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RANDY SCHEKMAN Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, USA
GENES AND PROTEINS THAT CONTROL THE SECRETORY PATHWAY Nobel Lecture, 7 December 2013 by RANDY SCHEKMAN Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, USA. Introduction George Palade shared the 1974 Nobel Prize with Albert Claude and Christian de Duve for their pioneering work in the characterization of organelles interrelated by the process of secretion in mammalian cells and tissues. These three scholars established the modern field of cell biology and the tools of cell fractionation and thin section transmission electron microscopy. It was Palade’s genius in particular that revealed the organization of the secretory pathway. He discovered the ribosome and showed that it was poised on the surface of the endoplasmic reticulum (ER) where it engaged in the vectorial translocation of newly synthesized secretory polypeptides (1). And in a most elegant and technically challenging investigation, his group employed radioactive amino acids in a pulse-chase regimen to show by autoradiograpic exposure of thin sections on a photographic emulsion that secretory proteins progress in sequence from the ER through the Golgi apparatus into secretory granules, which then discharge their cargo by membrane fusion at the cell surface (1). He documented the role of vesicles as carriers of cargo between compartments and he formulated the hypothesis that membranes template their own production rather than form by a process of de novo biogenesis (1). As a university student I was ignorant of the important developments in cell biology; however, I learned of Palade’s work during my first year of graduate school in the Stanford biochemistry department. -
Richard Doll
2825 Obituary: Richard Doll Sir Richard Doll died earlier this year at age 92. The most The studies by Doll are bold and original science. They celebrated epidemiologist of the 20th century, Doll is best represent an important part of the foundation of modern known for his work on smoking and lung cancer, but there was population-based chronic disease research. By the early 1960s, so much more to his career. they constituted adequate evidence for public health action to His father was a general practitioner in London, and it was reduce tobacco smoking; in 1964, the U.S. Surgeon General’s from St. Thomas’s that Doll himself graduated in Medicine in first report on the adverse health consequences of tobacco was 1937. Even as a student, he showed his interest in epidemi- published. Today, they continue to remind us how carefully ologic and statistical tools, publishing on the need for proper crafted observational studies can advance scientific knowledge analysis and statistical testing in population studies of disease. regarding social and health issues that are not amenable to Later, Doll served in the Royal Medical Corps in France and experimentation on human populations. the Middle East throughout the Second World War. He began Asbestos. By the early 1930s, work in the asbestos products his research career at the Middlesex Hospital, studying industry in Britain was known to increase the risk of a occupational factors in the development of peptic ulceration. sometimes fatal nonmalignant pulmonary disease, termed He married Dr. Joan Faulkner around this time, and it was she asbestosis. -
A Short History of DNA Technology 1865 - Gregor Mendel the Father of Genetics
A Short History of DNA Technology 1865 - Gregor Mendel The Father of Genetics The Augustinian monastery in old Brno, Moravia 1865 - Gregor Mendel • Law of Segregation • Law of Independent Assortment • Law of Dominance 1865 1915 - T.H. Morgan Genetics of Drosophila • Short generation time • Easy to maintain • Only 4 pairs of chromosomes 1865 1915 - T.H. Morgan •Genes located on chromosomes •Sex-linked inheritance wild type mutant •Gene linkage 0 •Recombination long aristae short aristae •Genetic mapping gray black body 48.5 body (cross-over maps) 57.5 red eyes cinnabar eyes 67.0 normal wings vestigial wings 104.5 red eyes brown eyes 1865 1928 - Frederick Griffith “Rough” colonies “Smooth” colonies Transformation of Streptococcus pneumoniae Living Living Heat killed Heat killed S cells mixed S cells R cells S cells with living R cells capsule Living S cells in blood Bacterial sample from dead mouse Strain Injection Results 1865 Beadle & Tatum - 1941 One Gene - One Enzyme Hypothesis Neurospora crassa Ascus Ascospores placed X-rays Fruiting on complete body medium All grow Minimal + amino acids No growth Minimal Minimal + vitamins in mutants Fragments placed on minimal medium Minimal plus: Mutant deficient in enzyme that synthesizes arginine Cys Glu Arg Lys His 1865 Beadle & Tatum - 1941 Gene A Gene B Gene C Minimal Medium + Citruline + Arginine + Ornithine Wild type PrecursorEnz A OrnithineEnz B CitrulineEnz C Arginine Metabolic block Class I Precursor OrnithineEnz B CitrulineEnz C Arginine Mutants Class II Mutants PrecursorEnz A Ornithine -
Sir Richard Doll, Epidemiologist – a Personal Reminiscence with a Selected Bibliography
