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Articles 961 - 990 of 1022
Full-Text Articles in Medical Sciences
Using Rna Interference To Study The Function Of The Tethering Protein P115 In Er-Golgi Traffic, Robert Grabski
Using Rna Interference To Study The Function Of The Tethering Protein P115 In Er-Golgi Traffic, Robert Grabski
All ETDs from UAB
Metazoan cells are characterized with elaborate network of intracellular membranous compartments. These membranes allow the cell to spatially separate antagonistic processes and environments, and maintain sequential order of reactions necessary for maturation and secretion of biosynthetic cargo. The core transport machinery consists of coat proteins, tethering factors, SNAREs and small Ras-like GTPases. We have explored the function of the tethering factor p115 in organellogenesis and in secretory traffic. The p115-depleted system was utilized to explore structurefunction relationships within p115. Here, we analyzed the architecture of the Golgi after RNAi induced depletion of p115. We show that in p115 depleted cells …
Mechanism Of The Cross Talk Between Growth Hormone Receptor And Epidermal Growth Factor Receptor, Xin Li
Mechanism Of The Cross Talk Between Growth Hormone Receptor And Epidermal Growth Factor Receptor, Xin Li
All ETDs from UAB
EGF receptor (EGFR) is a receptor tyrosine kinase, mediating cell growth from ectodermal and mesodermal origin. The overexpression and aberrant function of EGFR are involved in a wide range of human carcinomas. Growth hormone receptor (GHR) coexists with EGFR in various cell types and implicated in malignant tumor behavior. Previously in our lab, we found that via ERK activation GH can threonine phosphorylate EGFR and reduce EGF-induced EGFR downregulation. GH also synergizes with EGF in activating ERK. In this project, using reconstitution, we studied the mutation of the ERK phosphorylation consensus residue on EGFR, 669T. CHO-GHR cells, which lack EGFR …
Function Of Human Retinol Dehydrogenase 12 (Rdh12) In Retinoid Metabolism, Seung-Ah Lee
Function Of Human Retinol Dehydrogenase 12 (Rdh12) In Retinoid Metabolism, Seung-Ah Lee
All ETDs from UAB
Retinol dehydrogenase 12 (RDH12) is a member of the microsomal short-chain dehydrogenase/reductase superfamily of proteins that is highly expressed in photorecep-tor cells. Mutations in RDH12 are associated with severe early-onset autosomal recessive retinal dystrophy, leading to legal blindness. Disease-associated RDH12 variants exhibit lower protein levels when expressed in eukaryotic cells. However, the physiological role of RDH12 remains unclear. As established previously, RDH12 recognizes both retinoids and lipid peroxidation products (medium-chain aldehydes) as substrates and exhibits the highest catalytic efficiency for all-trans-retinaldehyde. As the main goal of this dissertation, we characterized the catalytic properties of RDH12 and its naturally occurring mutants …
Biogenesis, Trafficing, And Function Of Wild-Type And Mutant Cystic Fibrosis Transmembrane Conductance Regulator (Cftr), Asta Jurkuvenaite
Biogenesis, Trafficing, And Function Of Wild-Type And Mutant Cystic Fibrosis Transmembrane Conductance Regulator (Cftr), Asta Jurkuvenaite
All ETDs from UAB
Cystic fibrosis (CF) is a genetic disease resulting from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel that functions at the apical surface of epithelial cells and plays a critical role in mucociliary clearance. The most common mutation in the CFTR gene involves a deletion of phenylalanine at position 508 in the protein (ΔF508 CFTR). ΔF508 CFTR is recognized as misfolded in the endoplasmic reticulum (ER) and is degraded. In vitro manipulations such as culturing cells at 27°C can “rescue” ΔF508 CFTR to the plasma membrane (rΔF508 CFTR), but no pharmacological agent has produced comparable …
Changes In Hippocampal Excitability During Withdrawal From Chronic Nicotine, Rachel E. Penton
Changes In Hippocampal Excitability During Withdrawal From Chronic Nicotine, Rachel E. Penton
All ETDs from UAB
seeking behavior following chronic drug use lasts for many months or even years. Short-term withdrawal experiments have suggested that the neuroadaptations thought to underlie learning and memory may also contribute to addictive behavior. However, there is little information about the physiological mechanisms that participate in craving and relapse following long-term withdrawal. Here I show in hippocampal slices from rats treated with nicotine for 1 week that there is a change in the excitability of CA1 pyramidal cells that persists for up to 9 months following the cessation of drug treatment. The expression of this enhanced excitability is dependent on different …
