Medicine and Health Sciences Commons^™

Spatial Modulation Of Primate Inferotemporal Responses By Eye Position, Sidney R. Lehky, Xinmiao Peng, Carrie J. Mcadams, Anne B. Sereno

Journal Articles

BACKGROUND: A key aspect of representations for object recognition and scene analysis in the ventral visual stream is the spatial frame of reference, be it a viewer-centered, object-centered, or scene-based coordinate system. Coordinate transforms from retinocentric space to other reference frames involve combining neural visual responses with extraretinal postural information.

METHODOLOGY/PRINCIPAL FINDINGS: We examined whether such spatial information is available to anterior inferotemporal (AIT) neurons in the macaque monkey by measuring the effect of eye position on responses to a set of simple 2D shapes. We report, for the first time, a significant eye position effect in over 40% of …

A Functional Collagen Adhesin Gene, Acm, In Clinical Isolates Of Enterococcus Faecium Correlates With The Recent Success Of This Emerging Nosocomial Pathogen, Sreedhar R Nallapareddy, Kavindra V Singh, Pablo C Okhuysen, Barbara E Murray

Journal Articles

Enterococcus faecium recently evolved from a generally avirulent commensal into a multidrug-resistant health care-associated pathogen causing difficult-to-treat infections, but little is known about the factors responsible for this change. We previously showed that some E. faecium strains express a cell wall-anchored collagen adhesin, Acm. Here we analyzed 90 E. faecium isolates (99% acm(+)) and found that the Acm protein was detected predominantly in clinically derived isolates, while the acm gene was present as a transposon-interrupted pseudogene in 12 of 47 isolates of nonclinical origin. A highly significant association between clinical (versus fecal or food) origin and collagen adherence (P

Accelerated High Fidelity Prion Amplification Within And Across Prion Species Barriers, Kristi M. Green, Joaquín Castilla, Tanya S. Seward, Dana L. Napier, Jean E. Jewell, Claudio Soto, Glenn C. Telling

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Experimental obstacles have impeded our ability to study prion transmission within and, more particularly, between species. Here, we used cervid prion protein expressed in brain extracts of transgenic mice, referred to as Tg(CerPrP), as a substrate for in vitro generation of chronic wasting disease (CWD) prions by protein misfolding cyclic amplification (PMCA). Characterization of this infectivity in Tg(CerPrP) mice demonstrated that serial PMCA resulted in the high fidelity amplification of CWD prions with apparently unaltered properties. Using similar methods to amplify mouse RML prions and characterize the resulting novel cervid prions, we show that serial PMCA abrogated a transmission barrier …

An Sp1/Sp3 Binding Polymorphism Confers Methylation Protection., Yanis A. Boumber, Yutaka Kondo, Xuqi Chen, Lanlan Shen, Yi Guo, Carmen Tellez, Marcos R H Estécio, Saira Ahmed, Jean-Pierre J. Issa

Journal Articles

Hundreds of genes show aberrant DNA hypermethylation in cancer, yet little is known about the causes of this hypermethylation. We identified RIL as a frequent methylation target in cancer. In search for factors that influence RIL hypermethylation, we found a 12-bp polymorphic sequence around its transcription start site that creates a long allele. Pyrosequencing of homozygous tumors revealed a 2.1-fold higher methylation for the short alleles (P<0.001). Bisulfite sequencing of cancers heterozygous for RIL showed that the short alleles are 3.1-fold more methylated than the long (P<0.001). The comparison of expression levels between unmethylated long and short EBV-transformed cell lines showed no difference in expression in vivo. Electrophorectic mobility shift assay showed that the inserted region of the long allele binds Sp1 and Sp3 transcription factors, a binding that is absent in the short allele. Transient transfection of RIL allele-specific transgenes showed no effects of the additional Sp1 site on transcription early on. However, stable transfection of methylation-seeded constructs showed gradually decreasing transcription levels from the short allele with eventual spreading of de novo methylation. In contrast, the long allele showed stable levels of expression over time as measured by luciferase and approximately 2-3-fold lower levels of methylation by bisulfite sequencing (P<0.001), suggesting that the polymorphic Sp1 site protects against time-dependent silencing. Our finding demonstrates that, in some genes, hypermethylation in cancer is dictated by protein-DNA interactions at the promoters and provides a novel mechanism by which genetic polymorphisms can influence an epigenetic state.

