A View from the 21St Century SUGGESTED READINGS 1
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High-Affinity Binding Sites for the Deformed Protein Are Required for the Function of an Autoregulatory Enhancer of the Deformed Gene
Downloaded from genesdev.cshlp.org on October 9, 2021 - Published by Cold Spring Harbor Laboratory Press High-affinity binding sites for the Deformed protein are required for the function of an autoregulatory enhancer of the Deformed gene Michael Regulski,*'^ Scott Dessain/ Nadine McGinnis/ and William McGinnis*'^ Departments of Biology' and Molecular Biophysics and Biochemistry^ Yale University, New Haven, Connecticut 06511 USA The homeotic selector gene Deformed [Dfd) is required to specify the identity of head segments during Drosophila development. Previous experiments have shown that for the Dfd segmental identity function to operate in epidermal cells, the Dfd gene must be persistently expressed. One mechanism that provides persistent embryonic expression of Dfd is an autoregulatory circuit. Here, we show that the control of this autoregulatory circuit is likely to be directly mediated by the binding of Dfd protein to an upstream enhancer in Dfd locus DNA. In a 25-kb region around the Dfd transcription unit, restriction fragments with the highest binding affinity for Dfd protein map within the limits of the upstream autoregulatory element at approximately -5 kb. A minimal autoregulatory element, within a 920-bp segment of upstream DNA, has four moderate- to high-affinity binding sites for Dfd protein, with the two highest affinity sites sharing an ATCATTA consensus sequence. Site-specific mutagenesis of these four sites results in an element that has low affinity for Dfd protein when assayed in vitro and is nonfunctional when assayed in embryos. \Key Words: Deformed; autoregulatory circuit; homeo domain, homeotic protein] Received October 26, 1990; revised version accepted December 13, 1990. -
Perspectives
Copyright 0 1994 by the Genetics Society of America Perspectives Anecdotal, Historical and Critical Commentaries on Genetics Edited by James F. Crow and William F. Dove A Century of Homeosis, A Decade of Homeoboxes William McGinnis Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114 NE hundred years ago, while the science of genet- ing mammals, and were proposed to encode DNA- 0 ics still existed only in the yellowing reprints of a binding homeodomainsbecause of a faint resemblance recently deceased Moravian abbot, WILLIAMBATESON to mating-type transcriptional regulatory proteins of (1894) coined the term homeosis to define a class of budding yeast and an even fainter resemblance to bac- biological variations in whichone elementof a segmen- terial helix-turn-helix transcriptional regulators. tally repeated array of organismal structures is trans- The initial stream of papers was a prelude to a flood formed toward the identity of another. After the redis- concerning homeobox genes and homeodomain pro- coveryof MENDEL’Sgenetic principles, BATESONand teins, a flood that has channeled into a steady river of others (reviewed in BATESON1909) realized that some homeo-publications, fed by many tributaries. A major examples of homeosis in floral organs and animal skel- reason for the continuing flow of studies is that many etons could be attributed to variation in genes. Soon groups, working on disparate lines of research, have thereafter, as the discipline of Drosophila genetics was found themselves swept up in the currents when they born and was evolving into a formidable intellectual found that their favorite protein contained one of the force enriching many biologicalsubjects, it gradually be- many subtypes of homeodomain. -
