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New Mouse Models To Aid Studies Of The Role Of Primary Cilia In Limb Patterning And Bone Development, Amber Kathleen O'Connor Jan 2013

New Mouse Models To Aid Studies Of The Role Of Primary Cilia In Limb Patterning And Bone Development, Amber Kathleen O'Connor

All ETDs from UAB

Hedgehog (Hh) signaling is required for many developmental processes, and causes several diseases and cancers. Described in chapter one below, vertebrate Hh sig-naling is dependent on the primary cilium (PC), a small organelle that extends from the surface of most mammalian cell types. A better understanding of how the PC modulates Hh signaling is important, as defects in the structure or function of PC result in severe human disorders termed the ciliopathies. For example, patients with Meckel-Gruber Syndrome have extra digits and neural tube defects, which are Hh both related pheno-types. In chapter two we sought to further understand the …

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Phospho-Erk And Amyloid Beta: Targets Of Estrogen In The Brain, Thomas Reed Peavy Jan 2013

Phospho-Erk And Amyloid Beta: Targets Of Estrogen In The Brain, Thomas Reed Peavy

All ETDs from UAB

Estrogen replacement therapy (ERT) has been shown to improve memory function in menopausal women, but increases hormone sensitive cancers, prompting a more targeted investigation of estrogen's action in learning and memory to develop more targeted therapeutics. Estrogen improves performance on the novel object recognition task by increasing phosphorylation of extracellular signal-regulated kinase (pERK) within minutes in the hippocampus. Dr. Lori McMahon's lab showed that the improvement in novel object recognition can be seen 24 hours after subcutaneous injection of proestrous levels of estrogen (referred to as E24). Whether a corresponding increase in pERK occurs at the E24 time point had …

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The Origin, Regulation, And Function Of Tbet In Effector Cd4 T Cells During Chronic Autoimmune Disease, Wen-I Yeh Jan 2013

The Origin, Regulation, And Function Of Tbet In Effector Cd4 T Cells During Chronic Autoimmune Disease, Wen-I Yeh

All ETDs from UAB

Multiple Sclerosis (MS) is an autoimmune disease resulting from aberrant immune cells causing demyelination. We utilize the well-studied mouse model, experimental autoimmune encephalomyelitis (EAE), to decipher the underlying pathogenesis of MS. Effector CD4 T-cells play a critical role during EAE because the disease is induced by adoptively transferring myelin-specific CD4 T-cells into naïve mice. Classically, effector CD4 T-cells have been divided into distinct subsets based on their functional properties: Th1 cells produce IFNγ, Th2 cells secrete IL-4, IL-5, and IL-13, Th17 cells make IL-17A, IL-17F, IL-21, and IL-22, and regulatory T cells produce IL-10. Th1 cells were originally identified as …

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Investigation Of Death Receptor-5 Mediated Apoptosis And Inhibition Of Wnt/Ss-Catenin Signaling In Basal-Like Breast Cancer Stem Cells, Angelina Ix-Ik' Londono-Joshi Jan 2013

Investigation Of Death Receptor-5 Mediated Apoptosis And Inhibition Of Wnt/Ss-Catenin Signaling In Basal-Like Breast Cancer Stem Cells, Angelina Ix-Ik' Londono-Joshi

All ETDs from UAB

Basal-like breast cancers (BLBC) display aggressive clinical behavior attributed to the presence of cancer stem cells (CSCs). TRA-8, a monoclonal antibody that binds specifically to TRAIL death receptor 5, preferentially induces apoptosis in BLBC subtype cells; however it is unknown if TRA-8 is also cytotoxic to the CSC population. Moreover, some BLBC cell lines are resistant to TRA-8, and overcoming resistance is critical for clinical translation of this therapy. One potential approach to overcome TRA- 8 resistance is to target the Wnt/ß-catenin pathway. LRP6 is a cell surface receptor that is an indispensable element of the Wnt/ß-catenin signaling pathway that …

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Intracellular Quantitation And Pharmacokinetic Modeling Of Nucleoside Analogs In The Female Genital Tract, Amanda Marie James Jan 2013

