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Synthesis Of N-Acetyl And C-Tert-Butyl Natural Amino Acid Substrates That Mimic Residues Of Polypeptides And Their Reactivity With [Feiv(O)(N4py)]2+: Kinetic And Mechanistic Investigations, Ashley Ann Campanali

Wayne State University Dissertations

This dissertation is divided into two chapters, the first chapter includes an introduction to reactive oxygen species and their reactions with proteins. The introduction also covers metal-based oxidants, including both heme and non-heme enzymes that activate dioxygen as well as complexes that mimic these enzymes. The work discussed in chapter one concerns the synthesis of amino acid substrates that mimic amino acid residues. Substrates synthesized were derived from Gln, Asn, Ile, Cys and Tyr. Once synthesized, these substrates were reacted with [FeIV(O)(N4Py)]2+ under pseudo-first order conditions. The mechanisms for the reactions of the most reactive substrates were investigated. Electron-transfer proton-transfer …

Study Of Protein-Rna Interactions Using Fluorescence Resonance Energy Transfer (Fret) And Single-Molecule Fret, Rajan Lamichhane

Wayne State University Dissertations

In the cell, RNA and protein, interact to form ribonucleoprotein complexes (RNPs) that have vital structural, catalytic and regulatory roles. Despite their functional importance, the mechanistic details and dynamics of RNPs are poorly understood. Single-molecule Fluorescence Resonance Energy Transfer (smFRET) techniques that provide information about heterogeneity and dynamic behaviors of molecules have been developed to investigate inter- and intra-molecular interactions. Here we have used FRET in combination with smFRET to study three very different RNP systems.

Alternative splicing is a highly regulated biological process that plays a crucial role in proteomic diversity in eukaryotes. One splicing regulator, PTB, has been …

Improving Blood Pressure Control In Esrd Through A Supportive Educative Nursing Intervention, Zorica Kauric-Klein

Wayne State University Dissertations

ABSTRACT

IMPROVING BLOOD PRESSURE CONTROL IN ESRD THROUGH A

SUPPORTIVE EDUCATIVE NURSING INTERVENTION

by

ZORICA KAURIC-KLEIN

May 2011

Advisor: Dr. Nancy T. Artinian

Major: Nursing

Degree: Doctor of Philosophy

Problem: Hypertension in chronic hemodialysis (HD) patients contributes significantly to their morbidity and mortality. Statistics indicate the hypertension rate amongst HD patients ranges from 75 to 100 %. Studies have indicated that adherence rates to self-care behaviors related to salt and fluid intake and medication regimens are very poor in the HD population. Traditional hypertension management strategies have been found to be largely ineffective. There is modest evidence indicating that interventions …

The Role Of The Sparc Acidic Domain And Egf-Like Module In Glioma Migration, Invasion, And Signaling, Heather M. Mcclung

Wayne State University Dissertations

THE ROLE OF THE SPARC ACIDIC DOMAIN AND EGF-LIKE MODULE IN GLIOMA MIGRATION, INVASION, AND SIGNALING

HEATHER M. MCCLUNG

Advisor: Sandra A. Rempel, Ph.D.

Major: Pharmacology

Degree: Doctor of Philosophy

We have previously shown that Secreted Protein Acidic and Rich in Cysteine (SPARC) is upregulated in all astrocytoma grades and increases tumor cell migration and invasion. It is thought that different domains within the protein may regulate SPARC functions, suggesting domain-specific targeting to inhibit invasion. To enhance our understanding of SPARC-mediated invasion, we first confirm, at the protein level, our previous cDNA array results, that SPARC increases expression of the …

New Insights Into The Mechanism Of Dna Replication On Unmodified And Benzo[A]Pyrene Modified Templates Using Surface Plasmon Resonance, Richard George Federley

Wayne State University Dissertations

DNA synthesis is critical to cell survival, and the enzyme DNA polymerase has had a great deal of time to evolve efficient strategies to perform synthesis. A variety of effects are induced by the identity of the incoming dNTP, and its ability to effectively base pair with the templating base. The presence of the next correct dNTP is known to induce a conformational change of the polymerase and lead to an increase in KF-DNA binding. Conversely, the presence of an incorrect dNTP is shown to lead to a destabilization and reduction in the levels of KF-DNA complexes formed. Using surface …

Characterization Of Splicing Mechanisms By Single-Molecule Fluorescence, Krishanthi Sanjeewani Karunatilaka

Wayne State University Dissertations

Group II introns rank amongst the largest self-splicing ribozymes found in bacteria and organellar genomes of various eukaryotes. Despite the diversity in primary sequences, group II introns posses highly conserved secondary structures consisting of six domains (D1-D6). To perform its function, the large multidomain group II intron RNA must adopt the correctly folded structure. As a result, in vitro splicing of these introns requires high ionic strength and elevated temperatures. In vivo, this process is mainly assisted by protein cofactors. However, the exact mechanism of protein-mediated splicing of group II intron RNA is still not known.

