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Full-Text Articles in Medicine and Health Sciences

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 Jan 2008

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 …


Role Of Variant Sialylation In Regulating Tumor Cell Behavior, Faheem M. Shaikh Jan 2008

Role Of Variant Sialylation In Regulating Tumor Cell Behavior, Faheem M. Shaikh

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Many different tumors have been documented to have elevated levels of the enzyme ST6Gal I, a Golgi glycosyltransferase that adds α2-6 sialic acids to glycoproteins. Concurrently, upregulated ST6Gal I is associated with metastasis and poor patient prognosis. We initially showed that HD3 colonocytes made to express oncogenic-ras, a common mutation in colon carcinoma, have increased expression of ST6Gal I and elevated α2-6 sialylated integrins. Having established that ras regulates ST6Gal I expression in colon epithelial cells, we found that colonocytes carrying hyper α2-6 sialylated β1 integrins exhibit increased adhesion to and migration toward collagen I. Further, we found that β1 …


Adenovirus As A Platform For Assembly And Targeted Delivery Of Gold Nanoparticles To Tumor Cells, Vaibhav Saini Jan 2008

Adenovirus As A Platform For Assembly And Targeted Delivery Of Gold Nanoparticles To Tumor Cells, Vaibhav Saini

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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 …


Human Papillomavirus: Segregation And Replication, Luan D. Dao Jan 2008

Human Papillomavirus: Segregation And Replication, Luan D. Dao

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Human papillomavirus are small DNA tumor viruses. The viral genome is a small circular double stranded DNA that replicates autonomously as an extrachromosomal plasmid. Occasionally infections by the high risk HPV viruses can lead to DNA integration and progression to cancer. How the HPV DNA is maintained and becomes established in the dividing host cells is not well understood. Additionally, as a double-stranded DNA virus it is likely that double-stranded DNA breaks in the viral genome, either from replication or random damage, will trigger a DNA repair response from the host cell. Such responses have been alternatively reported to be …


Characterization Of Suds3 As A Brms1 Family Member In Breast Cancer, Alexandra C. Silveira Jan 2008

Characterization Of Suds3 As A Brms1 Family Member In Breast Cancer, Alexandra C. Silveira

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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 …


The Role Of Ddx3 In Regulating Apoptosis, P53 And Snail, Mianen Sun Jan 2008

The Role Of Ddx3 In Regulating Apoptosis, P53 And Snail, Mianen Sun

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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 …


Effects Of Hexosamine Biosynthesis On An In Vitro Model Of Cardiacischemia, Voraratt Champattanachai Jan 2008

Effects Of Hexosamine Biosynthesis On An In Vitro Model Of Cardiacischemia, Voraratt Champattanachai

All ETDs from UAB

Increased levels of protein O-linked-N-acetylglucosamine (O-GlcNAc) have been correlated with increased cell survival following stress. Therefore the goal of this study was to determine whether enhanced flux through the hexosamine biosynthesis pathway (HBP), which leads to elevated levels of O-GlcNAc, improved the tolerance of isolated neonatal rat ventricular myocytes (NRVMs) to ischemia/reperfusion (I/R) injury. NRVMs were exposed to hypoxic medium for 4 hours, followed by oxygenated complete medium for 16 hours. Acute treatment with 5 mM glucosamine showed an increase in viability and decreased both necrosis and apoptosis following I/R. Glucosamine increased O-GlcNAc levels maximally at 2 hours and went …


The Developmental Functions Of Bdnf And Mecp2 On Dendritic And Synaptic Structure, Christopher A. Chapleau Jan 2008

The Developmental Functions Of Bdnf And Mecp2 On Dendritic And Synaptic Structure, Christopher A. Chapleau

All ETDs from UAB

Mutations in the transcriptional repressor MeCP2 cause Rett Syndrome (RTT), a mental retardation disease associated with reduced dendritic architecture of cortical pyramidal neurons, in addition to a decrease in the number of dendritic spines. I present the first quantification analysis of spine density in postmortem human brain tissue, demonstrating that hippocampal CA1 pyramidal neurons have reduced spine densities in RTT patients throughout their lives. One gene that MeCP2 regulates is BDNF, an important developmental factor that modulates synaptic transmission and plasticity, as well as spine formation and maturation. In immature cultured hippocampal neurons, cell-autonomous expression of BDNF accelerates the differentiation …