Intracellular Quantitation And Pharmacokinetic Modeling Of Nucleoside Analogs In The Female Genital Tract, Amanda Marie James

All ETDs from UAB

Human Immunodeficiency Virus (HIV) is one of the leading infectious diseases in the world. In spite of substantial progress in the advancement of antiretroviral therapy for HIV treatment, new infections outpace the number of infected persons initiating ART. Therefore, the prevention of HIV remains a crucial health issue. Pre-Exposure Prophylaxis, (PrEP), which involves using one or more antiretroviral agents to reduce the risk of HIV infection prior to potential exposure, has shown effectiveness at reducing HIV transmission in study volunteers with different sexual orientation around the world. The clinical pharmacology of antiretroviral drugs, specifically tenofovir (TFV) and emtricitabine (FTC), in …

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Rhob Controls Coordination Of Adult Angiogenesis And Lymphangiogenesis Following Injury By Regulating Vezf1-Mediated Transcription., Damien Gerald, Irit Adini, Sharon Shechter, Carole Perruzzi, Joseph Varnau, Benjamin Hopkins, Shiva Kazerounian, Peter Kurschat, Stephanie Blachon, Santosh Khedkar, Mandrita Bagchi, David Sherris, George C Prendergast, Michael Klagsbrun, Heidi Stuhlmann, Alan C Rigby, Janice A Nagy, Laura E Benjamin Jan 2013

Rhob Controls Coordination Of Adult Angiogenesis And Lymphangiogenesis Following Injury By Regulating Vezf1-Mediated Transcription., Damien Gerald, Irit Adini, Sharon Shechter, Carole Perruzzi, Joseph Varnau, Benjamin Hopkins, Shiva Kazerounian, Peter Kurschat, Stephanie Blachon, Santosh Khedkar, Mandrita Bagchi, David Sherris, George C Prendergast, Michael Klagsbrun, Heidi Stuhlmann, Alan C Rigby, Janice A Nagy, Laura E Benjamin

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mechanisms governing the distinct temporal dynamics that characterize post-natal angiogenesis and lymphangiogenesis elicited by cutaneous wounds and inflammation remain unclear. RhoB, a stress-induced small GTPase, modulates cellular responses to growth factors, genotoxic stress and neoplastic transformation. Here we show, using RhoB null mice, that loss of RhoB decreases pathological angiogenesis in the ischaemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge. We link these unique and opposing roles of RhoB in blood versus lymphatic vasculatures to the RhoB-mediated differential regulation of sprouting and proliferation in primary human blood versus …

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The Development Of An In Vitro Surrogate Assay For Screening Protective Antibodies Against Pneumococcal Surface Protein A (Pspa), Kristopher Ruben Genschmer Jan 2013

The Development Of An In Vitro Surrogate Assay For Screening Protective Antibodies Against Pneumococcal Surface Protein A (Pspa), Kristopher Ruben Genschmer

All ETDs from UAB

PCV13 is the current pneumococcal protein conjugated vaccine made up of the 13 most clinically relevant capsular polysaccharides. While protective, it is limited to a small portion of the overall serotypes of Streptococcus pneumoniae. The possibility of "serotype replacement" by serotypes not covered by the vaccine and the high cost of producing this conjugated polysaccharide vaccine stress the need for a protein based vaccine, one that is more broad in its protection. Pneumococcal surface protein A (PspA) has been shown to be both immunogenic and protective in mice and is a promising protein vaccine candidate. However, there are no current …

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Experience-Dependent Synaptic Integration Of Adult-Generated Dentate Granule Cells, Jessica Hotard Chancey Jan 2013

Experience-Dependent Synaptic Integration Of Adult-Generated Dentate Granule Cells, Jessica Hotard Chancey

