Ligand Binding Module University of San Diego
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Functional Analysis of the Homeobox Gene Tur-2 During Mouse Embryogenesis
Functional Analysis of The Homeobox Gene Tur-2 During Mouse Embryogenesis Shao Jun Tang A thesis submitted in conformity with the requirements for the Degree of Doctor of Philosophy Graduate Department of Molecular and Medical Genetics University of Toronto March, 1998 Copyright by Shao Jun Tang (1998) National Library Bibriothèque nationale du Canada Acquisitions and Acquisitions et Bibiiographic Services seMces bibliographiques 395 Wellington Street 395, rue Weifington OtbawaON K1AW OttawaON KYAON4 Canada Canada The author has granted a non- L'auteur a accordé une licence non exclusive licence alIowing the exclusive permettant à la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distri%uteor sell reproduire, prêter' distribuer ou copies of this thesis in microform, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfiche/nlm, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fkom it Ni la thèse ni des extraits substantiels may be printed or otherwise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation. Functional Analysis of The Homeobox Gene TLr-2 During Mouse Embryogenesis Doctor of Philosophy (1998) Shao Jun Tang Graduate Department of Moiecular and Medicd Genetics University of Toronto Abstract This thesis describes the clonhg of the TLx-2 homeobox gene, the determination of its developmental expression, the characterization of its fiuiction in mouse mesodem and penpheral nervous system (PNS) developrnent, the regulation of nx-2 expression in the early mouse embryo by BMP signalling, and the modulation of the function of nX-2 protein by the 14-3-3 signalling protein during neural development. -
Organic Ligand Complexation Reactions On
Organic ligand complexation reactions on aluminium-bearing mineral surfaces studied via in-situ Multiple Internal Reflection Infrared Spectroscopy, adsorption experiments, and surface complexation modelling A thesis submitted to the University of Manchester for the degree of Doctor of Philosophy in the Faculty of Engineering and Physical Sciences 2010 Charalambos Assos School of Earth, Atmospheric and Environmental Sciences Table of Contents LIST OF FIGURES ......................................................................................................4 LIST OF TABLES ........................................................................................................8 ABSTRACT.................................................................................................................10 DECLARATION.........................................................................................................11 COPYRIGHT STATEMENT....................................................................................12 CHAPTER 1 INTRODUCTION ...............................................................................13 AIMS AND OBJECTIVES .................................................................................................38 CHAPTER 2 THE USE OF IR SPECTROSCOPY IN THE STUDY OF ORGANIC LIGAND SURFACE COMPLEXATION............................................40 INTRODUCTION.............................................................................................................40 METHODOLOGY ...........................................................................................................44 -
Crystal Field Theory (CFT)
Crystal Field Theory (CFT) The bonding of transition metal complexes can be explained by two approaches: crystal field theory and molecular orbital theory. Molecular orbital theory takes a covalent approach, and considers the overlap of d-orbitals with orbitals on the ligands to form molecular orbitals; this is not covered on this site. Crystal field theory takes the ionic approach and considers the ligands as point charges around a central metal positive ion, ignoring any covalent interactions. The negative charge on the ligands is repelled by electrons in the d-orbitals of the metal. The orientation of the d orbitals with respect to the ligands around the central metal ion is important, and can be used to explain why the five d-orbitals are not degenerate (= at the same energy). Whether the d orbitals point along or in between the cartesian axes determines how the orbitals are split into groups of different energies. Why is it required? The valence bond approach could not explain the Electronic spectra, Magnetic moments, Reaction mechanisms of the complexes. Assumptions of CFT: 1. The central Metal cation is surrounded by ligand which contain one or more lone pair of electrons. 2. The ionic ligand (F-, Cl- etc.) are regarded as point charges and neutral molecules (H2O, NH3 etc.) as point dipoles. 3. The electrons of ligand does not enter metal orbital. Thus there is no orbital overlap takes place. 4. The bonding between metal and ligand is purely electrostatic i.e. only ionic interaction. The approach taken uses classical potential energy equations that take into account the attractive and repulsive interactions between charged particles (that is, Coulomb's Law interactions). -
Hypochlorous Acid Handling
