Medicine and Health Sciences Commons^™

Erythroid Cell-Specific Α-Globin Gene Regulation By The Cp2 Transcription Factor Family, Ho C. Kang, Jui Hyung Chae, Yeon H. Lee, Mi-Ae Park, June Ho Shin, Sung-Hyun Kim, Sang-Kyu Ye, Yoon Shin Cho, Steven Fiering, Chul Geun Kim

Dartmouth Scholarship

We previously demonstrated that ubiquitously expressed CP2c exerts potent erythroid-specific transactivation of alpha-globin through an unknown mechanism. This mechanism is reported here to involve specific CP2 splice variants and protein inhibitor of activated STAT1 (PIAS1). We identify a novel murine splice isoform of CP2, CP2b, which is identical to CP2a except that it has an additional 36 amino acids encoded by an extra exon. CP2b has an erythroid cell-specific transcriptional activation domain, which requires the extra exon and can form heteromeric complexes with other CP2 isoforms, but lacks the DNA binding activity found in CP2a and CP2c. Transcriptional activation of …

Effects Of Estradiol On Lipopolysaccharide And Pam3cys Stimulation Of Ccl20/Macrophage Inflammatory Protein 3 Alpha And Tumor Necrosis Factor Alpha Production By Uterine Epithelial Cells In Culture, Mardi A. Crane-Godreau, Charles R. Wira

Dartmouth Scholarship

We have previously demonstrated that rat uterine epithelial cells (UEC) produce CCL20/macrophage inflammatory protein 3 alpha (MIP3alpha) and tumor necrosis factor alpha (TNF-alpha) in response to live and heat-killed Escherichia coli and to the pathogen-associated molecular patterns (PAMP) lipopolysaccharide (LPS) and Pam3Cys. To determine whether estradiol (E2) modulates PAMP-induced CCL20/MIP3alpha and TNF-alpha secretion, primary cultures of rat UEC were incubated with E2 for 24 h and then treated with LPS or Pam3Cys or not treated for an additional 12 h. E2 inhibited the constitutive secretion of TNF-alpha and CCL20/MIP3alpha into culture media. Interestingly, E2 pretreatment enhanced CCL20/MIP3alpha secretion due to …

Functionally Active T1-T1 Interfaces Revealed By The Accessibility Of Intracellular Thiolate Groups In Kv4 Channels., Guangyu Wang, Mohammad Shahidullah, Carmen A Rocha, Candace Strang, Paul J Pfaffinger, Manuel Covarrubias

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Gating of voltage-dependent K(+) channels involves movements of membrane-spanning regions that control the opening of the pore. Much less is known, however, about the contributions of large intracellular channel domains to the conformational changes that underlie gating. Here, we investigated the functional role of intracellular regions in Kv4 channels by probing relevant cysteines with thiol-specific reagents. We find that reagent application to the intracellular side of inside-out patches results in time-dependent irreversible inhibition of Kv4.1 and Kv4.3 currents. In the absence or presence of Kv4-specific auxiliary subunits, mutational and electrophysiological analyses showed that none of the 14 intracellular cysteines is …

Stress Levels, Psychological Symptoms, And C-Reactive Protein Levels In Covid-19: A Cross-Sectional Study, Jian Zhang, Wei Li, Hideo Hoshi, Stephen L Mills, Stephen C Massey

Faculty, Staff and Student Publications

The correlation between cholinergic sensitivity and the level of stratification for ganglion cells was examined in the rabbit retina. As examples, we have used ON or OFF alpha ganglion cells and ON/OFF directionally selective (DS) ganglion cells. Nicotine, a cholinergic agonist, depolarized ON/OFF DS ganglion cells and greatly enhanced their firing rates but it had modest excitatory effects on ON or OFF alpha ganglion cells. As previously reported, we conclude that DS ganglion cells are the most sensitive to cholinergic drugs. Confocal imaging showed that ON/OFF DS ganglion cells ramify precisely at the level of the cholinergic amacrine cell dendrites, …