Roles Of Extracellular Atp And Zinc In Pancreatic Ss-Cell Physiology, Clintoria Richards-Williams
Roles Of Extracellular Atp And Zinc In Pancreatic Ss-Cell Physiology, Clintoria Richards-Williams
All ETDs from UAB
Insulin secretory defects within pancreatic beta-cells (β-cells) of islets of Langerhans play a role in the pathogenesis of diabetes mellitus. Furthermore, it is also well established that ATP and zinc are co-secreted with insulin in response to elevated extracellular glucose. Despite this knowledge, the physiological roles of extracellular secreted ATP and zinc within islets are ill-defined. We hypothesized that secreted ATP and zinc are autocrine purinergic signaling molecules that activate P2X purinergic receptor (P2XR) channels expressed by β-cells to enhance glucose-stimulated insulin secretion (GSIS). To test this postulate, ELISA, luciferin/luciferase-based bioluminescence and zinquin-based fluorescence assays were utilized to examine insulin, …
The Role Of Tgfß Signaling In Skeletal Development, Hwa-Seon Seo
The Role Of Tgfß Signaling In Skeletal Development, Hwa-Seon Seo
All ETDs from UAB
skeletal element is essential for body movement along with the joints, muscles, tendons and ligaments. They also protect internal organs and serve as a reservoir for hematopoietic stem cells and minerals. To accomplish these multiple tasks, the size and shape of the skeletal elements need to be carefully designed during development of the embryo. Skeletal formation in vertebrae is a complex developmental processes controlled by dynamic and well-balanced interactions between a number of molecular signals. Intensive efforts in the past several decades have made substantial progress in understanding molecular and cellular mechanisms of skeletal development. Despite the fact that TGFß …
Adenovirus As A Platform For Assembly And Targeted Delivery Of Gold Nanoparticles To Tumor Cells, Vaibhav Saini
Adenovirus As A Platform For Assembly And Targeted Delivery Of Gold Nanoparticles To Tumor Cells, Vaibhav Saini
All ETDs from UAB
Novel combinatorial strategies need to be explored to achieve tumor eradication. In this regard, viral vector based gene therapy and nanotechnology offer unique possibilities for cancer therapy. As an example, multifunctional adenoviral (Ad) vectors capable of targeting, imaging, and successful cancer gene therapy have been advanced into multiple clinical trials. Similarly, novel multifunctional gold nanoparticles (AuNPs) have been utilized for drug delivery, targeting, imaging, and hyperthermia tumor therapy. Therefore, to accrue the benefits of both gene therapy and nanotechnology for cancer therapy, we proposed to combine Ad vectors and AuNPs in a single multifunctional nanodevice. Towards this goal, herein, we …
The Role Of Tgf-Ss And Wnt5a In Mammary Gland Development And Tumurorigenesis, Kevin Patrick Roarty
The Role Of Tgf-Ss And Wnt5a In Mammary Gland Development And Tumurorigenesis, Kevin Patrick Roarty
All ETDs from UAB
cancer is the second most common cancer worldwide behind lung cancer, affecting women of all ages, races, ethnicities, and socioeconomic strata. Concerted efforts have been made to understand this heterogeneous disease from the clinical stage down to the molecular level. Importantly, it has become clear that an understanding of the normal biology of the breast at all stages of development is needed to gain insight into how alterations in normal regulatory networks contribute to the initiation and development of breast cancer. TGF-ß plays a role in growth and patterning of the mammary gland and alterations in its signaling exhibit biphasic …
Correction Of Sickle Cell Disease By Homologous Recombination, Li-Chen Wu
Correction Of Sickle Cell Disease By Homologous Recombination, Li-Chen Wu
All ETDs from UAB
The hematological disorder sickle cell disease (SCD) is a prevalent human genetic disease. It causes severe tissue damage that can result in strokes, splenic infarction, kidney failure, liver and lung disorders, painful crises, and other complications. Although palliative therapies and allogenic stem cell transplantation therapies have been developed for this disorder, there is still no optimal treatment and SCD patients continue to suffer significant morbidity. Recently, several powerful technologies have been developed that increase the possibility for developing therapeutic treatments for SCD. Previously, our lab group demonstrated that SCD can be corrected in our humanized mouse model by transduction of …
