PHYSIOLOGY NEWS

summer 2009 I number 75

Calcium signalling insights from Sir Michael Berridge Physiology 2009 – back at UCD after an 18 year break Conference networking leads to post-doc position on a Japanese tropical island PowerLab : buy or rent Easy to use, easy to acquire

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ADI_InstStudent_UK_PhysioNews.indd 1 15/5/09 2:32:20 PM PHYSIOLOGY NEWS Editorial 3 Meetings The Society’s dog. ‘Rudolf Magnus 36th IUPS International Congress Yasushi Miyashita 4 gave me to Charles Sherrington, who Welcome to University College Dublin Katherine Howell, gave me to Henry Dale, who gave me James Jones 5 to The Physiological Society in October Physiological signalling: from genes to function Trevor Wardill 6 1942’ Epithelial form, function and environment Andreas Werner, Mike Gray 8 Published quarterly by The Physiological Society The ageing musculoskeletal system Carolyn Greig, Steve Contributions and queries Harridge, Di Newham, Sam Lucas 9 Senior Production Editor 22 years in the life of... Jill Berriman ... The Society’s Publications Office Linda Rimmer, Jill Berriman 10 Editorial Administrator Letter from Japan Ed Sexton Conference networking materialises into dream postdoctoral The Physiological Society Publications Office position on sub-tropical island Fiona Randall 11 PO Box 502, Cambridge CB1 0AL, UK Features Tel: +44 (0)1223 400180 When fatiguing cycling muscles complain, the brain Fax: +44 (0)1223 246858 insightfully responds! Markus Amann, Jerome Dempsey 13 Email: [email protected] Muscles under stress Silvestro Roatta, Dario Farina 15 Website: www.physoc.org/magazine Novel player in insulin resistance: focal adhesion kinase Bharti Bisht, K Srinivasan, Chinmoy Dey 17 Magazine Editorial Board Is brain carbohydrate consumption driven by adrenaline? Editor Thomas Seifert 20 Austin Elliott Parathyroid hormone-related protein (PTHrP): a modulator of University of Manchester, Manchester, UK fetal growth and development Mark Dilworth, Jocelyn Glazier 22 Members Calcium: it’s not just for bones! Brenda Finney, William Angus Brown Wilkinson, Paul Kemp, Daniela Riccardi 25 University of Nottingham, Nottingham, UK Where do we look while sleeping? Javier Márquez-Ruiz, Miguel Escudero 28 Patricia de Winter The peri-conceptional origins of the life-long physiological University College London, London, UK consequences of being a twin Frank Bloomfield 31 Sarah Hall Interview Cardiff University, Cardiff, UK Thinking the thoughts of a cell Michael Berridge, Austin Elliott 34 Munir Hussain Reports University of Bradford, Bradford, UK Tomorrow’s women, tomorrow’s world Valerie Gladwell 37 John Lee Profile: Emily avies,D participant on the BPS/Physiological Rotherham General Hospital, Rotherham, UK Society in vivo short course Judith Hall 38 Professor Tilli Tansey Inaugral Lecture John Berriman 39 Thelma Lovick Forty metre man leaves brain behind in Bristol Anne Cooke 40 University of Birmingham, Birmingham, UK The annual meeting of the Society for Gynaecologic Foreign Correspondents Investigation Jane Cleal 41 John Hanrahan Voice of Young Science Media workshop Ellen Forty 42 McGill University, Montreal, Canada 59th Annual Conference of the British Microcirculation John Morley Society 2009 Neena Kallia 43 University of Western Sydney, NSW, Australia Memorable physiologists In the footsteps of giants Patricia de Winter 44 Fiona Randall Unbelievable! 45 Okinawa Institute of Science and Technology, Okinawa, Japan Letter to the Editor 46 Book reviews 47 © 2009 The Physiological Society From the archives Austin Elliott 51 ISSN 1476-7996 Biosciences Federation–Society of Biology 52 The Physiological Society is registered in England as a Society update Mike Collis 53 company limited by guarantee: No 323575. Education Registered office: PO Box 11319, London WC1X 8WQ CaSE Liz Bell 54 Registered Charity: No 211585. The new invisible college: how globilisation is changing the Printed by The Lavenham Press Ltd landscape for scientific collaboration Liz Bell 55 Membership activities Irrum Magre 56 Exciting pupils about biology Fiona Wyllie 56 The Discovery Zone at Leeds Sue Deuchars 58 Hot topics meeting in pharmacology and physiology 2009 Liz Bell 59 Do we need more multiskilled scientists and engineers to manage economic recovery and change Liz Bell 59 The Society’s journals The Journal of Physiology 60 Experimental Physiology 61 New journal websites Liam McKay 62 Obituaries Cover image adapted from a model of membrane inositides (see Interview, p. 34) (with permission of The Hans Meves Hans-Christoph Lüttgau, Knox Chandler 63 Advancing the science of life Babraham Institute: www.babraham.ac.uk/inositide) Noticeboard 64 PHYSIOLOGY

NEWSSearch term PubMed hits Biology 770 (923) Guidelines for contributors ChemistryAction 1639 points (380) In this issue These guidelines are intended to assist PhysicsGrants 346 (236) authors in writing their contributions and Welcome to the Summer 2009 The Society offers funding through Physiology News Biochemistry 56 (142) to reduce the subsequent editing process. the following grant schemes: The Editorial Board of Physiology News Summer is traditionally conference MedicineTravel Grants, Non-Society122 (101) tries to ensure that all articles are written season, and in keeping with that this MolecularSymposia biology Grants, 212Outreach Grants, in a journalistic style so that they will Physiology News carries a bumper International Teaching and Research have an immediate interest value for a crop of conference previews and Pharmacology 516 (31) wide readership and will be readable and Grants and the Vacation Studentship reports (I think I counted 5 of each). Physiology 1706 (272) comprehensible to non-experts. Scientific and Departmental Seminar articles should give a good overview of I am also pleased to say this is a large SystemsSchemes. biology For full 57information, a field rather than focus entirely on the issue (64 pages), so it should prove ‘Molecular’please visit: 1337 authors’ own research. excellent for reading in airports, in http://www.physoc.org/grants Format of articles train stations, and in idle conference The main message or question posed moments – if you have any. Membership applications should be introduced in the first paragraph. The background for the topic The scientific content includes Applications for membership to The should then be established, leading up to muscle being stressed and fatigued Physiological Society are considered the final conclusion. (pp. 13–16) – I dare say a bit like on a rolling basis, and a decision is Length of articles most of us feel. We also have brains, normally made within 15 working This will be determined by the subject calcium, being born, growing and days. For full information, please matter and agreed with the Senior sleeping represented in the scientific visit: Publications Executive. features – so pretty much all aspects http://www.physoc.org/membership Submission of articles of life are represented in this issue. Authors should submit articles as a Word Is your membership information document attached to an email. Engagement in the broadest sense Illustrations should be sent as separate is likely to prove an increasing part correct? attachments (see below) and not of all our work in the years to come. Please check and update your embedded in the text. I am pleased to say we have several details at www.physoc.org, under Illustrations and authors’ photographs features with an engagement or ‘My Physoc Profile’. Authors are encouraged to submit outreach theme (see e.g. pp. 55–58), diagrams, drawings, photographs or other artwork with their articles, and a as well as an editorial asking all photograph of the author(s) should physiologists – you – to ‘do your bit’ Physiology News accompany submissions. Illustrations for physiology. and photographs may be colour or black Deadlines and white, and preferably TIFF, JPEG, And finally, on p. 10 we say our final Letters and articles and all other PNG, PDF or AI files with a minimum goodbye to our recently retired contributions for inclusion in the resolution of 300 dpi. Executive Editor, as she looks back Autumn 2009 issue, No. 76, should References over 22 years (sic) with The Society’s reach the Publications Office Authors are requested to keep the Publications Office and hands over to ([email protected]) by 9 July number of references to a minimum – her successors, Jill Berriman and Ed preferably no more than two or three. Sexton. 2009. Short news items Please cite all references in the style of and letters are encouraged, and The Journal of Physiology (see Instructions Austin Elliott can usually be included as late to Authors at http://jp.physoc.org). Editor copy if space permits. Suggestions for articles Suggestions for future articles are welcome. Please contact either the Editorial Assistant or a member of the Editorial Board of Physiology News (see contents page for details). Physiology News online Physiology News online: www.physoc.org/magazine

The Physiological Society permits the single copying of individual articles for private study or research. For permission to copy or reproduce for any other purpose, contact [email protected]. Opinions expressed in articles and letters submitted by, or commissioned from, Members, Affiliates or outside bodies are not necessarily those of The Physiological Society. EDITORIAL PN 3