Urotensin Ii Modulates Rapid Eye Movement Sleep Through Activation Of Brainstem Cholinergic Neurons, Salvador Huitron-Resendiz, Morten P. Kristensen, Stephen L. Grupke, Christopher Tyler, Olivier Civelli, Christopher S. Leonard, Luis De Lecea

NYMC Faculty Publications

Urotensin II (UII) is a cyclic neuropeptide with strong vasoconstrictive activity in the peripheral vasculature. UII receptor mRNA is also expressed in the CNS, in particular in cholinergic neurons located in the mesopontine tegmental area, including the pedunculopontine tegmental (PPT) and lateral dorsal tegmental nuclei. This distribution suggests that the UII system is involved in functions regulated by acetylcholine, such as the sleep-wake cycle. Here, we tested the hypothesis that UII influences cholinergic PPT neuron activity and alters rapid eye movement (REM) sleep patterns in rats. Local administration of UII into the PPT nucleus increases REM sleep without inducing changes …

A Critical Role For Kalirin In Ngf Signaling Through Trka, Kausik Chakrabarti, Rong Lin, Noraisha I. Schiller, Yanping Wang, David Koubi, Ying-Xin Fan, Brian B. Rudkin, Gibbes R. Johnson, Martin R. Schiller

Life Sciences Faculty Research

Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons. Although much is known about the effects of Kalirin on Rho GTPases and neuronal morphology, little is known about the association of Kalirin with the receptor/signaling systems that affect neuronal morphology. Our experiments demonstrate that Kalirin binds to and colocalizes with the TrkA neurotrophin receptor in neurons. In PC12 cells, inhibition of Kalirin expression using antisense RNA decreased nerve growth factor (NGF)-induced TrkA autophosphorylation and process extension. Kalirin overexpression potentiated neurotrophin-stimulated TrkA autophosphorylation and neurite outgrowth in PC12 cells at a low …

Manganese Distribution Across The Blood-Brain Barrier. Iv. Evidence For Brain Influx Through Store-Operated Calcium Channels, Janelle S. Crossgrove, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is a required co-factor for many ubiquitous enzymes; however, chronic Mn overexposure can cause manganism, a parkinsonian-like syndrome. Previous studies showed Mn influx into brain is carrier-mediated, though the putative carrier(s) were not established. Studies conducted with cultured bovine brain microvascular endothelial cells (bBMECs), which comprise the blood–brain barrier, revealed ⁵⁴Mn (II) uptake positively correlated with pH, was temperature-dependent, and was sodium- and energy-independent. Brain ⁵⁴Mn uptake correlated inversely with calcium (Ca) concentration, but ⁴⁵Ca uptake was unaltered by high Mn concentration. Lanthanum (La), a non-selective inhibitor of several Ca channel types, as well as …

Investigating The Causes Of Low Birth Weight In Contrasting Ovine Paradigms., J M Wallace, Timothy Regnault, S W Limesand, W W Hay, R V Anthony

Paediatrics Publications

Intrauterine growth restriction (IUGR) still accounts for a large incidence of infant mortality and morbidity worldwide. Many of the circulatory and transport properties of the sheep placenta are similar to those of the human placenta and as such, the pregnant sheep offers an excellent model in which to study the development of IUGR. Two natural models of ovine IUGR are those of hyperthermic exposure during pregnancy, and adolescent overfeeding, also during pregnancy. Both models yield significantly reduced placental weights and an asymmetrically growth-restricted fetus, and display altered maternal hormone concentrations, indicative of an impaired trophoblast capacity. Additionally, impaired placental angiogenesis …

