Digital Commons Network^™

Evolutionarily Conserved Cis-Acting Elements Regulate Lineage-Specific Expression Of Ifng, Anand Balasubramani

All ETDs from UAB

The ability to differentially manipulate available genetic information in order to generate diverse cellular identities represents an innovation of complex multicellular eukaryotic organisms. Cis-acting modules that regulate transcription play extremely important roles in ensuring lineage-specific expression of genes that define cellular identities. In our studies, using Interferon-gamma (IFN-gamma, a cytokine encoded by the gene Ifng), a cytokine encoded by T, NK and NKT cells as a model, we have identified and characterized the roles of key cis regulatory elements that facilitate T lineage specific induction as well as repression of Ifng transcription. In particular, our studies have highlighted the role …

Molecular Mechanisms Of Breast Cancer Metastasis: Gap Junction Intercellular Communication And The Bone Microenvironment, Thomas Morgan Bodenstine

All ETDs from UAB

Metastatic disease accounts for the overwhelming majority of cancer related deaths. More specifically, breast cancer remains one of the leading causes of death in women and breast cancer cells metastasize to bone more than any other secondary site. Upon arriving within the bone microenvironment, breast cancer cells interact with bone marrow cells, leading to changes in bone biology that favor growth of the cancer cells. Additionally, some cancer cells are capable of direct cellular communication with cells at metastatic sites via dysregulation of a family of proteins known as connexins. This direct, physical communication is known as gap junctional intercellular …

Preclinical Pharmacology Of Novel Synthetic Iminoquinones As Anticancer Agents, Scharri Ezell

All ETDs from UAB

Prostate cancer is the most common male malignancy and the second leading cause of cancer related death in the United States. Despite recent advances in the detection, diagnosis, and treatment of prostate cancer, there is a need for more effective therapies. Unfortunately, most conventional therapeutic modalities, such as androgen ablation therapy, frequently result in androgen-independent cancers. These cancers are typically more aggressive, metastatic, and resistant to chemotherapeutic agents than androgen-dependent prostate cancer. Therefore, agents that are effective against both androgen-sensitive and androgen-independent, as well as genetically diverse cancers are critically needed. The objective of the dissertation research was to address …

Identification And Validation Of Biodosimetry Markers In Multiple Models Of Radiation Exposure, Ashley Nicole Filiano

All ETDs from UAB

Following a radiological or nuclear disaster, radiation dose assessment is imperative to minimize morbidity and mortality through rationally directed medical intervention. Current methods of retrospective dosimetry are not amenable to mass exposure scenarios and remain limited to monitoring of clinical symptoms (nausea/vomiting and lymphocyte depletion) and cytogenetic analysis. The goal of this study was to identify radiation biomarkers capable of qualitative (non-irradiated/irradiated) and quantitative (dose) assessment of radiation exposure. Initial analyses revealed 17 radiation-responsive cytokine/chemokine genes in blood samples from 6 pediatric cancer patients undergoing fractionated total body irradiation (TBI). These 17 genes were combined with 29 additional IR-inducible genes …

Regulation Of Apoptosis By Smac, Iaps , And The Ubiquitin Proteasome System, Stephen Peter Burke

All ETDs from UAB

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The Effects Of Environmental Ozone Exposure On Vascular Function, Oxidative Stress, And Atherosclerosis, Gin Chuang

All ETDs from UAB

Exposure to air pollutants are known to induce airway inflammation, decrease lung function, and worsen existing pulmonary conditions such as asthma. Additionally, air pollutant exposure has also been shown to impact cardiovascular health. Although these pollutant-induced cardiovascular effects were considered to be mediated by the direct action of pollutants upon the cardiovascular tissue and/or the indirect release of pro-inflammatory factors into the circulation, the relative contribution of the two pathways remained equivocal. Recently, several epidemiology studies associated ozone exposure with cardiovascular mortalities. However, relatively few studies to date have examined ozone in this context. In order to address our hypothesis …

A Model For Understanding Epilepsy In Peromyscus, Kevin Ryan, Gabor Szalai

Journal of the South Carolina Academy of Science

No abstract provided.

Associative Learning In Larval Dosophila Melanogaster: The Role Of Heredity In Learning Speed And Persistence Of Leaning Into Adulthood, Jasmin Hicklen, Domonique Jones, Michelle Vieyra

Journal of the South Carolina Academy of Science

No abstract provided.