Hypochlorous Acid Handling 1 Identification of Petitioned Substance 2 Chemical Names: Hypochlorous acid, CAS Numbers: 7790-92-3 3 hypochloric(I) acid, chloranol, 4 hydroxidochlorine 10 Other Codes: European Community 11 Number-22757, IUPAC-Hypochlorous acid 5 Other Name: Hydrogen hypochlorite, 6 Chlorine hydroxide List other codes: PubChem CID 24341 7 Trade Names: Bleach, Sodium hypochlorite, InChI Key: QWPPOHNGKGFGJK- 8 Calcium hypochlorite, Sterilox, hypochlorite, UHFFFAOYSA-N 9 NVC-10 UNII: 712K4CDC10 12 Summary of Petitioned Use 13 A petition has been received from a stakeholder requesting that hypochlorous acid (also referred 14 to as electrolyzed water (EW)) be added to the list of synthetic substances allowed for use in 15 organic production and handling (7 CFR §§ 205.600-606). Specifically, the petition concerns the 16 formation of hypochlorous acid at the anode of an electrolysis apparatus designed for its 17 production from a brine solution. This active ingredient is aqueous hypochlorous acid which acts 18 as an oxidizing agent. The petitioner plans use hypochlorous acid as a sanitizer and antimicrobial 19 agent for the production and handling of organic products. The petition also requests to resolve a 20 difference in interpretation of allowed substances for chlorine materials on the National List of 21 Allowed and Prohibited Substances that contain the active ingredient hypochlorous acid (NOP- 22 PM 14-3 Electrolyzed water). 23 The NOP has issued NOP 5026 “Guidance, the use of Chlorine Materials in Organic Production 24 and Handling.” This guidance document clarifies the use of chlorine materials in organic 25 production and handling to align the National List with the November, 1995 NOSB 26 recommendation on chlorine materials which read: 27 “Allowed for disinfecting and sanitizing food contact surfaces. -
Interplay Between Gating and Block of Ligand-Gated Ion Channels
brain sciences Review Interplay between Gating and Block of Ligand-Gated Ion Channels Matthew B. Phillips 1,2, Aparna Nigam 1 and Jon W. Johnson 1,2,* 1 Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA; [email protected] (M.B.P.); [email protected] (A.N.) 2 Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA * Correspondence: [email protected]; Tel.: +1-(412)-624-4295 Received: 27 October 2020; Accepted: 26 November 2020; Published: 1 December 2020 Abstract: Drugs that inhibit ion channel function by binding in the channel and preventing current flow, known as channel blockers, can be used as powerful tools for analysis of channel properties. Channel blockers are used to probe both the sophisticated structure and basic biophysical properties of ion channels. Gating, the mechanism that controls the opening and closing of ion channels, can be profoundly influenced by channel blocking drugs. Channel block and gating are reciprocally connected; gating controls access of channel blockers to their binding sites, and channel-blocking drugs can have profound and diverse effects on the rates of gating transitions and on the stability of channel open and closed states. This review synthesizes knowledge of the inherent intertwining of block and gating of excitatory ligand-gated ion channels, with a focus on the utility of channel blockers as analytic probes of ionotropic glutamate receptor channel function. Keywords: ligand-gated ion channel; channel block; channel gating; nicotinic acetylcholine receptor; ionotropic glutamate receptor; AMPA receptor; kainate receptor; NMDA receptor 1. Introduction Neuronal information processing depends on the distribution and properties of the ion channels found in neuronal membranes. -
The Transcriptional Activator PAX3–FKHR
Downloaded from genesdev.cshlp.org on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press The transcriptional activator PAX3–FKHR rescues the defects of Pax3 mutant mice but induces a myogenic gain-of-function phenotype with ligand-independent activation of Met signaling in vivo Frédéric Relaix,1 Mariarosa Polimeni,2 Didier Rocancourt,1 Carola Ponzetto,3 Beat W. Schäfer,4 and Margaret Buckingham1,5 1CNRS URA 2375, Department of Developmental Biology, Pasteur Institute, 75724 Paris Cedex 15, France; 2Department of Experimental Medicine, Section of Anatomy, University of Pavia, 27100 Pavia, Italy; 3Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, 10126 Turin, Italy; 4Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University of Zurich, CH-8032 Zurich, Switzerland Pax3 is a key transcription factor implicated in development and human disease. To dissect the role of Pax3 in myogenesis and establish whether it is a repressor or activator, we generated loss- and gain-of-function alleles by targeting an nLacZ reporter and a sequence encoding the oncogenic fusion protein PAX3–FKHR into the Pax3 locus. Rescue of the Pax3 mutant phenotypes by PAX3–FKHR suggests that Pax3 acts as a transcriptional activator during embryogenesis. This is confirmed by a Pax reporter mouse. However, mice expressing PAX3–FKHR display developmental defects, including ectopic delamination and inappropriate migration of muscle precursor cells. These events result from overexpression of c-met, leading to constitutive activation of Met signaling, despite the absence of the ligand SF/HGF. Haploinsufficiency of c-met rescues this phenotype, confirming the direct genetic link with Pax3. The gain-of-function phenotype is also characterized by overactivation of MyoD. -