A Call to Arms someone call ‘physiology with more call to “…take arms against a sea of money’ – did rather poorly for an troubles”. We are The Physiological Earlier this week I went to see a man up-and-coming contender. Society. We are the foot soldiers of at University College London (UCL) physiology, and if we do not fight, about a job. He told me he would It could be argued that the word the battle is certainly lost. be in the Medical Sciences building. ‘physiology’ is used more generically It didn’t ring an immediate bell, so than the other terms – but note that So, write the word ‘physiology’ in I assumed it would be one of those it pipped even ‘molecular’, which every manuscript, grant proposal, new blocks springing up on every one might expect to receive a huge and lecture note. Use the word available spare patch of ground at number of generic hits. Whatever in every talk and lecture that you the UCL main campus. Following the reason for its popularity, it is very give. Say ‘I’m a physiologist’ and the map I found myself, to my slight good news that people are using the explain what it means. Exploit every surprise, walking towards a familiar word physiology. The word is alive; opportunity. Spread the word. arch and up the steps that lead to it has a pulse – and thus there is Get sixth-formers thinking about hallowed corridors where the likes hope. My previous state of gloom is physiology as a degree – to keep the of AV Hill, Bernard Katz and Ernest reversed. subject viable, we need to create a Starling once trod. The plaque read demand, especially from the next ‘Medical Sciences’. On some further thought, I generation. The Physiological Society realised that I, myself, am guilty is implementing initiatives to get Many readers will already know of contributing to the demise of the ball rolling, news of which will that the illustrious Department physiology – because I gave up appear in forthcoming issues of of Physiology that once housed responding ‘I’m a physiologist’ to the Physiology News. But meaningful Starling, Katz, and Hill has been question ‘What do you do?’ I grew action comes from individuals – from merged with neuroscience and fed up with explaining that it is not all of you. pharmacology. Search ‘UCL the same thing as physiotherapy, physiology’ in Google, click on the and changed my answer to ‘I’m a We need to keep as our motto top link and an ominous message scientist’. This is a mistake, because The Society’s charitable object ‘To states “The Physiology website is no it is a missed opportunity. Every promote physiology’. Physiology is longer available… for information on time I say ‘I’m a physiologist’ I can a distinguished scientific discipline, programmes, staff and research in seize the chance to explain what with an amazing history and a what was Department of Physiology, physiology is. I can, to use an abused prosperous future. It is worth saving. please use the following links…” Even phrase, raise awareness. Yes, the old slate “Medical Sciences” sign physiology departments have all but We already have a pretty good has been replaced with one bearing disappeared – but every time we ‘citation’ record in Nature. The rest is the corporate logo, which David fail to use the word, to write it, to up to us. Colquhoun amusingly describes on explain it, we hammer another nail Patricia de Winter his blog as ‘a bilious orange colour’ into the coffin. So this is a clarion [1] http://www.dcscience.net/?page_id=237 [1]. Is all this juggling of names and “brands” really how it has to be? Table 1. PubMed hits in Nature from June 2004 to May 14, 2009 for major traditional scientific disciplines and other biology-related disciplines, plus the Earlier this week, while reading word ‘molecular’ through Nature, I was struck by the number of times ‘physiology’ Search term PubMed hits cropped up – I am rather attuned to Biology 770 (923) the word as I regard it as somewhat Chemistry 1639 (380) of an endangered species. This Physics 346 (236) prompted me to conduct a Web of Knowledge (WoK) search of Biochemistry 56 (142) Nature over the past 5 years using Medicine 122 (101) the terms indicated in the first Molecular biology 212 column of Table 1, together with Pharmacology 516 (31) their adjectival derivatives (e.g. physiology, physiological, and not Physiology 1706 (272) to exclude our American cousins, Systems biology 57 physiologic). Somewhat surprisingly, ‘Molecular’ 1337 ‘physiology’ did exceedingly well, pretty much head to head with Numbers in parentheses are hits for adjectival derivatives of the main search term chemistry, another discipline some and include both British and American usage (see text for example). I selected Web of Knowledge because the searches in both PubMed and Nature itself produced claim is threatened with extinction. inconsistent results. Furthermore, the other database searches seemed to pick up I was amused to note that ‘systems names of journals in the reference list or affiliations, which are specifically excluded biology’ – which I recently heard by WoK. The results reported here include editorials as well as original articles.

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36th IUPS International Congress, 2009 Jul 27–Aug 1, Kyoto, Japan The city of Kyoto Function of life: elements and Yasushi Miyashita. It may be needless to say that Kyoto is a beautiful and historic city where integration presentations at which participants many foreign tourists visit the whole The meeting can discuss their scientific interests year round. It was the capital city of Japan for a long time and continues On behalf of the organizing with colleagues from many different countries. The total sum of the to attract visitors with its historic committee, it is my great pleasure places, including well-known temples and honour to extend this invitation abstracts of the congress will be more than 3000. and shrines. The motif of the logo to take part in the coming XXXVIth of the congress (above) is Kinkaku-ji, Congress of the International Union one of the most famous temples in of Physiological Sciences (IUPS), to Japan. Kiyomizu-dera (top left) is a be held in Kyoto, Japan, from July very popular place for tourists, also 27 to August 1, 2009 at the Kyoto good for souvenir shopping. Ryoan-ji International Conference Center. (left) is famous for its beautiful We believe we are now in the Japanese-style gardens paved with midst of developments leading to cobblestones. Besides the temples, a new era in physiological research, just walking in the city where fueled by the recent revolutionary classic-style houses are preserved progress in the biological sciences. will attract you as well. Finally the We have witnessed the sequencing architecture of the venue (far left) is of the human genome, dramatic worth seeing. progress in computer technology Speakers and bioinformatics, and the Named Lectures: determination of the structures Erwin Neher (Germany) of a variety of proteins including Akimichi Kaneko (Japan) membrane receptors and channels. Bruce S McEwen (USA) The congress will provide an Sten Grillner (Sweden) excellent opportunity to review To facilitate participation from all over the world, we supported 150 Brian M Barnes (USA) these rapid advances. Many René Bindels (The Netherlands) young researchers by our Travel distinguished speakers from all Tobias Wang (Denmark) Grants. parts of the world will be invited Special Lectures: to bring us all up to date on recent We are ready to invite you to the Frances M Ashcroft (UK) developments, both in basic and Congress under the title of "Function Stefan Bröer (Australia) clinical research, through 29 Invited of Life: Elements and Integration." Clara Franzini-Armstrong (USA) Lectures (7 Named Lectures, 17 Jeffrey M Friedman (USA) Special Lectures and 5 PSJ Named Information technology has Yoshinori Fujiyoshi (Japan) Lectures), and a wide variety of increased the volume and speed of Lily Y Jan (USA) symposia (57 regular symposia,17 information flow astronomically. Kenji Kangawa (Japan) whole-day symposia and 7 PSJ However, it is still no substitute for Ramón Latorre (Chile) symposia) which cover almost face-to-face communication. We Michel Lazdunski (France) all academic fields related to the hope you will be able to join us Atsushi Miyawaki (Japan) physiological sciences. to share in the exciting scientific Shigetada Nakanishi (Japan) dialogue and enjoyable social Denis Noble (UK) On top of these oral sessions, we will exchange that will take place in Fernando Nottebohm (USA) also have more than 2500 poster Mu-Ming Poo (USA) Kyoto. Nadia Rosenthal (Italy) Yasushi Miyashita Masatoshi Takeichi (Japan) President, 36th IUPS International Joseph S. Takahashi (USA) Congress, 2009 PSJ Named Lectures: Department of Physiology, The Masao Ito (Japan) University of Tokyo, School of Susumu Tonegawa (USA) Medicine Albert J. Hudspeth (USA) For further information please visit Yoram Rudy (USA) www.iups2009.com Osamu Hayaishi (Japan)

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Welcome to University College Dublin We extend a warm welcome to everyone attending the Main Meeting in Dublin, 7–10 July ‘And then I asked him with my eyes to clinical disorders: obstructive sleep and Ruth O’Connell. Techniques ask again yes and then he asked me apnoea, hypertension and faecal employed include whole body would I yes … and yes I said yes I will incontinence. We encourage free plethysmography, telemetry, force yes’. exchange of ideas, equipment and measurement and calcium imaging students; our School of Medicine and of isolated muscles. Ulysses by James Joyce Medical Science generously supports Vascular biology And yes the Meetings Secretary the translational medicine PhD said yes; The Physiological Society programme and associated journal For most of his career Stuart Bund will return after an absence of clubs. has been investigating the activity 18 years to University College Dublin of resistance arteries with particular The central control of faecal continence (UCD), the College that James emphasis on the arterial structure– Joyce attended over a century ago. James FX Jones in collaboration with function relationship in various An issue of fee payment cut short Professors O’Connell (Department of models of hypertension, particularly Joyce’s interest in medical science Surgery) and O’Herlihy (Department the spontaneously hypertensive rat and forced him to concentrate on of Obstetrics and Gynaecology) are (SHR) model. However, recent years literary pursuits. Physiologists who investigating the neurophysiological have seen a departure from the attended the UCD meeting of 1991 basis for sacral nerve root systemic arteries to the pulmonary will recall that Physiology at that stimulation in cases of intractable veins and latterly Stuart has nurtured time was led by Ronan G O’Regan faecal incontinence. an interest in the contractile function and was a satellite in the city centre, of ureteral smooth muscle. in a building on Earlsfort Terrace in front of that originally designed for the Great Dublin Exhibition of 1865. Paul McLoughlin now holds the Chair of Physiology and in January of 2007 we moved to the main campus at Belfield. Physiology is located within the Health Science Centre and a research institute, named after E J Conway, a physiologist who helped Postgraduate students (from left to In the corridors of light (from left to unravel the ionic basis of the resting right): Colin Peirce, Maria Buffini, Karen right): James Jones, Ken O’Halloran and membrane potential. Griffin and Ted O’Connor. Karen Griffin John Moynihan. is the principal organizer of the Young Physiologists’ symposium. Chronic hypoxia in the lung Chair of Physiology, Paul Effects of intermittent hypoxia on McLoughlin’s research group is control of the upper airway focused on understanding the key A team led by Ken O’Halloran is mechanisms in the development investigating the effects of chronic and progression of lung disease, intermittent hypoxia on respiratory in order to identify and validate plasticity and function of muscles of novel therapeutic strategies. His the upper airway. Members of the group is particularly interested team include Clodagh McMorrow, in the molecular mechanisms of Microscope based histology sessions Jayne Carberry, Richard Skelly, chronic hypoxia in the lung and the prove riveting for students and staff. Chrissie Shortt, Deirdre Edge associated alterations to vascular structure. His team includes Physiological research at University Christine Costello (senior scientist), College Dublin Pamela Donohue and Michelle Sands Translational medicine and animal (post doctoral researchers), Brian models of disease McCullagh (MD), PhD students Edwina Cahill and Mark Banahan, Drs Bund, Jones and O’Halloran Susan Harkin (MSc) and Sagarika employ animal models of disease Hewage (research assistant). that link clinical questions to recent advances in physiological Postgraduate students (from left to Continuing on the theme of hypoxic science. Current areas of interest right): Deirdre Edge, Chrissie Shortt and lung disease, Katherine Howell, include the following common Richard Skelly. with her PhD student Elaine Colfer,