Physiological Charactterization Of The Light Response Of Rod Photoreceptors In The Light Damaged Rat, Yuquan Wen
Physiological Charactterization Of The Light Response Of Rod Photoreceptors In The Light Damaged Rat, Yuquan Wen
All ETDs from UAB
Constant light exposure has long been known to induce photoreceptor degeneration. However, it is not known whether photoreceptors alter their physiology to adapt to the environmental stress caused by constant light exposure. In this study, we have developed a slow light damage model in rats to study changes in single rod physiology and retinal morphology after light damage. Rod physiology was documented by single rod recording using a suction electrode at 3 days (R3), 5 days (R5), 15 days (R15), and 30 days (R30) after 10 days of light damage, or sham light damage for controls. In addition, we used …
The Use Of Molecular Imaging To Evaluate Te Efficacy Of Treatments For Metastatic Breast Cancer, April Adams Szafran
The Use Of Molecular Imaging To Evaluate Te Efficacy Of Treatments For Metastatic Breast Cancer, April Adams Szafran
All ETDs from UAB
The development of molecular imaging technologies has allowed biomedical researchers to study the process of cancer metastasis in animal models of disease. Bioluminescence imaging has been a crucial tool for non-invasive monitoring of tumor growth, dissemination, and response to therapies. In this report, we have applied bioluminescence imaging to evaluate the efficacy of Death Receptor 5 agonist therapy for the treatment of breast cancer metastasis, predominately to the skeleton, in an athymic nude mouse model. Initially, we determined that bioluminescence imaging was the most ideal technology for studying secondary bone lesions in vivo when compared to both x-ray Computed Tomography …
The Role Of Ddx3 In Regulating Apoptosis, P53 And Snail, Mianen Sun
The Role Of Ddx3 In Regulating Apoptosis, P53 And Snail, Mianen Sun
All ETDs from UAB
Cancer is a common disease that causes high rates of lethality. Resistance to cancer therapy is one major obstacle for producing an effective cancer treatment. Clarifying mechanisms of cancer development, such as resistance to apoptosis and metastasis, can provide important information for developing effective cancer treatment strategies. In the present study, DDX3 was demonstrated to have effects on both responses to cancer treatment and cancer development. DDX3 together with glycogen synthase kinase-3 (GSK-3) was found to impede death receptor-induced apoptosis, which is important because death receptors are activated by some cancer treatments. Additionally, DDX3 was shown to regulate two proteins …
Characterization Of Suds3 As A Brms1 Family Member In Breast Cancer, Alexandra C. Silveira
Characterization Of Suds3 As A Brms1 Family Member In Breast Cancer, Alexandra C. Silveira
All ETDs from UAB
BRMS1 and SUDS3 belong to a protein family characterized by the Sds3-like domain. These proteins are core members of SIN3-HDAC chromatin remodeling complexes and thus, regulate transcription. BRMS1 decreases the expression of various metastasis-promoting proteins. This regulation contributes to BRMS1-mediated metastasis suppression through the inhibition of motility and by sensitizing cells to anoikis, as well as through other unidentified mechanisms related to growth at a secondary site. Although BRMS1 and SUDS3 share high sequence similarity and are found in the same complexes, studies have yet to address whether these similarities result in overlapping functions. Additionally, it is unclear how BRMS1 …
Trp-Ing Down A Trk: A New Role For Transient Receptor Potential Channels As Novel Mediators Of Brain-Derived Neurotrophic Factor Actions At Both Sides Of The Excitatory Synapse, Michelle Dawn Amaral
Trp-Ing Down A Trk: A New Role For Transient Receptor Potential Channels As Novel Mediators Of Brain-Derived Neurotrophic Factor Actions At Both Sides Of The Excitatory Synapse, Michelle Dawn Amaral
All ETDs from UAB
