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BMC Systems Biology Biomed Central
BMC Systems Biology BioMed Central Commentary Open Access The long journey to a Systems Biology of neuronal function Nicolas Le Novère* Address: EMBL-EBI, Wellcome-Trust Genome Campus, CB10 1SD Hinxton, UK Email: Nicolas Le Novère* - [email protected] * Corresponding author Published: 13 June 2007 Received: 13 April 2007 Accepted: 13 June 2007 BMC Systems Biology 2007, 1:28 doi:10.1186/1752-0509-1-28 This article is available from: http://www.biomedcentral.com/1752-0509/1/28 © 2007 Le Novère; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Computational neurobiology was born over half a century ago, and has since been consistently at the forefront of modelling in biology. The recent progress of computing power and distributed computing allows the building of models spanning several scales, from the synapse to the brain. Initially focused on electrical processes, the simulation of neuronal function now encompasses signalling pathways and ion diffusion. The flow of quantitative data generated by the "omics" approaches, alongside the progress of live imaging, allows the development of models that will also include gene regulatory networks, protein movements and cellular remodelling. A systems biology of brain functions and disorders can now be envisioned. As it did for the last half century, neuroscience can drive forward the field of systems biology. 1 Modelling nervous function, an ancient quest To accurately model neuronal function presents many Neurosciences have a long and successful tradition of challenges, and stretches the techniques and resources of quantitative modelling, where theory and experiment computational biology to their limits. -
Macromolecular and Electrical Coupling Between Inner Hair Cells in the Rodent Cochlea
ARTICLE https://doi.org/10.1038/s41467-020-17003-z OPEN Macromolecular and electrical coupling between inner hair cells in the rodent cochlea Philippe Jean 1,2,3,4,14, Tommi Anttonen1,2,5,14, Susann Michanski2,6,7, Antonio M. G. de Diego8, Anna M. Steyer9,10, Andreas Neef11, David Oestreicher 12, Jana Kroll 2,4,6,7, Christos Nardis9,10, ✉ Tina Pangršič2,12, Wiebke Möbius 9,10, Jonathan Ashmore 8, Carolin Wichmann2,6,7,13 & ✉ Tobias Moser 1,2,3,5,10,13 1234567890():,; Inner hair cells (IHCs) are the primary receptors for hearing. They are housed in the cochlea and convey sound information to the brain via synapses with the auditory nerve. IHCs have been thought to be electrically and metabolically independent from each other. We report that, upon developmental maturation, in mice 30% of the IHCs are electrochemically coupled in ‘mini-syncytia’. This coupling permits transfer of fluorescently-labeled metabolites and macromolecular tracers. The membrane capacitance, Ca2+-current, and resting current increase with the number of dye-coupled IHCs. Dual voltage-clamp experiments substantiate low resistance electrical coupling. Pharmacology and tracer permeability rule out coupling by gap junctions and purinoceptors. 3D electron microscopy indicates instead that IHCs are coupled by membrane fusion sites. Consequently, depolarization of one IHC triggers pre- synaptic Ca2+-influx at active zones in the entire mini-syncytium. Based on our findings and modeling, we propose that IHC-mini-syncytia enhance sensitivity and reliability of cochlear sound encoding. 1 Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany. 2 Collaborative Research Center 889, University of Göttingen, Göttingen, Germany. -
The Royal Society Medals and Awards
The Royal Society Medals and Awards Table of contents Overview and timeline – Page 1 Eligibility – Page 2 Medals open for nominations – Page 8 Nomination process – Page 9 Guidance notes for submitting nominations – Page 10 Enquiries – Page 20 Overview The Royal Society has a broad range of medals including the Premier Awards, subject specific awards and medals celebrating the communication and promotion of science. All of these are awarded to recognise and celebrate excellence in science. The following document provides guidance on the timeline and eligibility criteria for the awards, the nomination process and our online nomination system