書 名 等 発行年 出版社 受賞年 備考 N1 Ueber Das Zustandekommen Der
書 名 等 発行年 出版社 受賞年 備考 Ueber das Zustandekommen der Diphtherie-immunitat und der Tetanus-Immunitat bei thieren / Emil Adolf N1 1890 Georg thieme 1901 von Behring N2 Diphtherie und tetanus immunitaet / Emil Adolf von Behring und Kitasato 19-- [Akitomo Matsuki] 1901 Malarial fever its cause, prevention and treatment containing full details for the use of travellers, University press of N3 1902 1902 sportsmen, soldiers, and residents in malarious places / by Ronald Ross liverpool Ueber die Anwendung von concentrirten chemischen Lichtstrahlen in der Medicin / von Prof. Dr. Niels N4 1899 F.C.W.Vogel 1903 Ryberg Finsen Mit 4 Abbildungen und 2 Tafeln Twenty-five years of objective study of the higher nervous activity (behaviour) of animals / Ivan N5 Petrovitch Pavlov ; translated and edited by W. Horsley Gantt ; with the collaboration of G. Volborth ; and c1928 International Publishing 1904 an introduction by Walter B. Cannon Conditioned reflexes : an investigation of the physiological activity of the cerebral cortex / by Ivan Oxford University N6 1927 1904 Petrovitch Pavlov ; translated and edited by G.V. Anrep Press N7 Die Ätiologie und die Bekämpfung der Tuberkulose / Robert Koch ; eingeleitet von M. Kirchner 1912 J.A.Barth 1905 N8 Neue Darstellung vom histologischen Bau des Centralnervensystems / von Santiago Ramón y Cajal 1893 Veit 1906 Traité des fiévres palustres : avec la description des microbes du paludisme / par Charles Louis Alphonse N9 1884 Octave Doin 1907 Laveran N10 Embryologie des Scorpions / von Ilya Ilyich Mechnikov 1870 Wilhelm Engelmann 1908 Immunität bei Infektionskrankheiten / Ilya Ilyich Mechnikov ; einzig autorisierte übersetzung von Julius N11 1902 Gustav Fischer 1908 Meyer Die experimentelle Chemotherapie der Spirillosen : Syphilis, Rückfallfieber, Hühnerspirillose, Frambösie / N12 1910 J.Springer 1908 von Paul Ehrlich und S. -
Genetic and Epigenetic Mechanisms of the Regulation of Mouse Embryonic Stem Cells Self-Renewal by the Pluripotency Transcription Factor Nanog
Genetic and epigenetic mechanisms of the regulation of mouse embryonic stem cells self-renewal by the pluripotency transcription factor Nanog Victor HEURTIER Thèse de doctorat de Biologie Dirigée par Pablo NAVARRO GIL Laboratoire Epigénétique des cellules souches – Institut Pasteur Sorbonne Université Ecole doctorale Complexité du Vivant (ED 515) Présentée et soutenue publiquement le 18/09/2018 Devant un jury composé de : Président : Pr MOUCHEL-VIELH Emmanuèle, Professeur Rapporteur : Dr SAVATIER Pierre, Directeur de Recherche Rapporteur : Dr RADA-IGLESIAS Alvaro, Chef d’équipe Examinateur : Dr AZUARA Veronique, Maître de conférences Examinateur : Dr PINSKAYA Marina, Maître de conférences Directeur de thèse : Dr NAVARRO GIL Pablo, Chef d’équipe Abstract Mouse embryonic stem (ES) cells are derived from the pre-implantation blastocyst and are able to maintain their pluripotent state through virtually limitless cell divisions in vitro. The study of the mechanisms regulating the specific features of ES cells led to the discovery of the transcription factors (TFs) governing their unique transcriptome. Among those TFs, Nanog plays a central role in the gene regulatory network that supports ES cells self-renewal. However, the molecular mechanisms by which Nanog exerts its functions are not fully elucidated. We adapted an inducible CRISPR activation (CRISPRa) system in mouse ES cells and demonstrated its functionality to stimulate transcription at endogenous loci. We then accurately determined the list of Nanog responsive genes using gain (CRISPRa cell line) and loss of function experiments and total RNA sequencing. Moreover, the DNA binding profiles of distinct pluripotency TFs were assessed genome-wide by chromatin immunoprecipitation (ChIP) and sequencing upon Nanog depletion and revealed the importance of the latter in the regulation of the pluripotency network activity at thousands of loci. -