Chapter 21 D-Metal Organometalloc Chemistry
Chapter 21 d-metal organometalloc chemistry Bonding Ligands Compounds Reactions Chapter 13 Organometallic Chemistry 13-1 Historical Background 13-2 Organic Ligands and Nomenclature 13-3 The 18-Electron Rule 13-4 Ligands in Organometallic Chemistry 13-5 Bonding Between Metal Atoms and Organic π Systems 13-6 Complexes Containing M-C, M=C, and M≡C Bonds 13-7 Spectral Analysis and Characterization of Organometallic Complexes “Inorganic Chemistry” Third Ed. Gary L. Miessler, Donald A. Tarr, 2004, Pearson Prentice Hall http://en.wikipedia.org/wiki/Expedia 13-1 Historical Background Sandwich compounds Cluster compounds 13-1 Historical Background Other examples of organometallic compounds 13-1 Historical Background Organometallic Compound Organometallic chemistry is the study of chemical compounds containing bonds between carbon and a metal. Organometallic chemistry combines aspects of inorganic chemistry and organic chemistry. Organometallic compounds find practical use in stoichiometric and catalytically active compounds. Electron counting is key in understanding organometallic chemistry. The 18-electron rule is helpful in predicting the stabilities of organometallic compounds. Organometallic compounds which have 18 electrons (filled s, p, and d orbitals) are relatively stable. This suggests the compound is isolable, but it can result in the compound being inert. 13-1 Historical Background In attempt to synthesize fulvalene Produced an orange solid (ferrocene) Discovery of ferrocene began the era of modern organometallic chemistry. Staggered -
Genomic Targeting of Epigenetic Probes Using a Chemically Tailored Cas9 System
Genomic targeting of epigenetic probes using a chemically tailored Cas9 system Glen P. Liszczaka, Zachary Z. Browna, Samuel H. Kima, Rob C. Oslunda, Yael Davida, and Tom W. Muira,1 aDepartment of Chemistry, Princeton University, Princeton, NJ 08544 Edited by James A. Wells, University of California, San Francisco, CA, and approved December 13, 2016 (received for review September 20, 2016) Recent advances in the field of programmable DNA-binding proteins Here, we report a method that combines the versatility of have led to the development of facile methods for genomic pharmacologic manipulation with the specificity of a genetically localization of genetically encodable entities. Despite the extensive programmable DNA-binding protein. Our strategy uses a utility of these tools, locus-specific delivery of synthetic molecules chemically tailored dCas9 to display a pharmacologic agent at a remains limited by a lack of adequate technologies. Here we combine genetic locus of interest in live mammalian cells (Fig. 1). This is trans the flexibility of chemical synthesis with the specificity of a pro- accomplished using split intein-mediated protein -splicing grammable DNA-binding protein by using protein trans-splicing to (PTS) to site-specifically link a recombinant dCas9:guide RNA ligate synthetic elements to a nuclease-deficient Cas9 (dCas9) (gRNA) complex to the synthetic cargo of choice (22). Indeed, in vitro and subsequently deliver the dCas9 cargo to live cells. we show that the remarkable specificity, efficiency, and speed of PTS allow the direct generation of desired dCas9 conjugates The versatility of this technology is demonstrated by delivering within the cell culture media, thereby facilitating a streamlined dCas9 fusions that include either the small-molecule bromodomain “one-pot” approach for genomic targeting of the reaction product. -
Searching Coordination Compounds
CAS ONLINEB Available on STN Internationalm The Scientific & Technical Information Network SEARCHING COORDINATION COMPOUNDS December 1986 Chemical Abstracts Service A Division of the American Chemical Society 2540 Olentangy River Road P.O. Box 3012 Columbus, OH 43210 Copyright O 1986 American Chemical Society Quoting or copying of material from this publication for educational purposes is encouraged. providing acknowledgment is made of the source of such material. SEARCHING COORDINATION COMPOUNDS prepared by Adrienne W. Kozlowski Professor of Chemistry Central Connecticut State University while on sabbatical leave as a Visiting Educator, Chemical Abstracts Service Table of Contents Topic PKEFACE ............................s.~........................ 1 CHAPTER 1: INTRODUCTION TO SEARCHING IN CAS ONLINE ............... 1 What is Substructure Searching? ............................... 1 The Basic Commands .............................................. 2 CHAPTEK 2: INTKOOUCTION TO COORDINATION COPPOUNDS ................ 5 Definitions and Terminology ..................................... 5 Ligand Characteristics.......................................... 6 Metal Characteristics .................................... ... 8 CHAPTEK 3: STKUCTUKING AND REGISTKATION POLICIES FOR COORDINATION COMPOUNDS .............................................11 Policies for Structuring Coordination Compounds ................. Ligands .................................................... Ligand Structures........................................... Metal-Ligand -