Flexi-Grant. Timeline • Call for nominations opens 30 November 2020 • Call for nominations closes on 15 February 2021 • Royal Society contacts suggested referees from February to March if required. • Premier Awards, Physical and Biological Committees shortlist and seek independent referees from March to May • All other Committees score and recommend winners to the Premier Awards Committee by April • Premier Awards, Physical and Biological Committees score shortlisted nominations, review recommended winners from other Committees and recommend final winners of all awards by June • Council reviews and approves winners from Committees in July • Winners announced by August Eligibility Full details of eligibility can be found in the table. Nominees cannot be members of the Royal Society Council, Premier Awards Committee, or selection Committees overseeing the medal in question. More information about the selection committees for individual medals can be found in the table below. If the award is externally funded, nominees cannot be employed by the organisation funding the medal. Self-nominations are not accepted. -
Cambridge's 92 Nobel Prize Winners Part 2 - 1951 to 1974: from Crick and Watson to Dorothy Hodgkin
Cambridge's 92 Nobel Prize winners part 2 - 1951 to 1974: from Crick and Watson to Dorothy Hodgkin By Cambridge News | Posted: January 18, 2016 By Adam Care The News has been rounding up all of Cambridge's 92 Nobel Laureates, celebrating over 100 years of scientific and social innovation. ADVERTISING In this installment we move from 1951 to 1974, a period which saw a host of dramatic breakthroughs, in biology, atomic science, the discovery of pulsars and theories of global trade. It's also a period which saw The Eagle pub come to national prominence and the appearance of the first female name in Cambridge University's long Nobel history. The Gender Pay Gap Sale! Shop Online to get 13.9% off From 8 - 11 March, get 13.9% off 1,000s of items, it highlights the pay gap between men & women in the UK. Shop the Gender Pay Gap Sale – now. Promoted by Oxfam 1. 1951 Ernest Walton, Trinity College: Nobel Prize in Physics, for using accelerated particles to study atomic nuclei 2. 1951 John Cockcroft, St John's / Churchill Colleges: Nobel Prize in Physics, for using accelerated particles to study atomic nuclei Walton and Cockcroft shared the 1951 physics prize after they famously 'split the atom' in Cambridge 1932, ushering in the nuclear age with their particle accelerator, the Cockcroft-Walton generator. In later years Walton returned to his native Ireland, as a fellow of Trinity College Dublin, while in 1951 Cockcroft became the first master of Churchill College, where he died 16 years later. 3. 1952 Archer Martin, Peterhouse: Nobel Prize in Chemistry, for developing partition chromatography 4. -
CHIST1 Joseph Barcroft.Pmd
Anales de la Facultad de MedicinaJoseph Barcroft y la expedición anglo-americana a los Andes Peruanos ISSN 1025 - 5583 Universidad Nacional Mayor de San Marcos Págs. 159-173 Historia Joseph Barcroft y la expedición anglo-americana a los Andes Peruanos (1921-1922) Oscar G. Pamo 1,2 Resumen Joseph Barcroft (1872-1947), fisiólogo británico de Cambridge, vino al Perú hacia fines de 1921 liderando la expedición angloamericana para estudiar las características fisiológicas que permiten a los humanos aclimatarse a la vida en las grandes alturas. Arribaron a Cerro de Pasco, realizando diversas mediciones y a diferentes altitudes, en ellos, en el personal norteamericano de la mina y en algunos nativos. Esta experiencia, publicada dos años más tarde, generaría en el doctor Carlos Monge Medrano (1884-1970) y otros investigadores nacionales el interés de conocer la biología y la patología del hombre andino, en 1927. Palabras clave Historia de la medicina, Perú; altitud; ecosistema andino; Barcroft, Joseph. Joseph Barcroft and the Anglo-American lideró la expedición angloamericana que a fines de 1921 expedition to the Peruvian Andes (1921-1922) vino a los Andes peruanos a estudiar la fisiología Abstract respiratoria del humano sometido a baja presión Joseph Barcroft (1872-1947), British Cambridge atmosférica. Sus conclusiones, que publicó dos años physiologist, came to Peru at the end of 1921 leading the después, dieron lugar a una respuesta del Dr. Carlos Monge Anglo-American expedition in order to study the Medrano en 1927. De allí en adelante, se realizó numerosas physiological characteristics that let human beings investigaciones para estudiar la salud y la enfermedad del acclimatize to live at high altitude environments. -
