2’s osteogenic effects in vivo. The ability of Spp24 to affect BMP activity suggests an important role for Spp24 as a native, bioactive componentof bone that regulates bone development.

Spp24 was highly up-regulated in rat cortical …

Stream Ambient Noise, Spectrum And Propagation Of Sounds In The Goby Padogobius Martensii: Sound Pressure And Particle Velocity, Marco Lugli, Michael L. Fine

Biology Publications

The most sensitive hearing and peak frequencies of courtship calls of the stream goby, Padogobius martensii, fall within a quiet window at around 100Hz in the ambient noise spectrum. Acoustic pressure was previously measured although Padogobius likely responds to particle motion. In this study a combination pressure (p) and particle velocity (u) detector was utilized to describe ambient noise of the habitat, the characteristics of the goby’s sounds and their attenuation with distance. The ambient noise (AN) spectrum is generally similar for p and u (including the quiet window at noisy locations), although the energy distribution of uspectrum is …

The Ksga Methyltransferase: Characterization Of A Universally Conserved Protein Involved In Robosome Biogenesis, Heather Colleen O'Farrell

Theses and Dissertations

The KsgA enzymes comprise an ancient family of methyltransferases that are intimately involved in ribosome biogenesis. Ribosome biogenesis is a complicated process, involving numerous cleavage, base modification and assembly steps. All ribosomes share the same general architecture, with small and large subunits made up of roughly similar rRNA species and a variety of ribosomal proteins. However, the fundamental assembly process differs significantly between eukaryotes and eubacteria, not only in distribution and mechanism of modifications but also in organization of assembly steps. Despite these differences, members of the KsgA/Dim1 methyltransferase family and their resultant modification of small-subunit rRNA are found throughout …

Interleukin-10 Suppresses Mast Cell Ige Receptor Expression And Signaling In Vitro And In Vivo, Sarah B. Kennedy

Theses and Dissertations

Background: Mast cells are known for their role in allergy, asthma, and systemic anaphylaxis, and have been shown to play a role in inflammatory disease. Interleukin-10 can regulate inflammatory responses both in vitro and in vivo, and may be a natural regulator of mast cell activation.Objective: To examine Interleukin-10 mediated regulation of FcεRI expression and related downstream signaling molecules, and to determine how this affects mast cell function in vitro and in vivo.Methods: Mast cell FcεRI expression was evaluated with and without IL-10 treatment in human lung and skin mast cells, and on peritoneal mast cells from mice overexpressing IL-10 …

Investigation Of Age Related Differences In The Rewiring Of P2-Olfactory Receptor Neurons, Daniel Joseph Galante

Theses and Dissertations

Olfactory receptor neurons (ORNs) maintain the ability to regenerate. These neurons reside in the olfactory epithelium and project axons that connect to the olfactory bulbs. Despite the diffuse distribution of ORNs in the olfactory epithelium, they converge at discrete glomeruli in the olfactory bulb. In the P2 IRES tau-lacZ mouse, the P2 ORN subtype has been previously mapped to two glomeruli, using X-gal staining. To determine if age affects ORN regeneration, left olfactory nerve transections were performed on P2 mice from immature (five-weeks old) and mature (1 6-weeks old) groups. Following recovery, the olfactory bulbs were processed to observe ORN …

Induction Of Heme Oxygenase By A Carbon Monoxide-Releasing Molecule, Robert Andrew Kulina

Theses and Dissertations

We have recently demonstrated that heme oxygenase is expressed in both healing wounds and in pressure ulcers. Heme oxygenase has been shown to have important cytoprotective functions in myocardial ischemia-reperfusion injury and organ allograft survival. The cytoprotective effects of heme oxygenase are multifactorial. Besides reducing levels of pro-oxidant heme, heme oxygenase products (bilirubin, carbon monoxide, and iron) have been demonstrated to possess anti-oxidant, anti-inflammatory, anti-apoptotic, and anti-proliferative properties. These properties make heme oxygenase an attractive therapeutic target for the prevention and treatment of chronic wounds. The purpose of this study was two-fold: evaluate the effects of carbon monoxide (CO) on …

Signaling By Protease-Activated Receptors In Gastrointestinal Smooth Muscle, Wimolpak Sriwai

Theses and Dissertations

In the present study, we have examined the expression of protease-activated receptors (PARS) and characterized their signaling pathways in rabbit gastric muscle cells. Immunoblot analysis revealed expression of PARl and PAR2 but not PAR3 or PAR4 in smooth muscle. The PARl agonist TFLLR activated Gq, G12, and Gi3, but not Gil, Gi2, G13, Gs or Gz, whereas the PAR2 agonist SLIGRL activated Gq, G13, Gil, and Gi2, but not Gi3, G12, Gs, or Gz. Both PARl and PAR2 agonists stimulated PI hydrolysis and Rho kinase activity and inhibited cAMP formation. PAR1-stimulated PI hydrolysis was abolished in cells expressing Gαq minigene, …

Role Of Rok And Pkc In Permeabilized Rabbit Femoral Artery, Lyndsay Jacquelyn Clelland