Geometry, Epistasis, and Developmental Patterning
Geometry, epistasis, and developmental patterning Francis Corson and Eric Dean Siggia1 Center for Studies in Physics and Biology, The Rockefeller University, New York, NY 10021 This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected in 2009. Contributed by Eric Dean Siggia, February 6, 2012 (sent for review November 28, 2011) Developmental signaling networks are composed of dozens of (5) shows that even differentiation can be reversed. Yet they have components whose interactions are very difficult to quantify in provided a useful guide to experiments. an embryo. Geometric reasoning enumerates a discrete hierarchy These concepts admit a natural geometric representation, of phenotypic models with a few composite variables whose para- which can be formalized in the language of dynamical systems, meters may be defined by in vivo data. Vulval development in also called the geometric theory of differential equations (Fig. 1). ’ the nematode Caenorhabditis elegans is a classic model for the in- When the molecular details are not accessible, a system s effec- tegration of two signaling pathways; induction by EGF and lateral tive behavior may be represented in terms of a small number of signaling through Notch. Existing data for the relative probabilities aggregate variables, and qualitatively different behaviors enum- of the three possible terminal cell types in diverse genetic back- erated according to the geometrical structure of trajectories or grounds as well as timed ablation of the inductive signal favor topology. The fates that are accessible to a cell are associated with attractors—the valleys in Waddington’s “epigenetic landscape” one geometric model and suffice to fit most of its parameters. -
Genetic Dissection of Developmental Pathways*§ †
Genetic dissection of developmental pathways*§ † Linda S. Huang , Department of Biology, University of Massachusetts-Boston, Boston, MA 02125 USA Paul W. Sternberg, Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, CA 91125 USA Table of Contents 1. Introduction ............................................................................................................................1 2. Epistasis analysis ..................................................................................................................... 2 3. Epistasis analysis of switch regulation pathways ............................................................................ 3 3.1. Double mutant construction ............................................................................................. 3 3.2. Interpretation of epistasis ................................................................................................ 5 3.3. The importance of using null alleles .................................................................................. 6 3.4. Use of dominant mutations .............................................................................................. 7 3.5. Complex pathways ........................................................................................................ 7 3.6. Genetic redundancy ....................................................................................................... 9 3.7. Limits of epistasis ...................................................................................................... -
Glossary of Hazardous Materials Terms
GLOSSARY OF CHEMICAL HAZARD TERMS ACGIH - The American Conference of Governmental Industrial Hygienists consists of occupational safety and health professionals who recommend occupational exposure limits for many substances. Action Level - An OSHA concentration calculated as an 8-your time-weighted average, which initiates certain required activities such as exposure monitoring and medical surveillance. Acute Health Effect - A severe effect which occurs rapidly after a brief intense exposure to a substance. ANSI - American National Standards Institute is a private group that develops consensus standards. Acute toxicity -Acutely toxic substances cause adverse effects by any of the following exposure methods: 1. Oral or dermal administration of a single dose of a substance. 2. Multiple oral or dermal doses within a 24-hour period 3. An inhalation exposure of 4 hours. Asphyxiant - A chemical (gas or vapor) that can cause death or unconsciousness by suffocation. Aspiration hazard - A liquid or solid chemical that causes severe acute effects if it infiltrates into the trachea and lower respiratory tract. Possible effects include chemical pneumonia, pulmonary injury, or death Autoignition Temperature - The lowest temperature at which a substance will burst into flames without a source of ignition like a spark or flame. The lower the ignition temperature, the more likely the substance is going to be a fire hazard. Boiling Point - The temperature of a liquid at which its vapor pressure is equal to the gas pressure over it. With added energy, all of the liquid could become vapor. Boiling occurs when the liquid's vapor pressure is just higher than the pressure over it. Carcinogen - A substance that causes cancer in humans or, because it has produced cancer in animals, is considered capable of causing cancer in humans.