Cd5 Plays An Inhibitory Role In The Suppressive Function Of Murine Cd4+ Cd25+ TReg Cells, Trivikram Dasu, Joseph E. Qualls, Halide Tuna, Chander Raman, Donald A. Cohen, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

A subset of CD4⁺ T cells, the CD4⁺ CD25⁺ regulatory T (T_reg) cells in the lymphoid organs and peripheral blood are known to possess suppressive function. Previous in vitro and in vivo studies have indicated that T cell receptor (TCR) signal is required for development of such ‘natural regulatory (T_reg) cells’ and for activation of the effector function of CD4⁺ CD25⁺ regulatory T cells. CD5 is a cell surface molecule present on all T cells and a subtype of B lymphocytes, the B-1 cells, primarily localized to coelomic cavities, Peyer's patches, …

A Cyclin D1/Microrna 17/20 Regulatory Feedback Loop In Control Of Breast Cancer Cell Proliferation., Zuoren Yu, Chenguang Wang, Min Wang, Zhiping Li, Mathew C Casimiro, Manran Liu, Kongming Wu, James Whittle, Xiaoming Ju, Terry Hyslop, Peter Mccue, Richard G Pestell

Kimmel Cancer Center Faculty Papers

Decreased expression of specific microRNAs (miRNAs) occurs in human tumors, which suggests a function for miRNAs in tumor suppression. Herein, levels of the miR-17-5p/miR-20a miRNA cluster were inversely correlated to cyclin D1 abundance in human breast tumors and cell lines. MiR-17/20 suppressed breast cancer cell proliferation and tumor colony formation by negatively regulating cyclin D1 translation via a conserved 3' untranslated region miRNA-binding site, thereby inhibiting serum-induced S phase entry. The cell cycle effect of miR-17/20 was abrogated by cyclin D1 siRNA and in cyclin D1-deficient breast cancer cells. Mammary epithelial cell-targeted cyclin D1 expression induced miR-17-5p and miR-20a expression …

The Aryl Hydrocarbon Receptor Binds To E2f1 And Inhibits E2f1-Induced Apoptosis., Jennifer L Marlowe, Yunxia Fan, Xiaoqing Chang, Li Peng, Erik S Knudsen, Ying Xia, Alvaro Puga

Kimmel Cancer Center Faculty Papers

Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr(-/-) fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, gammaH2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of …

Structure Of The Hsp110:Hsc70 Nucleotide Exchange Machine, Jonathan P Schuermann, Jianwen Jiang, Jorge Cuellar, Oscar Llorca, Liping Wang, Luis E Gimenez, Suping Jin, Alexander B Taylor, Borries Demeler, Kevin A Morano, P John Hart, Jose M Valpuesta, Eileen M Lafer, Rui Sousa

Journal Articles

Hsp70s mediate protein folding, translocation, and macromolecular complex remodeling reactions. Their activities are regulated by proteins that exchange ADP for ATP from the nucleotide-binding domain (NBD) of the Hsp70. These nucleotide exchange factors (NEFs) include the Hsp110s, which are themselves members of the Hsp70 family. We report the structure of an Hsp110:Hsc70 nucleotide exchange complex. The complex is characterized by extensive protein:protein interactions and symmetric bridging interactions between the nucleotides bound in each partner protein's NBD. An electropositive pore allows nucleotides to enter and exit the complex. The role of nucleotides in complex formation and dissociation, and the effects of …

Programmed Death 1 Ligand Signaling Regulates The Generation Of Adaptive Foxp3+Cd4+ Regulatory T Cells, Li Wang, Kirina Pino-Lagos, Victor C. De Vries, Indira Guleria, Mohamed H. Sayegh, Randolph J. Noelle

Dartmouth Scholarship

Although mature dendritic cells (DCs) are potent initiators of adaptive immune response, immature steady-state DCs contribute to immune tolerance. In this study, we show that ex vivo splenic DCs are capable of inducing conversion of naïve CD4(+) T cells to adaptive Foxp3(+)CD4(+) regulatory T cells (aTreg) in the presence of TGF-beta. In particular, when compared with splenic CD8alpha(-) DCs, the CD8alpha(+) DC subset were superior in inducing higher frequencies of conversion. This was not attributable to the difference in basal level of costimulation, because deficiency of CD40 or CD80/86 signaling did not diminish the differential induction of Foxp3. Conversion was …

A Novel Application Of Quantile Regression For Identification Of Biomarkers Exemplified By Equine Cartilage Microarray Data, Liping Huang, Wenying Zhu, Christopher P. Saunders, James N. Macleod, Mai Zhou, Arnold J. Stromberg, Arne C. Bathke

Veterinary Science Faculty Publications

BACKGROUND: Identification of biomarkers among thousands of genes arrayed for disease classification has been the subject of considerable research in recent years. These studies have focused on disease classification, comparing experimental groups of effected to normal patients. Related experiments can be done to identify tissue-restricted biomarkers, genes with a high level of expression in one tissue compared to other tissue types in the body.