Activation Of Src Kinase Lyn By The Kaposi Sarcoma-Associated Herpesvirus K1 Protein: Implications For Lymphomagenesis, Om Prakash, O Rama Swamy, Xiochang Peng, Zhen-Ya Tang, Li Li, Janet E Larson, J Craig Cohen, Javed Gill, Gist Farr, Suizhao Wang, Felipe Samaniego

Faculty, Staff and Student Publications

The K1 gene of Kaposi sarcoma-associated herpesvirus (KSHV) encodes a transmembrane glycoprotein bearing a functional immunoreceptor tyrosine-based activation motif (ITAM). Previously, we reported that the K1 protein induced plasmablastic lymphomas in K1 transgenic mice, and that these lymphomas showed enhanced Lyn kinase activity. Here, we report that systemic administration of the nuclear factor kappa B (NF-kappaB) inhibitor Bay 11-7085 or an anti-vascular endothelial growth factor (VEGF) antibody significantly reduced K1 lymphoma growth in nude mice. Furthermore, in KVL-1 cells, a cell line derived from a K1 lymphoma, inhibition of Lyn kinase activity by the Src kinase inhibitor PP2 decreased VEGF …

Kinetics Of Exocytosis Is Faster In Cones Than In Rods., Katalin Rabl, Lucia Cadetti, Wallace B. Thoreson

Journal Articles: Ophthalmology

Cone-driven responses of second-order retinal neurons are considerably faster than rod-driven responses. We examined whether differences in the kinetics of synaptic transmitter release from rods and cones may contribute to differences in postsynaptic response kinetics. Exocytosis from rods and cones was triggered by membrane depolarization and monitored in two ways: (1) by measuring EPSCs evoked in second-order neurons by depolarizing steps applied to presynaptic rods or cones during simultaneous paired whole-cell recordings or (2) by direct measurements of exocytotic increases in membrane capacitance. The kinetics of release was assessed by varying the length of the depolarizing test step. Both measures …

Glutamate Receptors In Perirhinal Cortex Mediate Encoding, Retrieval, And Consolidation Of Object Recognition Memory., Boyer D Winters, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

Object recognition is consistently impaired in human amnesia and animal models thereof. Results from subjects with permanent brain damage have revealed the importance of the perirhinal cortex to object recognition memory. Here, we report evidence from rats for interdependent but distinct stages in object recognition memory (encoding, retrieval, and consolidation), which require glutamate receptor activity within perirhinal cortex. Transient blockade of AMPA receptor-mediated synaptic transmission within perirhinal cortex disrupted encoding for short- and long-term memory as well as retrieval and consolidation. In contrast, transient NMDA receptor blockade during encoding affected only long-term object recognition memory; NMDA receptor activity was also …

The Cns Role Of Toll-Like Receptor 4 In Innate Neuroimmunity And Painful Neuropathy, Flobert Y. Tanga, Nancy Nutile-Mcmenemy, Joyce A. Deleo

Dartmouth Scholarship

Neuropathic pain remains a prevalent and persistent clinical problem because of our incomplete understanding of its pathogenesis. This study demonstrates for the first time, to our knowledge, a critical role for CNS innate immunity by means of microglial Toll-like receptor 4 (TLR4) in the induction phase of behavioral hypersensitivity in a mouse and rat model of neuropathy. We hypothesized that after L5 nerve transection, CNS neuroimmune activation and subsequent cytokine expression are triggered by the stimulation of microglial membrane-bound TLR4. To test this hypothesis, experiments were undertaken to assess tactile and thermal hypersensitivity in genetically altered (i.e., TLR4 knockout and …

Ocular Surface Epithelia Contain Abcg2-Dependent Side Population Cells Exhibiting Features Associated With Stem Cells., Murat T Budak, Onder S Alpdogan, Mingyuan Zhou, Robert M Lavker, M A Murat Akinci, J Mario Wolosin