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7th James Black Conference Joint Meeting of the British Pharmacological Society and The Physiological Society Integrative Pharmacology and

Paul McLoughlin (extreme left) and researchers at the Conway Institute. Physiology: translating ‘omics’ into functional and clinical is interested in elucidating the role Cyclic nucleotides in the cardiovascular of vascular growth factors in the system applications co-ordinated maintenance of lung Albert Smolenski is studying the 1–3 September 2009, King’s structure in vivo. Her research basic mechanisms and protective College London, UK aims to further our understanding functions of the cyclic nucleotide of mechanisms involved in the signalling network in the pathogenesis of chronic lung cardiovascular system. His group diseases such as emphysema. focuses on the identification and Inflammatory lung diseases characterisation of new protein components involved in cAMP John Baugh’s research group is and cGMP signalling, to identify Abstract submission deadline: interested in the mechanisms in the new targets for anti-thrombotic 29 May 2009 onset and progression of aberrant therapy. His team includes Kristina tissue remodelling in inflammatory Early bird registration deadline: Gegenbauer and Sandra Biewers. lung diseases. In particular his 31 July 2009 research is specifically aimed We look forward to welcoming you Topics covered at elucidating the mechanisms to Dublin in the summer of 2009. that control fibroblast activation, Pain, inflammation and injury proliferation and differentiation in Models of cardiovascular and Katherine Howell respiratory disease-from bench to patients with idiopathic pulmonary James Jones bedside fibrosis. His group includes Lili Li, University College Dublin In vivo approaches to studying Chris Watson and Patrick Collier and metabolism PhD/MSc students Mickael Dubourd, Models of immuno-inflammation and Claire Robinson, Nadia Glezeva, YPS at Dublin infection: clinical predictive validity Maojia Xu and Eilika Wulfing. On Tuesday 7 July, Dublin will also Plenary speakers Transcriptional regulators of hypoxia play host to a Young Physiologists’ Andy Baker (University of Glasgow, Symposium, organised by a group of UK) Cormac Taylor’s group research is local, early-career physiologists. The Ian Kimber (University of Manchester, UK) directed towards expanding our meeting, entitled ‘Muscle physiology: Tony Lam (University of Toronto, understanding of the mechanisms function and dysfunction’, will include a Canada) morning session on ‘Skeletal muscle in by which hypoxia regulates the Steve McMahon (King’s College transcriptional events in epithelial health and disease’ and an afternoon London, UK) cells. His group is specifically session on ‘Physiological control of smooth muscle’. interested in the regulation of A £250 prize for the best poster global gene expression in response These symposia provide an excellent presentation by a young researcher to hypoxia and the modification of opportunity for physiologists at the (graduate students or newly transcriptional regulators which early stage of their career to come qualified postdoctoral workers underlies the induction of such together and share ideas in a less within 5 years of PhD) will be events, particularly in the setting daunting environment. The Society awarded. of inflammatory bowel disease. encourages individuals attending and/ Cormac Taylor’s group includes Eoin or presenting at the YPS in Dublin to Travel grants (£100 maximum) are Cummins and Terence Agbor (post register for the main meeting. available to student members of both the BPS and The Physiological doctoral researchers), PhD students Information about the symposium Society to attend this conference. Kathryn Oliver, Murtaza Tambulwala, is available on the website: John Garvey, Carsten Scholz, Ulrike www.ucd.ie/yps2009 For further information: Bruning, Bettina Schaible and MD If you would like any further web: www.bps.ac.uk student Colin Lenihan. information, please email [email protected] email: [email protected]

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Physiological of questions and discussion from the audience and judges. signalling: from genes I would like to thank all the to function organising committee for their On 6 and 7 April 2009, a group of tremendous efforts and all the other early-career physiologists at The people from the Department of University of Sheffield brought Biomedical Science that helped make together months of preparation the event extremely memorable and to deliver a Young Physiologists’ rewarding for all. Symposium, Physiological signalling: This event would not have been from genes to function, where possible without the generous the focus was on encouraging funding from The Physiological multidisciplinary approaches in Society, The Genetics Society, The physiological research. Department of Biomedical Science The first day started with and our commercial sponsors five presentations each from (Nanion, Cairn Research, VWR, cardiovascular physiology and Olympus, Qiagen and Newport). metabolism and endocrinology. After lunch, we received an inspiring Trevor Wardill presentation from Frances Ashcroft, Juusola Lab, Department of entitled ‘ATP-sensitive potassium Biomedical Science, University of channels: from molecule to malady’. Sheffield The presentation followed some of (on behalf of the Young Prof. Ashcroft’s scientific discoveries, Physiologists’ Symposium organising teaching the audience many lessons committee). about the difficulties of science. If you are interested in organising In the afternoon, about 35 delegates a Young Physiologists’ Symposium attended careers sessions in either at your university, please contact Evening in The Winter Garden (top) and [email protected] Fellowship and Grant Writing or the organising committee (below). Communicating Science. Both sessions were very well received and presentation entitled ‘Melanopsin: PHysiologists’ Image Library generated interesting feedback and a new light in the eye – from gene & TEaching Resource to function and behaviour’. This questions. The Society is developing Philter, a new, was a demonstration of a truly high quality web-based resource to help In the evening, the conference multidisciplinary research effort, Members illustrate and enliven lectures relocated to the Winter Gardens which spanned microarray genetic and seminars, and to give access to in the centre of Sheffield. The screens through to physiology teaching software. It will offer teachers Winter Gardens house 2500 plants characterisation and circadian and researchers an attractive platform from around the world, covering entrainment. to showcase their work: acceptance for Philter will become an acknowledged 70 m in length and 22 m in height. mark of quality. This impressive display provided The standard of YPS presentations the backdrop for 30 scientific was outstanding in science and Contributions are sought in most formats delivery, creating a monumental task (including JPG, PowerPoint, PDF, MS posters from the four themes of Word and .exe (PC) or Mac-compatible the symposium: Cardiovascular for our judges (Frances Ashcroft, Mark Hankins, Matthew Holley, self-contained programs). Anything Physiology, Metabolism and from single images to full PowerPoint Wen Jiang and Trevor Wardill). Endocrinology, Non-Excitable Cell lectures can be considered. Programs Signalling and Neuronal and Sensory Prizes were awarded for the best simulating and demonstrating physiology Physiology. Everyone really seemed oral presentation (Hannah Boycott, are welcome, as are movies of ‘classic’ or the very latest experiments. Once Philter to enjoy the venue and dinner, which Inhibition of T-type calcium channels by carbon monoxide), the best is fully implemented, submission will be prompted lots of discussion late into possible online. the night! poster (Moji Musa, Substance P regulation of mouse cremaster muscle Philter will reside on The Society’s The following day included five microvascular permeability) and the website, with some items ‘Members only’, presentations each from Non- students’ favourite presentation and others more tightly restricted (e.g. items featuring explicit animal work). Excitable Cell Signalling and (Dayne Beccano-Kelly, Voltage gated There will be links to related resources, Neuronal and Sensory Physiology. potassium channel Kv4.3 is modulated a discussion forum and, we hope, a After morning coffee, sponsored by hypoxia and the AD related peptide Wikipedia-like feature. by Cairn research, Mark W Aβ in rat and human tissue). These Submissions or enquiries should be Hankins delivered a motivational excellent presentations evoked lots emailed to [email protected]

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Epithelial form, Development of epithelial structures Bristol II Markus Affolter (Basle) function and Diane L Barber (San Francisco) The paraventricular environment John Sayer (Newcastle) nucleus in health and David Tosh (Bath) The first Physiological Society Nick Wright (London) disease Epithelial and Membrane Physiology and pathophysiology of Sunday 12 July 2009, Transport Themed Meeting, 6–8 epithelial solute transport 0900–1730. Baker’s Hall, September 2009, Newcastle Peter Agre (Baltimore) Brasserie Blanc, The Friary University Stefan Broer (Canberra) Edith Brot-Laroche (Paris) Building, Cabot Circus, Bristol, Epithelia separate the outside world Dianne Ford (Newcastle) UK from a well balanced internal milieu. Yuichi Sugiyama (Tokyo) The barriers are constantly challenged Epithelia under stress by a myriad of treats and threats – James Anderson (Chapel Hill) nutrients and information on the one side, pathogens and physical stress on Richard Boucher (Chapel Hill) the other. A detailed understanding Tomas Ganz (Los Angeles) of the processes that unfold around Marshall Montrose (Cincinnati) epithelial membranes is crucial and Ole Petersen (Liverpool) will ultimately help to prevent and Biller Prize Lecture Organised by: treat disease. Gavin Stewart (Dublin) Julian Paton (Bristol) environment impacts on this property, David Murphy (Bristol) as for example in the defence against Mike Ludwig (Edinburgh) pathogens. These three topics will be presented by world experts Registration is FREE and includes a in the field and the program will Raymond Blanc buffet lunch. be complemented with oral and More details and information at our poster communications from young website: http://www.bris.ac.uk/ scientists. In addition, it is our pleasure clinicalsciencesouth/hwline/symposium/ to host the Biller Prize lecture. Bristol II will take place directly after The broad medical and biological Physiology 2009 (the main meeting of relevance of the meeting aims to The Physiological Society, in Dublin 6–10 attract a multidisciplinary audience July 2009: www.physiology2009.org). both from the UK and abroad. Sponsored by: The Wellcome Trust, The The Epithelial Research Group at British Neuroendocrine Society, The Newcastle University has a strong Physiological Society, The University of tradition in investigating aspects of Florida, The Open Neuroendocrinology membrane transport and epithelial Journal and the The University of Bristol. defence, and the group have made a Confirmed speakers number of seminal contributions to Colin Sumners (Gainsville) the field. Recently, novel directions Roger Adan (Utrecht) such as translational research, Willis Samson (St Louis) epigenetics and novel model systems Song Yao (Bristol) are also being explored. John Russell (Edinburgh) Charles Bourque (Montreal) The organising committee is proud Jaideep Bains (Calgary) This meeting focuses on three key to host this prestigious meeting and Debora Colombari (Sao Paulo) aspects in epithelial membrane to welcome scientists from all over Javier Stern (Augusta) physiology. The first session is the globe to Newcastle. Newcastle is Glenn Toney (San Antonio) dedicated to the question of how a thriving cultural city with a strong Joseph Francis (Baton Rouge) barrier function is established, either research focus and an exciting night Emma Roberts (Bristol) de novo or after an insult, and how it life. In line with the embracing Giles Yeo (Cambridge) can repair itself. The second session character of the city the conference Scott Young (Bethesda) focuses on issues of border control: dinner comes with a special surprise! William Rostene (Paris) how selected substances cross the Join the meeting, visit Newcastle, all Charles Hindmarch (Bristol) membrane barrier and why others are are welcome. Full details are available Steve Lolait (Bristol) rejected, and the impact that disease at www.physoc.org Discussants has on this process. The third session Mohan Raizada (Gainsville); Alastair Ferguson (Kingston); Nina Japundzic- highlights the protective functions Andreas Werner Zigon (Belgrade); Stafford Lightman of the epithelium and how the Mike Gray (Bristol)

