Mrnas That Increase in the Absence of E2F1 and E2F2
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Faith and the Human Genome
Plenary Presenters Faith and the Human Genome Faith and the Human Genome Francis S. Collins Despite the best efforts of the American Scientific Affiliation to bridge the gap between science and faith, few gatherings of scientists involved in biology include any meaningful discussion about the spiritual significance of the current revolution in genetics and genomics. Most biologists and geneticists seem to have concluded that science and faith are incompatible, but few who embrace that conclusion seem to have seriously considered the evidence. From my perspective as director of the Human Genome Project, the scientific and religious world views are not only compatible but also inherently complementary. Hence the profound polarization of the scientific and religious perspectives, now glaringly apparent in the fields of biology and genetics, is a source of great distress. Hard-liners in either camp paint increasingly uncompromising pictures that force sincere seekers to choose one view over the other. How all of this must break God’s heart! The elegance and complexity of the human genome is a source of profound wonder. That wonder only strengthens my faith, as it provides glimpses of aspects of From my humanity, which God has known all along, but which we are just now beginning to discover. perspective as e are just on the edge of a whole You made him a little lower than the heav- director of the Whost of developments spurred on enly beings and crowned him with glory by genetics that are going to and honor. You made him ruler over the Human require careful and deliberative thought. -
Annexin A2 Flop-Out Mediates the Non-Vesicular Release of Damps/Alarmins from C6 Glioma Cells Induced by Serum-Free Conditions
cells Article Annexin A2 Flop-Out Mediates the Non-Vesicular Release of DAMPs/Alarmins from C6 Glioma Cells Induced by Serum-Free Conditions Hayato Matsunaga 1,2,† , Sebok Kumar Halder 1,3,† and Hiroshi Ueda 1,4,* 1 Pharmacology and Therapeutic Innovation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan; [email protected] (H.M.); [email protected] (S.K.H.) 2 Department of Medical Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan 3 San Diego Biomedical Research Institute, San Diego, CA 92121, USA 4 Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan * Correspondence: [email protected]; Tel.: +81-75-753-4536 † These authors contributed equally to this work. Abstract: Prothymosin alpha (ProTα) and S100A13 are released from C6 glioma cells under serum- free conditions via membrane tethering mediated by Ca2+-dependent interactions between S100A13 and p40 synaptotagmin-1 (Syt-1), which is further associated with plasma membrane syntaxin-1 (Stx-1). The present study revealed that S100A13 interacted with annexin A2 (ANXA2) and this interaction was enhanced by Ca2+ and p40 Syt-1. Amlexanox (Amx) inhibited the association between S100A13 and ANXA2 in C6 glioma cells cultured under serum-free conditions in the in situ proximity ligation assay. In the absence of Amx, however, the serum-free stress results in a flop-out of ANXA2 Citation: Matsunaga, H.; Halder, through the membrane, without the extracellular release. The intracellular delivery of anti-ANXA2 S.K.; Ueda, H. Annexin A2 Flop-Out antibody blocked the serum-free stress-induced cellular loss of ProTα, S100A13, and Syt-1. -
Propranolol-Mediated Attenuation of MMP-9 Excretion in Infants with Hemangiomas
Supplementary Online Content Thaivalappil S, Bauman N, Saieg A, Movius E, Brown KJ, Preciado D. Propranolol-mediated attenuation of MMP-9 excretion in infants with hemangiomas. JAMA Otolaryngol Head Neck Surg. doi:10.1001/jamaoto.2013.4773 eTable. List of All of the Proteins Identified by Proteomics This supplementary material has been provided by the authors to give readers additional information about their work. © 2013 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable. List of All of the Proteins Identified by Proteomics Protein Name Prop 12 mo/4 Pred 12 mo/4 Δ Prop to Pred mo mo Myeloperoxidase OS=Homo sapiens GN=MPO 26.00 143.00 ‐117.00 Lactotransferrin OS=Homo sapiens GN=LTF 114.00 205.50 ‐91.50 Matrix metalloproteinase‐9 