A Dual-Action, Armed Replicating Adenovirus For The Treatment Of Bone Metastases Of Breast Cancer, James Joseph Cody V Jan 2008

A Dual-Action, Armed Replicating Adenovirus For The Treatment Of Bone Metastases Of Breast Cancer, James Joseph Cody V

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Most patients with advanced breast cancer develop osteolytic bone metastases, which have numerous complications. Because current therapies are not curative, new treatments are needed. Conditionally replicating adenoviruses (CRAds) are anti-cancer agents designed to infect and lyse tumor cells. For increased efficacy, CRAds have been armed with therapeutic transgenes. Osteoprotegerin (OPG), an inhibitor of osteoclastic bone resorption, represents a promising candidate with which to arm a CRAd intended to treat osteolytic bone metastases. We hypothesize that a CRAd armed with OPG will inhibit breast cancer bone metastasis and reduce tumor burden in the bone by directly lysing tumor cells and by …


Effects Of Aerobic Exercise On The Asthmatic Lung, Matthew M. Hewitt Jan 2008

Effects Of Aerobic Exercise On The Asthmatic Lung, Matthew M. Hewitt

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Asthma is identified by the clinical symptoms of wheezing, chest tightness, dyspnea and cough, and by the presence of airway hyperresponsiveness (AHR) to inhaled stimuli. We have reported previously that repeated bouts of moderate intensity aerobic exercise attenuate airway inflammatory responses in a mouse model of atopic asthma. Because the effects of exercise on physiological responses are dependent upon several variables, including total exercise duration, the hypothesis of the current work was that differing amounts of moderate intensity aerobic exercise exert dissimilar effects on AHR and airway inflammation. The aims to test this hypothesis included: 1) determine the effect of …


Functionalizing Hydroxyapatite Biomaterials With Biomimetic Peptides Of Integrin Ligands, Kristin Marie Hennessy Jan 2008

Functionalizing Hydroxyapatite Biomaterials With Biomimetic Peptides Of Integrin Ligands, Kristin Marie Hennessy

All ETDs from UAB

Hydroxyapatite (HA) coatings of hard tissue implants have been shown to increase osseointegration, but the mechanisms by which HA improves implant integration are not well understood. Numerous studies have shown that modifying HA with adhesive peptides, including RGD, and the collagen I mimetics, DGEA and P15, stimulates the adhesion of mesenchymal stem cells (MSCs), a cell type that differentiates along the osteoblast lineage. However, HA is a highly adsorptive biomaterial, and therefore it is unlikely that cells at the implant site would ever encounter a peptidemodified HA surface in the absence of an adsorbed protein layer. In fact, our laboratory …


Molecular Regulation Of Pax5-Mediated Biological Functions, Ti He Jan 2008

Molecular Regulation Of Pax5-Mediated Biological Functions, Ti He

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B lineage cells are major players in the adaptive immune system. Pax5 is essential for B lineage cell development and function. Pax5 controls B lineage cell developmental progression by regulating expression of many B lineage specific genes and the B lineage specific VH to DJH recombination; and the meantime, Pax5 also represses the transcription of lineage- and developmental stage- inappropriate genes to restrict the B lineage developmental pathway. It is not clear how Pax5-mediated function can be regulated to fulfill its role in different biological reactions. In this dissertation, we focused on the study of the molecular regulation of Pax5-mediated …


Biogenesis, Trafficing, And Function Of Wild-Type And Mutant Cystic Fibrosis Transmembrane Conductance Regulator (Cftr), Asta Jurkuvenaite Jan 2008

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 …


The Role Of Tgf-Ss And Wnt5a In Mammary Gland Development And Tumurorigenesis, Kevin Patrick Roarty Jan 2008