Biochemistrystanford00kornrich.Pdf
University of California Berkeley Regional Oral History Office University of California The Bancroft Library Berkeley, California Program in the History of the Biosciences and Biotechnology Arthur Kornberg, M.D. BIOCHEMISTRY AT STANFORD, BIOTECHNOLOGY AT DNAX With an Introduction by Joshua Lederberg Interviews Conducted by Sally Smith Hughes, Ph.D. in 1997 Copyright 1998 by The Regents of the University of California Since 1954 the Regional Oral History Office has been interviewing leading participants in or well-placed witnesses to major events in the development of Northern California, the West, and the Nation. Oral history is a method of collecting historical information through tape-recorded interviews between a narrator with firsthand knowledge of historically significant events and a well- informed interviewer, with the goal of preserving substantive additions to the historical record. The tape recording is transcribed, lightly edited for continuity and clarity, and reviewed by the interviewee. The corrected manuscript is indexed, bound with photographs and illustrative materials, and placed in The Bancroft Library at the University of California, Berkeley, and in other research collections for scholarly use. Because it is primary material, oral history is not intended to present the final, verified, or complete narrative of events. It is a spoken account, offered by the interviewee in response to questioning, and as such it is reflective, partisan, deeply involved, and irreplaceable. ************************************ All uses of this manuscript are covered by a legal agreement between The Regents of the University of California and Arthur Kornberg, M.D., dated June 18, 1997. The manuscript is thereby made available for research purposes. All literary rights in the manuscript, including the right to publish, are reserved to The Bancroft Library of the University of California, Berkeley. -
Cancer-Milestones December 2020
www.nature.com/collections/cancer-milestones December 2020 Cancer Produced by: With support from: Nature Genetics and Nature Medicine Cancer MILESTONES S2 Foreword S3 Timeline S4 Routes to resistance S5 Tracking cancer in liquid biopsies S6 When cancer prevention went viral S7 A licence to kill S8 Sitting on the fence S9 Not a simple switch S10 Sequencing the secrets of the cancer genome S11 Unleashing the immune system against cancer S12 Engineering armed T cells for the fight S13 Oncohistones: epigenetic drivers of cancer S14 Tumour evolution: from linear paths to branched trees S15 Undruggable? Inconceivable S16 Good bacteria make for good cancer therapy S17 The AI revolution in cancer Credit: S.Fenwick/Springer Nature Limited CITING THE MILESTONES VISIT THE SUPPLEMENT ONLINE SUBSCRIPTIONS AND CUSTOMER SERVICES Nature Milestones in Cancer includes Milestone articles written The Nature Milestones in Cancer supplement can be found at Springer Nature, Subscriptions, by our editors and an online Collection of previously published www.nature.com/collections/cancer-milestones Cromwell Place, Hampshire International Business Park, material. To cite the full project, please use Nature Milestones: Lime Tree Way, Basingstoke, Cancer https://www.nature.com/collections/cancer-milestones CONTRIBUTING JOURNALS Hampshire RG24 8YJ, UK (2020). Should you wish to cite any of the individual Milestones, BMC Cancer, Nature, Nature Cancer, Nature Communications, Tel: +44 (0) 1256 329242 please list Author, A. Title. Nature Milestones: Cancer <Article URL> Nature Genetics, Nature Medicine, Nature Reviews Cancer, [email protected] (2020). For example, Milestone 1 is Valtierra, I. Routes to resistance. Nature Reviews Clinical Oncology, Nature Reviews Drug Discovery, Customer serviCes: www.nature.com/help Nature Milestones: Cancer https://www.nature.com/articles/ Nature Reviews Gastroenterology & Hepatology, d42859-020-00069-6 (2020). -
