Medicine and Health Sciences Commons^™

Characterization Of The Genes Involved In Biosynthesis And Transport Of Schizokinen, A Siderophore Produced By Rhizobium Leguminosarum Iari 917., David Jack Hammond

Electronic Theses and Dissertations

Iron is the 4th most abundant metal on the earth's crust and is required by most organisms as a cofactor for many enzymes; however, at physiological pH and aerobic conditions iron forms insoluble ferric oxyhydroxide polymers. Siderophores are low molecular weight compounds that scavenge ferric ions, bind with high affinity, and transport it into the cell via multicomponent transport systems. Rhizobia are soil dwelling organisms that form symbiotic relationships with host plants and fix atmospheric nitrogen, while the bacteria receive nutrients. R. leguminosarum IARI 917 produces a siderophore characterized as 'schizokinen'. In the present study, we have characterized the binding …

Abcb6 Is A Porphyrin Transporter With A Novel Trafficking Signal That Is Conserved In Other Abc Transporters, Yu Fukuda

Theses and Dissertations (ETD)

The ATP-binding cassette (ABC) transporters play an important role as a barrier to protect cells from the accumulation of toxic xenobiotics and metabolites due to their ability to translocate a wide array of compounds across lipid bilayers. However, many ABC transporters, especially the ones localized in the intracellular organelles, are involved in critical biological processes such as antigen presentation. The core unit of ABC transporters contains two functional domains: the membrane spanning domain (MSD) and the nucleotide binding domain. The full transporters contain two of these units in tandem in a single polypeptide, whereas the half transporters only contain one …

Manipulation Of The Moloney Murine Leukemia Virus Envelope Protein In An Effort To Develop Directly And Indirectly Targeted Retroviral Vectors For Use In Human Gene Therapy, Geneva M. Vasser

Theses and Dissertations (ETD)

Highly effective, targeted therapies against cancer would revolutionize the way people recover from this devastating illness. Gone would be the lingering side effects of the current non-specific treatments and in their place would be faster recovery times, better quality of life both during and after treatment, and less ambiguity about whether or not treatment was effective. This concept will elude modern medicine until treatments can be tailored to the patient's individual and unique disease. This concept of a transient, targeted, and tailored vehicle aimed at cancer cells lends itself to the use of replication deficient retroviral gene therapy vectors with …

C-Reactive Protein Polymorphism And Serum Levels As An Independent Risk Factor In Sickle Cell Disease, Elizabeth A. Chismark

Theses and Dissertations (ETD)

This study explored the relationship of a dinucleotide repeat polymorphism in the intron of the CRP gene and serum CRP levels as independent risk factors for end-organ dysfunction (mild vs. severe) in adults with sickle cell disease. The pathogenesis of secondary complications of sickle cell disease is complex and poorly understood. Predicting the severity of these complications could assist in therapeutic decision-making.

The study measured serum CRP levels and the number of CA intron repeats located on the CRP gene in 29 adults (31.74 ± 11.54 years) with sickle cell disease The hemoglobin genotypes were distributed as Hgb SS 48.6% …

Regulation Of The Human Parainfluenza Virus (Hpiv3) Fusion Protein, Amanda Ruth Chapman

Theses and Dissertations (ETD)

Paramyxoviruses include a number of important human pathogens, including measles virus, mumps virus, and the human parainfluenza viruses (hPIV) 1-4, as well as several animal pathogens, such as Sendai virus, Nipah virus and Hendra virus. The creation of effective drugs and vaccines against this family of viruses would play an important role in decreasing the prevalence of these viruses and contributing to the health of both humans and animals worldwide. The purpose of this work was to determine how the fusion (F) protein is regulated with a focus on the heptad repeat B (HRB) region of the F protein located …

Selective Non-Peptide Mu-Opioid Receptor Antagonist: Design, Synthesis And Biological Studies, Lindsey Aschenbach