OS=Homo sapiens GN=MMP9 5.00 36.00 ‐31.00 Neutrophil elastase OS=Homo sapiens GN=ELANE 24.00 48.00 ‐24.00 Bleomycin hydrolase OS=Homo sapiens GN=BLMH 3.00 25.00 ‐22.00 CAP7_HUMAN Azurocidin OS=Homo sapiens GN=AZU1 PE=1 SV=3 4.00 26.00 ‐22.00 S10A8_HUMAN Protein S100‐A8 OS=Homo sapiens GN=S100A8 PE=1 14.67 30.50 ‐15.83 SV=1 IL1F9_HUMAN Interleukin‐1 family member 9 OS=Homo sapiens 1.00 15.00 ‐14.00 GN=IL1F9 PE=1 SV=1 MUC5B_HUMAN Mucin‐5B OS=Homo sapiens GN=MUC5B PE=1 SV=3 2.00 14.00 ‐12.00 MUC4_HUMAN Mucin‐4 OS=Homo sapiens GN=MUC4 PE=1 SV=3 1.00 12.00 ‐11.00 HRG_HUMAN Histidine‐rich glycoprotein OS=Homo sapiens GN=HRG 1.00 12.00 ‐11.00 PE=1 SV=1 TKT_HUMAN Transketolase OS=Homo sapiens GN=TKT PE=1 SV=3 17.00 28.00 ‐11.00 CATG_HUMAN Cathepsin G OS=Homo -
S100A10 in Cancer Progression and Chemotherapy Resistance: a Novel Therapeutic Target Against Ovarian Cancer
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 15 October 2018 doi:10.20944/preprints201810.0318.v1 Peer-reviewed version available at Int. J. Mol. Sci. 2018, 19, 4122; doi:10.3390/ijms19124122 Review S100A10 in Cancer Progression and Chemotherapy Resistance: A Novel Therapeutic Target against Ovarian Cancer Tannith M Noye1, Noor A Lokman1 Martin K Oehler1, 2 and Carmela Ricciardelli1,* 1 Discipline of Obstetrics and Gynaecology, Adelaide Medical School, Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia emails: [email protected] (T.M.N.); [email protected] (N.A.L.); [email protected] (M.K.O); [email protected](C.R) 2 Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia * Correspondence: [email protected]; Tel.: +61-0883138255 Abstract: S100A10, which is also known as p11 is located in the plasma membrane and forms a heterotetramer with annexin A2. The heterotetramer, comprising of 2 subunits of annexin A2 and S100A10, activates the plasminogen activation pathway which is involved in cellular repair of normal tissues. Increased expression of annexin A2 and S100A10 in cancer cells leads to increased levels of plasmin which promote degradation of the extracellular matrix, increased angiogenesis and invasion of the surrounding organs. Although many studies have investigated the functional role of annexin A2 in cancer cells including ovarian cancer, S100A10 has been less studied. We recently demonstrated that high stromal annexin A2 and high cytoplasmic S100A10 expression is associated with a 3.4 fold increased risk of progression and 7.9 fold risk of death in ovarian cancer patients. -
Annexin A1 Is a New Functional Linker Between Actin Filaments and Phagosomes During Phagocytosis
578 Research Article Annexin A1 is a new functional linker between actin filaments and phagosomes during phagocytosis Devang M. Patel1, Syed Furquan Ahmad1, Dieter G. Weiss1, Volker Gerke2 and Sergei A. Kuznetsov1,* 1Institute of Biological Sciences, Cell Biology and Biosystems Technology, University of Rostock, Albert-Einstein Straße 3, Rostock 18059, Germany 2Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, University of Münster, Von-Esmarch-Straße 56, Münster 48149, Germany *Author for correspondence ([email protected]) Accepted 19 October 2010 Journal of Cell Science 124, 578-588 © 2011. Published by The Company of Biologists Ltd doi:10.1242/jcs.076208 Summary Remodelling of the actin cytoskeleton plays a key role in particle internalisation and the phagosome maturation processes. Actin- binding proteins (ABPs) are the main players in actin remodelling but the precise role of these proteins in phagocytosis needs to be clarified. Annexins, a group of ABPs, are known to be present on phagosomes. Here, we identified annexin A1 as a factor that binds to isolated latex bead phagosomes (LBPs) in the presence of Ca2+ and facilitates the F-actin–LBP interaction in vitro. In macrophages the association of endogenous annexin A1 with LBP membranes was strongly correlated with the spatial and temporal accumulation of F-actin at the LBP. Annexin A1 was found on phagocytic cups and around early phagosomes, where the F-actin was prominently concentrated. After uptake was completed, annexin A1, along with F-actin, dissociated from the nascent LBP surface. At later stages of phagocytosis annexin A1 transiently concentrated only around those LBPs that showed transient F-actin accumulation (‘actin flashing’). -