RESULTS: In this study, cartilage was compared with ten other body tissues using a two color array experimental design. Thirty-seven probe sets were identified as cartilage biomarkers. Of these, 13 (35%) have existing annotation associated with …

Effects Of Early Gestation Gh Administration On Placental And Fetal Development In Sheep., Casey D Wright, Ryan J Orbus, Timothy Regnault, Russell V Anthony

Paediatrics Publications

Ovine GH (oGH) is synthesized in placental tissue during maximal placental growth and development. Our objectives were to localize oGH mRNA in the placenta, and study the impact of exogenous GH on twin pregnancies during the normal window (35-55 days of gestational age; dGA) of placental expression. In situ hybridization localized oGH mRNA in uterine luminal epithelium but not in tissues of fetal origin. While maternal GH and IGF-I concentrations were increased (P

Water-Soluble Fullerene (C60) Derivatives As Nonviral Gene-Delivery Vectors, Balaji Sitharaman, Tatiana Y Zakharian, Anita Saraf, Preeti Misra, Jared Ashcroft, Su Pan, Quynh P Pham, Antonios G Mikos, Lon J Wilson, David A Engler

Journal Articles

A new class of water-soluble C60 transfecting agents has been prepared using Hirsch-Bingel chemistry and assessed for their ability to act as gene-delivery vectors in vitro. In an effort to elucidate the relationship between the hydrophobicity of the fullerene core, the hydrophilicity of the water-solubilizing groups, and the overall charge state of the C60 vectors in gene delivery and expression, several different C60 derivatives were synthesized to yield either positively charged, negatively charged, or neutral chemical functionalities under physiological conditions. These fullerene derivatives were then tested for their ability to transfect cells grown in culture with DNA carrying the green …

Synaptic Vesicle Dynamics In Mouse Rod Bipolar Cells, Qun-Fang Wan, Alejandro Vila, Zhen-Yu Zhou, Ruth Heidelberger

Journal Articles

To better understand synaptic signaling at the mammalian rod bipolar cell terminal and pave the way for applying genetic approaches to the study of visual information processing in the mammalian retina, synaptic vesicle dynamics and intraterminal calcium were monitored in terminals of acutely isolated mouse rod bipolar cells and the number of ribbon-style active zones quantified. We identified a releasable pool, corresponding to a maximum of 7 s. The presence of a smaller, rapidly releasing pool and a small, fast component of refilling was also suggested. Following calcium channel closure, membrane surface area was restored to baseline with a time …

Brain Fiber Tract Plasticity In Experimental Spinal Cord Injury: Diffusion Tensor Imaging, Jaivijay Ramu, Juan Herrera, Raymond Grill, Tobias Bockhorst, Ponnada Narayana

Journal Articles

Diffusion tensor imaging (DTI) and immunohistochemistry were performed in spinal cord injured rats to understand the basis for activation of multiple regions in the brain observed in functional magnetic resonance imaging (fMRI) studies. The measured fractional anisotropy (FA), a scalar measure of diffusion anisotropy, along the region encompassing corticospinal tracts (CST) indicates significant differences between control and injured groups in the 3 to 4 mm area posterior to bregma that correspond to internal capsule and cerebral peduncle. Additionally, DTI-based tractography in injured animals showed increased number of fibers that extend towards the cortex terminating in the regions that were activated …

Beta3 Integrin Haplotype Influences Gene Regulation And Plasma Von Willebrand Factor Activity, Katie E. Payne, Paul F. Bray, Peter J. Grant, Angela M. Carter