All ETDs from UAB

The dentate gyrus (DG) contains neural stem cells that continually generate new neurons throughout life. The contribution of adult neurogenesis to hippocampal function is not well understood, but ablation or silencing of adult-generated neurons in the DG disrupts learning and memory, and neurogenesis is altered in many pathologies associated with impaired cognition including Alzheimer's Disease, epilepsy, and schizophrenia. Neurogenesis in the DG is a stepwise process in which neural stem cells leave the cell cycle and undergo an approximately two month long maturation process to form fully functional dentate granule cells (GCs) that are indistinguishable from those formed during development. …

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The Role Of O-Glcnacylation In Synaptic Function, Erica Wynette Taylor Jan 2013

The Role Of O-Glcnacylation In Synaptic Function, Erica Wynette Taylor

All ETDs from UAB

O-GlcNAcylation is a dynamic protein posttranslational modification that adds the monosaccharide ß-N-acetylglucosamine (GlcNAc) to specific serine and threonine residues on nucleocytoplasmic proteins. The hippocampus is a part of brain that has been shown to play a crucial role in learning and memory. Hippocampal neurons have high expression of O-GlcNAc transferase and O-GlcNAcase, which catalyze the addition and removal of GlcNAc from proteins respectively. Moreover, synaptic plasticity which is the strengthening or weakening of synaptic function on short- and long-term time scales is believed to be a cellular correlate of learning and memory. Several forms of synaptic plasticity have been characterized …

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Role Of Kca3.1, A Calcium-Activated Potassium Channel, In Cell Migration In The Adult Brain, Kathryn L. Turner Jan 2013

Role Of Kca3.1, A Calcium-Activated Potassium Channel, In Cell Migration In The Adult Brain, Kathryn L. Turner

All ETDs from UAB

A limited amount of migration occurs in the adult brain, including migration of neuroblasts during adult neurogenesis and pathological migration of primary brain tumors. Ion channels are commonly utilized during migration to allow shape and volume changes required for cell movement, and we specifically examine the role of KCa3.1 in the adult brain. These channels are well-suited to facilitate movement because they respond to common migration signals, i.e. intracellular Ca2+ changes, and efflux K+, allowing the outflow of water and cell volume regulation. Our findings suggest that KCa3.1 is highly expressed in migratory cells, adult neuroblasts and glioma cells, but …

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The Role Of Pneumococcal Choline-Binding Protein A (Pcpa) In The Mechanism Of Virulence And Protective Immunity, Melissa Marie Walker Jan 2013

The Role Of Pneumococcal Choline-Binding Protein A (Pcpa) In The Mechanism Of Virulence And Protective Immunity, Melissa Marie Walker

All ETDs from UAB

pcpA is under control of the Mn 2-dependent repressor PsaR. In the high manganese environment of mucosal sites pcpA gene expression is repressed and at the low manganese environment of the lung and blood derepression of pcpA gene expressionis observed. Previous data has shown that immunization of mice with rPcpA elicits protection against pneumonia and sepsis but had no effect on nasal colonization. We and others have shown that pcpA expression significantly enhances adherence of pneumococci to lung epithelial cell lines and although it is a virulence factor for pneumonia in mice there is no biologically relevant role for PcpA …

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Anti-Group B Streptococci Monoclonal Antibodies Protect Against Invasive Aspergillosis, Rebekah Wharton Jan 2013

Anti-Group B Streptococci Monoclonal Antibodies Protect Against Invasive Aspergillosis, Rebekah Wharton

All ETDs from UAB

Aspergillus fumigatus is a ubiquitous saprophytic fungus which can potentially cause life-threatening infections in immunocompromised individuals. Although a serious threat, current treatments are largely ineffective at reducing morbidity and mortality. To this end, we have characterized a monoclonal antibody generated against Group B Streptococci, type Ib, which also recognizes Aspergillus fumigatus conidia and hyphae. We show that this antibody appears to bind a similar epitope on both pathogens and provides a significant degree of protection in a murine model of invasive aspergillosis via a mechanism that appears to be dependent on complement. The studies we performed using this antibody should …

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Genetic And Biochemical Characterizations Of The Capsular Glycosyltransferases In Streptococcus Pneumoniae Serotype 2, David Boyd Anthony James Jan 2013