Apoptosis and Differentiation Commitment: Novel Insights Revealed by Gene Profiling Studies in Mouse Embryonic Stem Cells
Cell Death and Differentiation (2006) 13, 564–575 & 2006 Nature Publishing Group All rights reserved 1350-9047/06 $30.00 www.nature.com/cdd Apoptosis and differentiation commitment: novel insights revealed by gene profiling studies in mouse embryonic stem cells D Duval1,2,4, M Trouillas3,4, C Thibault2, D Dembele´ 2, Introduction F Diemunsch2, B Reinhardt2, AL Mertz2, A Dierich2 Mouse embryonic stem (ES) cells, which are maintained and H Bœuf*,3 pluripotent in vitro with leukemia inhibitory factor (LIF) cytokine, are instrumental to study LIF-dependent cell 1 UMR5096-CNRS/UP/IRD, Perpignan, France 2 IGBMC/CNRS/INSERM, Strasbourg, France pluripotency as well as the first steps of differentiation 3 UMR-5164-CNRS-CIRID/Universite´ Bordeaux2, Bordeaux, France commitment triggered upon LIF starvation. As we recently 4 These authors contributed equally to this work reported, these cells could also be used to unravel the early * Corresponding author: H Bœuf, UMR-5164-CNRS-CIRID, Universite´ steps of apoptosis, a physiological cell death process Bordeaux2, Bat.1B, BP14, 146 rue Le´o Saignat, 33076 Bordeaux, France. occurring during the first embryogenesis stages. Indeed, the Tel: þ 05 57 57 46 33; Fax: þ 05 57 57 14 72; formation of the cavities, which starts at the blastocyst stage, E-mail:helene.bœ[email protected] is dependent on a specific cell death program, which includes caspase 3 cleavage and induction of the apoptosis-inducing Received 10.3.05; revised 01.9.05; accepted 01.9.05; published online 25.11.05 1 Edited by R De Maria factor (AIF)-complex proteins. -
Supplemental Table1a.Xlsx
Electronic Supplementary Material (ESI) for Analyst This journal is © The Royal Society of Chemistry 2013 Supplemental Table 1A This table includes the taxonomically significant peptides from HeLa cultured VACV samples purified by filter purification. The peptide, uniprot ID and protein name from one of the homologous proteins is provided. The species specificity is provided along with the frequency of observation (n = 10). Peptides observed in more than replicate data set are included. Peptide Uniprot ID Protein Description Specificity Freq. LLNENSYVPR P02786 protein 1 Primates, racoon 0.9 LATQLTGPVMPVR A8K4C8 60S ribosomal protein L13 Homo sapiens 0.8 HVGK B0JYN6 Alpha-2-HS-glycoprotein Bos taurus0.8 LAVDEEENADNNTK F8WBE5 protein 1 Great Apes 0.8 VTLTSEEEAR B4DJI1 L-lactate dehydrogenase Primates, Hamster 0.7 LGEYGFQNELIVR B0JYQ0 ALB protein Bos taurus 0.6 GTVTDFPGFDER D6RCN3 Annexin A5 Elephant 0.6 YTPSGQAGAAASESLF Fructose-bisphosphate Great apes, cucumber VSNHAY H3BR68 aldolase A (Fragment) and some rodents 0.6 VGGHAAEYGAEALER P01966 Hemoglobin subunit alpha Bos taurus 0.6 ALTGHLEEVVLALLK P04083 Annexin A1 some rodents 0.5 AQGPAASAEEPKPVEA Brain acid soluble protein PAANSDQTVTVKE P80723 1 Homo sapiens 0.5 FYALSASFEPFSNK P27797 Calreticulin Primates not gorilla 0.5 PK P02081 beta Bos taurus0.5 NLK F5H6B1 protein 1Gorilla 0.5 K P02786 protein 1Primates 0.5 YNSQLLSFVR P02786 protein 1 Great Apes 0.5 TPIVGQPSIPGGPVR B0JYN6 Alpha-2-HS-glycoprotein Bos taurus 0.4 AGTDLLNFLSSFIDPK P81644 Apolipoprotein A-II Bos taurus 0.4 SELPLDPLPVPTEEGNP -
Non-Coding Rnas in the Cardiac Action Potential and Their Impact on Arrhythmogenic Cardiac Diseases
Review Non-Coding RNAs in the Cardiac Action Potential and Their Impact on Arrhythmogenic Cardiac Diseases Estefania Lozano-Velasco 1,2 , Amelia Aranega 1,2 and Diego Franco 1,2,* 1 Cardiovascular Development Group, Department of Experimental Biology, University of Jaén, 23071 Jaén, Spain; [email protected] (E.L.