Department of Medicine Faculty Papers

The Leu33Pro polymorphism of the gene encoding beta(3) integrin (ITGB3) is associated with acute coronary syndromes and influences platelet aggregation. Three common promoter polymorphisms have also been identified. The aims of this study were to (1) investigate the influence of the ITGB3 -400C/A, -425A/C and -468G/A promoter polymorphisms on reporter gene expression and nuclear protein binding and (2) determine genotype and haplotype associations with platelet alpha(IIb)beta(3) receptor density. Promoter haplotypes were introduced into an ITGB3 promoter-pGL3 construct by site directed mutagenesis and luciferase reporter gene expression analysed in HEL and HMEC-1 cells. Binding of nuclear proteins was assessed by electrophoretic …

Investigating The Complexity Of Respiratory Patterns During The Laryngeal Chemoreflex, Andrei Dragomir, Yasemin Akay, Aidan K. Curran, Metin Akay

Dartmouth Scholarship

The laryngeal chemoreflex exists in infants as a primary sensory mechanism for defending the airway from the aspiration of liquids. Previous studies have hypothesized that prolonged apnea associated with this reflex may be life threatening and might be a cause of sudden infant death syndrome. In this study we quantified the output of the respiratory neural network, the diaphragm EMG signal, during the laryngeal chemoreflex and eupnea in early postnatal (3–10 days) piglets. We tested the hypothesis that diaphragm EMG activity corresponding to reflex-related events involved in clearance (restorative) mechanisms such as cough and swallow exhibit lower complexity, suggesting that …

Neurological And Behavioral Abnormalities, Ventricular Dilatation, Altered Cellular Functions, Inflammation, And Neuronal Injury In Brains Of Mice Due To Common, Persistent, Parasitic Infection, Gretchen Hermes, James W. Ajioka, Krystyna A. Kelly, Ernest Mui, Fiona Roberts, Kristen Kasza, Thomas Mayr, Michael J. Kirisits, Robert Wollman, David J.P Ferguson, Craig W. Roberts, Jong-Hee Hwang, Toria Trendler, Richard P. Kennan, Yasuhiro Suzuki, Catherine Reardon, William F. Hickey, Lieping Chen, Rima Mcleod

Dartmouth Scholarship

Background:

Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences.

Methods:

To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. …

Role Played By Serum, A Biological Cue, In The Adherence Of Enterococcus Faecalis To Extracellular Matrix Proteins, Collagen, Fibrinogen, And Fibronectin, Sreedhar R Nallapareddy, Barbara E Murray

Journal Articles

BACKGROUND: Most previous studies have found that Enterococcus faecalis isolates do not show significant adherence to fibronectin and fibrinogen.

METHODS: The influence of various conditions on E. faecalis adherence to extracellular matrix (ECM) proteins was evaluated using a radiolabeled-cell adherence assay.

RESULTS: Among the conditions studied, growth in 40% horse serum (a biological cue with potential clinical relevance) elicited adherence of all 46 E. faecalis strains tested to fibronectin and fibrinogen but not to elastin; adherence levels were independent of strain source, and adherence was eliminated by treating cells with trypsin. As previously reported, serum also elicited adherence to collagen. …

Aluminum Bioavailability From Basic Sodium Aluminum Phosphate, An Approved Food Additive Emulsifying Agent, Incorporated In Cheese, Robert A. Yokel, Clair L. Hicks, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of approximately 1g cheese containing 1.5% or 3% basic SALP resulted in oral Al bioavailability (F) of approximately 0.1% and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8-9h. These Al bioavailability …

Nerve Growth Factor Regulation Of Cyclin D1 In Pc12 Cells Through A P21ras Extracellular Signal-Regulated Kinase Pathway Requires Cooperative Interactions Between Sp1 And Nuclear Factor-Kappab., Francesco Marampon, Mathew C Casimiro, Maofu Fu, Michael J Powell, Vladimir M Popov, Jaime Lindsay, Bianca M Zani, Carmela Ciccarelli, Genichi Watanabe, Richard J Lee, Richard G Pestell

Department of Cancer Biology Faculty Papers

The PC12 pheochromocytoma cell line responds to nerve growth factor (NGF) by exiting from the cell cycle and differentiating to induce extending neurites. Cyclin D1 is an important regulator of G1/S phase cell cycle progression, and it is known to play a role in myocyte differentiation in cultured cells. Herein, NGF induced cyclin D1 promoter, mRNA, and protein expression via the p21(RAS) pathway. Antisense- or small interfering RNA to cyclin D1 abolished NGF-mediated neurite outgrowth, demonstrating the essential role of cyclin D1 in NGF-mediated differentiation. Expression vectors encoding mutants of the Ras/mitogen-activated protein kinase pathway, and chemical inhibitors, demonstrated NGF …