In order to …

Metabolomic Profiling To Investigate Effect Of Curcumin In Lung Cancer, Arvind Goja

Wayne State University Dissertations

Lung cancer is the leading cause of cancer deaths in the US, in part due to poor diagnosis. Prognosis can be improved, if detected at an early stage. The objective of this study was to use the metabolomic approach to investigate early potential biomarkers for lung cancer. Golden Syrian hamsters were randomized into two groups (treatment and control). Lung cancer was induced in treatment group by a chemical carcinogen, N-nitrosobis-2-(oxopropyl) amine (BOP) while the control animals were injected with saline. Urine was collected weekly throughout the study and frozen at -800 C. Proton nuclear magnetic resonance (1H NMR) spectra, acquired …

Reinforced Chitosan-Based Heart Valve Scaffold And Utility Of Bone Marrow-Derived Mesenchymal Stem Cells For Cardiovascular Tissue Engineering, Mohammad Z. Albanna

Wayne State University Dissertations

Recent research has demonstrated a strong correlation between the differentiation profile of mesenchymal stem cells (MSCs) and scaffold stiffness. Chitosan is being widely studied for tissue engineering applications due to its biocompatibility and biodegradability. However, its use in load-bearing applications is limited due to moderate to low mechanical properties. In this study, we investigated the effectiveness of a fiber reinforcement method for enhancing the mechanical properties of chitosan scaffolds. Chitosan fibers were fabricated using a solution extrusion and neutralization method and incorporated into porous chitosan scaffolds. The effects of different fiber/scaffold mass ratios, fiber mechanical properties and fiber lengths on …

Palmitoylation And The Yeast Casein Kinase Yck2, Irene Papanayotou

Wayne State University Dissertations

Palmitoylation is a post-translational lipid modification that allows proteins to interact with membranes. In the yeast Saccharomyces cerevisiae, the casein kinase Yck2 is palmitoylated twice at its two C-terminal palmitoyl-accepting cysteine residues, by the palmitoyl-transferring enzyme Akr1. Once palmitoylated, Yck2 traffics through the well characterized secretory pathway to the plasma membrane where it participates in many cellular functions, including bud morphogenesis, cytokinesis, nutrient sensing, and receptor internalization. While the hydrophilic Yck2 is presumably synthesized on cytosolic ribosomes, it gains access to the membrane system by interaction with the six transmembrane-spanning Golgi-localized Akr1. Since palmitoylation occurs at membranes and the palmitoyl-transferases …

Identification Of The Role Of The Sal Locus In Streptococcus Pyogenes Virulence During Host-Pathogen Interactions, Phanramphoei Namprachan-Frantz

Wayne State University Dissertations

The pathogenesis of Streptococcus pyogenes is due to its ability to overcome and adapt to the harsh environment created by the host immune response. The focus of this project was the SalKR two-component regulatory system, which facilitates bacterial adaptation by responding to environmental signals during host pathogen-interactions. The first goal of this project was to determine a role in virulence for the SalKR regulatory system. The complete deletion of the salKR genes in the wild type S. pyogenes strain HSC5 produced a highly attenuated mutant in a Zebrafish infection model. The ΔsalKR mutant appeared to lose the ability to survive …

Parent Adherence To Psychologist Recommendations: The Role Of Expressed Emotion About Child And Reaction To Diagnosis, Lesley Ann Hetterscheidt

Wayne State University Dissertations

For the majority of children with significant behavioral or academic problems at school, the first course of action is to participate in a psychological evaluation. Upon completion of the evaluation parents receive an integrative report containing numerous recommendations for how to improve the well-being of their child. 51 child clients who

were referred and completed a comprehensive assessment for behavioral or academic problems were recruited for this study. A year or more after the evaluations were completed, parents of the children were asked about each written report recommendation, whether or not it was followed, and reasons for non-adherence. Expressed Emotion …

Laser-Assisted Single-Molecule Refolding, Rui Zhao

Wayne State University Dissertations

Non-coding RNAs must fold into precise secondary and tertiary structures in order to perform the biological functions. Due to the flexibility of RNA, the RNA folding energy landscape can be rugged and full of local minimum (kinetic trap). To provide a means to study kinetically trapped RNAs, we have developed a new technique combining single-molecule FRET detection with laser induced temperature jump. We have calibrated the magnitude of the temperature jump with 1˚C accuracy using gold micro-size sensor. The accuracy of temperature calibration was confirmed by close agreement between single-molecule and bulk DNA duplex melting experiments.