Theses and Dissertations

There are currently many opioid agonists available for clinical use as analgesics. However, many of these opioid agonists have notorious side effects including respiratory depression and may lead to addiction and dependence. Problems associated with these opioid agonists are determined to come from their interactions with the mu-opioid receptor. Opioid antagonists, such as naltrexone, have shown to aid in the treatment of opioid addiction. Although naltrexone has high affinity to the mu-opioid receptor, it lacks selectivity. Novel selective mu-opioid receptor antagonists were designed based on the identification of important pharmacophore elements in several known mu-opioid receptor agonists and antagonists. These …

Arginine Vasopressin And Male Attachment: A Marital And Family Therapy Perspective, Calvin James Thomsen

Loma Linda University Electronic Theses, Dissertations & Projects

Social neuroscience offers a promising way to understand some dimensions of adult attachment. Arginine vasopressin (AVP) is a neuropeptide with significant implications for human social behavior and it provides an important testing ground to explore links between social/interpersonal neurobiology and attachment. It has a distinctive impact on the social/relational behavior of certain male animals, most notably prairie voles. It fosters monogamy, creates attachment to both mate and offspring, and increases affiliation and a desire for physical proximity with other animals of the species. There has been much speculation that it might play a similar role with human males. This study …

Sex Differences In Nicotine-Conditioned Hyperactivity In A Model Of Dopamine D2 Receptor Priming: Roles Of Dopamine D2 And D3 Receptor Subtypes., Ashley Brianna Sheppard

Electronic Theses and Dissertations

The aim of this investigation was to determine the effect of a nicotine-conditioned context on locomotor hyperactivity in an animal model of D2-priming, and whether conditioned hyperactivity could be blocked by the D2 antagonist eticlopride or the D3 antagonist nafadotride. D2-primed male rats showed enhanced nicotine sensitization as evidenced by statistically significant differences in horizontal activity. D2-primed female rats administered nicotine demonstrated an increased hypoactive response after initial sensitization and increased stereotypy. Eticlopride and nafadotride blocked sensitization to nicotine in both D2-primed and non D2-primed males and females. Eticlopride blocked conditioned hyperactivity in females but not in males. D2-primed female …

The Association Of Maternal Intention To Breastfeed, Early Skin-To-Skin Mother/Infant Contact, And Exclusive Breastfeeding During The Maternity Hospital Stay, Leslie Mary Bramson

Loma Linda University Electronic Theses, Dissertations & Projects

Breastfeeding is the optimal method to nourish and nurture an infant. Exclusive breastfeeding rates in the United States have reached the goal of Healthy People 2010 that 75% of mother's breastfeed in the immediate postpartum period. Yet, less than 35% of San Bernardino county mothers and 47.7% of Riverside county mothers are exclusively breastfeeding during their maternity hospital stays, with as many as 50% of the infants being weaned from the breast in the first 14 days of life.

This prospective study examined archived data collected by Perinatal Services Network (PSN) of Loma Linda University Medical Center/Children's Hospital for the …

Dna Sequence Analysis Of A Bioluminescent Marine Bacterium, Benjamin Ryder

Master's Theses, Dissertations, Graduate Research and Major Papers Overview

Studies the sequencing of the DNA fragment containing the gene phaC (PHA synthase) and undertakes the search for open reading frames and putative gene matches in a bioluminescent marine bacterium.

Novel Binding Domains Mediate Binding Of Hpv 16 E6 To Fadd And Procaspase 8, Sandy S. Tungteakkhun

Loma Linda University Electronic Theses, Dissertations & Projects

To evade the host response to infection, viruses have developed means to survive and propagate. HPV 16, a causative agent of cervical cancer and of some cases of oropharyngeal cancers, is one example. We have reported that the early viral protein E6 binds to proteins necessary for propagation of the apoptotic signal following receptor/ligand interactions, such as those mediated by FADD DED and procaspase 8 DED. E6 expression leads to the dose-dependent accelerated degradation of FADD and the protection of E6-expressing cells from Fas-induced apoptosis. Surprisingly, the splice isoforms of E6, E6_large and E6*, affect the stability of procaspase …

