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Differential Synergy of Notch and T Cell Receptor Signaling Determines Αβ
ARTICLE Diff erential synergy of Notch and T cell receptor signaling determines αβ versus γδ lineage fate Annette I. Garbe,1 Andreas Krueger,1 Fotini Gounari,1,2 Juan Carlos Zúñiga-Pfl ücker,3 and Harald von Boehmer1 1Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 2Tufts-New England Medical Center, Boston, MA 02111 3University of Toronto, Toronto, Ontario, M4N 3M5 Canada Thymic precursors expressing the pre–T cell receptor (TCR), the TCR, or the TCR can all enter the CD4+8+ lineage, albeit with different effi cacy. Here it is shown that proliferation and differentiation of precursors with the different TCRs into lineage cells require Notch signaling at the DN3 stage of thymic development. At the DN4 stage, Notch signaling still signifi cantly contributes to the generation of T cells. In particular, in lineage commitment, the pre-TCR synergizes more effi ciently with Notch signals than the other two TCRs, whereas TCR-expressing cells can survive and expand in the absence of Notch signals, even though Notch signaling enhances their proliferation. These observations suggest a new model of versus lineage choice in which lineage fate is determined by the extent of synergy between TCR and Notch signaling and in which the evolutionarily recent advent of the cell-autonomously signaling pre-TCR increased the effi cacy of T cell generation. CORRESPONDENCE The mammalian immune system contains sev- essential for the rescue of DP cells from pro- Harald von Boehmer: eral T lymphocyte lineages of which the grammed cell -
Nobel Prizes in Physiology Or Medicine with an Emphasis on Bacteriology
J Med Bacteriol. Vol. 8, No. 3, 4 (2019): pp.49-57 jmb.tums.ac.ir Journal of Medical Bacteriology Nobel Prizes in Physiology or Medicine with an Emphasis on Bacteriology 1 1 2 Hamid Hakimi , Ebrahim Rezazadeh Zarandi , Siavash Assar , Omid Rezahosseini 3, Sepideh Assar 4, Roya Sadr-Mohammadi 5, Sahar Assar 6, Shokrollah Assar 7* 1 Department of Microbiology, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. 2 Department of Anesthesiology, Medical School, Kerman University of Medical Sciences, Kerman, Iran. 3 Department of Infectious and Tropical Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. 4 Department of Pathology, Dental School, Shiraz University of Medical Sciences, Shiraz, Iran. 5 Dental School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. 6 Dental School, Shiraz University of Medical Sciences, Shiraz, Iran. 7 Department of Microbiology and Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. ARTICLE INFO ABSTRACT Article type: Background: Knowledge is an ocean without bound or shore, the seeker of knowledge is (like) the Review Article diver in those seas. Even if his life is a thousand years, he will never stop searching. This is the result Article history: of reflection in the book of development. Human beings are free and, to some extent, have the right to Received: 02 Feb 2019 choose, on the other hand, they are spiritually oriented and innovative, and for this reason, the new Revised: 28 Mar 2019 discovery and creativity are felt. This characteristic, which is in the nature of human beings, can be a Accepted: 06 May 2019 motive for the revision of life and its tools and products. -
REVIEW Modern Japanese Medical History and the European In¯Uence
REVIEW Modern Japanese medical history and the European in¯uence Yoshio Izumi and Kazuo Isozumi1 Department of Neurology, Tokai University School of Medicine, Kanagawa 1 Department of Neurology, Ashikaga Red Cross Hospital, Tochigi, Japan (Received for publication on January 19, 2001) Abstract. Before the ®rst European visited Japan in 1549, traditional Chinese medicine was mainly employed in Japan. Francisco de Xavier, a missionary of the Society of Jesus, tried to promote the introduction of Christianity by providing a medical service for Japanese citizens. However, Japan implemented a national isolation policy in 1639 and cut off diplomatic relations with the rest of the