Theses and Dissertations

Discoveries made with KCl-induced contractions have elucidated the more complex reactions involved in GPCRs signaling; once the mechanisms of smooth muscle Ca2+ sensitization and desensitization are fully understood, then the development of advanced treatments for vascular disorders such as hypertension, cerebral and coronary vasospasm, and vascular hyporeactivity following hemorrhagic shock may be possible. Studies have shown that KCl-induced contractions induce Ca2+-sensitization. Therefore, we tested the hypothesis that KCl induced Ca2+-sensitization is due to ROK activation by the increase in [Ca2+]i. To test this hypothesis, rabbit femoral arteries were permeabilized with 20µg/ml α-toxin and 1% Triton X-100 and subjected to different …

Genetic Variations In Interferon-Induced Genes And Hcv Recurrence After Liver Transplantation, Benjamin Cameron Whitehill

Theses and Dissertations

Hepatitis C Virus (HCV) infection represents a worldwide pandemic and is currently the leading cause of cirrhosis and liver transplantation. After transplantation recurrence is almost universal with 96% of patients testing positive for viral RNA and exhibiting histological evidence of infection within the first year. Type I interferons (IFN) and interferon inducible genes are responsible for the innate antiviral state and single nucleotide polymorphisms (SNPs) within these genes may affect the patients ability to respond post-transplantation. We hypothesize the elucidation of associations between SNPs in Type-I Interferon and Interferon inducible genes and HCV recurrence post-liver transplantation might help to identify …

The Role Of Sphingosine Kinase 2 In Cell Growth And Apoptosis, Heidi M. Sankala

Theses and Dissertations

Two isoforms of sphingosine kinase (SphK) catalyze the formation of sphingosine-1-phosphate (SIP). Whereas, SphKl stimulates cell growth and survival, it was found that when overexpressed in mouse NIH 3T3 fibroblasts SphK2 enhances caspase-dependent apoptosis in response to serum deprivation, independently of S1P receptors. Sequence analysis revealed that SphK2 contains a 9 amino acid motif similar to that present in BH3-only proteins. Studies showed that the BH3-only domain, catalytic activity, endoplasmic reticulum (ER) stress, and uptake of calcium by the mitochondria may all contribute to the apoptotic effects of overexpressed SphK2 in NIH 3T3 cells. Further studies in human carcinoma cells …

The Expression Of Neutrophil Products, Myeloperoxidase And Matrix Metalloproteinase 8, In Systemic Vasculature Of Obese And Preeclamptic Women, Juhi Shukla

Theses and Dissertations

Evidence shows the activation of neutrophils in the systemic vasculature of obese and preeclamptic women. In this study, I evaluated whether expression of neutrophil products, myeloperoxidase (MPO) and matrix metalloproteinase 8 (MMPS), was associated with neutrophil infiltration in systemic vascular tissue of obese and preeclamptic women. I tested my hypotheses by using immunohistochemical studies to look at the expression of MPO and MMP8 in the vasculature of obese and preeclamptic women. There was a significantly greater expression of MPO and MMP8 in the vasculature of preeclamptic women as compared to normal pregnant and normalnonpregnant women. The vasculature of obese women …

Role Of Ceramide-1-Phosphate As A Specific And Potent Activator Of Group Iva Cytosolic Phospholipase A2 Alpha, Preeti Subramanian

Theses and Dissertations

Eicosanoids are potent mediators of inflammatory response whose role has been well established in inflammatory disorders. Release of arachidonic acid by group IVA cytosolic phospholipase A2 α (cPLA2α) is the initial rate limiting step for the production of eicosonoids in response to inflammatory mediators. Previous findings from our laboratory have demonstrated that cPLA2α is directly activated by the emerging bioactive sphingolipid, ceramide-1-phosphate (C1P). In this study, we have developed a modified Triton X-100/phosphatidylcholine (PC) mixed micelle assay which was utilized to determine the kinetics and specificity of this lipid-enzyme interaction. Using this assay, the activity of the enzyme increased in …

Divergent Roles Of Pi3k And Akt In Rapamycin-Induced Cardioprotection Against Ischemia-Reperfusion Injury, Shivani Kirit Desai

Theses and Dissertations

Coronary heart disease (CHD) is one of the leading causes of death every year with nearly three-fourths of all deaths caused by the disease. The challenge scientists are facing today is discovering new drugs to protect the heart against cellular damage caused by ischemia-reperfusion injury (I-R injury). Rapamycin is one such drug that has been shown to protect the heart against ischemia-induced cellular injury. Rapamycin(sirolimus) inhibits protein synthesis through inhibition of the mammalian target ofrapamycin (mTOR). This property of rapamycin has led to its current clinical applications in drug-eluting stents and in immunosuppresive treatment to organ transplant patients. The mechanism …

Corticular Photosynthetic Dynamics For A Coastal Evergreen Shrub: Myrica Cerifera, Jaclyn K. Vick