Autotaxin: A Regulator Of Oligodendrocyte Differentiation, Larra Yuelling

Theses and Dissertations

In order for oligodendrocyte progenitor cells (OPCs) to differentiate into fully mature, myelinating oligodendrocytes, they must be specified at the correct times and undergo coordinated changes in both gene expression and morphology. As oligodendrocytes differentiate, they transition from a bipolar morphology into a morphology characterized by a complex network of multiple processes, which will eventually generate membranous structures necessary for myelination of axonal segments. As changes are observed in cellular morphology, oligodendrocytes also undergo changes in their gene expression profile and express genes necessary for both early and later stages of development such as olig1 and myelin basic protein (mbp), …

Effectiveness Of Weight Control Through Weight Watch Programs, V. A. Black, P. Boumtje

Journal of the Arkansas Academy of Science

Linear probability estimation and survey data are employed to quantify the influence of the lifestyles of individuals on the change in their body mass index (BMI). The analysis also explores the effects of demographic characteristics (age, gender, and ethnicity) in weight management. Results suggest evidence of association between changes in lifestyle and changes in the BMI of individuals.

Ligand-Protein Interactions Of Inhibitors With Dengue Virus Type 2 Serine Protease : A Structural Study., Rozana Othman

Student Works (2010-2019)

Dengue is a serious infectious disease that is endemic in over 100 countries. There has been an estimate of 50 million infection per year globally, with more than 2.5 billion people are at risk for epidemic transmission. Two principal illnesses associated with dengue are Dengue Fever (DF) and Dengue Haemorrhagic Fever (DHF). To date, there is no licensed vaccine or therapeutic drug available for these illnesses, although there have been reports of some vaccine candidates in clinical trials. Treatments have only been supportive thus far. This thesis describes part of our ongoing effort to search for a lead therapeutic agent …

Estimation Of The Product Yield And Collection Efficiency Of Peripheral Blood Stem Cell Harvesting Using Peripheral Blood Cd34[+] Cells Quantification., Habsah Aziz

Student Works (2010-2019)

Peripheral blood stem cells (PBSC) have been used for transplantation since the early 1990s. CD34+ has been used as a marker of hematopoietic stem cells to determine the optimal timing for PBSC harvesting. However, a wide ranges of CD34+ cells cut-off values from 8/ul to 66/ul have been used to initiate PBSC harvesting in autologous patients. We performed here a study to determine the peripheral blood CD34+ cells cut-off value for the prediction of stem cell yield of 2 x106 CD34+ cells/kg body weight patients, to study the correlation between peripheral blood CD34+ cells and stem cell yield, to study …

Genotype And Allele Frequencies Of Nine Str Loci In Sikhs From Malaysia., Tan Chin Teck

Student Works (2010-2019)

Allele frequencies for nine short tandem repeats (STRs) gene loci (CSF1PO, TPOX,TH01, F13A01, FESFPS, vWA, D16S539, D7S820, D13S317) were obtained from analyses of saliva DNA from 109 unrelated healthy Sikh individuals residing in Malaysia. DNA was extracted using phenol/chloroform/isoamly alcohol method. 2ng of DNA for each sample was amplified following the instruction in GenePrint® STR Systems (Promega Corporation) CTT, FFv and SilverSTR III Multiplex kits. PCR products were separated in denaturing polyacrylamide gel electrophoresis and silver stained using Promega DNA Silver Staining System. The results were then calculated and processed to establish a statistical database for Sikh community. Chi-square test …

Regulation Of Apoptotic Effects Of Erythrocarpine E, A New Cytotoxic Limonoid Extracted From Chisocheton Erythrocarpus., Norliza Shah Jehan Muttiah

Student Works (2010-2019)

The aim of this study is to determine the cytotoxic and apoptotic effects of erythrocarpine E (CEB4), a new limonoid extracted from Chisocheton erythrocarpus. MTT assay, Live/Dead® Viability/Cytotoxicity assay, cell cycle analysis, annexin V analysis, PARP cleavage analysis, DNA fragmentation assay, sandwich ELISA assay and Western blot analysis were performed on five CEB4 treated cancer cell lines; HSC4COX2- and HSC2 (oral), CaSki (cervical), HepG2 (liver), MCF7 (breast) and NHBE (normal human bronchial epithelial cell line). CEB4 treated HSC4COX2-, HSC2, CaSki, HepG2 and MCF7 cells demonstrated a cytotoxic effect and inhibited cell proliferation in a dose and time dependent manner. CEB4 …