world, except Holland and China. For over 200 years, until the American admiral Matthew Perry forced Japan to open its doors in 1853, Japan learned about western medicine only from doctors of the Dutch merchants' of®ce or from Dutch medical books. After 1853, Western medicine was rapidly introduced into Japan, and great achievements by Japanese medical doctors soon followed, such as the serum therapy for tetanus, the discovery of the plague and dysentery bacilli, the invention of Salvarsan for the treatment of syphilis, and the demonstration of the neurosyphilis spirochete. (KeioJMed50(2): 91±99, June 2001) Key words: Kaitai-Shinsho, Seishu Hanaoka, Siebold, Pompe, Shibasaburo Kitasato Xavier's Visit to Japan and Obtaining the permission of the feudal lord of Satsuma, ``Southern Barbarian Style Surgery'' Shimazu, he engaged in missionary work in the western parts of Japan. According to the record of Nippon- The God of medicine in Europe is Asclepius, but the Seikyo-Shi (History of Western Religion in Japan), person honored as the founder of medicine is Hippo- Xavier nursed sick persons during his missionary work. -
Deciphering Thymic Development
View metadata, citation and similar papers at core.ac.uk brought to you by CORE OPINION ARTICLE published: 08provided October by 2014 Frontiers - Publisher Connector doi: 10.3389/fimmu.2014.00424 Deciphering thymic development Harald Von Boehmer 1,2* 1 Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA 2 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA *Correspondence: [email protected] Edited by: Kendall A. Smith, Weill Medical College of Cornell University, USA Reviewed by: Herman Waldmann, University of Oxford, UK Keywords: MHC-restricted antigen recognition, T cell clones, TCR alpha/beta cDNA clones, HY antigen, TCR transgenic mice, negative thymic selection, positive thymic selection In 1979, some of us were surprised by beta genes from one T cell clone to asked Hans Georg Rammensee who was the (1) conclusion of Doherty and Zinker- another allowed us to unequivocally con- in the same office a related question. I nagel on MHC-restricted antigen recogni- clude that the MHC-restricted specificity leave it to the audience to imagine what tion following the lead of Katz, Hamaoka, was encoded by a single receptor long Michael Steinmetz told Georges Koehler and Benacerraf (2) describing the same before crystallographic studies reached or better what he did not tell him, even for the interaction of T helper cells with the same conclusion (5). This surprised though one cannot be completely sure of B cells as well as Rosenthal and Shevach some molecular biologists somewhat who it. So Georges did not produce the mice (3) describing it for the interaction of T thought that the cloning of the TCR put but Anton Berns in Amsterdam cooper- cells with macrophages. -
EDITORIAL Year's Comments for 2005
EDITORIAL INTERNATIONAL MICROBIOLOGY (2005) 8:231-234 Year’s comments for 2005 Ricardo Guerrero Editor-in-Chief, INT. MICROBIOL. E-mail: [email protected] For several years, new sequences of microbial genomes have dogma. Conclusive evidence for a pathogenic role of H. pylori been the highlights of microbiology and a major topic of our came from trials showing that elimination of the bacterium dra- yearly comments. But sequencing has become “routine” and, at matically changed the clinical course of ulcer. This finding was the time this editorial is being written, the complete sequences confirmed by Marshall, who swallowed a broth of H. pylori and of 284 prokaryotic genomes and 40 eukaryotic genomes have soon thereafter developed gastritis, the prelude to ulcers. He been published. This allows us to focus our comments on those recovered from the disease after treatment with antibiotics. events from 2005 that have attracted the attention of both (Warren could not join him in the experiment because he already researchers and the media. These include the Nobel Prize in suffered from peptic ulcer.) Subsequently, the two investigators Physiology or Medicine, which was awarded for the discovery successfully treated other people suffering from ulcers, in the of the role of Helicobacter pylori as the causal agent of gastric process clearly identifying the bacterium as the culprit. In 1994, ulcers; the worldwide effort to fight malaria, a disease that main- H. pylori was the first bacterium, and the second infectious ly affects developing countries; and the global spread of avian organism after hepatitis B virus, to be classified as a class I car- influenza, which is becoming a panzootic. -