Physiology News | No. 75 | Summer 2009 | www.physoc.org KCL MEETING PN 9

process is at the cellular level to the The ageing musculo- rather grim reality of mortality rate skeletal system for hip fractured elderly patients (15% in the first year of recovery). A figure Human and Exercise that remains etched in my mind is that Physiology KCL 09 Themed of life expectancy for people living in Meeting the western world plotted against the years spent living without illness, with As well as Gordon Brown and assorted the latter not increasing at the same world leaders, there was another rate. Although we may live longer important group of people in London and be able to see our grandchildren on 1 April: Members, Affiliates and grow up, and if we are lucky our great guests of The Physiological Society grandchildren, if we want to do more at the first Human and Exercise than just watch them from a bed, then Physiology Themed Meeting, held at the news is not so great. For me this the Guy’s Campus of King’s College meeting was a step along the way to London. The meeting was organised addressing this widening gap. by Steve Harridge (King’s College) and Carolyn Greig (University of Edinburgh) While we cannot, and perhaps should interesting submissions for our next (co-convenors of the Human Physiology not, stop the ageing process, a Human and Exercise Themed Meeting SIG group) and Di Newham (King’s common theme that emerged from which we hope will take place in 2011. College). the meeting was the important role We thank everyone who contributed to that exercise has in slowing the age- Tom Kirkwood started the meeting the success of this event, with special related decline in our physiology. This by defining human ageing. He was thanks to Fiona Cook (Steve and Di’s was the silver lining in an otherwise followed by a further 17 eminent PA), Clive Daws (Teaching Services gloomy forecast. Slowing this decline national and international experts, Manager at KCL) and of course to The may be an answer to increasing our including the Editor-in-Chief elect Physiological Society events team. healthy life expectancy and thus of The Journal of Physiology, Michael improving the quality of life for the Rennie. Topic sessions included Carolyn Greig elderly. Data presented during the mechanisms underlying sarcopenia, Steve Harridge meeting indicated that resistance metabolism and contractility of Di Newham aged muscle, ageing bone and and strength training appears more tendon, adaptation to exercise and beneficial for some aspects of ageing maintenance of physical independence. health (e.g. mobility), while in other The multi-disciplinary approach, from aspects aerobic exercise appears more cellular and molecular perspectives beneficial (e.g. immune function through to the science behind falls and weight loss). So just like having prevention programmes, worked well. a healthy balanced diet through Sam Lucas. Although the focus was on ageing, the life, it would seem that we need to meeting attracted presentations on balance our exercise programmes too. Maintaining muscle strength other aspects of human and exercise In early April 2009 the western and quality into old age appears very physiology. The meeting attracted 184 world’s attention was focused on important in delaying dependence and participants with 19 selected oral and London where the leaders of the 20 frailty, and aerobic training may help 48 poster communications presented largest economies had gathered to immune function in the aged and help during the course of the meeting. discuss the global recession. While control weight gain. These data are The Society’s Blue Riband poster these leaders were looking at ways important for all society and although prize winners were Thomas Bowen to lessen the impact of an acute (one we may not have all the answers to (University of Leeds), Jamie McPhee, hopes) credit crisis, ‘across town’ this ageing challenge, there appears to (Manchester Metropolitan University) The Physiological Society’s Human be some positive interventions that we and Daniel Cannon (University of and Exercise Physiology Themed can use to improve our ageing health. Leeds). meeting had gathered at King’s There was ample opportunity for College, London, to discuss an issue I would like to acknowledge the New informal discussion and networking. that will have an impact on all facets Zealand National Heart Foundation, Thanks to the Spring sunshine, the of society for a far greater period. The The Physiological Society and participants were able to do this theme of the meeting was the ageing the School of Physical Education, alfresco between sessions. musculoskeletal system and I had University of Otago for their assistance travelled from New Zealand to present with my travel expenses. The Society’s dinner was held on HMS data about age-related changes in Belfast (see photo above), with the brain blood flow. Sam Lucas opportunity for a pre-dinner tour of the ship’s museum. The presentations were of a very Department of Physiology, School high quality and ranged from of Physical Education, University of Feedback from participants has been understanding what the ageing Otago, New Zealand excellent and we look forward to

Physiology News | No. 75 | Summer 2009 | www.physoc.org 10 PN 22 YEARS IN THE LIFE OF...

22 years in the life of The Society’s Publications Office Linda Rimmer looks back on changing times … It is hard to believe that so much time has passed since I arrived in Cambridge with two toddlers in tow, back in 1986. Since leaving school I had been employed in a string of jobs from the From left to right: Jill Berriman, United Nations Association to the Linda Rimmer and Ed Sexton. weekly newspaper Hospital Doctor, via the House of Commons (twice), the order, and not; a change of publishers to the ‘Big Apple’. With problems World Health Organization in Geneva, after 125 years (accompanied by an like work visas, I continued with The the Royal Institute of British Architects, office move); the Publications Office Society as a Production Editor working Roger Williams’ Liver Unit at King’s staff go from 5 to 20 and back to the from home, but with home just a bit College Hospital and the British Journal current 10; the arrival of Richard Dyer’s further from the office than for ‘normal’ of Family Planning, with stops in the USA Biosciences Federation in our office home workers. We had a fantastic on the way. Trevor Lamb, then Press (which certainly livens us up when the couple of years in New York, but eventually decided to return to the UK, Secretary in The Society’s Publications corks are popping and the paella pan where I settled back into The Journal Office, felt this prepared me for a role is fired up) – all against the backdrop of Physiology, plus work on meetings as his part-time Editorial Assistant, but of the ever-changing format, content, I doubt he expected me to be here abstracts. It wasn’t until the imminent rebranding and publishing procedures departure of Linda, when The Society almost 23 years later, albeit in another of The Journal of Physiology and guise. were looking for someone else to take Physiology News. over the production of Physiology News, that I thought that this might be a Things were very different back then However, now that the long-since – submitted (paper) manuscripts were great opportunity to get involved in a ex-toddlers have made their own lives – different side of The Society. entered manually in a large day book, one with Hearing Dogs for Deaf People mailed to outlying Distribution Offices and the other in music PR – it is time to I was used to journal work being for review and then returned to us by pursue other interests that have been very predictable – you get your mail for typesetting by Cambridge on hold for far too long. I leave the manuscripts and figures and these University Press or rejection. But Trevor production side of Physiology News in fit into a regular template. You never was soon dragging us kicking and the very capable hands of Jill Berriman have to worry where the next paper is coming from – there are always screaming into the newly developing (who has been with The Society almost papers to be done. The magazine is a technological age, installing a computer as long as me) and the rest of my different kettle of fish – never knowing in our office and setting up the first of work with Ed Sexton (who has been several manuscript databases. When I quite which articles will be submitted, working in The Journal of Physiology’s how they will go together, and the was able to work longer hours, I took Distribution Office since May 2008). on The Journal of Physiology’s Editorial possibility of someone deciding not to write an article at the last minute etc. Board, Executive Committee and It has been a pleasure to know so many (mentioning no names, of course). Officers (can I really have seen eight of you through my various roles in The Editors-in-Chief come and seven go?), Society – I wish you all a fond farewell. Linda and I had discussed all the organising symposia, handling budgets, magazine work carefully and she had working with The Society’s Publications Linda Rimmer pointed out the need to work within and Publication Ethics Committees, the budget, so I was a little perturbed ... and Jill Berriman reflects on the producing Society Grey Books and to find, once all the articles were in production of her first issue of Meeting Programmes and, last but far for PN74, that my target of 52 pages Physiology News from least, bringing production of The had been totally lost. It seemed as though it was going to be a bumper Society’s magazine, Physiology News, Like Linda, I also have been with the issue – 64 pages. Too late to change, in-house. Society for many years (since 1991) and have gone from role to role – first as we proceeded with all the articles but I have seen The Journal’s Editorial Copy Editor and Proof Reader within the I have been warned – the next issue must be smaller. Board change from predominantly Cambridge University Press building, UK-based to mostly international to Senior, then Chief Production Editor, It hardly needs saying that Linda will be membership and their meetings go before progressing to Managing Editor. a hard act to follow. Over the 18 years I remember my husband John telling from a leisurely couple of hours on a I have been working with her, she me when I first applied for the job that Saturday afternoon in London (with has always impressed me with her I would be much too bored after a wonderful picnic baskets of homemade calm unflappable thoroughness. I feel few months – but that was assuming honoured to have had her as a coach on lunch provided by Barbara Fulton) to that things never change. They do regular 2-day marathons in the US; Physiology News. If I can do as good a and often. I gave up that post when, job as her, I will be well satisfied. backlogs of manuscripts come and in 2004, my husband and I decided to go; authors names in alphabetical change our lives completely by moving Jill Berriman