British Journal of Cancer (2005) 93, 963 – 966 & 2005 Cancer Research UK All rights reserved 0007 – 0920/05 $30.00 www.bjcancer.com Obituary Sir Richard Doll, epidemiologist – a personal reminiscence with a selected bibliography The death of Richard Doll on 24 July 2005 at the age of 92 after a short illness ended an extraordinarily productive life in science for which he received widespread recognition, including Fellowship of The Royal Society (1966), Knighthood (1971), Companionship of Honour (1996), and many honorary degrees and prizes. He is unique, however, in having seen both universal acceptance of his work demonstrating smoking as the main cause of the most common fatal cancer in the world and the relative success of strategies to reduce the prevalence of the habit. In 1950, 80% of the men in Britain smoked but this has now declined to less than 30%. Richard Doll qualified in medicine at St Thomas’ Hospital in 1937, but his epidemiological career began after service in the Second World War when he worked with Francis Avery Jones at the Central Middlesex Hospital on occupational factors in the aetiology of peptic ulceration. The completeness of Doll’s tracing of previously surveyed men so impressed Tony Bradford Hill that he offered him a post in the MRC Statistical Research Unit to investigate the causes of lung cancer. For the representations of Percy Stocks (Chief Medical Officer to the Registrar General) and Sir Ernest Kennaway had prevailed against the then commonly held view that the marked rise in lung cancer deaths in Britain since 1900 was due only to improved diagnosis. -
Understanding Genetics: DNA, Genes, and Their Real-World Applications Parts I & II Professor David Sadava
Understanding Genetics: DNA, Genes, and Their Real-World Applications Parts I & II Professor David Sadava THE TEACHING COMPANY ® Table of Contents Understanding Genetics: DNA, Genes, and Their Real-World Applications Professor Biography..............................................................................................................................................iii Course Scope...........................................................................................................................................................1 Lecture One Our Inheritance...................................................................................................................................2 Lecture Two Mendel and Genes..............................................................................................................................4 Lecture Three Genes and Chromosomes................................................................................................................7 Lecture Four The Search for the Gene—DNA.......................................................................................................9 Lecture Five DNA Structure and Replication.......................................................................................................12 Lecture Six DNA Expression in Proteins..............................................................................................................14 Lecture Seven Genes, Enzymes, and Metabolism.................................................................................................17 -
Article the Effect of Lowering LDL Cholesterol on Vascular
Article The Effect of Lowering LDL Cholesterol on Vascular Access Patency: Post Hoc Analysis of the Study of Heart and Renal Protection William Herrington, Jonathan Emberson, Natalie Staplin, Lisa Blackwell, Bengt Fellstro¨m, Robert Walker, Adeera Levin, Lai Seong Hooi, Ziad A. Massy, Vladimir Tesar, Christina Reith, Richard Haynes, Colin Baigent, and Martin J. Landray on behalf of the SHARP Investigators Due to the number of contributing authors, Abstract the affiliations are Background and objectives Reducing LDL cholesterol (LDL-C) with statin-based therapy reduces the risk of provided in the major atherosclerotic events among patients with CKD, including dialysis patients, but the effect of lowering Supplemental LDL-C on vascular access patency is unclear. Material. Design, setting, participants, & measurements The Study of Heart and Renal Protection (SHARP) randomized Correspondence: Dr. Martin J. Landray, patients with CKD to 20 mg simvastatin plus 10 mg ezetimibe daily versus matching placebo. This study aimed to Clinical Trial Service explore the effects of treatment on vascular access occlusive events, defined as any access revision procedure, Unit and access thrombosis, removal of an old dialysis access, or formation of new permanent dialysis access. Epidemiological Studies Unit, Nuffield Results Among 2353 SHARP participants who had functioning vascular access at randomization, allocation to Department of Population Health, simvastatin plus ezetimibe resulted in a 13% proportional reduction in vascular access occlusive events (355 Richard Doll Building, [29.7%] for simvastatin/ezetimibe versus 388 [33.5%] for placebo; risk ratio [RR], 0.87; 95% confidence interval Old Road Campus, [95% CI], 0.75 to 1.00; P=0.05). -
Humankind 2.0: the Technologies of the Future 6. Biotech