Department of Medical Oncology Faculty Papers

When cell populations are incubated with the DNA-binding dye Hoechst 33342 and subjected to flow cytometry analysis for Hoechst 33342 emissions, active efflux of the dye by the ABCG2/BCRP1 transporter causes certain cells to appear as a segregated cohort, known as a side population (SP). Stem cells from several tissues have been shown to possess the SP phenotype. As the lack of specific surface markers has hindered the isolation and subsequent biochemical characterization of epithelial stem cells this study sought to determine the existence of SP cells and expression of ABCG2 in the epithelia of the ocular surface and evaluate …

Microsomal Prostaglandin E Synthase-1: The Inducible Synthase For Prostaglandin E2, Annaleise V. Sampey, Seetha Monrad, Leslie J. Crofford

Internal Medicine Faculty Publications

Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme that catalyzes the conversion of prostaglandin (PG)H2 to PGE2. Proinflammatory stimuli markedly increase levels of mPGES-1 expression both in vivo and in vitro. mPGES-1 knockout studies and animal models of inflammatory arthritis also provide a strong basis for the contribution of mPGES-1 in the increased local production of PGE2 observed in inflammatory arthritis. The focus of this article is to review some recent advances in our understanding of mechanisms specific to the regulation of inducible mPGES-1 in inflammatory arthritis.

Effect Of Serum And Cumulus Cell Expansion On Marker Gene Transcripts In Bovine Cumulus-Oocyte Complexes During Maturation In Vitro., Michele D Calder, Anita N Caveney, Marc-Andre Sirard, Andrew J Watson

Obstetrics & Gynaecology Publications

OBJECTIVE: To determine the distribution of transcripts encoding the FSH receptor (FSHr), LH receptor (LHr), connexin 43 (Cx43), cyclooxygenase-2 (COX-2), and prostaglandin E(2) receptors 2 and 3 (EP2 and EP3) within bovine cumulus-oocyte complexes (COCs) and denuded oocytes and investigate the influence of gonadotropins, serum, and cumulus cell expansion on the abundance of transcripts encoding these genes.

DESIGN: Prospective controlled animal study.

SETTING: University research laboratory.

PATIENT(S): Animal models for human studies.

INTERVENTION(S): Cumulus-oocyte complexes were treated in culture with serum and gonadotropin-supplemented media to examine the effects to mRNA transcript levels.

MAIN OUTCOME MEASURE(S): Variation in mRNA transcript levels. …

Role For Akt3/Protein Kinase Bγ In Attainment Of Normal Brain Size, Rachel M. Easton, Han Cho, Kristin Roovers, Diana W. Shineman

Dartmouth Scholarship

Studies of Drosophila and mammals have revealed the importance of insulin signaling through phosphatidylinositol 3-kinase and the serine/threonine kinase Akt/protein kinase B for the regulation of cell, organ, and organismal growth. In mammals, three highly conserved proteins, Akt1, Akt2, and Akt3, comprise the Akt family, of which the first two are required for normal growth and metabolism, respectively. Here we address the function of Akt3. Like Akt1, Akt3 is not required for the maintenance of normal carbohydrate metabolism but is essential for the attainment of normal organ size. However, in contrast to Akt1^−/− mice, which display a …

Quantitative 1h Magnetic Resonance Spectroscopic Imaging Determines Therapeutic Immunization Efficacy In An Animal Model Of Parkinson's Disease., Michael D. Boska, Travis B. Lewis, Christopher J. Destache, Eric J. Benner, Jay A. Nelson, Mariano Uberti, R. Lee Mosley, Howard Gendelman

Journal Articles: Radiology

Nigrostriatal degeneration, the pathological hallmark of Parkinson's disease (PD), is mirrored by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. MPTP-treated animals show the common behavioral, motor, and pathological features of human disease. We demonstrated previously that adoptive transfer of Copaxone (Cop-1) immune cells protected the nigrostriatal dopaminergic pathway in MPTP-intoxicated mice. Herein, we evaluated this protection by quantitative proton magnetic resonance spectroscopic imaging (1H MRSI). 1H MRSI performed in MPTP-treated mice demonstrated that N-acetyl aspartate (NAA) was significantly diminished in the substantia nigra pars compacta (SNpc) and striatum, regions most affected in human disease. When the same regions were coregistered with immunohistochemical stains for …