HIV 1 DIS RNAs …

Emotional Risk Factors For Substance Abuse In A Chronic Pain Population: Developing A Predictive Model And Testing Methods For Assessing Stigmatized Behaviors, Lindsay Margaret-Sander Oberleitner

Wayne State University Dissertations

There are currently few factors guiding physicians' decisions as to whether an individual patient may need additional regulation of pain medications because of risks. The limited predictive factors applied to prescription opioid abuse in chronic pain patients is surprising given the breadth of personal, cognitive, and emotional factors explored in both chronic pain and substance abuse literatures broadly. The present study had two purposes. First, concurrent risk factors for prescription misuse and substance abuse in chronic pain patients were explored, specifically examining whether the addition of emotional factors to the traditionally used risk factors improves prediction of prescription and substance …

The Impact Of Folate Deficiency On The Base Excision Repair Pathway: Analysis Of Enzyme Coordination In Response To Dna Damage And Imbalanced Repair, Amanda Pilling

Wayne State University Dissertations

The condition of folate deficiency has been implicated in carcinogenesis, with the strongest evidence formulated in colon cancer. The role of folate in DNA repair, DNA synthesis and methylation reactions renders this nutrient an valuable target for studying the onset and progression of cancer. Using molecular techniques to determine gene and protein expression, enzyme activity and methylation status elucidates the mechanism of DNA repair and damage in folic acid deficient animals in response to carcinogen. The findings presented in this study indicate failure to remove and repair damage in the condition of folate deficiency and suggest that the accumulation of …

Artificial And Natural Nucleic Acid Self Assembling Systems, Marcus Wood

Wayne State University Dissertations

Nucleic acids are good candidates for nanomachine construction. They participate in all the processes of life, and so can function as structural building blocks and dynamic catalysts. However, to use nucleic acids as nanomachines, a better understanding of their material properties, how to design structures using them, and their dynamics is needed. We have tried to address these issues, in a small way, with nucleic acid force field development, an attempt at nanostructural design and synthesis using DNA, and a study of the RNA/protein regulatory dynamics of the tryptophan regulatory attenuation protein.

A Novel Integrated Platform Combining Atomic Force Microscopy And Fluorescence Correlation Spectroscopy, Venkatesh Subba Rao

Wayne State University Dissertations

At the nanoscale near an interface, the discrete nature of liquids is expected to influence various properties, such as density, viscosity or diffusion constants. Understanding interfacial properties of liquids is important for the development of nanotechnology, especially for the fields of nano-rheology and nano-tribology, and also for understanding various mechanisms in biological systems at the molecular level, such as protein folding or the self-assembly of lipid vesicles, which invariably involve liquids. Atomic force microscope (AFM) and fluorescence correlation spectroscope (FCS) are two complimentary techniques that are commonly employed investigate mechanics and dynamics of liquids at interfaces. In this thesis, the …

Development Of Chemical Inducers Of Dimerization For Screening Competitive Histone Deactelyase Inhibitors, Emily Lynn Aubie

Wayne State University Dissertations

Histone Deacetylase (HDAC) proteins are transcriptional regulators that affect histone proteins, which are involved in packaging of DNA into chromosomes. HDACs have been linked to the proliferation of cancer through their role in transcriptional regulation. Due to these findings, HDAC inhibitors have been explored as anti-cancer agents. Several HDAC inhibitors are currently in various stages of clinical trials, and the inhibitor suberoyl anilide hydroxamic acid (SAHA) has been FDA approved for treatment of cutaneous T-Cell lymphoma. Currently, most of the known HDAC inhibitors are non-selective, which causes non-specific binding to the active sites of all HDAC isoforms, including those not …

Circadian Rhythm Of Cortisol And Estradiol In Healthy Women, Karyn G. Butler

Wayne State University Dissertations

ABSTRACT

CIRCADIAN RHYTHM OF CORTISOL AND ESTRADIOL IN HEALTHY WOMEN

by

KARYN G. BUTLER

AUGUST 2011

Advisor: Dr. Jean E. Davis

Major: Nursing

Degree: Doctor of Philosophy

Daily variation in human processes and behaviors has been identified for centuries. Study of these circadian rhythms demonstrates their role in human health. Sickness behaviors include alterations in affect, sleep quality and energy. The study of the relationship between circadian rhythms has been limited to isolated rhythms. The role of temporal relationships among rhythms has received little attention. Sickness behaviors are prevalent in many disorders including depression, cancer, and autoimmune disorders. Two hormones …