Over the years, various roles for neurotrophins have been revealed, being initially described as survival signals for neurons making their initial synaptic contacts in the developing brain. Eventually, it was discovered that these molecules also play important modulatory roles in the adult brain. The work encompassed in this dissertation serves to characterize one particular neurotrophin, brain-derived neurotrophic factor (BDNF), which has been implicated in long-term potentiation (LTP), and its effects at CA3-CA1 synapses in the hippocampus following acute application in vitro. To this end, we have demonstrated the presence of a novel, non-selective cationic current that is initiated by BDNF …
Characterization Of Sortase And Its Effect On The Virulence Of Streptococcus Pneumoniae, Allison E. Bennett
Characterization Of Sortase And Its Effect On The Virulence Of Streptococcus Pneumoniae, Allison E. Bennett
All ETDs from UAB
Sortases are transpeptidases that covalently link surface proteins to the stempeptide on the cell wall peptidoglycan of Gram-positive bacteria. This work endeavored to characterize the various sortase enzymes and their effect on the virulence of Streptococcus pneumoniae. The genome of S. pneumoniae may encode up to four sortase enzymes. We found that 38 of 54 strains of serotype 6B clonal complex 14 (CC14) carry the genes for the secondary sortases srtB, srtC, and srtD. The presence of these sortases did not seem to influence the ability of strains within CC14 to infect the nasopharynx, lungs, or blood of strains within …
Localization And Function Of G2e3, William Samuel Brooks
Localization And Function Of G2e3, William Samuel Brooks
All ETDs from UAB
A microarray study was performed which identified G2E3 as a novel, putative ubiquitin ligase that was both G2/M-specific in expression and down regulated at the transcriptional level following DNA damage by γ-irradiation. The initial characterization of this protein is described herein. G2E3 is composed of three PHD/RING (plant homoedomain/really interesting new gene) domains within its amino-terminal half and a carboxy-terminal HECT (homologous to E6AP carboxy-terminus) domain. G2E3 is regulated in part by its subcellular localization. The protein normally resides within the nucleoplasm of cultured cells and distinctly within the nucleolus of HeLa cells. G2E3 is a nucleo-cytoplasmic shuttling protein with …
Loss Of Pias3 Expression In Glioblastoma Multiforme Tumors:Implications For Stat-3 Activation And Gene Expression, Emily Claire Brantley
Loss Of Pias3 Expression In Glioblastoma Multiforme Tumors:Implications For Stat-3 Activation And Gene Expression, Emily Claire Brantley
All ETDs from UAB
Glioblastoma multiforme (GBM) is the most common form of cancer in the central nervous system in adults. Because of the infiltrative and aggressive nature of GBM, current treatments including surgical resection, radiation and chemotherapy provide little benefit to patients diagnosed with this tumor. Median survival, after treatment, is less than one year. Despite advances in the basic understanding of cancer biology, this poor prognosis has remained virtually unchanged for several decades. Given the continuing difficulty of clinical treatment of GBMs, a molecular appreciation of relevant signaling pathways has grown. Signal Transducers and Activators of Transcription (STATs) function to activate gene …
Characterization And Functional Analysis Of Usp14, Stephen Lewis Crimmins
Characterization And Functional Analysis Of Usp14, Stephen Lewis Crimmins
All ETDs from UAB
The ubiquitin proteasome system (UPS) is essential for regulated protein degrada-tion, a requirement for numerous neuronal process, including vesicle cycling, neuro-transmitter release, spine morphology, and synaptic plasticity. Better understanding of UPS function in neurons will increase our knowledge of neurological diseases caused by alterations in ubiquitin signaling. I utilized the ataxia (axJ) mice as a tool to study the UPS in the nervous system. The axJ mice have lowered expression of ubiquitin-specific protease 14 (Usp14) in all tissues; this decreased expression results from an intracisternal-A particle insertion into Usp14. The axJ mice are phenotypically indistinguishable from wild type littermates at …
Characterization Of A Novel Acetyltransferase Found Only In Pathogenic Strains Of Mycobacterium Tuberculosis, David K. Crossman
Characterization Of A Novel Acetyltransferase Found Only In Pathogenic Strains Of Mycobacterium Tuberculosis, David K. Crossman
All ETDs from UAB