Toward The Synthesis Of Nuclease Models., Enni Nina Fomumbod

Electronic Theses and Dissertations

Nucleases are enzymes that can specifically recognize nucleic acids and hydrolyze their phosphodiester bonds effectively. As is the case with many hydrolases, nucleases often carry one or more metal centers. Cooperation between such metal centers and other interactions involving general acid-base activities are believed to be essential in multifunctional catalyses. Combination of such interactions in model compounds often resulted in larger than additive effects.

This work is aimed at synthesizing nuclease models that combine the ability to recognize phosphate groups and/or nitrogen bases of DNA together with the ability to catalyze phosphodiester hydrolysis. These models were designed to achieve optimum …

Expression, Purification, And Characterization Of The Mast Cell Proteases Chymase And Cathepsin G., Brent E. Lockhart

Electronic Theses and Dissertations

Human mast cells have been associated with wound healing, allergies, inflammation, and defense against pathogens and have been detected in tissues close to blood vessels especially in the areas between the inside of the body and the external environment, such as the skin, lungs, digestive tract, mouth, and nose. Previous studies have shown that mast cells contain large granules filled with histamine, heparin, cytokines, eicosanoids, and the serine proteases, tryptase, Chymase, and cathepsin G (CatG). These proteases are stored and released from mast-cell granules upon activation by antigen binding to IgE immunoglobulins on the cell surface or by direct injury. …

The N-Terminal Domain Of The Y-Box Binding Protein Yb-1 Plays A Major Role In Cell Proliferation And Apoptosis, Payal Khandelwal

Theses and Dissertations (ETD)

Y-box binding protein, YB-1, is a member of the cold shock domain superfamily of proteins. It is involved in a plethora of cellular functions, including cell proliferation. The molecular mechanisms governing the involvement of YB-1 in cell proliferation are still unclear. Earlier studies done in chicken pre-B lymphocyte DT-40 cells in our laboratory have shown that a targeted disruption in one allele of chicken YB-1

(Chk-Yb-1b) gene at its N-terminal domain resulted in multiple abnormalities in the heterozygous mutants, including slower growth rate, abnormal cell morphology, increased cell size, increased genomic DNA content and significant changes in levels of cell …

Cdc45 Function Alters Cell Sensitivity To Dna Topoisomerase I Poisons, Cynthia Sue Lancaster

Theses and Dissertations (ETD)

Eukaryotic DNA topoisomerase I (Top1) is a highly conserved enzyme that functions to manage the torsional strain of DNA during cellular processes such as transcription, replication, chromatid condensation and recombination. The enzyme binds duplex DNA and through a series of strand cleavage and religation reactions removes positive or negative supercoils relieving torsional strain. Top1 is the sole cellular target of the anticancer agent camptothecin, which stabilizes the covalent complex. CPT cytotoxicity is S-phase dependent. It has been suggested that the mechanism of this S-phase toxicity is due to the advancing replication forks either colliding with the stabilized drug-enzyme-DNA intermediate or …

Transcriptional Regulation Of Azole Antifungal Resistance In Candida Albicans, Teresa T. Liu

Theses and Dissertations (ETD)

Candida albicans is a pathogenic fungi found in the mucosa, gastrointestinal, and urogenital tracts of humans. Oropharyngeal candidiasis (OPC), an opportunistic mucosal infection caused by C. albicans, occurs most frequently in patients infected with human immunodeficiency virus (HIV). OPC is usually treated with azole antifungals, a class of antifungals that target ergosterol biosynthesis, at low doses over long periods of time. This course of treatment allows for the development of azole resistance.