Understanding Biological Design from Synthetic Circuits
REVIEWS MODELLING Synthetic biology: understanding biological design from synthetic circuits Shankar Mukherji* and Alexander van Oudenaarden‡ Abstract | An important aim of synthetic biology is to uncover the design principles of natural biological systems through the rational design of gene and protein circuits. Here, we highlight how the process of engineering biological systems — from synthetic promoters to the control of cell–cell interactions — has contributed to our understanding of how endogenous systems are put together and function. Synthetic biological devices allow us to grasp intuitively the ranges of behaviour generated by simple biological circuits, such as linear cascades and interlocking feedback loops, as well as to exert control over natural processes, such as gene expression and population dynamics. 10–12 Modularity One of the most astounding findings of the Human potential clinical applications . In this Review, however, A property of a system such Genome Project was that our genome contains as many we focus on how synthetic circuits help us to under- that it can be broken down into genes as that of Drosophila melanogaster. This finding stand how natural biological systems are genetically discrete subparts that perform begged the question: how do you get one organism to assembled and how they operate in organisms from specific tasks independently of look like a fly and another like a human with the same microbes to mammalian cells. In this light, synthetic the other subparts. number of genes? One possibility is that the rich rep- circuits have been crucial as simplified test beds in Bioremediation ertoire of non-protein-coding sequences found in the which to refine our ideas of how similarly structured The treatment of pollution with genomes of complex organisms adds many new parts natural networks function, and they have served as microorganisms. -
2012 Annual Report
Memorial Sloan-Kettering Cancer Center 2012 ANNUAL REPORT A SHARED VISION A SINGULAR MISSION Nurse practitioner Naomi Cazeau, of the Adult Bone Marrow Transplant Service. PING CHI PHYSICIAN-SCIENTIST 10 STEPHEN SOLOMON ALEXANDER RUDENSKY INTERVENTIONAL IMMUNOLOGIST RADIOLOGIST 16 12 VIVIANE TABAR The clinicians and scientists of NEUROSURGEON Memorial Sloan-Kettering share a vision and 18 a singular mission — to conquer cancer. STEPHEN LONG STRUCTURAL BIOLOGIST They are experts united against a 20 SIMON POWELL complex disease. Each type of cancer R ADIATION ONCOLOGIST 24 ETHEL LAW is different, each tumor is unique. Set free NURSE PRACTITIONER in surroundings that invite the sharing of 26 ideas and resources, they attack the CHRISTINA LESLIE complexity of cancer from every angle COMPUTATIONAL BIOLOGIST and every discipline. 34 SCOTT ARMSTRONG PEDIATRIC ONCOLOGIST 30 TO JORGE REIS-FILHO EXPERIMENTAL PATHOLOGIST CONQUER 38 CANCER 04 Letter from the Chairman and the President A complete version of this report — 42 Statistical Profile which includes lists of our donors, 44 Financial Summary doctors, and scientists — 46 Boards of Overseers and Managers is available on our website at 49 The Campaign for Memorial Sloan-Kettering www.mskcc.org/annualreport. 4 5 Letter from the Chairman In 2012 the leadership of Memorial Sloan-Kettering endorsed Douglas A. Warner III These programmatic investments require leadership and and the President a $2.2 billion investment in a clinical expansion that will set vision. Our new Physician-in-Chief, José Baselga, joined the stage for a changing care paradigm into the next decade us on January 1, 2013. An internationally recognized and beyond. -