An Investigation Of The Biomechanical Response From Shock Wave Loading To The Head, Alessandra Dal Cengio Leonardi

Wayne State University Dissertations

There is a pressing need for a comprehensive explanation of the mechanism of brain injury after exposure to blast and several hypotheses have been suggested. The focus of this research was to investigate one of the hypotheses for primary brain injury due to blast: multimodal skull flexure. The significance of this research is twofold. First, resolution of the mode of energy transfer and of the induced stresses within the skull-brain system will allow for creations of mitigation/protective techniques/equipment, as well as design of experiments investigating live-cell response using more reliable physical models. Second, the data obtained experimentally will be available …

Estrogen Sulfotransferase (Sult1e1) Expression And Function In Mcf10a-Series Breast Epithelial Cells: Role As A Modifier Of Breast Carcinogenesis And Regulation By Proliferation State, Jiaqi Fu

Wayne State University Dissertations

Estrogen sulfotransferase (SULT1E1) catalyzes the sulfonation of estrogens, which limits estrogen mitogenicity. TaqMan Gene Expression assays were used to profile the mRNA expression of estrogen receptor (ERα and ERβ) and estrogen metabolism enzymes including cytosolic sulfotransferases (SULT1E1, SULT1A1, SULT2A1, and SULT2B1), steroid sulfatase (STS), aromatase (CYP19), 17β-hydroxysteroid dehydrogenases (17βHSD1 and 2), CYP1B1, and catechol-O-methyltransferase (COMT) in an MCF10A-derived lineage cell culture model for basal-like human breast cancer progression and in ERα-positive luminal MCF7 breast cancer cells. Low levels of ERα and ERβ mRNA were present in MCF10A-derived cell lines. SULT1E1 mRNA was more abundant in confluent relative to subconfluent MCF10A …

Raman Spectroscopy For The Microbiological Characterization And Identification Of Medically Relevant Bacteria, Khozima Mahmoud Hamasha

Wayne State University Dissertations

The detection and identification of pathogenic bacteria has become more important than ever due to the increase of potential bioterrorism threats and the high mortality rate of bacterial infections worldwide. Raman spectroscopy has recently gained popularity as an attractive robust approach for the molecular characterization, rapid identification, and accurate classification of a wide range of bacteria.

In this dissertation, Raman spectroscopy utilizing advanced statistical techniques was used to identify and discriminate between different pathogenic and non-pathogenic bacterial strains of E. coli and Staphylococcus aureus bacterial species by probing the molecular compositions of the cells.

The five-carbon sugar xylitol, which cannot …

Hedgehog Signaling: A Potential Therapeutic Target For Non-Small Cell Lung Cancer, Ma'in Yehya Maitah

Wayne State University Dissertations

The American Cancer Society estimated that 222,520 Americans were diagnosed with lung cancer and 157,300 died of lung cancer in 2010 (Jemal et al. 2009, 225-249;Jemal et al. 2011, 69-90). The clinical outcome of patients diagnosed with non-small cell lung cancer (NSCLC), the major lung cancer sub-types, is very poor, which calls for innovative research for finding novel therapeutic targets and agents for better treatment outcome.

Emerging evidences have suggested that a phenomenon called Epithelial-to-Mesenchymal Transition (EMT), which shares similar molecular characteristics with cancer stem-like cells, contributes to lung cancer treatment failure. In view of the fact that EMT process …

Testing The Impact Of Anger Awareness And Expression Training And Relaxation Training On Chronic Headaches, Olga Slavin-Spenny

Wayne State University Dissertations

Chronic headache is a serious and common problem (World Health Organization [WHO], 2004). There is a heavy social and economic burden associated with chronic headaches. Relaxation training, which is thought to work by decreasing arousal/anxiety, is a commonly used behavioral treatment for chronic headache and has been shown to be effective. However, other research has suggested that anger may be an important emotion in the experience of pain, and that suppression of anger may lead to worse pain (Quartana et al., 2006). Although existing literature has demonstrated that anger suppression leads to worse pain, it has not addressed the question …