Theses and Dissertations

I quantified seasonal variations in corticular photosynthesis in 1st through 5th order branches of Myrica cerifera L. (Myricaceae) in order to determine whether corticular photosynthesis contributes to whole plant carbon gain by reducing respirational CO2 loss. Maximum % refixation was 110 ± 39 % of CO2 efflux in the dark (Rd) in 1st order branches during winter, minimum was 18 ± 3 % in 5th order branches during summer. Variations in % refixation paralleled changes in photosynthetically active radiation (PAR). As light attenuated with increasing branch order % refixation decreased. Increased PAR in the winter due to a more sparse …

Effects Of Cxcl8 Overexpression On Tumor Cell Proliferation And Migration In An Hnscc Cell Model, Emil Paul Christofakis

Theses and Dissertations

Head and neck squamous cell carcinoma is the 6th most common malignancyworldwide. Recently, a link between cancer and inflammation has been found. Mediatingthis relationship are the chemotactic cytokines known as chemokines. CXCL8 (Interleukin-8), a CXC ELR+ Chemokine mainly responsible for neutrophil chemoattraction, has beenimplicated in increased tumor proliferation, migration and angiogenesis. The current studytests the effects of CXCL8 on the tumor proliferation and metastasis. By genetically modifying cells to knockdown or overexpress the CXCL8 gene we tested its biological rolein head and neck cancer progression. Overexpression of CXCL8 in HN4 tumor cells withlow endogenous CXCL8 levels was found to increase …

Addressing Issues In The Detection Of Gene-Environment Interaction Through The Study Of Conduct Disorder, Elizabeth Prom-Wormley

Theses and Dissertations

This work addresses issues in the study of gene-environment interaction (GxE) through research of conduct disorder (CD) among adolescents and extends the recent report of significant GxE and subsequent replication studies. A sub-sample of 1,299 individual participants/649 twin pairs and their parents from the Virginia Twin Study of Adolescent and Behavioral Development was used for whom Monoamine Oxidase A (MAOA) genotype, diagnosis of CD, maternal antisocial personality symptoms, and household neglect were obtained. This dissertation (1) tested for GxE by gender using MAOA and childhood adversity using multiple approaches to CD measurement and model assessment, (2) determined whether other mechanisms …

The Influence Of Adenoviral Infection And The Group Via Calcium-Independent Phospholipase A2 On Hepatic Lipid Metabolism, William Palmer Wilkins Iii

Theses and Dissertations

Sterol regulatory element-binding proteins (SREBP) are transcription factors that regulate genes involved in lipid metabolism especially in the liver. Therefore, hepatic SREBP is significant regulator of systemic lipid metabolism. Evidence demonstrates that insulin and dietary unsaturated fatty acid (UFA) regulate SREBP1 expression and subsequent SREBP1-mediated gene transcription, events that in many instances result in modulation of systemic fatty acid and triglyceride (TG) homeostasis. A series of investigations was designed to uncover novel regulators of SREBP1. Dietary and exogenous addition of UFA has been shown to regulate SREBP function yet, an endogenous source of UFA capable of modulating SREBP remains elusive. …

A Comparison Of The Pectoral Spines In Virginia Catfishes, Amanda Dawn Duvall

Theses and Dissertations

Catfish pectoral spines are an anti-predator defense mechanism. They can be bound or locked, making the fish harder to swallow, or used to produce distress calls by rubbing ridges on the dorsal process against a channel in the wall of the pectoral girdle. Growth of the pectoral spine and girdle were examined in relation to fish size within and across species that occur throughout central and eastern Virginia. These included blue catfish (Ictalurus furcatus), channel catfish (Ictalurus punctatus), white catfish (Ameiurus catus), brown bullheads (Ameiurus nebulosus), yellow bullheads (Ameiurus natalis), flathead catfish (Pylodictis olivaris), margined madtom (Noturus insignis), and tadpole …

Electrospun Blends Of Polydioxanone And Fibrinogen For Urological Applications, Joshua Ford Grant

Theses and Dissertations

The need for tissue and organ replacements cannot be satisfied by autograft and allografts alone. The purpose of this study was to investigate the feasibility of electrospinning a blend of polydioxanone and fibrinogen to produce an engineered tissue scaffold. Fiber diameter and pore size of blends were characterized, as well as mechanical strength. Cell proliferation assays for 1 and 7 day cultures were preformed, and a histological evaluation was performed to determine how favorable the various blends were to cell infiltration and proliferation. Some ratios of blends were identified that contained both acceptable mechanical properties and properties that facilitated cell …

Spatial And Temporal Patterns Of Anadromous Fish Passage At Boshers Dam Vertical Slot Fishway On The James River, Richmond, Virginia, Matthew Thomas Fisher

Theses and Dissertations

Boshers dam vertical slot fishway, James River, Virginia, U.S.A., opened in 1999 and restored connectivity to 543.3 km of spawning habitat for anadromous fish. The fishway also allowed local movement of resident species. Video observation from 2001-2005 was used to evaluate environmental predictors of American shad (Alosa sapidissima) and sea lamprey (Petromyzon marinus) passage. The ecological effects of restoring connectivity to upstream habitat for gizzard shad (Dorosoma cepedianum) and blue catfish (Ictalurus furcatus) are also discussed. Regression analysis determined that the best predictor of increased daytime American shad passage is higher water temperatures and discharge and for increased daytime sea …