-V.); [email protected] (A.A.) 2 Fundación Medina, 18016 Granada, Spain * Correspondence: [email protected] Abstract: Cardiac arrhythmias are prevalent among humans across all age ranges, affecting millions of people worldwide. While cardiac arrhythmias vary widely in their clinical presentation, they possess shared complex electrophysiologic properties at cellular level that have not been fully studied. Over the last decade, our current understanding of the functional roles of non-coding RNAs have progressively increased. microRNAs represent the most studied type of small ncRNAs and it has been demonstrated that miRNAs play essential roles in multiple biological contexts, including normal development and diseases. In this review, we provide a comprehensive analysis of the functional contribution of non-coding RNAs, primarily microRNAs, to the normal configuration of the cardiac action potential, as well as their association to distinct types of arrhythmogenic cardiac diseases. Keywords: cardiac arrhythmia; microRNAs; lncRNAs; cardiac action potential Citation: Lozano-Velasco, E.; Aranega, A.; Franco, D. Non-Coding RNAs in the Cardiac Action Potential 1. The Electrical Components of the Adult Heart and Their Impact on Arrhythmogenic The adult heart is a four-chambered organ that propels oxygenated blood to the entire Cardiac Diseases. Hearts 2021, 2, body. It is composed of atrial and ventricular chambers, each of them with distinct left and 307–330. -
Differential Proteomic Analysis of Hepatocellular Carcinomas From
CANCER GENOMICS & PROTEOMICS 17 : 669-685 (2020) doi:10.21873/cgp.20222 Differential Proteomic Analysis of Hepatocellular Carcinomas from Ppp2r5d Knockout Mice and Normal (Knockout) Livers CAROLINE LAMBRECHT 1, GABRIELA BOMFIM FERREIRA 2, JUDIT DOMÈNECH OMELLA 1, LOUIS LIBBRECHT 3, RITA DE VOS 4, RITA DERUA 1, CHANTAL MATHIEU 2, LUT OVERBERGH 2, ETIENNE WAELKENS 1 and VEERLE JANSSENS 1,5 1Laboratory of Protein Phosphorylation and Proteomics, Department Cellular and Molecular Medicine, University of Leuven (KU Leuven), Leuven, Belgium; 2Clinical and Experimental Endocrinology, Department Clinical and Experimental Medicine, University of Leuven (KU Leuven), Leuven, Belgium; 3Department of Pathology, Université Catholique de Louvain (UCL), Brussels, Belgium; 4Translational Cell and Tissue Research, Department Imaging and Pathology, University of Leuven (KU Leuven), Leuven, Belgium; 5LKI, KU Leuven Cancer Institute, Leuven, Belgium Abstract. Background: Hepatocellular carcinoma (HCC) ‘gastrointestinal disease’ as top hits. Conclusion: We is the major type of primary liver cancer. Mice lacking the identified several proteins for further exploration as novel tumor-suppressive protein phosphatase 2A subunit B56 δ potential HCC biomarkers, and independently underscored (Ppp2r5d ) spontaneously develop HCC, correlating with the relevance of Ppp2r5d knockout mice as a valuable increased c-MYC oncogenicity. Materials and Methods: We hepatocarcinogenesis model. used two-dimensional difference gel electrophoresis-coupled matrix-assisted laser desorption/ionization time-of-flight Hepatocellular carcinoma (HCC) is the most common primary mass spectrometry to identify differential proteomes of livers liver cancer, and the second leading cause of cancer-related death from wild-type, non-cancerous and HCC-affected B56 δ worldwide (1). Most patients with HCC are diagnosed at an knockout mice. -
2812 Matrix Vesicles: Structure, Composition, Formation and Function in Ca
[Frontiers in Bioscience 16, 2812-2902, June 1, 2011] Matrix vesicles: structure, composition, formation and function in calcification Roy E. Wuthier Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208 TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Morphology of matrix vesicles (MVs) 3.1. Conventional transmission electron microscopy 3.2. Cryofixation, freeze-substitution electron microscopy 3.3. Freeze-fracture studies 4. Isolation of MVs 4.1. Crude collagenase digestion methods 4.2. Non-collagenase dependent methods 4.3. Cell culture methods 4.4. Modified collagenase digestion methods 4.5. Other isolation methods 5. MV proteins 5.1. Early SDS-PAGE studies 5.2. Isolation and identification of major MV proteins 5.3. Sequential extraction, separation and characterization of major MV proteins 5.4. Proteomic characterization of MV proteins 6. MV-associated extracellular matrix proteins 6.1. Type VI collagen 6.2. Type X collagen 6.3. Proteoglycan link protein and aggrecan core protein 6.4. Fibrillin-1 and fibrillin-2 7. MV annexins – acidic phospholipid-dependent ca2+-binding proteins 7.1. Annexin A5 7.2. Annexin A6 7.3. Annexin A2 7.4. Annexin A1 7.5. Annexin A11 and Annexin A4 8. MV enzymes 8.1. Tissue-nonspecific alkaline phosphatase(TNAP) 8.1.1. Molecular structure 8.1.2. Amino acid sequence 8.1.3. 3-D structure 8.1.4. Disposition in the MV membrane 8.1.5. Catalytic properties 8.1.6. Collagen-binding properties 8.2. Nucleotide pyrophosphate phosphodiesterase (NPP1, PC1) 8.3. PHOSPHO-1 (Phosphoethanolamine/Phosphocholine phosphatase 8.4. Acid phosphatase 8.5. -