Effects Of Different Extenders, Cryoprotectants, Equilibration And Vapour Exposure On Freezability Of African Catfish(Clarias Gariepinus) Sperm., Noor Azlina Kamaruding

Student Works (2010-2019)

The aim of this study was to develop an optimal freezing protocol for African catfish(Clarias gariepinus) sperm with special reference to type of extender and cryoprotectant, molarity, equilibration duration, vapour temperature and vapour exposure duration. Using Tris-Citric Acid Yolk Extender (TCAYE), a 3x3x3x3 factorial experiment was carried out consisting of 3 molarities of glycerol (0.5, 1.0 and 2.0 M), 3 equilibration durations (120,140 and 160 minutes), 3 vapour temperatures (-80, -90 and -100oC) and 3 vapour exposure durations (5, 10 and 15 minutes). In addition, using Fish-Ringer Extender (FRE), a 3x3x3 factorial experiment was also conducted involving 3 equilibration durations …

Molecular Staging Estimates Occult Tumor Burden In Colorectal Cancer, Alex Mejia, Stephanie Schulz, Terry Hyslop, David S. Weinberg, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Tumor cells in regional lymph nodes are a key prognostic marker of survival and predictive marker of response to adjuvant chemotherapy in colorectal cancer. However, clinicopathologic techniques to detect lymph node metastases remain imperfect, and ~30% of patients with lymph nodes negative by histology (pN0) develop recurrent disease, reflecting occult metastases that escape detection. These observations underscore an unmet clinical need for accurate approaches to identify occult nodal metastases in colorectal cancer patients. GUCY2C is a receptor whose expression normally is restricted to intestinal epithelial cells, but is universally over-expressed by colorectal cancer cells. A prospective, multicenter, blinded clinical trial …

Functional Characterization Of Nuclear Receptor And Co-Activator Binding Loci In The Human Genome, Kim Maguire

Masters

Steroid hormones, such as oestrogen, mediate their effects via activation of oestrogen regulated genes using nuclear receptors. Selective oestrogen receptor modulators (SERMs), such as Tamoxifen, are used to treat oestrogen responsive breast cancers, hctioning to act as oestrogen antagonists, preventing the oestrogen receptor biding DNA and blocking gene expression. However, Tamoxifen has been identified as an oestrogen agonist in other tissues which can often lead to secondary tumors in the years following the treatment. Identification of the genomic regions where SERMs can act as oestrogen agonists can possibly lead to the development of gene targeted therapies or other alternatives to …

Patterned Cell Cultures For High Throughput Studies Of Cell Electrophysiology And Drug Screening Applications, Anupama Natarajan

Electronic Theses and Dissertations

Over the last decade, the field of tissue and bio-engineering has seen an increase in the development of in vitro high-throughput hybrid systems that can be used to understand cell function and behavior at the cellular and tissue levels. These tools would have a wide array of applications including for implants, drug discovery, and toxicology, as well as for studying cell developmental behavior and as disease models. Currently, there are a limited number of efficient, functional drug screening assays in the pharmacology industry and studies of cell-surface interactions are complicated and invasive. Most cell physiology studies are performed using conventional …

Studies On A Novel Human Cardiospecific Transcription Factor And Its Involvement In Omi/Htra2 Mediated Cell Death, Meenakshi Puthucode Balakrishnan

Electronic Theses and Dissertations

Omi/HtrA2 is a mitochondrial serine protease that is known to translocate to the cytoplasm upon induction of apoptosis and to activate caspase-dependent and caspase-independent cell death. The molecular mechanism of Omi/HtrA2's function is not clear but involves degradation of specific substrates. These substrates include cytoplasmic, mitochondrial, as well as nuclear proteins. We have isolated a new Omi/HtrA2 interactor, the THAP5 protein. THAP5 is a fifth member of a large family of transcription factors that are involved in cell proliferation, apoptosis, cell cycle control, chromosome segregation, chromatin modification and transcriptional regulation. THAP5 is an approximately 50kDa nuclear protein, with a restricted …