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 Jan 2008

Correction Of Sickle Cell Disease By Homologous Recombination, Li-Chen Wu

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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 Jan 2008

Physiological Charactterization Of The Light Response Of Rod Photoreceptors In The Light Damaged Rat, Yuquan Wen

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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 Jan 2008

The Use Of Molecular Imaging To Evaluate Te Efficacy Of Treatments For Metastatic Breast Cancer, April Adams Szafran

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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 …


Microbial Biofilm Attachment To Caenorhabditis Elegans, Kevin Drace Jan 2008

Microbial Biofilm Attachment To Caenorhabditis Elegans, Kevin Drace

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The closely related bacterial species Xenorhabdus nematophila, Yersinia pestis and Y. pseudotuberculosis make biofilms capable of adhering to the head of the model nematode Caenorhabditis elegans. Y. pestis uses biofilms to block the digestive tract of its vector, the flea, in order to enhance its efficiency of transmission. I investigated the role of biofilms in X. nematophila and found that, like its Yersinia sp. counterparts, production of biofilm requires a four-gene operon: hmsHFRS. X. nematophila is an insect pathogen and an obligate symbiont of the nematode Steinernema carpocapsae. However, an X. nematophila hmsH mutant that failed to make biofilms on …


Analysis Of The Role Of Fcrl5 And Figlers In B Cell Development, Signaling, And Malignancy, Christopher L. Haga Jan 2008

Analysis Of The Role Of Fcrl5 And Figlers In B Cell Development, Signaling, And Malignancy, Christopher L. Haga

All ETDs from UAB

The regulation of signaling and migration is critical to B lymphocyte development, activation, and proliferation. This dissertation reports a functional role for Fc receptor-like molecule 5 (FCRL5), a B cell specific member of the Fc receptor-like family of molecules, and the discovery of a novel family of conserved transmembrane proteins with fibronectin, immunoglobulin, and leucine-rich repeat domains (FIGLER) expressed in bone marrow and B lineage cells. Until now, the signaling potential of FCRL5 was unknown. A panel of FcRIIB/FCRL5 chimeric receptors were created and expressed in a B cell line lacking endogenous FcRIIB. Coligation of the chimeric receptor with the …


Role Of The Gm/Gn Glycoprotein Complex In The Final Assembly And Egress Of The Human Cytomegalovirus (Hcmv), Magdalena Anna Krzyzaniak Jan 2008

Role Of The Gm/Gn Glycoprotein Complex In The Final Assembly And Egress Of The Human Cytomegalovirus (Hcmv), Magdalena Anna Krzyzaniak

All ETDs from UAB

HCMV consists of a dsDNA genome enclosed by, an icosahedral capsid surrounded by a layer of tegument proteins; the virion structure is enclosed in a lipid envelope rich in virus expressed glycoproteins. The HCMV envelope contains an incompletely defined number of glycoproteins. The glycoprotein M (gM) and glycoprotein N (gN) form a gM/gN protein complex which is the most abundant protein component of the HCMV envelope. Recent studies have indicated that deletion of the viral gene encoding either gM or gN is lethal for HCMV. The gM C-terminal cytoplasmic tail (gM-CT) revealed an acidic cluster and a tyrosine-based trafficking motifs. …


The Role Of Centaurin Alpha-1 In The Regulation Of Neuron Al Differentiation, Carlene Drucilla Moore Jan 2008

The Role Of Centaurin Alpha-1 In The Regulation Of Neuron Al Differentiation, Carlene Drucilla Moore

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In the nervous system, PI 3-kinase has been implicated in neuronal differentiation. My studies have focused on a candidate neuronal PI 3-kinase target centaurin alpha-1, which binds PtdIns(3,4,5)P3, and is an Arf6 GAP. Centaurin alpha-1 is localized in dendrites, dendritic spines and synapses, and is required for neuronal differentiation and spine morphogenesis. In dissociated neuronal cultures, expression of centaurin alpha-1 enhances dendritic branching, and increases dendritic filopodia, lamellipodia and spine-like protrusions. Expression of centaurin alpha-1 GAP inactive mutant or knocking down centaurin alpha-1 levels using siRNA leads to inhibition of dendritic outgrowth and branching. Manipulations of centaurin alpha-1 also disrupt …