Genetic And Biochemical Characterizations Of The Capsular Glycosyltransferases In Streptococcus Pneumoniae Serotype 2, David Boyd Anthony James

All ETDs from UAB

The principle objective of this dissertation is to develop a thorough understanding of the genetics and biochemistry of capsule synthesis. Specifically, it involves the identification and characterization of the capsular glycosyltransferases in Streptococcus pneumoniae serotype 2, with investigations into their regulation. S. pneumoniae (the pneumococcus) is a significant human pathogen that has the ability to persist as a commensal and then transition to a virulent state, the latter of which is a major contributor to global morbidity and mortality. The capsular polysaccharide (CPS) of S. pneumoniae is a protective surface structure that plays an integral role in this disease process. …

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Marcks Is A Regulator Of Growth, Radiation Sensitivity And Is A Novel Prognostic Factor For Glioblastoma Multiforme, John Jarboe Jan 2013

Marcks Is A Regulator Of Growth, Radiation Sensitivity And Is A Novel Prognostic Factor For Glioblastoma Multiforme, John Jarboe

All ETDs from UAB

Glioblastoma multiforme (GBM) is the most common and deadly primary brain malignancy necessitating improved understanding of GBM biology. In this study, we explore the role of Myristoylated Alanine Rich C-Kinase Substrate (MARCKS) in the context of GBM. We have discovered that the MARCKS protein regulates GBM growth as well as response to radiation therapy through its effects on proliferation, senescence, and DNA repair based on our studies in cell culture and in patient-derived xenograft tumors implanted in mice. Importantly, our analysis of clinical patient data demonstrates that MARCKS is an independent predictor for outcome in GBM patients. Indeed, high MARCKS …

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The Role Of Histone Deacetylase Inhibitors In Ameliorating Memory Dysfunction Of An Alzheimer's Disease Mouse Model, Mark Kilgore Jan 2013

The Role Of Histone Deacetylase Inhibitors In Ameliorating Memory Dysfunction Of An Alzheimer's Disease Mouse Model, Mark Kilgore

All ETDs from UAB

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid beta plaques and neurofibrillary tangles, along with cognitive impairments that progress to dementia and eventually death. The development of drug treatments that rescue memory deficits could be a promising therapy given in the early stages of AD. In the following studies, we tested the potential for systemic treatment with histone deacetylase (HDAC) inhibitors to ameliorate cognitive deficits in a mouse model of AD. Using the APPSwe/PS1dE9 mouse model of AD, we showed that giving HDAC inhibitors systemically for 3 weeks reversed contextual memory deficits, stably maintained memories over a 2-week …

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Cyclic Gmp Phosphodiesterase As A Novel Target For Colorectal Cancer Chemoprevention, Nan Li Jan 2013

Cyclic Gmp Phosphodiesterase As A Novel Target For Colorectal Cancer Chemoprevention, Nan Li

All ETDs from UAB

Nonsteroidal anti-inflammatory drugs (NSAIDs) display promising antineoplastic activity for colorectal and other cancers, but toxicity from cyclooxygenase (COX) inhibition limits their long-term use for chemoprevention. However, many investigators have concluded that COX-independent mechanisms are responsible for their antineoplastic activity. We previously reported that cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) is a non-COX target of sulindac sulfide (SS). However, the specific isozyme families involved have not been well studied. Here we demonstrate that SS inhibits the growth of colon tumor cells through a novel mechanism involving inhibition of two cGMP degrading isozymes, PDE5 and PDE10, to activate cGMP-dependent protein kinase (PKG). …

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Surveying The Serum Proteome For Biomarkers Of Early-Stage Pancreatic Cancer, Michael Robert Ludwig Jan 2013

Surveying The Serum Proteome For Biomarkers Of Early-Stage Pancreatic Cancer, Michael Robert Ludwig