ILAE Historical Wall02.Indd 10 6/12/09 12:04:44 PM
2000–2009 2001 2002 2003 2005 2006 2007 2008 Tim Hunt Robert Horvitz Sir Peter Mansfi eld Barry Marshall Craig Mello Oliver Smithies Luc Montagnier 2000 2000 2001 2002 2004 2005 2007 2008 Arvid Carlsson Eric Kandel Sir Paul Nurse John Sulston Richard Axel Robin Warren Mario Capecchi Harald zur Hauser Nobel Prizes 2000000 2001001 2002002 2003003 200404 2006006 2007007 2008008 Paul Greengard Leland Hartwell Sydney Brenner Paul Lauterbur Linda Buck Andrew Fire Sir Martin Evans Françoise Barré-Sinoussi in Medicine and Physiology 2000 1st Congress of the Latin American Region – in Santiago 2005 ILAE archives moved to Zurich to become publicly available 2000 Zonismide licensed for epilepsy in the US and indexed 2001 Epilepsia changes publishers – to Blackwell 2005 26th International Epilepsy Congress – 2001 Epilepsia introduces on–line submission and reviewing in Paris with 5060 delegates 2001 24th International Epilepsy Congress – in Buenos Aires 2005 Bangladesh, China, Costa Rica, Cyprus, Kazakhstan, Nicaragua, Pakistan, 2001 Launch of phase 2 of the Global Campaign Against Epilepsy Singapore and the United Arab Emirates join the ILAE in Geneva 2005 Epilepsy Atlas published under the auspices of the Global 2001 Albania, Armenia, Arzerbaijan, Estonia, Honduras, Jamaica, Campaign Against Epilepsy Kyrgyzstan, Iraq, Lebanon, Malta, Malaysia, Nepal , Paraguay, Philippines, Qatar, Senegal, Syria, South Korea and Zimbabwe 2006 1st regional vice–president is elected – from the Asian and join the ILAE, making a total of 81 chapters Oceanian Region -
Of Rabbits and Men: the Tale of Paul Ehrlich in Our Modern World Of
Of Rabbits and Men: The Tale of Paul Ehrlich In our modern world of chemotherapy, antibiotics and antivirals, it might come as a surprise to find that the origin of all these treatments can be traced back to rabbits; the cute and fluffy kind. To understand why, we need to go all the way back to 1882 Berlin. A talented, if aimless, young German doctor, Paul Ehrlich, had just met the great microbiologist Robert Koch. Koch was giving a lecture in which he identified the pathogen responsible for tuberculosis. Ehrlich was instantly fascinated by Koch and microbiology. Unknown to himself, he had just taken the first step on a path that would help change the way disease is tackled forever1. The late 1800’s were a time of dynamic change in the sciences. Charles Darwin had proposed his Theory of Natural Selection and Thomas Edison had given us the light bulb. Amongst the many fashionable topics of the time, some biologists were fascinated by dyes; specifically the staining of living tissue. Spending all day bent over a microscope looking at the pretty colours might not seem like worthwhile science by modern standards, but these dyes had interesting properties. Dyes displayed a high level of specificity; they would only stain certain structures and pass through others. Ehrlich noticed this and soon started to think of applications for these properties. These were times when catching a chill could kill. Many well-known individuals of the time were killed in their prime due to infectious disease. Emily Brontë died from tuberculosis2, René Descartes from pneumonia3 and Pyotr Tchaikovsky died from cholera4. -
Table of Contents