Humankind 2.0: The Technologies of the Future 6. Biotech Piero Scaruffi, 2017 See http://www.scaruffi.com/singular/human20.html for the full text of this discussion A brief History of Biotech 1953: Discovery of the structure of the DNA 2 A brief History of Biotech 1969: Jon Beckwith isolates a gene 1973: Stanley Cohen and Herbert Boyer create the first recombinant DNA organism 1974: Waclaw Szybalski coins the term "synthetic biology” 1975: Paul Berg organizes the Asilomar conference on recombinant DNA 3 A brief History of Biotech 1976: Genentech is founded 1977: Fred Sanger invents a method for rapid DNA sequencing and publishes the first full DNA genome of a living being Janet Rossant creates a chimera combining two mice species 1980: Genentech’s IPO, first biotech IPO 4 A brief History of Biotech 1982: The first biotech drug, Humulin, is approved for sale (Eli Lilly + Genentech) 1983: Kary Mullis invents the polymerase chain reaction (PCR) for copying genes 1986: Leroy Hood invents a way to automate gene sequencing 1986: Mario Capecchi performs gene editing on a mouse 1990: William French Anderson’s gene therapy 1990: First baby born via PGD (Alan Handyside’s lab) 5 A brief History of Biotech 1994: FlavrSavr Tomato 1994: Maria Jasin’s homing endonucleases for genome editing 1996: Srinivasan Chandrasegaran’s ZFN method for genome editing 1996: Ian Wilmut clones the first mammal, the sheep Dolly 1997: Dennis Lo detects fetal DNA in the mother’s blood 2000: George Davey Smith introduces Mendelian randomization 6 A brief History of Biotech -
Guide to Biotechnology 2008
guide to biotechnology 2008 research & development health bioethics innovate industrial & environmental food & agriculture biodefense Biotechnology Industry Organization 1201 Maryland Avenue, SW imagine Suite 900 Washington, DC 20024 intellectual property 202.962.9200 (phone) 202.488.6301 (fax) bio.org inform bio.org The Guide to Biotechnology is compiled by the Biotechnology Industry Organization (BIO) Editors Roxanna Guilford-Blake Debbie Strickland Contributors BIO Staff table of Contents Biotechnology: A Collection of Technologies 1 Regenerative Medicine ................................................. 36 What Is Biotechnology? .................................................. 1 Vaccines ....................................................................... 37 Cells and Biological Molecules ........................................ 1 Plant-Made Pharmaceuticals ........................................ 37 Therapeutic Development Overview .............................. 38 Biotechnology Industry Facts 2 Market Capitalization, 1994–2006 .................................. 3 Agricultural Production Applications 41 U.S. Biotech Industry Statistics: 1995–2006 ................... 3 Crop Biotechnology ...................................................... 41 U.S. Public Companies by Region, 2006 ........................ 4 Forest Biotechnology .................................................... 44 Total Financing, 1998–2007 (in billions of U.S. dollars) .... 4 Animal Biotechnology ................................................... 45 Biotech -
Documenting the Biotechnology Industry in the San Francisco Bay Area
Documenting the Biotechnology Industry In the San Francisco Bay Area Robin L. Chandler Head, Archives and Special Collections UCSF Library and Center for Knowledge Management 1997 1 Table of Contents Project Goals……………………………………………………………………….p. 3 Participants Interviewed………………………………………………………….p. 4 I. Documenting Biotechnology in the San Francisco Bay Area……………..p. 5 The Emergence of An Industry Developments at the University of California since the mid-1970s Developments in Biotech Companies since mid-1970s Collaborations between Universities and Biotech Companies University Training Programs Preparing Students for Careers in the Biotechnology Industry II. Appraisal Guidelines for Records Generated by Scientists in the University and the Biotechnology Industry………………………. p. 33 Why Preserve the Records of Biotechnology? Research Records to Preserve Records Management at the University of California Records Keeping at Biotech Companies III. Collecting and Preserving Records in Biotechnology…………………….p. 48 Potential Users of Biotechnology Archives Approaches to Documenting the Field of Biotechnology Project Recommendations 2 Project Goals The University of California, San Francisco (UCSF) Library & Center for Knowledge Management and the Bancroft Library at the University of California, Berkeley (UCB) are collaborating in a year-long project beginning in December 1996 to document the impact of biotechnology in the Bay Area. The collaborative effort is focused upon the development of an archival collecting model for the field of biotechnology to acquire original papers, manuscripts and records from selected individuals, organizations and corporations as well as coordinating with the effort to capture oral history interviews with many biotechnology pioneers. This project combines the strengths of the existing UCSF Biotechnology Archives and the UCB Program in the History of the Biological Sciences and Biotechnology and will contribute to an overall picture of the growth and impact of biotechnology in the Bay Area. -