Dynamic Changes In Mcl-1 Expression Regulate Macrophage Viability Or Commitment To Apoptosis During Bacterial Clearance, Helen M. Marriott, Colin D. Bingle, Robert C. Read, Karen E. Braley, Guido Kroemer, Paul G. Hellewell, Ruth W. Craig, Moira K.B. Whyte, David H. Dockrell

Dartmouth Scholarship

Macrophages are critical effectors of bacterial clearance and must retain viability, despite exposure to toxic bacterial products, until key antimicrobial functions are performed. Subsequently, host-mediated macrophage apoptosis aids resolution of infection. The ability of macrophages to make this transition from resistance to susceptibility to apoptosis is important for effective host innate immune responses. We investigated the role of Mcl-1, an essential regulator of macrophage lifespan, in this switch from viability to apoptosis, using the model of pneumococcal-associated macrophage apoptosis. Upon exposure to pneumococci, macrophages initially upregulate Mcl-1 protein and maintain viability for up to 14 hours. Subsequently, macrophages reduce expression …

Multiple Metabolic Hits Converge On Cd36 As Novel Mediator Of Tubular Epithelial Apoptosis In Diabetic Nephropathy., Katalin Susztak, Emilio Ciccone, Peter Mccue, Kumar Sharma, Erwin P Böttinger

Department of Medicine Faculty Papers

BACKGROUND: Diabetic nephropathy (DNP) is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED) and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.

METHODS AND FINDINGS: We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC) apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced …

Transient Inactivation Of Perirhinal Cortex Disrupts Encoding, Retrieval, And Consolidation Of Object Recognition Memory., Boyer D Winters, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

Damage to perirhinal cortex (PRh) impairs object recognition memory in humans, monkeys, and rats when tested in tasks such as delayed nonmatching to sample, visual paired comparison, and its rodent analog, the spontaneous object recognition task. In the present study, we have capitalized on the discrete one-trial nature of the spontaneous object recognition task to investigate the role of PRh in several distinct stages of object recognition memory. In a series of experiments, transient inactivation of PRh was accomplished with bilateral infusions of lidocaine directly into PRh immediately before the sample phase (encoding), immediately before the choice phase (retrieval), or …

Endothelial-Specific Expression Of Caveolin-1 Impairs Microvascular Permeability And Angiogenesis, Philip M. Bauer, Jun Yu, Yan Chen, Reed Hickey, Pascal N. Bernatchez, Robin Looft-Wilson, Yan Huang, Frank Giordano, Radu V. Stan, William C. Sessa

Dartmouth Scholarship

The functions of caveolae and/or caveolins in intact animals are beginning to be explored. Here, by using endothelial cell-specific transgenesis of the caveolin-1 (Cav-1) gene in mice, we show the critical role of Cav-1 in several postnatal vascular paradigms. First, increasing levels of Cav-1 do not increase caveolae number in the endothelium in vivo. Second, despite a lack of quantitative changes in organelle number, endothelial-specific expression of Cav-1 impairs endothelial nitric oxide synthase activation, endothelial barrier function, and angiogenic responses to exogenous VEGF and tissue ischemia. In addition, VEGF-mediated phosphorylation of Akt and its substrate, endothelial nitric oxide synthase, were …