Physiology News | No. 75 | Summer 2009 | www.physoc.org LETTER FROM JAPAN PN 11

Letters from Japan 1 I buy what looks like milk and it is yoghurt. The world outside work is – Conference less familiar than the world in the lab, where most equipment, even if networking labelled in Japanese, looks familiar. materialises into It is strangely easier to work out a microscope function here than a dream postdoctoral bottle of milk. I spent my first few months in a state of, well, excited position on sub- confusion. I was learning a new brain tropical island area and some new techniques and In January I got on a plane to Fiona and her rig. wasn’t even competent to buy milk. Okinawa, a sub-tropical island in to allow my dad to regulate my It was funny most of the time but Japan, to begin a 2 year postdoctoral affairs – luckily my bank account sometimes I felt I was losing my position. Image search for Okinawa was empty anyway! I did two trips to mind. on Google and combine those London to the Japanese Embassy to pictures in your head with a great collect a visa. Because my contract scientific job and you’ll understand in Japan could not be processed until my enthusiasm! I’m going to share I had my PhD, organisation for the some of my new experiences in the move remained in the air and then next issues of Physiology News. As seemed to happen very fast. I got the young scientists, we all think about exact flight times 4 days before I got moving abroad in our careers and a on the plane and had no idea what I diary of my experiences may be of needed to do when I arrived. But the interest to people considering taking uncertainty and chaos masked the this direction. real anxiety about the move. Fiona and Marianela Garcia-Munoz So, first, how did I decide on Japan? check out the new Brain Mechanisms At the Federation of European for Behaviour office at the building site Neurosciences conference in Geneva for the new laboratories due to open in in July 2008 I overheard a gentleman 2010. say, ‘so, if you know anyone who is Three months in, I feel that Okinawa looking for a postdoc on a tropical is home. I have a great apartment, island let me know’, and I thought a convertible car (it is a waste not ‘me’. We got chatting, but worked in to when you see the sun so much) different areas so didn’t really discuss and know my way around in the science in detail. In my search for lab. Work is going well and I am postdoctoral positions online I came Fiona and Emma-Karin Millers, a fellow presenting my first talk in Dublin at postdoctoral researcher in Okinawa from across an advert for a postdoctoral Physiology 2009. The institute here electrophysiologist at the Okinawa Sweden sample some local cuisine after a day at the beach. in Okinawa is new and we move to Institute of Science and Technology our new laboratories at the end of in Japan. Although a new brain area the year. There is a lot of exciting Upon arrival in Okinawa I was to that I worked on for my PhD, science happening here and I know greeted by a driver with a board the techniques required were the that in the future I will look back and saying ‘Dr Fiona Randall’ – then ones I used and the advertiser was feel very proud to have been a part I felt I had made it! Bright and the gentleman from the lobby at of this new institute. I am taking part early the next day I was in the lab, FENS! So, I applied, mentioning the in an English club at a local school familiarising myself with equipment chat in the lobby at FENS, went for which gives me chance to spend and discussing project plans with interview and here I am writing this time with Japanese people and learn my new boss, Gordon Arbuthnott. A article from my office in Okinawa. more about their culture, as well as thing I never thought of until I came Conference networking can have tell them about mine. Skype and the to Japan was the different alphabet very exciting results – take note! internet make it easy to talk to the – this makes it difficult to even guess people I left behind: in fact I probably In the weeks before I left I had the what things are. There is a lot of speak to them more now than I did stresses of moving away (a long way) paperwork to be done in Japan for in the UK. I have also had chance from home. Obviously I was sad to immigration, apartment rental, bank to learn to scuba dive, kickbox and leave my family, friends and pets. I accounts etc. none of which I can deep-sea fish. I can even say a few had to rent my house, sell my car and read. A trip to the supermarket can words in Japanese. find homes for my horse and two take hours as I debate with myself cats. I had to sign a legal document over what things are – sometimes Fiona Randall

Physiology News | No. 75 | Summer 2009 | www.physoc.org

FEATURES PN 13

When fatiguing cycling muscles complain, the brain insightfully responds! When oxygen transport from the faster), central neural drive and lungs to the legs is reduced (e.g. consequently power output/speed at altitude), the muscles utilized to is down-regulated, whereas during ride a bicycle (locomotor muscles) the same time trial performed while fatigue faster and a person’s cycling breathing 100% oxygen (locomotor time to exhaustion – against a muscles fatigue slower), central fixed resistance – is significantly neural drive and power output/ shorter compared with sea level. speed is up-regulated compared On the other hand, when oxygen with sea level. Astonishingly, Markus Amann (left) and Jerome A transport to the locomotor muscles despite the different performances Dempsey. is increased (e.g. via blood doping achieved in these three time trials or breathing 100% oxygen), the rate (fastest with 100% oxygen and of peripheral locomotor muscle of fatigue of the working muscles slowest at altitude), the magnitude fatigue; however, end-exercise is a lot slower and the person’s of locomotor muscle fatigue at locomotor muscle fatigue was still time to exhaustion is substantially end-exercise was identical (Amann et limited to that ‘threshold’. It seems longer compared with sea level. al. 2006). Considering this, it appears like the brain, consciously and/or Interestingly, at exhaustion (subject that the down-regulation of central subconsciously, senses peripheral is not able to continue exercise neural drive and power output at fatigue and alterations in the against the same fixed resistance), altitude ensured that the rate of associated intramuscular metabolic whether it is reached during development of locomotor muscle milieu (and/or it’s rate of change) cycling at sea level, or on the top fatigue was slowed and end-exercise – presumably via the cortical of a 3000 m mountain, or while peripheral fatigue prevented from projection of metabosensitive breathing 100% oxygen, the level of exceeding a certain limit. On the peripheral locomotor muscle fatigue other hand, the up-regulation of small-diameter muscle afferents – and the associated intramuscular central neural drive and power (group III/IV) – and regulates milieu determining this level – is output while breathing 100% oxygen central neural drive to restrict the identical (Hogan et al. 1999; Amann accelerated the rate of development development of locomotor muscle et al. 2006, 2007)! Also interesting, when the fatigued muscle of a human, who just reached the point where he is unable to voluntarily continue the exercise against a fixed resistance (i.e. exhaustion), is artificially innervated – or ‘driven’ – via transcutaneous electric motor Figure 1. Schematic illustration nerve stimulation, the muscle is able of our proposed and tested to continue the exercise (Löscher model. The continuous red line indicates efferent nerve activity et al. 1996). These observations (central motor drive), the dashed suggest that humans stop exercising white line indicates afferent once a certain level of locomotor nerve activity. This regulatory muscle fatigue is reached and mechanism shows that the that, by stopping the exercise at cortical projection of muscle this particular level of peripheral afferents (inhibitory feedback) fatigue, a certain degree of muscular affects the determination of the functional reserve is preserved. magnitude of central motor drive which in turn determines power The situation is somewhat similar output of the locomotor muscles. with time trial exercise. During a The magnitude of power output time trial performed on a bicycle determines the metabolic milieu within the working muscles which ergometer, subjects cover a set in turn determines the magnitude distance as fast as possible and are of the inhibitory afferent able to adjust power output (i.e. feedback. Based on our data, the speed) by switching gears – just purpose of this feedback loop is to like on a real bike. We recently limit peripheral locomotor muscle observed that during a 5 km cycling fatigue to an individual threshold time trial performed at simulated which is never exceeded. From altitude (locomotor muscles fatigue Amann & Dempsey (2009).