Demyelinating And Nondemyelinating Strains Of Mouse Hepatitis Virus Differ In Their Neural Cell Tropism., Jayasri Das Sarma, Kathryn Iacono, Lilli Gard, Ryan Marek, Lawrence C. Kenyon, Michael Koval, Susan R. Weiss

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Some strains of mouse hepatitis virus (MHV) can induce chronic inflammatory demyelination in mice that mimics certain pathological features of multiple sclerosis. We have examined neural cell tropism of demyelinating and nondemyelinating strains of MHV in order to determine whether central nervous system (CNS) cell tropism plays a role in demyelination. Previous studies demonstrated that recombinant MHV strains, isogenic other than for the spike gene, differ in the extent of neurovirulence and the ability to induce demyelination. Here we demonstrate that these strains also differ in their abilities to infect a particular cell type(s) in the brain. Furthermore, there is …

Skeletal Abnormalities In Mice Lacking Extracellular Matrix Proteins, Thrombospondin-1, Thrombospondin-3, Thrombospondin-5, And Type Ix Collagen, Karen L Posey, Kurt Hankenson, Alka C Veerisetty, Paul Bornstein, Jack Lawler, Jacqueline T Hecht

Journal Articles

Thrombospondin-5 (TSP5) is a large extracellular matrix glycoprotein found in musculoskeletal tissues. TSP5 mutations cause two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia; both show a characteristic growth plate phenotype with retention of TSP5, type IX collagen (Col9), and matrillin-3 in the rough endoplasmic reticulum. Whereas most studies focus on defining the disease process, few functional studies have been performed. TSP5 knockout mice have no obvious skeletal abnormalities, suggesting that TSP5 is not essential in the growth plate and/or that other TSPs may compensate. In contrast, Col9 knockout mice have diminished matrillin-3 levels in the extracellular matrix and early-onset osteoarthritis. …

A New Model For Hemoglobin Ingestion And Transport By The Human Malaria Parasite Plasmodium Falciparum., Michelle D Lazarus, Timothy G Schneider, Theodore F Taraschi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The current model for hemoglobin ingestion and transport by intraerythrocytic Plasmodium falciparum malaria parasites shares similarities with endocytosis. However, the model is largely hypothetical, and the mechanisms responsible for the ingestion and transport of host cell hemoglobin to the lysosome-like food vacuole (FV) of the parasite are poorly understood. Because actin dynamics play key roles in vesicle formation and transport in endocytosis, we used the actin-perturbing agents jasplakinolide and cytochalasin D to investigate the role of parasite actin in hemoglobin ingestion and transport to the FV. In addition, we tested the current hemoglobin trafficking model through extensive analysis of serial …

Neuromyelitis Optica Pathogenesis And Aquaporin 4, David J. Graber, Michael Levy, Douglas Kerr, William F. Wade

Dartmouth Scholarship

Neuromyelitis optica (NMO) is a severe, debilitating human disease that predominantly features immunopathology in the optic nerves and the spinal cord. An IgG1 autoantibody (NMO-IgG) that binds aquaporin 4 (AQP4) has been identified in the sera of a significant number of NMO patients, as well as in patients with two related neurologic conditions, bilateral optic neuritis (ON), and longitudinal extensive transverse myelitis (LETM), that are generally considered to lie within the NMO spectrum of diseases. NMO-IgG is not the only autoantibody found in NMO patient sera, but the correlation of pathology in central nervous system (CNS) with tissues that normally …

Feedback From Horizontal Cells To Rod Photoreceptors In Vertebrate Retina., Wallace B. Thoreson, Norbert Babai, Theodore M M. Bartoletti

Journal Articles: Ophthalmology

Retinal horizontal cells (HCs) provide negative feedback to cones, but, largely because annular illumination fails to evoke a depolarizing response in rods, it is widely believed that there is no feedback from HCs to rods. However, feedback from HCs to cones involves small changes in the calcium current (I(Ca)) that do not always generate detectable depolarizing responses. We therefore recorded I(Ca) directly from rods to test whether they were modulated by feedback from HCs. To circumvent problems presented by overlapping receptive fields of HCs and rods, we manipulated the membrane potential of voltage-clamped HCs while simultaneously recording from rods in …