Palm Is Expressed In Both Developing And Adult Mouse Lens And Retina., Meryl Castellini, Louise V Wolf, Bharesh K Chauhan, Deni S Galileo, Manfred W Kilimann, Ales Cvekl, Melinda K Duncan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Paralemmin (Palm) is a prenyl-palmitoyl anchored membrane protein that can drive membrane and process formation in neurons. Earlier studies have shown brain preferred Palm expression, although this protein is a major water insoluble protein in chicken lens fiber cells and the Palm gene may be regulated by Pax6. METHODS: The expression profile of Palm protein in the embryonic, newborn and adult mouse eye as well as dissociated retinal neurons was determined by confocal immunofluorescence. The relative mRNA levels of Palm, Palmdelphin (PalmD) and paralemmin2 (Palm2) in the lens and retina were determined by real time rt-PCR. RESULTS: In the …

Global Gene Expression Profiling Of Cells Overexpressing Smc3., Giancarlo Ghiselli, Chang-Gong Liu

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: The Structural Maintenance of Chromosome 3 protein (SMC3) plays an essential role during the sister chromatid separation, is involved in DNA repair and recombination and participates in microtubule-mediated intracellular transport. SMC3 is frequently elevated in human colon carcinoma and overexpression of the protein transforms murine NIH3T3 fibroblasts. In order to gain insight into the mechanism of SMC3-mediated tumorigenesis a gene expression profiling was performed on human 293 cells line stably overexpressing SMC3. RESULTS: Biotinylated complementary RNA (cRNA) was used for hybridization of a cDNAmicroarray chip harboring 18,861 65-mer oligos derived from the published dEST sequences. After filtering, the hybridization …

Duration Of Streptozotocin-Induced Diabetes Differentially Affects P38-Mitogen-Activated Protein Kinase (Mapk) Phosphorylation In Renal And Vascular Dysfunction, H. Chen, S. Brahmbhatt, A. Gupta, Avadhesh C. Sharma

PCOM Scholarly Works

Background: In the present study we tested the hypothesis that progression of streptozotocin (STZ)-induced diabetes (14-days to 28-days) would produce renal and vascular dysfunction that correlate with altered p38- mitogen-activated protein kinase (p38-MAPK) phosphorylation in kidneys and thoracic aorta. Methods: Male Sprague Dawley rats (350-400 g) were randomized into three groups: sham (N = 6), 14-days diabetic (N = 6) and 28-days diabetic rats (N = 6). Diabetes was induced using a single tail vein injection of STZ (60 mg/kg, I.V.) on the first day. Rats were monitored for 28 days and food, water intake and plasma glucose levels were …

Mitochondrial Dna Mutations, Apoptosis, And The Misfolded Protein Response., Justin L. Mott, Dekui Zhang, Hans Peter Zassenhaus

Journal Articles: Biochemistry & Molecular Biology

Studies of transgenic mice with accelerated accumulation of mtDNA mutations specifically in the heart lead us to propose that apoptotic signaling and cell death is central to the pathogenesis of mtDNA mutations in aging. It is the cellular response to that apoptotic signaling and the organ?s compensatory response to a loss of cells that specify the phenotype of an accumulation of mtDNA mutations. In the heart, cardiomyocytes induce a vigorous anti-apoptotic, pro-survival response to counteract mitochondrial apoptotic signaling. The heart up-regulates contractility of remaining myocytes in order to maintain cardiac output. We hypothesize that mutant mitochondrial proteins originate apoptotic signaling …

The Use Of Time-Resolved Fluorescence Imaging In The Study Of Protein Kinase C Localisation In Cells., Christopher D Stubbs, Stanley W Botchway, Simon J Slater, Anthony W Parker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Two-photon-excitation fluorescence lifetime imaging (2P-FLIM) was used to investigate the association of protein kinase C alpha (PKCalpha) with caveolin in CHO cells. PKCalpha is found widely in the cytoplasm and nucleus in most cells. Upon activation, as a result of increased intracellular Ca2+ and production of DAG, through G-protein coupled-phospholipase C signalling, PKC translocates to a variety of regions in the cell where it phosphorylates and interacts with many signalling pathways. Due to its wide distribution, discerning a particular interaction from others within the cell is extremely difficult. RESULTS: Fluorescence energy transfer (FRET), between GFP-PKCalpha and DsRed-caveolin, was used …