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is still a major threat to the human population. Roughly one third of the world population is asymptomatically infected and two million people die each year of TB. Effective treatments are available as a multi-drug regimen, but there is an ever increasing problem with the rise of multi-drug resistant strains that newer drug targets and a better understanding of how M. tuberculosis affects the host need to be elucidated. The primary target of M. tuberculosis in the human host is the macrophage where M. tuberculosis secretes virulence factors that inhibit various signal …
Coupling Selection Of The Hiv- 1 Trna Primer Used For Reverse Transcription With Viral Translation And Encapsidation, Uros V. Djekic
Coupling Selection Of The Hiv- 1 Trna Primer Used For Reverse Transcription With Viral Translation And Encapsidation, Uros V. Djekic
All ETDs from UAB
HIV-1 belongs to the Retroviridae family. A hallmark of retroviral replication is the process of reverse transcription. Viral reverse transcriptase requires placement of a cellular tRNA primer onto the primer binding site (PBS) in order to initiate conversion of the viral RNA genome into a double stranded DNA copy. Mutation of the HIV-1 PBS forces the virus to utilize the non-cognate primer. Even though extensive studies have been done over the past 15 years, the mechanism of HIV-1 primer selection has yet to be completely elucidated. HIV-1 captures free tRNA during a yet undefined step in viral replication. However, our …
The Role Of The Cytoskeleon In Achr Clustering, G Clement Dobbins
The Role Of The Cytoskeleon In Achr Clustering, G Clement Dobbins
All ETDs from UAB
The human brain contains billions of neurons which are designed to receive and integrate a range of electrical and biochemical signals. The ability to convey information between these cells depends on synapses. A precise apposition between the pre and post synapse must exist for efficient transmission to occur. The neuromuscular junction (NMJ) has become a model for studying synaptogenesis. Although much is known about the steps in NMJ formation, only recently have there been insights into the mechanism behind NMJ development. Much of this research has focused on how acetylcholine receptors (AChRs) at the postsynapse form clusters directly apposed to …
A Study Into The Protein/Protein Interactions Involved In Hiv-1 Capsid Assembly, Chanel Catherine Douglas
A Study Into The Protein/Protein Interactions Involved In Hiv-1 Capsid Assembly, Chanel Catherine Douglas
All ETDs from UAB
The aim of this work was to build an understanding of the protein/protein interactions involved in HIV-1 capsid assembly as it relates to the condensation of capsid within the virion. This was undertaken in an attempt to (i) understand how capsid subunits recognize and interact with each other, (ii) gain insight into the protein-protein interactions involved in the process, and (iii) determine if the protein-protein interactions involved in virus cap-sid assembly can be used as a target for viral inhibition. Within this dissertation you will find two approaches to this investigation. The first examines the role of electrostatics in the …
Visualizing The Function And Migration Of T Cells, Kari J. Dugger
Visualizing The Function And Migration Of T Cells, Kari J. Dugger
All ETDs from UAB
Lymphocytes are highly mobile cells that can travel throughout the body in response to a multitude of stimuli. Identifying lymphocyte trafficking patterns in vivo is essential for a complete understanding of immune function. Cell-cell and cell-tissue interactions in immune development and in lymphocyte response to stimuli can be comprehended with these investigations. Although the location of cell populations in various tissues at any given point in time may be investigated by techniques such as flow cytometry and immunofluorescence, these methods are not easily used in the assessment of dynamic cell migration patterns in vivo. In the past years, technologies for …
Molecular Determinants Of Picrotoxin Inhibition, Brian E. Erkkila
Molecular Determinants Of Picrotoxin Inhibition, Brian E. Erkkila
All ETDs from UAB
PTX is a non-competitive antagonist of many LGICs, and its site of action is believed to be within the ion-conducting pore. This study will examine, through the use of mutagenesis, electrophysiology and homology modeling, the binding interaction between the LGIC receptors and the PTX molecule. The data provides evidence that an interaction between the PTX molecule and uncharged polar amino acids at the 6’ level of the M2 transmembrane domain are essential for PTX inhibition. While the work will focus on the γ-aminobutyric type A receptor, the pharmacological and structural relevance is attributable to the LGIC family as a whole.