Philosophy in Biology and Medicine: Biological Individuality and Fetal Parthood, Part I
Oslo, Norway July 7–12, 2019 ISHP SS B BOOK OF ABSTRACTS 2 Index 11 Keynote lectures 17 Diverse format sessions 47 Traditional sessions 367 Individual papers 637 Mixed media and poster presentations A Aaby, Bendik Hellem, 369 Barbosa, Thiago Pinto, 82 Abbott, Jessica, 298 Barker, Matthew, 149 Abir-Am, Pnina Geraldine, 370 Barragán, Carlos Andrés, 391 D’Abramo, Flavio, 371 Battran, Martin, 158 Abrams, Marshall, 372 Bausman, William, 129, 135 Acerbi, Alberto, 156 Baxter, Janella, 56, 57 Ackert, Lloyd, 185 Bayir, Saliha, 536 Agiriano, Arantza Etxeberria, 374 Beasley, Charles, 392 Ahn, Soohyun, 148 Bechtel, William, 259 El Aichouchi, Adil, 375 Bedau, Mark, 393 Airoldi, Giorgio, 376 Ben-Shachar, Erela Teharlev, 395 Allchin, Douglas, 377 Beneduce, Chiara, 396 Allen, Gar, 328 Berry, Dominic, 56, 58 Almeida, Maria Strecht, 377 Bertoldi, Nicola, 397 Amann, Bernd, 40 Betzler, Riana, 398 Andersen, Holly, 19, 20 Bich, Leonardo, 41 Anderson, Gemma, 28 LeBihan, Soazig, 358 Angleraux, Caroline, 378 Birch, Jonathan, 22 Ankeny, Rachel A., 225 Bix, Amy Sue, 399 Anker, Peder, 230 Blais, Cédric, 401 Ardura, Adrian Cerda, 380 Blancke, Stefaan, 609 Armstrong-Ingram, Tiernan, 381 Blell, Mwenza, 488 Arnet, Evan, 383 Blute, Marion, 59, 62 Artiga, Marc, 383 Bognon-Küss, Cécilia, 23 Atanasova, Nina, 20, 21 Bokulich, Alisa, 616 Au, Yin Chung, 384 Bollhagen, Andrew, 402 DesAutels, Lane, 386 Bondarenko, Olesya, 403 Aylward, Alex, 109 Bonilla, Jorge Armando Romo, 404 B Baccelliere, Gabriel Vallejos, 387 Bonnin, Thomas, 405 Baedke, Jan, 49, 50 Boon, Mieke, 235 Baetu, -
POPPER's GEWÖHNUNGSTHEORIE ASSEMBLED and FACED with OTHER THEORIES of LEARNING1 Arne Friemuth Petersen2
POPPER’S GEWÖHNUNGSTHEORIE ASSEMBLED AND FACED WITH OTHER THEORIES OF LEARNING1 Arne Friemuth Petersen2 Former Professor of General Psychology University of Copenhagen Abstract. With the publication of Popper’s Frühe Schriften (2006), renewed possibilities for inquiring into the nature and scope of what may be termed simply ‘Popperian Psychology’ have arisen. For although Popper would never have claimed to develop such psychology there is, however, from his earliest to his last works, a wealth of recommendations as to how to come to grips with problems of the psyche without falling victim of inductivist and subjectivist psychology. The fact that most theories of learning, both traditional and modern, have remained inductivist, and therefore logically invalid, places Popper’s hypothetico- deductive approach to learning and the acquisition of knowledge among the most important conjectures in that entire domain, akin to Edelman’s biological theory of consciousness. Central to Popper’s approach and his final rejection of all inductive procedures is his early attempt at a theory of habit-formation, Gewöhnungstheorie (in ‘Gewohnheit’ und ‘Gesetzerlebnis’ in der Erziehung, 1927) – a theory not fully developed at the time but nevertheless of decisive importance for his view on education and later works on epistemology, being ‘of lasting importance for my life’ (2006, p. 501). Working from some of the original descriptions and examples in ‘Gewohnheit’ und ‘Gesetzerlebnis’, updated by correspondence and discussions with Popper this paper presents a tentative reconstruction of his Gewöhnungstheorie, supplemented with examples from present-day behavioural research on, for example, ritualisation of animal and human behaviour and communication (Lorenz), and briefly confronted with competing theories, notably those by representatives of the behaviourist tradition of research on learning (Pavlov and Kandel). -