All ETDs from UAB

SURVEYING THE SERUM PROTEOME FOR BIOMARKERS OF EARLY STAGE PANCREATIC CANCER MICHAEL ROBERT LUDWIG MICROBIOLOGY ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is a uniformly fatal disease due to its refractory nature to conventional therapies at the time of initial diagnosis. In order to in-crease the curative potential of surgical resection, early detection of organ-confined neoplasia is needed. Currently, no effective diagnostic tools are available to detect early-stage pancreatic ductal lesions termed pancreatic intraepithelial neoplasia (PanIN) or lo-cally invasive, organ-confined disease. One way to identify biomarkers that may be use-ful for the early detection of PDAC is through the study of the …

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Characterizing The Roles Of Il-11 And Cd68 In Breast Cancer Bone Metastasis, Erin Mills Mccoy Jan 2013

Characterizing The Roles Of Il-11 And Cd68 In Breast Cancer Bone Metastasis, Erin Mills Mccoy

All ETDs from UAB

The molecular mechanisms regulating the preferential metastasis of breast cancer to bone have not been fully elucidated, but it is hypothesized that local conditions in the bone create an environment conducive to colonization by breast cancer cells and that the breast cancer cells interact directly with cells in the bone. In this dissertation, two goals were pursued: (1) to explore breast cancer secreted interleukin (IL)-11's role on osteoclast function and (2) investigate the expression and potential role of CD68 in breast cancer adhesion to bone. Higher rates of bone metastasis occur in human breast cancer tumors expressing IL-11, a cytokine …

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The Role Of Complement In Experimental Cerebral Malaria, Theresa N. Ramos Jan 2013

The Role Of Complement In Experimental Cerebral Malaria, Theresa N. Ramos

All ETDs from UAB

Cerebral malaria (CM) is one of the most severe clinical complications of P. falciparum malaria with a fatality rate of 15-30%, and 10% of CM survivors have permanent neurological sequelae. Since inflammation is a central pathophysiological tenet of CM, we began examining the role of the complement system in pathogenesis of experimental cerebral malaria (ECM) using Plasmodium berghei ANKA (PbA) model. Previous studies using this model indicated that mice naturally deficient in complement component C5 were protected from cerebral complications, and wild type mice treated with anti-C5aR antibody were also protected. To determine the protective mechanism of naturally-C5 deficient mice, …

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Commensal Microbiota And Its Impact On Health And Autoimmune Diabetets, Kyle James Wolf Jan 2013

Commensal Microbiota And Its Impact On Health And Autoimmune Diabetets, Kyle James Wolf

All ETDs from UAB

Environmental exposures such as diet, use of antibiotics, and lifestyle have significant impact on the health of an individual. One mechanism that acts as a major pathway in these environmental exposures is the role intestinal commensal microbiota play in both metabolic and immunological responses. Metabolic pathways are altered through changes in metabolites provided by commensal microbiota; alterations in microbial make-up can have drastic impacts on metabolic function. Similarly, the development and maturation of the immune system is dependent on the intestinal microbes to induce tolerance and act as both an immune modulator as well as a barrier against pathogens. We …

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Characterization Of The Mumps Virus Replicase, Robert Marsden Cox Jan 2013

Characterization Of The Mumps Virus Replicase, Robert Marsden Cox

All ETDs from UAB

Negative strand RNA viruses (NSV) are unique because their nucleocapsids are used directly as the template for both transcription and replication. The viral genomic RNA is coated by the nucleoprotein (N) for the entirety of the NSV replication cycle. The viral polymerase, which is composed of the L and P proteins, can only recognize encapsidated RNA as the template for RNA synthesis. Our previous studies have solved the EM structure of the MuV N-RNA complex at 25Ņ. This structure revealed how the nucleocapsid is assembled and provides an initial model for examining how the viral polymerase may recognize the …

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Sulindac Sulfide Amide As A Novel Agent For The Prevention And Treatment Of Lung Cancer, Evrim Gurpinar Jan 2013

Sulindac Sulfide Amide As A Novel Agent For The Prevention And Treatment Of Lung Cancer, Evrim Gurpinar