The Impact of NMR and MRI
WELLCOME WITNESSES TO TWENTIETH CENTURY MEDICINE _____________________________________________________________________________ MAKING THE HUMAN BODY TRANSPARENT: THE IMPACT OF NUCLEAR MAGNETIC RESONANCE AND MAGNETIC RESONANCE IMAGING _________________________________________________ RESEARCH IN GENERAL PRACTICE __________________________________ DRUGS IN PSYCHIATRIC PRACTICE ______________________ THE MRC COMMON COLD UNIT ____________________________________ WITNESS SEMINAR TRANSCRIPTS EDITED BY: E M TANSEY D A CHRISTIE L A REYNOLDS Volume Two – September 1998 ©The Trustee of the Wellcome Trust, London, 1998 First published by the Wellcome Trust, 1998 Occasional Publication no. 6, 1998 The Wellcome Trust is a registered charity, no. 210183. ISBN 978 186983 539 1 All volumes are freely available online at www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/ Please cite as : Tansey E M, Christie D A, Reynolds L A. (eds) (1998) Wellcome Witnesses to Twentieth Century Medicine, vol. 2. London: Wellcome Trust. Key Front cover photographs, L to R from the top: Professor Sir Godfrey Hounsfield, speaking (NMR) Professor Robert Steiner, Professor Sir Martin Wood, Professor Sir Rex Richards (NMR) Dr Alan Broadhurst, Dr David Healy (Psy) Dr James Lovelock, Mrs Betty Porterfield (CCU) Professor Alec Jenner (Psy) Professor David Hannay (GPs) Dr Donna Chaproniere (CCU) Professor Merton Sandler (Psy) Professor George Radda (NMR) Mr Keith (Tom) Thompson (CCU) Back cover photographs, L to R, from the top: Professor Hannah Steinberg, Professor -
How Old Is Biotechnology? the Word Biotechnology Can Be Traced to 1917, When It Was Used to Refer to a Large-Scale Production of Materials from Microbes Grown in Vats
How Old Is Biotechnology? The word biotechnology can be traced to 1917, when it was used to refer to a large-scale production of materials from microbes grown in vats. But the roots of the technology are as familiar and as ancient as baking yeast breads - traceable back 6,000 years. • 4000 BC: Classical biotechnology: Dairy farming develops in the Middle East; Egyptians use yeasts to bake leavened bread and to make wine. • 3000 BC: Peruvians select and cultivate potatoes. • 2000 BC: Egyptians, Sumerians and Chinese develop techniques of fermentation, brewing and cheese-making. • 500 BC: Mediterraneans develop marinating and Europeans develop salting, which leads to curing and pickling to flavor and preserve food. • 1500 AD: Acidic cooking techniques lead to sauerkraut and yogurt - two examples of using beneficial bacteria to flavor and preserve food. Aztecs make cakes from Spirulina algae. How Old Is Biotechnology? (continued) • 1859: On the Origin of Species - English naturalist Charles Darwin's theory of evolution - is published in London. • 1861: French chemist Louis Pasteur develops pasteurization - preserving food by heating it to destroy harmful microbes. • 1865: Austrian botanist and monk Gregor Mendel describes his experiments in heredity, founding the field of genetics. • 1879: William James Beal develops the first experimental hybrid corn • 1910: American biologist Thomas Hunt Morgan discovers that genes are located on chromosomes. • 1928: F. Griffith discovers genetic transformation - genes can transfer from one strain of bacteria to another. • 1941: Danish microbiologist A. Jost coins the term genetic engineering in a lecture on sexual reproduction in yeast. How Old Is Biotechnology? (continued) • 1943: Oswald Avery, Colin MacLead and Maclyn McCarty use bacteria to show that DNA carries the cell's genetic information. -
Downloaded From
A Thesis Submitted for the Degree of PhD at the University of Warwick Permanent WRAP URL: http://wrap.warwick.ac.uk/149337 Copyright and reuse: This thesis is made available online and is protected by original copyright. Please scroll down to view the document itself. Please refer to the repository record for this item for information to help you to cite it. Our policy information is available from the repository home page. For more information, please contact the WRAP Team at: [email protected] warwick.ac.uk/lib-publications A Randomized Trial of Neprilysin Inhibition with Sacubitril/valsartan vs Irbesartan in Chronic Kidney Disease by Dr Parminder Kaur Judge Thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy (PhD) in Medicine University of Warwick & Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford Submitted June 2020 1 Contents Section Page List of Tables 7 List of Figures 9 Acknowledgements 10 Declarations 12 Inclusion of Published Work 13 Abstract 14 Chapters 1 List of abbreviations 15 2 Introduction 19 3 Natriuretic peptide system and neprilysin 35 2 4 Angiotensin receptor-neprilysin inhibitor (ARNI) 46 Effects on renal function 50 Effects on albuminuria 53 5 Methods 65 Trial organisation 70 Staff training 70 Data management 70 Trial treatments 70 Consent 72 Biological samples 73 Randomized treatment and blinding 76 Blood and urine samples 76 3 Adverse events and compliance with trial treatment 77 Physical measurements