The Overexpression Of Homeotic Complex Gene Ultrabithorax In The Post-Embryonic Neuronal Lineages Of The Ventral Nervous System In Drosophila Melanogaster, Katie Dry

Master’s Theses

This study uses a molecular technique called MARCM (Mosaic Analysis with a Repressible Cell Marker) to label neuronal lineages that overexpress the Hox gene Ultrabithorax (Ubx) in an unlabeled, wild type background. The results indicate that the overexpression of Ubx is sufficient to transform more anterior neuronal lineages to themorphology of their more posterior counterparts. The data presented here begin to elucidate the role that the Hox genes have in shaping segment-specific neural connections in the post-embryonic ventral nervous system.

Spatial Learning And Stress Response Of Male Rats Prenatally Exposed To Dexamethasone, Joseph John Donohoe

Master’s Theses

Dexamethasone is routinely administered to women at risk for a preterm birth in order to enhance fetal lung development and reduce uterine contractions. Research has demonstrated possible behavioral abnormalities in adulthood as a result of dexamethasone treatment. Using nonlinear mixed effects modeling, this study found thatprenatal dexamethasone treatment impaired spatial learning and memory of adult male Sprague-Dawley rats. Prenatal dexamethasone treatment also led to more anxiety related behaviors on Elevated Plus Maze testing 1.5 hours after a stress challenge. Because theassumptions underlying the independent samples t-test were violated, the randomization test was used to compare groups on the Elevated Plus …

Effects Of Prenatal Dexamethasone On Hipopcampal Serotonin 1a Receptors In Adult Male Rats, Rahul Vijay

Master’s Theses

The main activation route for the stress response is the hypothalamo-pituitaryadrenal axis (HPA) and the sympatho-adrenomedullary system. The HPA axis is a neuroendocrine feedback loop mediated by an array of tissue specific hormones, receptors and neurotransmitters that regulate glucocorticoid (GC) release. GCs are steroidal hormones produced by the adrenal glands and are key players in a negativefeedback loop controlling HPA activity. They influence the HPA axis through glucocorticoid receptors in the hypothalamus and pituitary and through both glucocorticoid (GR) and mineralcorticoid receptors (MR) that are co-localized in the hippocampus. Repeated or chronic stress exerts a negative influence on these HPA …

Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets With Alopecia Resulting From A Novel Missense Mutation In The Dna-Binding Domain Of The Vitamin D Receptor., Peter J. Malloy, Jining Wang, Tarak Srivastava, David Feldman

Manuscripts, Articles, Book Chapters and Other Papers

The rare genetic recessive disease, hereditary vitamin D resistant rickets (HVDRR), is caused by mutations in the vitamin D receptor (VDR) that result in resistance to the active hormone 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3) or calcitriol). In this study, we examined the VDR from a young boy with clinical features of HVDRR including severe rickets, hypocalcemia, hypophosphatemia and partial alopecia. The pattern of alopecia was very unusual with areas of total baldness, adjacent to normal hair and regions of scant hair. The child failed to improve on oral calcium and vitamin D therapy but his abnormal chemistries and his bone X-rays normalized …

The Interictal State In Epilepsy And Behavior, Daniel Tice Barkmeier

Wayne State University Dissertations

Epilepsy is one of the most common neurological diseases, affecting up to 1% of the world population. Epilepsy remains poorly understood and there are currently no medications to cure it. Patients with epilepsy have both seizures as well as another type of abnormal activity between seizures, known as interictal spikes. Interictal spikes have thus far been poorly researched, yet growing evidence supports an important role for them in epilepsy. In this project, we first show the high variability between reviewers in marking interictal spikes on intracranial EEG, and then develop and test an automated detection method to solve this problem. …

Activation Of Tumor Cell Death Program By Targeting The Ubiquitin-Proteasome Pathway: Significance In Cancer Treatment And Prevention, Michael Joseph Frezza

Wayne State University Dissertations

ACTIVATION OF TUMOR CELL DEATH PROGRAM BY TARGETING THE UBIQUITIN-PROTEASOME PATHWAY: SIGNIFICANCE IN CANCER TREATMENT AND PREVENTION

by

MICHAEL FREZZA

August 2010

Advisor: Dr. Q. Ping Dou

Major: Cancer Biology

Degree: Doctor of Philosophy

The ubiquitin-proteasome pathway serves as a quality control mechanism to regulate the degradation of intracellular proteins involved in a wide array of cellular processes including tumorigeneis. Thus targeting key features of protein turnover responsible for the growth and proliferation of cancer have emerged as a favorable approach in cancer therapy. Both in vitro and in vivo experimental and clinical results have demonstrated the potential use of …