Cancer Immunology Research Table of Contents July 2014 Volume 2 Issue 7 EDITORIAL RESEARCH ARTICLES 591 Cancer Immunology Research: A One-Year 616 Immunotherapy Converts Nonimmunogenic Anniversary Pancreatic Tumors into Immunogenic Foci of Immune Regulation Eric R. Lutz, Annie A. Wu, Elaine Bigelow, Rajni Sharma, Guanglan Mo, Kevin Soares, Sara Solt, MASTERS OF IMMUNOLOGY Alvin Dorman, Anthony Wamwea, Allison Yager, Daniel Laheru, Christopher L. Wolfgang, 592 The Thymus in Immunity and in Malignancy Jiang Wang, Ralph H. Hruban, Robert A. Anders, Harald von Boehmer Elizabeth M. Jaffee, and Lei Zheng Synopsis: Lutz and colleagues show that an allogeneic vaccine given with or without low-dose cyclophosphamide converted pancreatic cancer into an immunogenic cancer CANCER IMMUNOLOGY AT THE with infiltrating effector lymphocytes and formation of CROSSROADS: EXPERIMENTAL tertiary lymphoid aggregates that are regulatory structures IMMUNOTHERAPIES of adaptive immunity. 632 598 Hostile, Hypoxia–A2-Adenosinergic Tumor Bevacizumab plus Ipilimumab in Patients with Biology as the Next Barrier to Overcome for Metastatic Melanoma Tumor Immunologists F. Stephen Hodi, Donald Lawrence, Cecilia Lezcano, Xinqi Wu, Jun Zhou, Tetsuro Sasada, Wanyong Zeng, Michail V. Sitkovsky, Stephen Hatfield, Anita Giobbie-Hurder, Michael B. Atkins, Robert Abbott, Bryan Belikoff, Dmitriy Lukashev, Nageatte Ibrahim, Philip Friedlander, and Akio Ohta Keith T. Flaherty, George F. Murphy, Scott Rodig, Elsa F. Velazquez, Martin C. Mihm Jr, Sara Russell, MILESTONES IN CANCER -
Syphilis - Its Early History and Treatment Until Penicillin, and the Debate on Its Origins
History Syphilis - Its Early History and Treatment Until Penicillin, and the Debate on its Origins John Frith, RFD Introduction well as other factors such as education, prophylaxis, training of health personnel and adequate and rapid “If I were asked which is the most access to treatment. destructive of all diseases I should unhesitatingly reply, it is that which Up until the early 20th century it was believed that for some years has been raging with syphilis had been brought from America and the New impunity ... What contagion does World to the Old World by Christopher Columbus in thus invade the whole body, so much 1493. In 1934 a new hypothesis was put forward, resist medical art, becomes inoculated that syphilis had previously existed in the Old World so readily, and so cruelly tortures the before Columbus. I In the 1980’s palaeopathological patient ?” Desiderius Erasmus, 1520.1 studies found possible evidence that supported this hypothesis and that syphilis was an old treponeal In 1495 an epidemic of a new and terrible disease broke disease which in the late 15th century had suddenly out among the soldiers of Charles VIII of France when evolved to become different and more virulent. Some he invaded Naples in the first of the Italian Wars, and recent studies however have indicated that this is not its subsequent impact on the peoples of Europe was the case and it still may be a new epidemic venereal devastating – this was syphilis, or grande verole, the disease introduced by Columbus from America. “great pox”. Although it didn’t have the horrendous mortality of the bubonic plague, its symptoms were The first epidemic of the ‘Disease of Naples’ or the painful and repulsive – the appearance of genital ‘French disease’ in Naples 1495 sores, followed by foul abscesses and ulcers over the rest of the body and severe pains. -
Managing Complex Systems 9-13 June 2014
Managing Complex Systems 9-13 June 2014 CONFERENCE COMMITTEE Founding Chair Publications Chair Mo Jamshidi – University of Texas, USA Tim Ferris – University of South Australia, Australia Conference General Co-Chairs Military Liaison Stephen Cook – University of South Australia, Australia Anne-Marie Grisogono - DSTO Vernon Ireland – University of Adelaide, Australia Asia & Pacific Liaisons Program Co-Chairs Saeid Nahavandi – Deakin University, Australia Quoc Do – Frazer Nash, Australia Bob Cavana – Victoria University, NZ Alex Gorod – University of Adelaide, Australia Fei- Yue Wang – Chinese Academy of Sciences, China Ramakrishnan Raman – Honeywell, India Tutorial and Organised Sessions Chair: Yeo Tat Soon, National University of Singapore, Singapore Matthew Joordens – Deakin University, Australia Tim Ferris – University of South Australia, Australia Europe Liaison Michael Henshaw – Loughborough