Physiology News | No. 75 | Summer 2009 | www.physoc.org 14 PN FEATURES fatigue to a certain threshold that power output which exceeded their References varies between individuals. Based on aerobic capacity and quickly resulted Amann M & Dempsey JA (2009). Ensemble these observations, we formulated a in severe muscle acidosis, leading input of group III/IV muscle afferents to hypothesis claiming that locomotor to a curtailed power output during CNS: a limiting factor of central motor drive muscle afferent feedback exerts the second half of the race – despite during endurance exercise from normoxia to moderate hypoxia. Adv Exp Med Biol (in press). an inhibitory influence on the continuing high central motor drive. determination of central motor drive Amann M, Eldridge MW, Lovering AT, Although the overall time trial Stickland MK, Pegelow DF & Dempsey JA during high-intensity, whole-body performance was similar between (2006). Arterial oxygenation influences central endurance exercise and restricts the trials, the induced acidosis in the motor output and exercise performance the development of peripheral fentanyl race accelerated the rate of via effects on peripheral locomotor muscle locomotor muscle fatigue to an development of locomotor muscle fatigue. J Physiol 575, 937–952. individual critical threshold (Fig. 1) fatigue – but this was, due to the Amann M, Proctor LT, Sebranek JJ, Eldridge (Amann et al. 2006). MW, Pegelow DF & Dempsey JA (2008). missing neural feedback, ‘unseen’ Somatosensory feedback from the limbs by the brain. Therefore, the brain To experimentally evaluate whether exerts inhibitory influences on central neural ‘allowed’ or ‘tolerated’ the exercise- drive during whole body endurance exercise. J ascending sensory pathways induced development of locomotor Appl Physiol 105, 1714–1724. affect the magnitude of central muscle fatigue significantly beyond Amann M, Proctor LT, Sebranek JJ, Pegelow motor drive, we recently blocked levels as observed following the DF & Dempsey JA (2009). Opioid-mediated locomotor muscle afferents during muscle afferents inhibit central motor a 5 km cycling time trial via lumbar placebo race, i.e. with intact neural drive and limit peripheral muscle fatigue epidural anaesthesia (lidocaine). feedback system. All athletes development in humans. J Physiol 587, 271–283. In the absence of neural feedback substantially exceeded their from the legs, central motor drive critical threshold which resulted in Amann M, Romer LM, Subudhi AW, Pegelow DF & Dempsey JA (2007). Severity of arterial was substantially higher compared severely impaired locomotor muscle functions and acute ambulatory hypoxaemia affects the relative contributions with the control race performed of peripheral muscle fatigue to exercise with an intact regulatory feedback problems (Amann et al. 2009). performance in healthy humans. J Physiol 581, 389–403. mechanism as illustrated in Fig. 1. In conclusion, our results suggest However, since local anaesthetics that neural feedback from the Hogan MC, Richardson RS & Haseler LJ also reduce efferent nerve traffic (1999). Human muscle performance and working and fatiguing muscles PCr hydrolysis with varied inspired oxygen between the injection site and the exerts inhibitory influences on the fractions: a 31P-MRS study. J Appl Physiol 86, end-organ, less ‘push’ arrived at determination of the magnitude 1367–1373. the locomotor muscles and time of central motor drive during Löscher WN, Cresswell AG & Thorstensson A trial performance was expectedly high-intensity endurance exercise. (1996). Central fatigue during a long-lasting reduced (i.e. longer time to finish the submaximal contraction of the triceps surae. Furthermore, it appears that neural race) (Amann et al. 2008). Exp Brain Res 108, 305–314. influence of exercising muscles on the brain causes a restriction of To circumvent this problem and to Get involved and write an adequately determine the effect the exercise-induced development of locomotor muscle afferents of peripheral muscle fatigue to article for Physiology News on exercise performance and the an individual’s critical threshold Have you done something in your development of peripheral fatigue, – presumably to prevent severely studies you would like to recommend we repeated the study and used impaired muscle functions and to other young scientists, attended placebo vs fentanyl, an opioid to preserve a functional muscle an amazing training course or got an analgesic, to selectively block reserve following exhaustion issue you’d like to get off your chest? the activity in ascending sensory induced via whole-body endurance If you enjoy writing then why not pathways without affecting motor exercise. Finally, we propose contribute to Physiology News. We nerve activity (Amann et al. 2009). that somatosensory feedback is have an annual prize of £200 for the We clearly emphasize that we only necessary to match/adjust central best published article written by an blocked opioid-mediated afferents; motor drive to the metabolic milieu Affiliate or young scientist. If that other ascending pathways were of the working muscles to avoid isn’t enough incentive, contributing unaffected by this intervention. acidosis and guarantee optimal to the magazine is a great extra Similar to the first study, blocking exercise performance. on your CV and a nice way to tell a broader audience about the things somatosensory feedback from the 1,2 legs released a centrally mediated Markus Amann you do. We are always looking for 2 people to contribute to the Affiliate ‘brake’ on central motor drive but Jerome A Dempsey pages in the magazine and would this time, exercise performance 1University of Utah, Department love to hear from anyone who would was substantially improved over of Internal Medicine, Salt Lake like to get involved. the first half of the race. Evidently, City, UT, USA and 2University of the missing neural feedback tricked Wisconsin, John Rankin Laboratory Email us for more information or to the athletes to overestimate their of Pulmonary Medicine, Madison, discuss ideas at: work capacity and they ‘chose’ a WI, USA [email protected]

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Muscles under stress It is often assumed that skeletal muscles are not among the targets of the sympathetic nervous system (SNS). However, muscles receive abundant (nor)adrenergic innervation, mostly but not exclusively addressed to arterioles, and are affected by the hormone adrenaline, released by the adrenal medulla (under sympathetic control). In fact, catecholamines modulate many functions of skeletal muscle fibres, ranging from excitability to contractility to metabolism The first evidence of adrenergic during panic attacks but not by cold modulation of muscle function dates exposure. back to the end of the 19th century, before the biochemical identification Catecholamines exert an anti-fatigue of catecholamines. At that time, action on muscle fibres. By + + scientists investigated the function potentiating the action of the Na -K of the adrenal gland by systemic pump they help in counteracting the administration of 'suprarenal decrease of ionic gradients across extracts' in experimental animals. Silvestro Roatta (left) and Dario Farina. the cell membrane that occurs under The results were puzzling as the intense activity and that impairs the animals exhibited reactions leading is characterized by a generalized excitability of muscle fibres, thus to death with different time courses activation of the sympathetic contributing to fatigue. and symptoms, so that the gland nervous system (SNS) that is aimed at Moreover, by acting presynaptically at was believed to be a poison collector. supporting the intense motor activity the motor end-plate, catecholamines Oliver & Schäfer (1895) first described necessary to face or to escape from potentiate the neuromuscular specific effects of suprarenal extract the threat; this occurs in animals transmission. This action does not on skeletal muscle as well as on the as well as humans. Although in the have a functional consequence in heart and other organs and observed latter the motor component is often normal conditions, given the high increased amplitude and prolonged suppressed by social constraints, reliability of the motor end-plate in duration of the twitch force of the the autonomic activation still occurs transmitting excitation to the muscle frog gastrocnemius muscle (Fig. 1). under stressful conditions, with several side effects. In addition, it is fibre. However, in conditions in which Since then, the issue has been worth emphasizing that circulating the fibre excitability is impaired (e.g. investigated extensively, and adrenaline (ADR), rather than during intense muscle activity), this catecholamines are now known neurally released noradrenaline, is the effect may be useful. to modulate several processes in main mediator of the sympathetic Catecholamines increase the skeletal muscle fibres (Bowman, action on skeletal muscles, given availability of energy substrates 1980; Roatta & Passatore, 2008), the much higher affinity of ADR for by promoting glycogenolysis and particularly through β (mainly β2) the β2 adrenergic receptors. This is glucose absorption. β2 agonists adrenergic receptors. Most of these important from the functional point also affect protein metabolism by actions are functionally meaningful of view, since there is a different slowing proteolytic processes and by in the context of a 'fight-or-flight' release of the two substances potentiating protein synthesis. They reaction, i.e. the state of alertness depending on the context and on the are indeed employed as anabolic generally provoked by an impending stressor. For instance, ADR release drugs in the livestock industry and threat or danger. This condition is stimulated by painful stimuli and in certain power-related sports, e.g. weight lifting and bodybuilding.

Finally, going back to the initial observation of Oliver and Schäfer, catecholamines modulate the contractility of muscle fibres (inotropic effect). In his extensive review, Bowman provided evidence that the adrenergic action depends on the muscle fibre type: the twitch force is increased in amplitude and duration in fast-twitch muscle fibres whereas the opposite effect Figure 1. Two figures taken from the original work of Oliver & Schäfer (1895) measuring the effect of ADR injection on different organs. Left panel, diagram of is exhibited by slow-twitch fibres method employed to record the contractions of the parts of the mammalian heart. (Bowman, 1980) (Fig. 2). More Right panel, effect of suprarenal extract upon muscle contraction in the frog. A, recent in vitro studies elucidated normal muscle-curve of gastrocnemius; B, curve taken during suprarenal poisoning, the mechanisms underlying these but otherwise under the same conditions as A. Time 0.01". effects. The twitch potentiation is

Physiology News | No. 75 | Summer 2009 | www.physoc.org 16 PN FEATURES

power would be expected. It should be noted, however, that (1) the big, fast-twitch motor units are not affected by this action; and (2) the maximal (tetanic) force of slow-twitch motor units is not impaired by this effect, although a higher discharge rate will be required to attain it.

Moreover, a faster relaxation rate of slow muscle fibres may be useful in the fast movements required in the Figure 2. Effect of adrenaline injection (ADR) on single twitch force (A and C, effect 'flight'. In this respect, it is interesting of ADR indicated by the arrow) and on subtetanic electrically elicited contractions that chronic administration of β2 (C and D) of fast-twitch (A and B) and slow-twitch muscles (C and D) in anaesthetized agonists produces a transformation animal preparations. In B and D the vertical marks in the lower trace indicate the of type-I (slow-twitch) to type-II electrical stimulation. Vertical calibrations, 5 N. Modified from Bowman (1980). (fast-twitch) in muscle fibres.

2+ mediated by enhanced Ca release while the activity of low-threshold On the other hand, some of from the sarcoplasmatic reticulum, (presumably slow-twitch) motor these actions may be harmful to and this mechanism is shared units was recorded from the tibialis the muscles under stress-related by both fibre types. The twitch anterior muscle during isometric adrenergic overload, and it has been decrease and shortening is instead ankle dorsi-flexion. The experiments hypothesized that they might be 2+ related to an increased rate of Ca showed that, as compared to control implicated in the development of re-uptake into the sarcoplasmatic conditions, the discharge rates of the musculoskeletal disorders. reticulum, an effect mediated recruited motor units increased in by phospholamban, a regulatory order to attain the same force level Silvestro Roatta1 protein controlling the activity of (10% of the maximum voluntary Dario Farina2 Ca2+ pumps (Ha et al. 1999). In a contraction) during CPT (Fig. 3). This similar way, catecholamines increase observation indicated a weakening 1Dipartimento di Neuroscienze, the relaxation rate of the heart effect of SNS activation on the Sezione di Fisiologia, Università di (positive lusitropic effect). This investigated muscle. In addition, Torino, Torino, Italy effect is not exhibited by fast twitch the twitches of single motor units, 2Center for Sensory-Motor muscle fibres because they lack estimated by the spike-triggered Interaction (SMI), Department of phospholamban, whereas it may be averaging technique, exhibited an Health Science and Technology, responsible for a marked weakening increased relaxation rate during Aalborg University, Aalborg, of slow-twitch fibres (Fig. 2D), CPT, confirming the observations Denmark as documented in many animal in animal experiments. Although experiments and in vitro studies. We these data need to be confirmed and References recently investigated whether this substantiated by other experiments, Bowman WC (1980). Effects of arenergic phenomenon is functionally relevant they indicate that the influence activators and inhibitors on skeletal muscles. by analysing it during voluntary of the SNS on skeletal muscle is In Handbook of Experimental Pharmacology, Adrenergic Activators and Inhibitors, ed. contractions and physiological not negligible as it can produce Szekeres L, pp. 47–128. Springer, Berlin, activation of the SNS in humans appreciable changes in muscle Heidelberg, New York. (Roatta et al. 2008). In this study, function and motor control. Ha TN, Posterino GS & Fryer MW (1999). healthy men were subjected to the Effects of terbutaline on force and intracellular cold pressor test (CPT, a sympathetic One may wonder how a 'weakening' calcium in slow-twitch skeletal muscle fibres activation test based on the painful effect could fit with the 'fight-or- of the rat. Br J Pharmacol 126, 1717–1724. immersion of a hand in icy water) flight' reaction where more muscle Oliver G & Schäfer EA (1895). The physiological effects of extracts of the Figure 3. Average discharge suprarenal capsules. J Physiol 18, 230–276. rate of tibialis anterior motor Roatta S, Arendt-Nielsen L & Farina D (2008). units in isometric contraction Sympathetic-induced changes in discharge (10% of maximum voluntary rate and spike-triggered average twitch contractions) is increased during torque of low-threshold motor units in hand immersion in icy water humans. J Physiol 586, 5561–5574. (CPT), as compared with the other Roatta S & Passatore M (2008). Autonomic conditions: no hand immersion effects on skeletal muscle. In Encyclopedia of (control, post1, post2) and Neuroscience, ed. Binder MD, Hirokawa N & immersion in water at neutral Windhorst U, pp. 250–253. Springer, Berlin, temperature (neutral); *P < 0.05. Heidelberg New York (DOI: 10.1007/978-3- From Roatta et al. (2008). 540-29678-2).