All ETDs from UAB

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac sulfide (SS) have shown promising antineoplastic activity in multiple tumor types, but toxicities resulting from cyclooxygenase (COX) inhibition limit their use in cancer prevention. We recently described a N,N-dimethylethyl amine derivative of SS, sulindac sulfide amide (SSA), that does not inhibit COX-1 or -2, yet displays potent tumor cell growth inhibitory activity. Here, we studied the basis for the growth inhibitory effects of SSA on human lung adenocarcinoma cell lines and evaluated its preclinical pharmacology. SSA potently inhibited the growth of lung tumor cells with IC50 values of 2-5 μ compared with 44-52 …

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Clinical Consequences Of Micrornas In Colorectal Cancer, Liselle C. Bovell Jan 2013

Clinical Consequences Of Micrornas In Colorectal Cancer, Liselle C. Bovell

All ETDs from UAB

Colorectal cancer (CRC) is a heterogeneous disease, and factors such as tumor location, the environment, genetics, and ethnic differences, can influence its development and progression. Over the last few decades, overall CRC mortality rates have declined; however, racial disparities in mortality rates have increased. The discovery of biomarkers that focus on identifying individual differences based on confounders such as tumor stage and patient race/ethnicity is needed, for such biomarkers can lead to development of personalized therapeutic approaches to target these molecules. MicroRNAs (miRNAs) are a class of small molecules that regulate genes at the post-transcriptional level. Altered miRNA expression levels …

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Therapeutic Potential Of Genetically-Engineered Mesenchymal Stem Cells In Multiple Myeloma, Jerome T. Higgs Jan 2013

Therapeutic Potential Of Genetically-Engineered Mesenchymal Stem Cells In Multiple Myeloma, Jerome T. Higgs

All ETDs from UAB

ABSTRACT Multiple Myeloma (MM) remains the second most common hematologic malig-nancy occurring in adults, which primarily affects the skeletal system causing severe bone destruction, spinal cord compression and hypercalcemia. Current therapies, which include chemotherapy, radiotherapy, autologouos stem cell transplantation and in some cases surgery, have extended the median survival between 3 and 10 years. However, MM is still incurable and therefore improving current therapies or developing newer ones to reduce the burden of osteolytic damage and extend survival rate will be highly beneficial for patient management. The long-term goal of this study is to develop a novel therapeutic approach to …

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Determinant Of G-Chain Mediated Fc Receptor Signaling, Spandan Shah Jan 2013

Determinant Of G-Chain Mediated Fc Receptor Signaling, Spandan Shah

All ETDs from UAB

Fc receptors provide an interface between humoral immunity and cellular immunity by binding to the Fc portion of immunoglobulin and mediating effector functions. Cells expressing Fc receptors play a major role in immune complex clearance via phagocytosis, leading to a context dependent pro- or anti-inflammatory environment. Signaling by multi-chain Fc receptor complexes, including FcgRI, FcgRIII, FceRI and FcaRI is mediated by the ITAM-containing common FceRIg (g-chain) subunit. However, despite the use of a common g-chain, different Fc receptor complexes elicit specific cellular programs, suggesting additional layers of regulation of tyrosine based signaling by g-chain. We hypothesized that the unique g-chain …

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Neuropathological Alterations In Alzheimer's Disease: An Up Close Look At Sympathetic Sprouting, Amy Renee Nelson Jan 2013

Neuropathological Alterations In Alzheimer's Disease: An Up Close Look At Sympathetic Sprouting, Amy Renee Nelson

All ETDs from UAB

Pathological hallmarks of AD include neurofibrillary tau tangles, amyloid beta (Abeta) accumulation and cholinergic degeneration. Cholinergic degeneration can be mimicked in rats by lesioning cholinergic neurons in medial septum. Hippocampal cholinergic denervation disrupts retrograde transport of nerve growth factor (NGF), leading to its accumulation, which subsequently triggers sprouting of noradrenergic sympathetic fibers from the superior cervical ganglia into hippocampus. Dr. McMahon's lab previously reported that coincident with this sprouting, there is an increase in cholinergic innervation that correlates with a recovery of M1 muscarinic receptor dependent plasticity at CA3-CA1 synapses and visual cortex. These findings suggest that noradrenergic sympathetic sprouting …