Former Fellows Biographical Index Part
Former Fellows of The Royal Society of Edinburgh 1783 – 2002 Biographical Index Part Two ISBN 0 902198 84 X Published July 2006 © The Royal Society of Edinburgh 22-26 George Street, Edinburgh, EH2 2PQ BIOGRAPHICAL INDEX OF FORMER FELLOWS OF THE ROYAL SOCIETY OF EDINBURGH 1783 – 2002 PART II K-Z C D Waterston and A Macmillan Shearer This is a print-out of the biographical index of over 4000 former Fellows of the Royal Society of Edinburgh as held on the Society’s computer system in October 2005. It lists former Fellows from the foundation of the Society in 1783 to October 2002. Most are deceased Fellows up to and including the list given in the RSE Directory 2003 (Session 2002-3) but some former Fellows who left the Society by resignation or were removed from the roll are still living. HISTORY OF THE PROJECT Information on the Fellowship has been kept by the Society in many ways – unpublished sources include Council and Committee Minutes, Card Indices, and correspondence; published sources such as Transactions, Proceedings, Year Books, Billets, Candidates Lists, etc. All have been examined by the compilers, who have found the Minutes, particularly Committee Minutes, to be of variable quality, and it is to be regretted that the Society’s holdings of published billets and candidates lists are incomplete. The late Professor Neil Campbell prepared from these sources a loose-leaf list of some 1500 Ordinary Fellows elected during the Society’s first hundred years. He listed name and forenames, title where applicable and national honours, profession or discipline, position held, some information on membership of the other societies, dates of birth, election to the Society and death or resignation from the Society and reference to a printed biography. -
Cells of the Nervous System
3/23/2015 Nervous Systems | Principles of Biology from Nature Education contents Principles of Biology 126 Nervous Systems A flock of Canada geese use auditory and visual cues to maintain a V formation in flight. How are these animals able to respond so quickly to environmental cues? All animals possess neurons, cells that form a complex network capable of transmitting and receiving signals. This neural network forms the nervous system. The nervous system coordinates the movement and internal physiology of an organism, as well as its decisionmaking and behavior. In all but the simplest animals, neurons are bundled into nerves that facilitate signal transmission. More complex animals have a central nervous system (CNS) that includes the brain and nerve cords. Vertebrates also have a peripheral nervous system (PNS) that transmits signals between the body and the CNS. Cells of the Nervous System Structure of the neuron. Figure 1 shows the general structure of a neuron. The organelles and nucleus of a neuron are contained in a large central structure called the cell body, or soma. Most nerve cells also have multiple dendrites in addition to the cell body. Dendrites are short, branched extensions that receive signals from other neurons. Each neuron also has a single axon, a long extension that transmits signals to other cells. The point of attachment of the axon to the cell body is called the axon hillock. The other end of the axon is usually branched, and each branch ends in a synaptic terminal. The synaptic terminal forms a synapse, or junction, with another cell. -
IEB at 50: a Scientific Timeline