Changes in the Cytosolic Proteome of Aedes Malpighian Tubules
329 The Journal of Experimental Biology 212, 329-340 Published by The Company of Biologists 2009 doi:10.1242/jeb.024646 Research article Signaling to the apical membrane and to the paracellular pathway: changes in the cytosolic proteome of Aedes Malpighian tubules Klaus W. Beyenbach1,*, Sabine Baumgart2, Kenneth Lau1, Peter M. Piermarini1 and Sheng Zhang2 1Department of Biomedical Sciences, VRT 8004, Cornell University, Ithaca, NY 14853, USA and 2Proteomics and Mass Spectrometry Core Facility, 143 Biotechnology Building, Cornell University, Ithaca, NY 14853, USA *Author for correspondence (e-mail: [email protected]) Accepted 6 November 2008 Summary Using a proteomics approach, we examined the post-translational changes in cytosolic proteins when isolated Malpighian tubules of Aedes aegypti were stimulated for 1 min with the diuretic peptide aedeskinin-III (AK-III, 10–7 mol l–1). The cytosols of control (C) and aedeskinin-treated (T) tubules were extracted from several thousand Malpighian tubules, subjected to 2-D electrophoresis and stained for total proteins and phosphoproteins. The comparison of C and T gels was performed by gel image analysis for the change of normalized spot volumes. Spots with volumes equal to or exceeding C/T ratios of ±1.5 were robotically picked for in- gel digestion with trypsin and submitted for protein identification by nanoLC/MS/MS analysis. Identified proteins covered a wide range of biological activity. As kinin peptides are known to rapidly stimulate transepithelial secretion of electrolytes and water by Malpighian tubules, we focused on those proteins that might mediate the increase in transepithelial secretion. We found that AK- III reduces the cytosolic presence of subunits A and B of the V-type H+ ATPase, endoplasmin, calreticulin, annexin, type II regulatory subunit of protein kinase A (PKA) and rab GDP dissociation inhibitor and increases the cytosolic presence of adducin, actin, Ca2+-binding protein regucalcin/SMP30 and actin-depolymerizing factor. -
Transcriptomic Uniqueness and Commonality of the Ion Channels and Transporters in the Four Heart Chambers Sanda Iacobas1, Bogdan Amuzescu2 & Dumitru A
www.nature.com/scientificreports OPEN Transcriptomic uniqueness and commonality of the ion channels and transporters in the four heart chambers Sanda Iacobas1, Bogdan Amuzescu2 & Dumitru A. Iacobas3,4* Myocardium transcriptomes of left and right atria and ventricles from four adult male C57Bl/6j mice were profled with Agilent microarrays to identify the diferences responsible for the distinct functional roles of the four heart chambers. Female mice were not investigated owing to their transcriptome dependence on the estrous cycle phase. Out of the quantifed 16,886 unigenes, 15.76% on the left side and 16.5% on the right side exhibited diferential expression between the atrium and the ventricle, while 5.8% of genes were diferently expressed between the two atria and only 1.2% between the two ventricles. The study revealed also chamber diferences in gene expression control and coordination. We analyzed ion channels and transporters, and genes within the cardiac muscle contraction, oxidative phosphorylation, glycolysis/gluconeogenesis, calcium and adrenergic signaling pathways. Interestingly, while expression of Ank2 oscillates in phase with all 27 quantifed binding partners in the left ventricle, the percentage of in-phase oscillating partners of Ank2 is 15% and 37% in the left and right atria and 74% in the right ventricle. The analysis indicated high interventricular synchrony of the ion channels expressions and the substantially lower synchrony between the two atria and between the atrium and the ventricle from the same side. Starting with crocodilians, the heart pumps the blood through the pulmonary circulation and the systemic cir- culation by the coordinated rhythmic contractions of its upper lef and right atria (LA, RA) and lower lef and right ventricles (LV, RV).