The Role Of Chloride In The Volume Regulation Of Human Glioma Cells, Nola Jean Ernest
The Role Of Chloride In The Volume Regulation Of Human Glioma Cells, Nola Jean Ernest
All ETDs from UAB
According to the Central Brain Tumor Registry of the United States, the most common primary brain tumors are gliomas, tumors composed of cells of glial origin, most commonly astrocytes and oligodendrocytes. The most aggressive of these tumors are characterized by hyperproliferation, marked cellular and nuclear atypia, extensive infiltration into surrounding normal brain tissue, and large areas of cell and tissue death. Previous data published by our lab and others suggest that these biological processes may involve regulated cell volume changes. Using cell volume regulation in the presence of an anisosmotic challenge as a model for cell swelling and shrinkage, cell …
Protease Dysregulation: Role In Neutrophilic Inflammation In Cystic Fibrosis, Amit Gaggar
Protease Dysregulation: Role In Neutrophilic Inflammation In Cystic Fibrosis, Amit Gaggar
All ETDs from UAB
Cystic fibrosis (CF) is a lethal disorder characterized by abnormal epithelial ion transport; this disorder is characterized by an ongoing airway remodeling and neutrophilic inflammation. Much of the airway remodeling is due to activation of a group of enzymes known as proteases; human neutrophil elastase (HNE) is a prominent protease found in the CF airway. While specific cytokines/chemokines are well-known for their role in the inflammation seen in CF, it is unknown how the protease-rich environment in CF lung disease influences airway inflammation. Recently, our group has characterized a novel collagen-derived fragment, proline-glycine-proline (PGP), which causes neutrophil influx through mechanisms …
Pneumococcal Choline-Binding Protein A: Its Role In Virulence And Its Utility As A Streptococcus Pneumoniae Vaccine Antigen, David Tawayne Glover
Pneumococcal Choline-Binding Protein A: Its Role In Virulence And Its Utility As A Streptococcus Pneumoniae Vaccine Antigen, David Tawayne Glover
All ETDs from UAB
Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. S. pneumoniae is a leading cause of pneumonia, meningitis, septicemia, and otitis media. Although all age groups can be affected, children and the elderly are espccially susceptible to infection. Currently there is a conjugate vaccine available for use, but this vaccine only contains capsular polysaccahride antigens from the seven most prevelant S. pneumoniae serotypes. The use of the conjugate vaccine has led to serotype shift, with more disease being caused by non-vaccine serotype bacteria. The studies presented in this dissertation identify and characterize a novel S. penumoniae vaccine candidate …
Protein Interaction And Cell Surface Trafficking Differences Between Wild-Type And Δf508 Cystic Fibrosis Transmembrane Conductance Regulator, Rebecca F. Goldstein
Protein Interaction And Cell Surface Trafficking Differences Between Wild-Type And Δf508 Cystic Fibrosis Transmembrane Conductance Regulator, Rebecca F. Goldstein
All ETDs from UAB
Cystic fibrosis (CF) is caused by mutation of one protein, the cystic fibrosis transmembrane conductance regulator (CFTR), which normally functions as a chloride channel at the apical surface of epithelial cells. The most common CFTR mutation results in the deletion of a single amino acid (phenylalanine) at position 508, which causes the protein to fold improperly. The ΔF508 CFTR is a temperature-sensitive (TS) processing mutant: At the restrictive temperature, 37°C, ΔF508 CFTR misfolds in the endoplasmic reticulum (ER) and is degraded, but at the permissive temperature, 27°C, it is “rescued” from degradation (rΔF508). In particular, rΔF508 CFTR folds correctly enough …
Interference With Hiv-1 Primer Selection By Sirna Directed To The Hiv-1 Primer Binding Site, Wenlong Han
Interference With Hiv-1 Primer Selection By Sirna Directed To The Hiv-1 Primer Binding Site, Wenlong Han
All ETDs from UAB
The replication of Human immunodeficiency virus type 1 (HIV-1) is characterized by the process of reverse transcription, which converts the viral RNA genome into a DNA intermediate prior to integration into the host cell chromosome. The initiation of reverse transcription needs a cellular tRNA primer, which binds to a region in the viral RNA genome, designated as the primer binding site (PBS). The 18-nucleotide PBS region of HIV-1, which is complementary to the 3′ terminal 18 nucleotides of tRNALys,3, is absolutely conserved among all HIV-1. The highly conserved PBS is a very good target for HIV-1 therapy. My dissertation research …