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Novel player in insulin resistance: focal adhesion kinase Focal adhesion kinase (FAK) has recently been implicated in the regulation of insulin resistance in vitro. We hope the results of this study will provide a new strategy for the synthesis of new chemicals for FAK activation and promote development of new drugs against insulin resistance

Development of insulin resistance in increased association of IRS-1 with the peripheral organs is one of the p85α, SHP-2 and Grb 2. Lebrun et key defects associated with type 2 al. (2000) presented an interesting diabetes and obesity. However, the finding utilizing FAK-knockout precise regulatory mechanisms of fibroblasts where IRS-1 expression insulin resistance is not completely was observed to be abolished in deciphered. Reports suggest FAK-knock out cells. Cheung et al. cross-talk between focal adhesion (2000) evaluated the role of FAK kinase (FAK) and insulin signalling. in TNF-α-induced insulin-resistant Recent studies have associated hepatocytes demonstrating that FAK with insulin resistance. In insulin acts as an activator of vitro as well as in vivo studies have FAK by increasing its tyrosine highlighted the role of FAK as a phosphorylation. A new dimension potential, novel player regulating Bharti Bisht, K Srinivasan and Chinmoy S was added to FAK functions when Dey. insulin resistance. These studies have Huang et al. (2002) reported tremendous potential in presenting tyrosine kinase found at the focal regulation of glycogen synthesis by FAK as a possible drug target and adhesions (Schlaepfer et al. 1999). FAK expression in hepatic cells. Data in creating possibilities of new FAK, a highly conserved protein showed a direct interaction of FAK drug development against insulin expresses and undertakes a variety with GSK3-ß which made the group resistance. of functions in most tissues and conclude that FAK acts downstream Insulin resistance and search for a cell types. Phosphorylated FAK can to IR, IRS-1 and PI3K via interaction novel target(s) bind and integrate with multiple with Akt and GSK3-ß. Recently Insulin resistance is a condition signalling pathways thereby acting the research group of Brayer-Ash in which normal concentrations as a molecular ‘switch’ in response knocked down FAK expression of insulin produce a subnormal to signals from the external by 50% and reported impaired biological response in the primary environment and regulating various insulin-stimulated 2-deoxyglucose target tissues such as skeletal muscle cellular processes (Romer et al. (2 DOG) uptake and concluded that and adipose tissue (Taniguchi et al. 2006). the integrin signalling pathway potentially plays an important 2006), and exhibit reduced insulin- In 1995, Knight et al. reported that regulatory role in muscle insulin stimulated glucose uptake and insulin causes dephosphorylation of action (Huang et al. 2006). In light metabolism. Insulin resistance is a FAK, thus suggesting an antagonistic of the above findings, it is safe to defect of insulin signal transduction. action of insulin on the integrin conclude that FAK has important A variety of protein kinases and signalling. Co-immunoprecipitation roles to play in regulating insulin their substrates have been shown to of insulin receptor substrate-1 signalling. However, questions be important regulators of insulin (IRS-1) with α ß integrin after insulin v 3 regarding the physiological role resistance at the molecular level. stimulation indicated a putative of FAK in the regulation of insulin However, the signalling mechanisms co-operation between two signalling signalling, especially under involved remain elusive. Current proteins (Vuori & Ruoslahti, 1994). pathophysiological conditions like estimates suggest that there will be Czech and co-workers reported over 350 million people worldwide evidence for the crosstalk between insulin resistance, remain an enigma. affected by type 2 diabetes by the integrin and insulin signalling year 2030 (Turner & Heilbronn, molecules (Guilherme et al. 1998). FAK and insulin resistance 2008). Thus, considering the Baron and her group have provided In an effort to unwind the explosion of insulin resistance world the first evidence demonstrating intertwined cascade of FAK, insulin wide there is an immediate need FAK as a direct substrate of insulin signalling and insulin resistance, to explore novel and efficient drug and a direct interplay between FAK during 2007–2008 we have reported targets. and IRS-1; however, no interaction studies implicating FAK in the was observed between FAK and regulation of insulin resistance Focal adhesion kinase (FAK) and the insulin receptor (IR) (Lebrun et in vitro (Bisht et al. 2007; Bisht & insulin signalling al. 1998). Further, it was observed Dey, 2008) and in vivo (Bisht et al. FAK is a non-receptor and that FAK could induce IRS-1 tyrosine 2008), establishing the role of FAK in non-membrane-associated protein phosphorylation resulting in an regulating insulin resistance.

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In order to understand the molecular FAK and loss of function by silencing uptake (Bisht et al. 2007). These regulation of insulin resistance, we FAK. A significant decrease in effects were reversed by expression have developed insulin-resistant tyrosine phosphorylation of FAK of kinase activity mutant FAK or C2C12 skeletal muscle cells in our was observed in insulin-resistant suppression of endogenous FAK laboratory (Kumar & Dey, 2003). C2C12 cells. Overexpression of by siRNA. FAK was also found to To understand the role of FAK, we FAK in insulin-resistant C2C12 interact downstream of IRS-1, approached the problem in two ways skeletal muscle cells increased phosphatidylinositol 3-kinase i.e. gain of function by overexpessing insulin sensitivity and glucose (PI3K) and protein kinase C (PKC), leading to glucose transporter-4 (Glut-4) translocation and in up-regulation of glucose uptake. The study demonstrated for the first time, a direct role of FAK in insulin-resistant skeletal muscle cells. However, the underlying mechanism for FAK-mediated Glut-4 translocation leading to glucose uptake still remained unknown. We observed that overexpression of FAK induces actin remodelling and enhances co-localization of Glut-4 with actin, and thus elicits glucose uptake under insulin-resistant conditions (Bisht & Dey, 2008). FAK silencing by siRNA prevented actin remodelling, negatively affecting Glut-4 translocation and resulting in insulin resistance (Fig. 1). Further we observed that FAK regulates Glut-4 translocation via a PI3K-dependent pathway. Our study provided evidence that strongly supports the idea that modulation of FAK expression regulates insulin sensitivity in skeletal muscle cells in culture.

To prove conclusively the role of FAK in insulin resistance we down-regulated FAK expression using hydrodynamic tail vein injection of FAK-specific siRNA in Figure 1. Effect of FAK expression on insulin-mediated actin remodelling and mice in vivo (Bisht et al. 2008). We Glut-4 translocation in C2C12 skeletal muscle cells. Glut-4-transfected observed that FAK silencing impaired wt/+ cells expressing endogenous level of FAK (C2Glut-4 ), overexpressing FAK insulin signalling, altered glucose wt/+ wt/+ wt/+ wt/– (C2Glut‑4 FAK ) and underexpressing (silenced) FAK (C2Glut-4 FAK ) were tolerance associated with weight differentiated under insulin-sensitive (MF) and insulin-resistant conditions (MFI), gain and developed hyperglycaemia serum starved (4 h) and stimulated with and without 100 nM insulin for 30 min at 37°C, followed by fixation and permeabilization. Actin filaments were labelled with and hyperinsulinaemia (Fig. 2). Phalloidin Texas Red, nucleus with DAPI. Images were captured from different fields FAK silencing resulted in inhibition and a representative image of 3 experiments is presented. Bars represent 5 μm. A, of IRS-1 expression which in B and C: C2Glut-4wt/+, C2Glut-4wt/+FAKwt/+ and C2Glut-4wt/+FAKwt/- cells differentiated turn inhibited the downstream under insulin-sensitive condition; D, E and F: C2Glut-4wt/+, C2Glut-4wt/+FAKwt/+ and pathway leading to impaired insulin C2Glut‑4wt/+FAKwt/– cells differentiated under insulin-sensitive conditions, stimulated signalling. This provided direct and wt/+ wt/+ wt/+ wt/+ wt/– with insulin; G, H and I: C2Glut-4 , C2Glut-4 FAK and C2Glut-4 FAK conclusive evidence that FAK is a wt/+ cells differentiated under insulin-resistant conditions; J, K and L: C2Glut-4 , crucial mediator of insulin resistance C2Glut‑4wt/+FAKwt/+ and C2Glut-4wt/+FAKwt/– cells differentiated under insulin-resistant in vivo. conditions, stimulated with insulin. White arrowheads represent actin filaments, yellow arrowheads represent Glut-4 molecules and blue arrowheads indicate We believe our findings in vitro and co-localized actin with Glut-4 (Bisht & Dey, 2008). MF: MCDB201 and Ham’s F-12 in vivo will certainly be helpful in medium (1 : 1) + 0.5% BSA. MFI: MCDB201 and Ham’s F-12 medium (1 : 1) + 0.5% BSA + 100 nM insulin. understanding the molecular basis