Two major mechanisms of azole resistance exist in C. albicans, the up-regulation of genes encoding efflux pumps and the up-regulation of ERG11, a gene encoding the azole drug …

The Structural And Functional Study Of Git1 Paxillin Binding Domain, Ziwei Zhang

Theses and Dissertations (ETD)

The G protein coupled receptor (GPCR)-kinase (GRK) interacting protein 1 (GIT1) is a multidomain protein that plays an important role in cell adhesion, motility, cytoskeletal remodeling, and membrane trafficking. GIT1 mediates the localization of p21-activated kinase (PAK) and PAK-interactive exchange factor (PIX) to focal adhesions, and its activation is regulated by the interaction between its C terminal paxillin-binding domain (PBD) and the LD motifs of paxillin.

In this dissertation, we determined the solution structure of rat GIT1 PBD by nuclear magnetic resonance (NMR) spectroscopy. The PBD folds into a four-helix bundle, which is structurally similar to the focal adhesion targeting …

Designing Non-Saccharide Heparin/Heparan Sulfate Mimics, Arjun Raghuraman

Theses and Dissertations

Glycosaminoglycans (GAGs) are complex biopolymers that play important roles in inflammation, coagulation, angiogenesis, cell adhesion and viral invasion by interacting with several different proteins.1,2 Structurally, GAGs are built up of several different sulfated disaccharide units.3 Specific GAG sequences that uniquely recognize their cognate proteins exist. Such specificity typically arises from the binding of unique sulfation patterns on the linear GAG chain to highly electropositive protein domains. Thus, these highly charged, sulfated biopolymers potentially represent a new class of therapeutics. Yet, the major stumbling block to the development to these agents is their extremely complicated and tedious chemical synthesis. We hypothesized …

Radiation-Induced Glutamate Transport Alterations In Neuron-Astrocyte Coupling, Martha Celia Sanchez

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure of the central nervous system (CNS) to ionizing radiation is known to result in behavioral, cognitive, and motor deficits - effects similar to those seen in many neurodegenerative disorders. Neurons and astrocytes, two principal cell types in the brain, coexist as an interdependent metabolic unit via the neurotransmitter glutamate. Disruption of this metabolic coupling would have widespread effects within the CNS, therefore it is hypothesized that ionizing radiation impairs glutamate transport and metabolism, and increases oxidative stress, ultimately impairing neuron-astrocyte coupling. We propose to investigate the mechanism and determine the impetus for radiation-induced neurotoxicity by measuring the temporal sequence …

5-Ht3 Receptor Ligands And Their Effect On Psychomotor Stimulants, Jessica Nicole Worsham

Theses and Dissertations

Drug abuse and addiction are considered to be a result, at least in part, of the rewarding effects produced by increasing dopamine levels. 5-HT3 serotonin receptors have been shown to indirectly affect dopamine levels. Therefore, the effect of the 5-HT3 receptor partial agonist, MD-354, on the actions of psychomotor stimulants was analyzed in mouse locomotor activity assays to determine whether MD-354 is working through a 5-HT3 receptor agonist or antagonist mode of action. Studies with (+)amphetamine and (+)methamphetamine in combination with MD-354 indicated MD-354 is either devoid of action or is behaving similar to the 5-HT3 receptor antagonist, ondansetron. This …

Characterization Of Yeast 18s Rrna Dimethyl Transferase, Dim1p, Nagesh Pulicherla

Theses and Dissertations

Eukaryotic ribosome biogenesis, a dynamic and coordinated multistep process which requires more than 150 trans-acting factors, has been intensely studied in the yeast Saccharomyces cerevisiae. This evolutionarily conserved process involves numerous cleavages of pre-rRNA, modification of nucleotides, and concomitant assembly of the ribosomal proteins onto the rRNA. Considerable information is available about the importance of conserved pre-rRNA cleavage events in ribosome biogenesis; however, very little is known about the exact role of modified nucleotides, which cluster within the functionally important regions of the ribosome. One conserved group of modifications is the dimethylation of two adjacent adenosines at the 3´ end …