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Ash2 Acts As An Ecdysone Receptor Coactivator By Stabilizing The Histone Methyltransferase Trr., Albert Carbonell, Alexander Mazo, Florenci Serras, Montserrat Corominas Jan 2013

Ash2 Acts As An Ecdysone Receptor Coactivator By Stabilizing The Histone Methyltransferase Trr., Albert Carbonell, Alexander Mazo, Florenci Serras, Montserrat Corominas

Department of Biochemistry and Molecular Biology Faculty Papers

The molting hormone ecdysone triggers chromatin changes via histone modifications that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with transcriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdysone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr …

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Identification Of Phosphorylation Sites In The Cooh-Terminal Tail Of The Μ-Opioid Receptor., Ying-Ju Chen, Sue Oldfield, Adrian J. Butcher, Andrew B. Tobin, Kunal Saxena, Vsevolod V. Gurevich, Jeffrey L. Benovic, Graeme Henderson, Eamonn Kelly Jan 2013

Identification Of Phosphorylation Sites In The Cooh-Terminal Tail Of The Μ-Opioid Receptor., Ying-Ju Chen, Sue Oldfield, Adrian J. Butcher, Andrew B. Tobin, Kunal Saxena, Vsevolod V. Gurevich, Jeffrey L. Benovic, Graeme Henderson, Eamonn Kelly

Department of Biochemistry and Molecular Biology Faculty Papers

Phosphorylation is considered a key event in the signalling and regulation of the μ opioid receptor (MOPr). Here, we used mass spectroscopy to determine the phosphorylation status of the C-terminal tail of the rat MOPr expressed in human embryonic kidney 293 (HEK-293) cells. Under basal conditions, MOPr is phosphorylated on Ser(363) and Thr(370), while in the presence of morphine or [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO), the COOH terminus is phosphorylated at three additional residues, Ser(356) , Thr(357) and Ser(375). Using N-terminal glutathione S transferase (GST) fusion proteins of the cytoplasmic, C-terminal tail of MOPr and point mutations of the same, we …

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The Effect Of Exogenous Leptin On Dendritic Cell Migration And Interactions With T Cells, Amanda L. Gonzales Jan 2013

The Effect Of Exogenous Leptin On Dendritic Cell Migration And Interactions With T Cells, Amanda L. Gonzales

Open Access Theses & Dissertations

Obesity is a complex, chronic disease that has reached epidemic proportions in the United States and shows no indication of receding. It is a state of chronic low-grade inflammation that is initiated by morphological changes in large accumulations of adipose tissue. Leptin is a pleiotropic hormone secreted by adipose tissue, presenting a possible link between obesity and inflammation. In this study, we assessed the effect of leptin on bone marrow-derived (BM) dendritic cells (DC) (BM-DC) function, antigen presenting cells vital for the activation of naí¯ve T cells. Previous data produced in our laboratory established that the addition of leptin to …

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Using The Theory Of Planned Behavior As A Predictor Of Radiologic Technologists' Use Of Patient Radiation Protection Best Practices: A Regional Study, Brenda L. Boyd Jan 2013

Using The Theory Of Planned Behavior As A Predictor Of Radiologic Technologists' Use Of Patient Radiation Protection Best Practices: A Regional Study, Brenda L. Boyd

Dissertations

Problem. A growing concern exists that patients are receiving an increase in radiation exposure while undergoing medical imaging exams. According to a March 2009 report by the National Council on Radiation Protection and Measurements (NCRP), the U.S. population's total exposure to ionizing radiation has nearly doubled over the past two decades. With the introduction of new digital radiology equipment, patient dose is on the rise. Possible reasons for a radiologic technologist's behavior include: influence by availability or lack of equipment, policies, social pressure, attitudes, and a safety culture. Little research has been done in this area, specifically with applying a …

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