388 A Structure Of Cytoplasmic Polyhedrosis Virus By Cryo-Electron Microscopy, Xuekui Yu, Lei Jin, Z Hong Zhou

Journal Articles

Cytoplasmic polyhedrosis virus (CPV) is unique within the Reoviridae family in having a turreted single-layer capsid contained within polyhedrin inclusion bodies, yet being fully capable of cell entry and endogenous RNA transcription. Biochemical data have shown that the amino-terminal 79 residues of the CPV turret protein (TP) is sufficient to bring CPV or engineered proteins into the polyhedrin matrix for micro-encapsulation. Here we report the three-dimensional structure of CPV at 3.88 A resolution using single-particle cryo-electron microscopy. Our map clearly shows the turns and deep grooves of alpha-helices, the strand separation in beta-sheets, and densities for loops and many bulky …

The Synthetic Triterpenoid Cddo-Methyl Ester Modulates Microglial Activities, Inhibits Tnf Production, And Provides Dopaminergic Neuroprotection, Thi A. Tran, Melissa K. Mccoy, Michael B. Sporn, Malú G. Tansey

Dartmouth Scholarship

Recent animal and human studies implicate chronic activation of microglia in the progressive loss of CNS neurons. The inflammatory mechanisms that have neurotoxic effects and contribute to neurodegeneration need to be elucidated and specifically targeted without interfering with the neuroprotective effects of glial activities. Synthetic triterpenoid analogs of oleanolic acid, such as methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me, RTA 402) have potent anti-proliferative and differentiating effects on tumor cells, and anti-inflammatory activities on activated macrophages. We hypothesized that CDDO-Me may be able to suppress neurotoxic microglial activities while enhancing those that promote neuronal survival. Therefore, the aims of our study were to identify specific …

Atf4 Is An Oxidative Stress–Inducible, Prodeath Transcription Factor In Neurons In Vitro And In Vivo, Philipp Lange, Juan Chavez, John T. Pinto, Giovanni Coppola, Chiao-Wang Sun, Tim Townes, Rajiv Ratan

NYMC Faculty Publications

Oxidative stress is pathogenic in neurological diseases, including stroke. The identity of oxidative stress-inducible transcription factors and their role in propagating the death cascade are not well known. In an in vitro model of oxidative stress, the expression of the bZip transcription factor activating transcription factor 4 (ATF4) was induced by glutathione depletion and localized to the promoter of a putative death gene in neurons. Germline deletion of ATF4 resulted in a profound reduction in oxidative stress-induced gene expression and resistance to oxidative death. In neurons, ATF4 modulates an early, upstream event in the death pathway, as resistance to oxidative …

Rest Maintains Self-Renewal And Pluripotency Of Embryonic Stem Cells., Sanjay K Singh, Mohamedi N Kagalwala, Jan Parker-Thornburg, Henry Adams, Sadhan Majumder

Journal Articles

The neuronal repressor REST (RE1-silencing transcription factor; also called NRSF) is expressed at high levels in mouse embryonic stem (ES) cells, but its role in these cells is unclear. Here we show that REST maintains self-renewal and pluripotency in mouse ES cells through suppression of the microRNA miR-21. We found that, as with known self-renewal markers, the level of REST expression is much higher in self-renewing mouse ES cells than in differentiating mouse ES (embryoid body, EB) cells. Heterozygous deletion of Rest (Rest+/-) and its short-interfering-RNA-mediated knockdown in mouse ES cells cause a loss of self-renewal-even when these cells are …

Bovine Oocytes And Early Embryos Express Staufen And Elavl Rna-Binding Proteins., M D Calder, P Madan, A J Watson

Obstetrics & Gynaecology Publications

RNA-binding proteins (RBP) influence RNA editing, localization, stability and translation and may contribute to oocyte developmental competence by regulating the stability and turnover of oogenetic mRNAs. The expression of Staufen 1 and 2 and ELAVL1, ELAVL2 RNA-binding proteins during cow early development was characterized. Cumulus-oocyte complexes were collected from slaughterhouse ovaries, matured, inseminated and subjected to embryo culture in vitro. Oocyte or preimplantation embryo pools were processed for RT-PCR and whole-mount immunofluorescence analysis of mRNA expression and protein distribution. STAU1 and STAU2 and ELAVL1 mRNAs and proteins were detected throughout cow preimplantation development from the germinal vesicle (GV) oocyte to …