University, UK Special Sessions Chair Roberto Sacile – University of Genova, Italy Saeid Nahavandi – Deakin University, Australia Abdelmadjid Bouabdallah, Technical University of Compiegne, France Mikhail Belov – IBS, Russia Local Arrangements Chair Daniel Drob – Ecole Polytechnique, France Jaci Pratt – DSTO, Australia US Liaison Alex Gorod – University of Adelaide, Australia Industrial Liaisons Mo Jamshidi – University of Texas San Antonio, USA Garry Roedler – Lockheed Martin Corp, USA Paul Rad – Rackspace Open Cloud Company, USA IT Chair Saeid Nahavandi – Deakin University, Australia William Scott – University of South Australia, Australia See -
The Winners'guide to the Nobel Prize
The Winners’Guide to the Nobel Prize TEACHERS NOTES Prepared by Cris Kennedy THE WINNERS’ GUIDE TO THE NOBEL PRIZE TEACHERS Notes PAGE 1 Synopsis What does it take to win a Nobel Prize? Guts? Brilliance? Eccentricity? This film travels behind the scenes of the world’s most prestigious prize and into the minds of two of the people who have reached this pinnacle of excellence. In the most isolated capital city in the world, Perth, Western Australia, two scientists are interrupted while enjoying their fish and chips lunch by a phone call from Stockholm, Sweden. They have just been informed that they have been awarded the 2005 Nobel Prize for Medicine and could they make it to the awards ceremony? Australian scientists Barry Marshall and Robin Warren journey to the prize-winners’ podium is more than just a trip to the opposite side of the world to sub-zero temperatures, cultural pomp and extreme Swedish scheduling—it has been a career of trial and error, endless research and Aussie-battler-style stubborn determination. Today, this odd couple of science travel the globe as heroes—ambassadors to the science world—but it was 23 years ago in a modest hospital laboratory in Perth, that Marshall and Warren discovered a bacterium that survived in the human stomach that they called Helicobacter pylori. They believed that this bacterium, not stress, caused gastritis and peptic stomach ulcers, much to the chagrin of the medical world, which at the time scorned them. After years of careful observation, luck and persistence, they finally had the breakthrough they needed, but not before Marshall infected himself, using his own body as a guinea pig to test their theory. -
Nobel Laureates with Their Contribution in Biomedical Engineering
NOBEL LAUREATES WITH THEIR CONTRIBUTION IN BIOMEDICAL ENGINEERING Nobel Prizes and Biomedical Engineering In the year 1901 Wilhelm Conrad Röntgen received Nobel Prize in recognition of the extraordinary services he has rendered by the discovery of the remarkable rays subsequently named after him. Röntgen is considered the father of diagnostic radiology, the medical specialty which uses imaging to diagnose disease. He was the first scientist to observe and record X-rays, first finding them on November 8, 1895. Radiography was the first medical imaging technology. He had been fiddling with a set of cathode ray instruments and was surprised to find a flickering image cast by his instruments separated from them by some W. C. Röntgenn distance. He knew that the image he saw was not being cast by the cathode rays (now known as beams of electrons) as they could not penetrate air for any significant distance. After some considerable investigation, he named the new rays "X" to indicate they were unknown. In the year 1903 Niels Ryberg Finsen received Nobel Prize in recognition of his contribution to the treatment of diseases, especially lupus vulgaris, with concentrated light radiation, whereby he has opened a new avenue for medical science. In beautiful but simple experiments Finsen demonstrated that the most refractive rays (he suggested as the “chemical rays”) from the sun or from an electric arc may have a stimulating effect on the tissues. If the irradiation is too strong, however, it may give rise to tissue damage, but this may to some extent be prevented by pigmentation of the skin as in the negro or in those much exposed to Niels Ryberg Finsen the sun.