Calmodulin Binding To Cellular Flice Like Inhibitory Protein Modulates Fas-Induced Signaling And Tumorigenesis In Cholangiocarcinoma, Pritish Subhash Pawar Jan 2008

Calmodulin Binding To Cellular Flice Like Inhibitory Protein Modulates Fas-Induced Signaling And Tumorigenesis In Cholangiocarcinoma, Pritish Subhash Pawar

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Cholangiocarcinoma, a fatal tumor arising from biliary epithelium, has very poor 5-year survival rate due to lack of early diagnosis and effective therapies. Induction of the Fas-mediated apoptosis is a promising therapeutic target in this tumor. Studies from our group and others have indicated that Fas-expression correlates inversely with disease progression and that CaM-antagonists induce apoptosis in cholangiocarcinoma cells in a Fas related manner. Further, we reported a direct and dynamic interaction of CaM and Fas and that CaM is recruited into the Fas-stimulated death inducing signaling complex (DISC), suggesting a cross talk between Fas and CaM pathways. The studies …


Investigation Of Lipoteichoic Acid Structure And Function To Establish Its Role In Gram-Positive Bacterial Infections, Ho Seong Seo Jan 2008

Investigation Of Lipoteichoic Acid Structure And Function To Establish Its Role In Gram-Positive Bacterial Infections, Ho Seong Seo

All ETDs from UAB

Lipoteichoic acid (LTA) is an essential bacterial membrane polysaccharide (cell wall component) that is linked to a glycerol backbone with two acyl chains. Since an antibody to LTA has been shown to protect from Gr+ bacterial infections or colonization, and the mutant Gr+ bacteria which produce less amount of LTA have less pathogenic than WT, LTA may be an important role in Gr+ bacterial infection and inflammation. The currently accepted structure of pneumococcal LTA has the pentameric repeating unit bound to the lipid anchor {Glc(β1��3)AATGal(β1��3)Glc(α1��3)-acyl2Gro}. Unlike the lipid anchor of other Gr+ bacterial LTA, this pneumococcal LTA lipid anchor has …


Analysis Of The Hedgehog Pathway In Pancreatic Adenocarcinoma, Adam Steg Jan 2008

Analysis Of The Hedgehog Pathway In Pancreatic Adenocarcinoma, Adam Steg

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Pancreatic adenocarcinoma (PAC) is the fourth leading cause of cancer mortality in the United States. Despite the use of highly aggressive treatment regimens (surgery, chemotherapy and radiation), almost all patients succumb to metastatic disease within 6-10 months of diagnosis. The hedgehog (HH) signaling pathway was originally discov-ered to play a critical role in mammalian embryological development. Interestingly, re-cent studies have suggested that aberrant expression of this pathway is involved in the initiation and continued growth of PAC. Small molecules that antagonize the transmem-brane protein Smoothened (Smo), a critical signaling component of the HH pathway, have proven effective in decreasing PAC …


Characterization Of Sortase And Its Effect On The Virulence Of Streptococcus Pneumoniae, Allison E. Bennett Jan 2008

Characterization Of Sortase And Its Effect On The Virulence Of Streptococcus Pneumoniae, Allison E. Bennett

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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 …


Growth Hormone Signaling And Action In Osteoblasts, Douglas J. Digirolamo Jan 2008

Growth Hormone Signaling And Action In Osteoblasts, Douglas J. Digirolamo

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Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) exert profound growth promoting actions during pre- and post-natal skeletal development. GH and IGF- 1 appear to cause these anabolic actions by influencing a variety of effects on osteoblast proliferation, differentiation, and survival. However, because GH stimulates the production of IGF-1 from the liver and other GH-responsive peripheral tissues, including bone, the individual contributions of these two molecules to anabolic responses in bone remains poorly defined. In this dissertation research, I sought to distinguish the direct and indirect (IGF-1 dependent) GH actions on osteoblasts. In the first section of this thesis, I …