IEB at 50: a scientific timeline Alcalá de Henares, 12 September 2013, Jonathan Ashmore When the Inner Ear Biochemistry Workshop started in 1964, we knew of giants who had given us some the key ideas. They included Alfonso Corti Robert Barany Georg von Bekesy Halliwell Davis and many others…… What science had happened be fore the workshop started? 1 Elsewhere we had seen the birth of molecular biology “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying method for the genetic material.” Elsewhere: we had seen the birth of cellular biophysics Alan Hodgkin and Andrew Huxley J. Physiol 1952 2 As Jochen Schact describes, Sigurd Rauch convened the first workshop to enable a research interface between clinicians and biochemists: Sigurd Rauch Invitation: 1st Workshop November 6 & 7, 1964 To be followed in 1965 by a 2nd Workshop on Inner Ear Biochemistry Topics Mucopolysaccharides in the inner ear Inner ear fluids: composition, secretion and absorption Membrane problems : electron microscopy and electrophysiology Ototoxicity: pharmacology and pathology 3 How the 1965 discussions were divided up Mucopolysaccharides Ototoxicity Electrophysiology and electron microscopy Inner ear fluids Timelines : 1964 1st Workshop on Inner Ear Biochemistry 1968 5th Workshop on Inner Ear Biology SfN 1971 ARO 1976 MoH 1980 MBHD 1992 2013 4 How has inner ear biology developed? Here are (some!) enabling technologies 1950s - Electron microscopy 1960s - Recording from nerves and cells (1976 – low noise patch -
Sir Frederick Gowland Hopkins O.M., M.A., M.B., D.Sc., Hon. Sc.D., Hon. LL.D., Hon. D.Sc., F.R.C.P., F.R.S
Downloaded from https://doi.org/10.1079/BJN19470004 VOl. I Obituary 3 Barcroft‘s interest in the science of nutrition arose not only from the catholicity of his physiological outlook, but also more directly from the fact that since 1937 he had https://www.cambridge.org/core been Chairman of the Food Investigation Board, and hence intimately concerned in their activities relating to such matters as the processing of food and the conservation of its nutritive value. Barcroft married, in 1903, Mary A. Ball, daughter of the late Sir Robert Ball, the celebrated astronomer. One of their sons is Henry Barcroft, Professor of Physiology at Queen’s University, Belfast. LESLIE J. HARRIS . IP address: SIR FREDERICK GOWLAND HOPKINS, O.M., M.A., M.B., D.Sc., 170.106.202.58 Hon. Sc.D., Hon. LL.D., Hon. D.Sc., F.R.C.P., F.R.S. Ry the death of Sir Frederick Hopkins, which occurred in Cambridge on 16 May in his 86th year, Nutritional Science lost one of its great pioneers, and its doyen. He had , on long been recognized as the leading biochemist of his time; he was also greatly beloved 29 Sep 2021 at 04:37:19 as a man. In discussing his life’s work in another place,* I wrote that Hopkins’s scientific renown was based on his explorations into at least four or five different avenues of biochemistry: lactic acid in muscle activity; the discovery of the amino-acid tryptophan, and the demonstration of its ‘specific biological value’; his classical experiments on , subject to the Cambridge Core terms of use, available at the need for accessory factors in normal diets (by which he is best known to the man in the street); and his isolation of the cell-catalyst, glutathione (which will perhaps prove scientifically the most significant of all his contributions). -
The Role of Potassium Recirculation in Cochlear Amplification
The role of potassium recirculation in cochlear amplification Pavel Mistrika and Jonathan Ashmorea,b aUCL Ear Institute and bDepartment of Neuroscience, Purpose of review Physiology and Pharmacology, UCL, London, UK Normal cochlear function depends on maintaining the correct ionic environment for the Correspondence to Jonathan Ashmore, Department of sensory hair cells. Here we review recent literature on the cellular distribution of Neuroscience, Physiology and Pharmacology, UCL, Gower Street, London WC1E 6BT, UK potassium transport-related molecules in the cochlea. Tel: +44 20 7679 8937; fax: +44 20 7679 8990; Recent findings e-mail: [email protected] Transgenic animal models have identified novel molecules essential for normal hearing Current Opinion in Otolaryngology & Head and and support the idea that potassium is recycled in the cochlea. The findings indicate that Neck Surgery 2009, 17:394–399 extracellular potassium released by outer hair cells into the space of Nuel is taken up by supporting cells, that the gap junction system in the organ of Corti is involved in potassium handling in the cochlea, that the gap junction system in stria vascularis is essential for the generation of the endocochlear potential, and that computational models can assist in the interpretation of the systems biology of hearing and integrate the molecular, electrical, and mechanical networks of the cochlear partition. Such models suggest that outer hair cell electromotility can amplify over a much broader frequency range than expected from isolated cell studies. Summary These new findings clarify the role of endolymphatic potassium in normal cochlear function. They also help current understanding of the mechanisms of certain forms of hereditary hearing loss. -