Ccl20/Macrophage Inflammatory Protein 3Α And Tumor Necrosis Factor Alpha Production By Primary Uterine Epithelial Cells In Response To Treatment With Lipopolysaccharide Or Pam3cys, M. A. Crane-Godreau, C. R. Wira

Dartmouth Scholarship

Having previously shown that CCL20/macrophage inflammatory protein 3 and tumor necrosis factor alpha (TNF-alpha) are released by polarized primary rat uterine epithelial cells (UEC) in response to Escherichia coli but not to Lactobacillus rhamnosus , we sought to determine if epithelial cells are responsive to pathogen-associated molecular patterns (PAMP), including lipopolysaccharide (LPS), lipoteichoic acid (LTA), and Pam 3 Cys, a bacterial lipoprotein analog. Epithelial cells were grown to confluence on Nunc cell culture inserts prior to apical treatment with PAMPs. In response to LPS, LTA, and Pam 3 Cys (EMC Microcollection GmbH, Tu ̈- bingen, Germany), CCL20 levels increased (4- …

Inhibition Modifies The Effects Of Slow Calcium-Activated Potassium Channels On Epileptiform Activity In A Neuronal Network Model, Keun-Hang Susan Yang, Piotr J. Franaszczuk, Gregory K. Bergey

Mathematics, Physics, and Computer Science Faculty Articles and Research

Generation of epileptiform activity typically results from a change in the balance between network excitation and inhibition. Experimental evidence indicates that alterations of either synaptic activity or intrinsic membrane properties can produce increased network excitation. The slow Ca2+-activated K+ currents (sI AHP) are important modulators of neuronal firing rate and excitability and have important established and potential roles in epileptogenesis. While the effects of changes in sI AHP on individual neuronal excitability are readily studied and well established, the effects of such changes on network behavior are less well known. The experiments here utilize a defined small network model of …

Genetic Networks Controlling Retinal Injury, Felix R Vazquez-Chona, Amna N Khan, Chun K Chan, Anthony N Moore, Pramod K Dash, M Rosario Hernandez, Lu Lu, Elissa J Chesler, Kenneth F Manly, Robert W Williams, Eldon E Geisert

Faculty, Staff and Student Publications

PURPOSE: The present study defines genomic loci underlying coordinate changes in gene expression following retinal injury.

METHODS: A group of acute phase genes expressed in diverse nervous system tissues was defined by combining microarray results from injury studies from rat retina, brain, and spinal cord. Genomic loci regulating the brain expression of acute phase genes were identified using a panel of BXD recombinant inbred (RI) mouse strains. Candidate upstream regulators within a locus were defined using single nucleotide polymorphism databases and promoter motif databases.

RESULTS: The acute phase response of rat retina, brain, and spinal cord was dominated by transcription …

Prime-Boost Vaccination With Plasmid And Adenovirus Gene Vaccines Control Her2/Neu+ Metastatic Breast Cancer In Mice, Xiaoyan Wang, Jian-Ping Wang, Xiao-Mei Rao, Janet E Price, Heshan S Zhou, Lawrence B Lachman

Faculty, Staff and Student Publications

INTRODUCTION: Once metastasis has occurred, the possibility of completely curing breast cancer is unlikely, particularly for the 30 to 40% of cancers overexpressing the gene for HER2/neu. A vaccine targeting p185, the protein product of the HER2/neu gene, could have therapeutic application by controlling the growth and metastasis of highly aggressive HER2/neu+ cells. The purpose of this study was to determine the effectiveness of two gene vaccines targeting HER2/neu in preventive and therapeutic tumor models.

METHODS: The mouse breast cancer cell line A2L2, which expresses the gene for rat HER2/neu and hence p185, was injected into the mammary fat pad …