Mechanism Of Interferon-Beta-Mediated Inhibition Of Il-8 Gene Expression, Travis Laver Jan 2008

Mechanism Of Interferon-Beta-Mediated Inhibition Of Il-8 Gene Expression, Travis Laver

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Interleukin-8 (IL-8) is a potent chemoattractant of numerous cells, particularly neutrophils, in the innate immune response. In addition to immune functions, IL-8 is known to contribute to the pathogenesis of a number of diseases, including cancer. Interferon-β (IFN-β), a Type I interferon, inhibits the expression of IL-8, but the details of this effect are not known. In this study we investigate transcriptional control of the IL- 8 gene and the mechanism by which IFN-β exerts inhibitory effects on IL-8. Herein we show that stimulation of U87-MG glioma cells with phorbol 12-myristate 13-acetate (PMA) results in a rapid recruitment of NF-κB …


The Au-Rich Element Mrna Decay-Promoting Activity Of Brf1 Is Regulated By Mitogen-Activated Protein Kinase Activated Protein Kinase 2, Sushmit Maitra Jan 2008

The Au-Rich Element Mrna Decay-Promoting Activity Of Brf1 Is Regulated By Mitogen-Activated Protein Kinase Activated Protein Kinase 2, Sushmit Maitra

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Regulated mRNA decay is a highly important process for the tight control of gene expression. Inherently unstable mRNAs contain AU-rich elements (AREs) in the 3’ untranslated regions that direct rapid mRNA decay by interaction with decay-promoting ARE-binding proteins (ARE-BPs). The decay of ARE-containing mRNAs is regulated by signaling pathways, which are believed to directly target ARE-BPs. Here, we show that BRF1 involved in ARE-mediated mRNA decay (AMD) is phosphorylated by MAPK-activated protein kinase 2, MK2. In vitro kinase assays using different BRF1 fragments suggest that MK2 phosphorylates BRF1 at four distinct sites, S54, S92, S203, and an unidentified site at …


Modulation Of Transforming Growth Factor (Tgf)-Ss1 And Its Implications In Breast Cancer Metastasis, Lakisha Dionne Moore Jan 2008

Modulation Of Transforming Growth Factor (Tgf)-Ss1 And Its Implications In Breast Cancer Metastasis, Lakisha Dionne Moore

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Overexpresssion of transforming growth factor (TGF)-β has been implicated in promoting immune suppression, tumor angiogenesis, tumor cell migration, and invasion in many cancers including carcinoma of the breast. Thus, targeted downregulation of TGF-β1 expression in breast cancer in situ and determination of its implications potentially could provide new treatment approaches for disease management. siRNA constructs targeting TGF-β1 were validated and used to develop clonal derivatives of the MDA-MB-435 metastatic breast cancer cell line. Inhibition of TGF-β1 expression in MDA-MB-435 cells showed decrease in migration and invasion in vitro with an increase in proliferation. In vivo analysis indicated a 90% decrease …


Changes In Short-Term Facilitation Are Opposite At Schaffer Collateral And Temporoammonic Ca1 Synapses In The Developing Rat Hippocampus, Haley E. Speed Jan 2008

Changes In Short-Term Facilitation Are Opposite At Schaffer Collateral And Temporoammonic Ca1 Synapses In The Developing Rat Hippocampus, Haley E. Speed

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Hippocampal CA1 pyramidal neurons integrate and filter spatial, temporal, and sensory information from the entorhinal cortex (EC) for memory storage. Synaptic transmission mediates the processing of incoming information, and recent studies have demonstrated that long-term changes in synaptic strength at CA1 synapses are important for learning and memory. Short-term changes in synaptic strength, occurring on a timescale of milliseconds to minutes, do not require lasting modifications and are rapidly reversible. Termed short-term plasticity, it is known to be important for dynamic gain control of synaptic transmission and neural computation. During late postnatal development, there are extensive developmental changes in rat …