Dynamics Of Nanoparticles In Complex Fluids., Rami Ahmad Saleh Omari

Wayne State University Dissertations

Soft matter is a subfield of condensed matter including polymers, colloidal dispersions, surfactants, and liquid crystals. These materials are familiar from our everyday life- glues, paints, soaps, and plastics are examples of soft materials. Many phenomena in these systems have the same underlying physical mechanics. Moreover, it has been recognized that combinations of these systems, like for example polymers and colloids, exhibit new properties which are found in each system separately. These mixed systems have a higher degree of complexity than the separate systems. In order to understand their behavior, knowledge from each subfields of soft matter has to be …

Properties And Biomedical Applications Of Magnetic Nanoparticles, Rajesh Kumar Regmi

Wayne State University Dissertations

Magnetic nanoparticles have a number of unique properties, making them promising agents for applications in medicine including magnetically targeted drug delivery, magnetic hyperthermia, magnetic resonance imaging, and radiation therapy. They are biocompatible and can also be coated with biocompatible surfactants, which may be further functionalized with optically and therapeutically active molecules. These nanoparticles can be manipulated with non-invasive external magnetic field to produce heat, target specific site, and monitor their distribution in vivo. Within this framework, we have investigated a number of biomedical applications of these nanoparticles. We synthesized a thermosensitive microgel with iron oxide adsorbed on its surface. An …

Pamam Dendrimer-Based Therapeutic And Diagnostic Nanodevices, Admira Bosnjakovic

Wayne State University Dissertations

Dendrimers are ideal materials to be used in the emerging field of nanomedicine. Their nanoscale size and high density of functional groups on their peripheries allow them to be used for various biomedical applications. This work exploits dendrimers as drug delivery vehicles and a versatile platform for capturing biomarkers with improved sensitivity and specificity. Hydroxyl terminated poly(amidoamine) dendrimer (PAMAM-OH) was modified with a linker having amine group at the end and conjugated to two drugs, erythromycin (EM) and allopregnanonolne, respectively and evaluated in vitro. Both drugs were provided with a linker having carboxylic group required for conjugation reaction with dendrimer. …

Individual Differences In Hemispheric Lateralization Of Language Processing, Sarah Ann Van Dyke

Wayne State University Dissertations

Conclusions in the literature regarding the relationship between a lateralized bias in the processing of information and individual differences (e.g., biological sex, gender identity, ability, personality) are inconsistent. We compared two different measures of laterality: dichotic listening and lateralized semantic priming and their relation to sex, verbal and visual-spatial ability, gender identity, and personality.

Eighty-nine adults (44 women, 45 men) were administered the Wechsler Abbreviated Scale of Intelligence, Bem Sex Role Inventory, and Big Five Inventory in addition to a dichotic listening task and a lateralized semantic priming task that compared ipsilateral and contralateral priming in order to determine the …

The Effects Of Participation In A Human Sexuality Workshop On The Attitudes Of Counselors In Training Toward Homosexuality, Lawrence Craig Perry

Wayne State University Dissertations

The purpose of this study was to examine the impact of an educational workshop on the implicit and explicit attitudes of graduate counseling students toward homosexuality. Counseling students' attitudes toward sexuality and homosexuality were measured before and after participating in an educational workshop on human sexuality. The setting for the study was a human sexuality workshop being taught within a counselor education graduate program. The weekend workshop was an elective class for graduate students who were enrolled at a large urban university. A total of 23 individuals volunteered to participate in the study.

The participants were asked to complete three …

Base Excision Repair, Folate Deficiency And Cancer, Archana Unnikrishnan

Wayne State University Dissertations

Folate, an essential water soluble vitamin has been implicated in the etiology of many types of cancer especially colorectal cancer. Folate deficiency has been reported to incapacitate DNA repair pathways and thereby affect the genomic stability. Our lab has reported previously and here again through this research that folate deficiency affects the DNA damage inducibility of base excision repair pathway. Our study shows the differential effect folate deficiency has on the expression of the genes involved in this pathway. Further, our study shows the increase in preneoplastic lesions in the colon of mice exposed to folate deficiency in response to …

Examination Of Dispositions And Practices In Diversity: The Impact Of A Teacher Education Course Promoting Culturally And Responsive Pedagogy, Deuslene Leite Bastos

Wayne State University Dissertations

Assimilation ideology guiding teachers and policy makers to mainstream immigrant children into the American schools has prevailed in spite of pluralists' efforts for reform schools to provide more opportunities for culturally and linguistically diverse students. Research shows a need to change assimilation driven policies and practices which are harmful to students into a reconstructivist ideology that has shown to be more conducive for the application of culturally responsive teaching. Teacher education courses aimed to prepare teacher candidates for diverse classrooms have shown limitations due to abundant focus on theory or lack of elements in course work that are known to …