Immunomodulatory Effect Of Host And Fungal Eicosanoids During Host-Pathogen Interactions With Candida Albicans, Gitanjali Kundu

Wayne State University Dissertations

Candida albicans, an opportunistic fungal pathogen, poses a significant clinical threat to immunocompromised patients. Diseases associated with this fungus ranges from superficial mucosal infection to life-threatening systemic candidiasis. The mechanisms by which Candida persists at mucosal surfaces in the face of an adaptive response are unclear. Candida produces immunomodulatory oxylipins that cross-react functionally with host eicosanoids, which are considered to play important role in regulating innate and adaptive immune responses. Our objective was to characterize the role of prostaglandins produced by the host and this fungus during host pathogen interactions, both in vitro with dendritic cells (DCs) and macrophages, and …

Defensins In Ocular Immunity, Minhao Wu

Wayne State University Dissertations

Corneal infection with P. aeruginosa results in corneal perforation in susceptible

B6, but not resistant BALB/c mice. This study explored their role mBD 1-4 in corneal

infection, and their potential synergy. Immunostaining and real-time RT-PCR data

demonstrated that their expression was either constitutive (mBD1 and mBD2) or

inducible (mBD3 and mBD4) in normal BALB/c and B6 corneas, and disparately

regulated in BALB/c vs B6 corneas after infection. Knock down studies using siRNA

treatment indicated that mBD2 and mBD3, but neither mBD1 nor mBD4, is required in

ocular defense. Moreover, in vivo studies demonstrated individual and combined effects

of mBD2 and …

Visual Learning And Discrimination Of Abstract Visual Shapes By Crayfish, Matthew J. Boeve, Daniel A. Bergman

Student Summer Scholars Manuscripts

In nature, animals commonly experience multiple combinations of stimuli at various points in time. When two or more seemingly unrelated stimuli are detected at the same time using different sensory systems, there is the potential for an association to form between the stimuli. The animal may learn and show a response originally associated with one stimulus when it now detects the second stimulus. These stimuli are the unconditioned and conditioned stimulus of classical and operant conditioning. Many species of animals are known to learn via operant conditioning and a variety of responses can become associated with formerly neutral stimuli. Crayfish …

Characterization And Optimization Of Microelectrode Arrays For Glutamate Measurements In The Rat Hippocampus, Pooja Mahendra Talauliker

University of Kentucky Doctoral Dissertations

An overarching goal of the Gerhardt laboratory is the development of an implantable neural device that allows for long-term glutamate recordings in the hippocampus. Proper L-glutamate regulation is essential for hippocampal function, while glutamate dysregulation is implicated in many neurodegenerative diseases. Direct evidence for subregional glutamate regulation is lacking in previous in vivo studies because of limitations in the spatio-temporal resolution of conventional experimental techniques. We used novel enzyme-coated microelectrode arrays (MEAs) for rapid measurements (2Hz) of extracellular glutamate in urethane-anesthetized rats. Potassium-evoked glutamate release was highest in the cornu ammonis 1 (CA1) subregion and lowest in the cornu ammonis …

Studies Of The Effects Of Dopamine Neuron Stimulating Peptides In Rodent Models Of Normal And Dysfunctional Dopaminergic Systems, Joshua Lee Fuqua

University of Kentucky Doctoral Dissertations

A theoretical post-translational processing model of the proprotein form of glial cell line-derived neurotrophic factor (GDNF) likely produces three biologically active peptides. The three prospective peptides formed are 5, 11, and 17 amino acid peptides, entitled dopamine neuron stimulating peptide -5 (DNSP-5), -11 (DNSP-11), and -17 (DNSP-17), respectively. The DNSPs were hypothesized to increase dopaminergic neuron function because of their relationship to GDNF: a molecule with established neurotrophic actions on dopaminergic neurons. The DNSPs have the potential to provide a therapeutic molecule similar to GDNF, but with increased ease of delivery and improved bioavailability.

Neurochemical effects of DNSPs were examined …