A Systems Approach to Biology
A systems approach to biology SB200 Lecture 1 16 September 2008 Jeremy Gunawardena [email protected] Jeremy Walter Johan Gunawardena Fonatana Paulsson Topics for this lecture What is systems biology? Why do we need mathematics and how is it used? Mathematical foundations – dy namical systems. Cellular decision making What is systems biology? How do the collective interactions of the components give rise to the physiology and pathology of the system? Marc Kirschner, “ The meaning of systems biology”, Cell 121:503-4 2005. Top-down ª-omicsº system = whole cell / organism model = statistical correlations data = high-throughput, poor quality too much data, not enough analysis Bottom-up ªmechanisticº system = network or pathway model = mechanistic, biophysical data = quantitative, single-cell not enough data, too much analysis Why do we need mathematics? There have always been two traditions in biology ... Descriptive Analytical 1809-1882 1822-1884 Mathematics allows you to guess the invisible components before anyone works out how to find them ... Bacterial potassium channel closed (left) and open (right) – Dutta & Goodsell, “Mo lecule of the Month” , Feb 2003, PDB. but these days we know many of the components – and there are an awful lot of them – so how are models used in systems biology? Thick models More detail leads to improved quantitative prediction simulation of electrical activity in a mechanically realistic whole heart Dennis Noble, “ Modeling the heart – from genes to cells to the whole organ” , Science 295:1678-82 2002. Thick models E coli biochemical circuit screen shot of simulated E coli swimming in 0.1mM Asp Bray, Levin & Lipkow, “ The chemotactic behaviour of computer-based surrogate bacteria” , Curr Biol 17:12-9 2007. -
FM1-43 Reveals Membrane Recycling in Adult Inner Hair Cells of the Mammalian Cochlea
The Journal of Neuroscience, May 15, 2002, 22(10):3939–3952 FM1-43 Reveals Membrane Recycling in Adult Inner Hair Cells of the Mammalian Cochlea Claudius B. Griesinger, Chistopher D. Richards, and Jonathan F. Ashmore Department of Physiology, University College London, London WC1E 6BT, United Kingdom Neural transmission of complex sounds demands fast and surface area of the cell per second. Labeled membrane was sustained rates of synaptic release from the primary cochlear rapidly transported to the base of IHCs by kinesin-dependent receptors, the inner hair cells (IHCs). The cells therefore require trafficking and accumulated in structures that resembled syn- efficient membrane recycling. Using two-photon imaging of the aptic release sites. Using confocal imaging of FM1-43 in ex- membrane marker FM1-43 in the intact sensory epithelium cised strips of the organ of Corti, we show that the time within the cochlear bone of the adult guinea pig, we show that constants of fluorescence decay at the basolateral pole of IHCs IHCs possess fast calcium-dependent membrane uptake at and apical endocytosis were increased after depolarization of their apical pole. FM1-43 did not permeate through the stereo- IHCs with 40 mM potassium, a stimulus that triggers calcium cilial mechanotransducer channel because uptake kinetics influx and increases synaptic release. Blocking calcium chan- were neither changed by the blockers dihydrostreptomycin and nels with either cadmium or nimodipine during depolarization D-tubocurarine nor by treatment of the apical membrane with abolished the rate increase of apical endocytosis. We suggest BAPTA, known to disrupt mechanotransduction. Moreover, the that IHCs use fast calcium-dependent apical endocytosis for fluid phase marker Lucifer Yellow produced a similar labeling activity-associated replenishment of synaptic membrane.