Moore Noller
2002 Ada Doisy Lectures Ada Doisy Lecturers 2003 in BIOCHEMISTRY Sponsored by the Department of Biochemistry • University of Illinois at Urbana-Champaign Dr. Peter B. 1970-71 Charles Huggins* and Elwood V. Jensen A76 1972-73 Paul Berg* and Walter Gilbert* Moore 1973-74 Saul Roseman and Bruce Ames Department of Molecular carbonyl Biophysics & Biochemistry Phe 1974-75 Arthur Kornberg* and Osamu Hayaishi Yale University C75 1976-77 Luis F. Leloir* New Haven, Connecticutt 1977-78 Albert L. Lehninger and Efraim Racker 2' OH attacking 1978-79 Donald D. Brown and Herbert Boyer amino N3 Tyr 1979-80 Charles Yanofsky A76 4:00 p.m. A2486 1980-81 Leroy E. Hood Thursday, May 1, 2003 (2491) 1983-84 Joseph L. Goldstein* and Michael S. Brown* Medical Sciences Auditorium 1984-85 Joan Steitz and Phillip Sharp* Structure and Function in 1985-86 Stephen J. Benkovic and Jeremy R. Knowles the Large Ribosomal Subunit 1986-87 Tom Maniatis and Mark Ptashne 1988-89 J. Michael Bishop* and Harold E. Varmus* 1989-90 Kurt Wüthrich Dr. Harry F. 1990-91 Edmond H. Fischer* and Edwin G. Krebs* 1993-94 Bert W. O’Malley Noller 1994-95 Earl W. Davie and John W. Suttie Director, Center for Molecular Biology of RNA 1995-96 Richard J. Roberts* University of California, Santa Cruz 1996-97 Ronald M. Evans Santa Cruz, California 1998-99 Elizabeth H. Blackburn 1999-2000 Carl R. Woese and Norman R. Pace 2000-01 Willem P. C. Stemmer and Ronald W. Davis 2001-02 Janos K. Lanyi and Sir John E. Walker* 12:00 noon 2002-03 Peter B. -
Michael S. Brown, MD
DISTINGUISHED PHYSICIANS AND Michael S. Brown, M.D. Sir Richard Roberts, Ph.D. Winner, 1985 Nobel Prize in Physiology or Medicine Winner, 1993 Nobel Prize in Physiology or Medicine MEDICAL SCIENTISTS MENTORING Winner, 1988 Presidential National Medal of Science A globally prominent biochemist and molecular biologist, DELEGATES HAVE INCLUDED... Dr. Brown received the world’s most prestigious medical Dr. Roberts was awarded the Nobel Prize for his prize for his work describing the regulation of the groundbreaking contribution to discovering RNA splicing. cholesterol metabolism. His work laid the foundation for Dr. Roberts is dedicating his future research to GMO crops the class of drugs now called statins taken daily by more than 20 million and food sources, and demonstrating the effect they have on humanity. — GRANDg MASTERS — people worldwide. Ferid Murad, M.D., Ph.D. Mario Capecchi, Ph.D. Boris D. Lushniak, M.D., M.P.H Winner, 1998 Nobel Prize in Physiology or Medicine Academy Science Director The Surgeon General of the United States (acting, 2013-2014) Winner, 2007 Nobel Prize in Physiology or Medicine A world-renowned pioneer in biochemistry, Dr. Murad’s Winner, 2001 National Medal of Science Rear Admiral Lushniak, M.D., M.P.H., was the United award-winning research demonstrated that nitroglycerin Winner, 2001 Lasker Award States’ leading spokesperson on matters of public health, and related drugs help patients with heart conditions by Winner, 2003 Wolf Prize in Medicine overseeing the operations of the U.S. Public Health Service releasing nitric oxide into the body, thus relaxing smooth Mario Capecchi, Ph.D., a biophysicist, is a Distinguished Commissioned Corps, which consists of approximately muscles by elevating intracellular cyclic GMP, leading to vasodilation and Professor of Human Genetics at the University of Utah School of Medicine.