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Bisht B, Srinivasan K & Dey CS (2008). In vivo inhibition of focal adhesion kinase causes insulin resistance. J Physiol 586, 3825–3837. Cheung AT, Wang J, Ree D, Kolls JK & Bryer- Ash M (2000). Tumor necrosis factor-α induces hepatic insulin resistance in obese zucker (fa/ fa) rats via interaction of leukocyte antigen- related tyrosine phosphatases with focal adhesion kinase. Diabetes 49, 810–819. Guilherme A, Torres K & Czech MP (1998). Cross-talk between insulin receptor and integrin signaling pathways. J Biol Chem 273, 22899–22903. Huang D, Cheung AT, Parsons JT & Bryer- Ash M (2002). Focal adhesion kinase (FAK) regulates insulin-stimulated glycogen synthesis in hepatocytes. J Biol Chem 277, 18151–18160. Huang D, Kohe M, Ilic D & Bryer-Ash M (2006). Reduced expression of focal adhesion kinase disrupts insulin action in skeletal muscle cells. Endocrinology 147, 3333–3343. Knight JB, Yamauchi K & Pessin JE (1995). Divergent insulin and platelet-derived growth factor regulation of focal adhesion kinase (pp125fak) tyrosine phosphorylation, and rearrangement of actin stress fibers. J Biol Chem 270, 10199–10203. Kumar N & Dey CS (2003). Development of insulin resistance and reversal by thiazolidinediones in C2C12 skeletal muscle cells. Biochem Pharmacol 65, 249–257. Lebrun P, Baron V, Hauck CR, Schlaepfer DD & Van Obberghen E (2000). Cell adhesion and focal adhesion kinase regulates insulin receptor substrate-1 expression. J Biol Chem 275, 38371–38377. Lebrun P, Mothe-Satney I, Delahaye L, Van Figure 2. Effect of FAK silencing on glucose tolerance. Male mice (Swiss albino, Obberghen E & Baron V (1998). Insulin receptor substrate-1 as a signaling molecule 10–11 g weight) were injected with 2500 nM of siRNA once weekly for 2 weeks. The for focal adhesion kinase pp125fak and glucose tolerance tests (GTT) were performed after 16 h of fasting. A, plasma glucose pp60src. J Biol Chem 273, 32244–32253. levels after glucose administration at different time intervals. B, plasma insulin levels after glucose administration at different time intervals. Data are shown as Romer LH, Birukov GK & Garcia Joe GN (2006). means ± S.E.M. (n = 6). *P < 0.05, **P < 0.01 (Bisht et al. 2008). Focal adhesions paradigm for a signaling nexus. Circ Res 98, 606–616. Schlaepfer DD, Hauck CR & Sieg DJ (1999). of insulin resistance. Considering the National Institute of Pharmaceutical Signaling through focal adhesion kinase. Prog lethality of the FAK gene knockout Education and Research (NIPER) Biophys Mol Biol 71, 435–478. approach, our study will provide a Sector 67, S.A.S. Nagar, Punjab 160 Taniguchi CM, Emanuelli B & Khan CR (2006). new strategy for in vivo inhibition 062, India Critical nodes in signaling pathways: insights into insulin action. Nat Rev Mol Cell Biol 7, of FAK. Furthermore, the study 2 Current address: Department of 85–96. will certainly motivate chemists to Biology, Indian Institute of Science synthesize new chemical entities Turner N & Heilbronn LK (2008). Is Education and Research (IISER), mitochondrial dysfunction a cause of insulin for FAK activation and promote Mohali, Transit Campus: MGSIPAP resistance? Trends Endocrinol Metab 19, development of new drugs against Complex, Sector 26, Chandigarh 160 324–330. insulin resistance. 019, India Vuori K & Ruoslahti E (1994) Association of insulin receptor substrate-1 with integrins. Bharti Bisht1,2 References Science 266, 1576–1578. K Srinivasan3 Bisht B & Dey CS (2008). Focal adhesion Acknowledgment kinase contributes to insulin-induced actin 1 Chinmoy S Dey reorganization into a mesh harboring glucose This study was supported by a grant from the Department of Biotechnology, 1 transporter-4 in insulin resistant skeletal Signal Transduction Research muscle cells. BMC Cell Biol 9, 48. Government of India, New Delhi to C.S.D. Laboratory, Department of (BT/HRD/34/04/2004; BT/PR3994/620 Bisht B, Goel HL & Dey CS (2007). Focal Biotechnology, and 3Department MED/14/498/2003). B.B. was a recipient adhesion kinase regulates insulin resistance in of a Research Fellowship from the C.S.I.R, of Pharmacology and Toxicology, skeletal muscle. Diabetologia 50, 1058–1069. Government of India, New Delhi.

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Is brain carbohydrate consumption driven by adrenaline? Many people use exercise to switch the brain off following a stressful day. While low intensity exercise can be performed almost automatically, strenuous exercise requires intense brain activation to keep the muscles working. Brain activation is accompanied by increased carbohydrate uptake and an increase in plasma adrenaline, rather than in noradrenaline, appears to be important for this uptake, suggesting that cerebral glycolysis is driven by a β2-adrenergic mechanism

Cerebral metabolism at rest in the O2–carbohydrate index: OCI

At rest, cerebral energy metabolism [O2/(glucose + ½ lactate)]. A value is covered almost exclusively by of ~5.7 is often reported at rest oxidation of glucose since the molar although OCI may be as low as ~4 ratio between the brain’s oxygen (Seifert et al. 2009) or above 6.

(O2) uptake to that of glucose is ~6. However, glucose is not the Cerebral metabolism during only substrate that supports brain exercise Thomas Seifert. metabolism. Lactate is recognized During light exercise OCI is maximal ergometer rowing with as an energy substrate for neurons maintained near its resting value, an arterial lactate concentration of and, therefore, the total amount of but during intense to maximal ~20 mM. The mechanism responsible carbohydrates taken up by the brain exercise, OCI decreases to the for the decrease in OCI is not yet relative to that of O is considered lowest reported value of 1.7 during 2 established (Dalsgaard, 2003), but OCI decreases independently

of O2 availability. Even though cerebral lactate uptake increases in proportion to the arterial lactate concentration, OCI also decreases in the absense of a significant increase in arterial lactate concentration (<2 mM) during prolonged exercise. Also, the uptake of free fatty acids, glycerol, glutamine, alanine and pyruvate cannot explain the decrease in OCI during cerebral activation. Rather, cerebral glycogen metabolism may explain the decrease in OCI since the glycogen deposit in the brain (~10 μmol g–1) is of the same order of magnitude as the surplus uptake of carbohydrate during intense exercise (Dalsgaard, 2006). During cerebral activation the surplus uptake of carbohydrate could replenish the cerebral glycogen deposit. Figure 1. The effect of adrenaline on cerebral carbohydrate metabolism. O2, glucose (G) and arterial lactate (aLa) are used by the neurons for oxidative energy In order to accommodate the generation. O diffuses from the capillaries to the neurons, whereas glucose is 2 increased energy demand during transported through the vessel membrane and from the interstitium to the neuron via the glucose transporters (GLUT; specific GLUTs indicated). Lactate is transported cerebral activation, additional to the neuron via the monocarboxylate transporters (MCT; specific MCTs indicated) glucose and lactate are taken up by located in the luminal and abluminal membranes of the vessel and in the membrane the brain to support oxidation in of the neuron. Glucose is also transported to the astrocyte, where it can be used neurons supplemented by glycolysis for glycogen (Gly) synthesis or metabolised to lactate. The intense brain activation in astrocytes that provide lactate to required for maximal exercise increases adrenergic glycolysis in astrocytes and neurons for oxidation. Evidence of glycogen is converted to glucose and lactate. Lactate is either transported to the increased cerebral glycolysis during neurons for oxidation or the circulation eliminates it. At rest there is a net release of brain activation is obtained using lactate, that shifts to an uptake during exercise and, in some situations lactate has 13C-labelled lactate to demonstrate a glucose-sparing effect. Intense exercise increases the cerebral metabolic rate of a 2-fold increased lactate uptake at O2 ~25% related to a Q10 effect and the release of lactate from the brain is at least doubled. an arterial concentration of ~4 mM,

Physiology News | No. 75 | Summer 2009 | www.physoc.org FEATURES PN 21 whereas the release is unaffected. in the visual cortex from a resting Together these observations indicate However, during exercise with an value of 4.1 to 2.8 in response to that OCI decreases in response to arterial lactate concentration of intense visual stimulation (Fox et sympathetic stimulation and OCI ~7 mM, the cerebral lactate uptake al. 1988). Similarly, a mental task decreases in response to infusion increases ~6-fold and the release decreases OCI as determined by of adrenaline at a rate establishing increases 2-fold (Fig. 1). Since arterial and internal jugular venous an arterial plasma concentration virtually all lactate taken up by the blood sampling (Madsen et al. comparable to that elicited during brain is metabolized at rest (~100%) 1995). Following catheterization, strenuous exercise (70% of maximal as well as during exercise (~87 %), there is some recovery of OCI, oxygen uptake; VO2max) during the increased lactate release from e.g. from ~4 to ~5 over an hour which OCI decreases (Fig. 1; Seifert the brain during intense exercise (Seifert et al. 2009) suggesting that et al. 2009). In contrast, infusion of supports the idea that the rate of OCI decreases in response to the noradrenaline is without an effect glycolysis increases with metabolism. associated discomfort (Fig. 2). Such on OCI at an arterial concentration Glycolysis may be needed during a psychological effect could also comparable to that established maximal exercise for which the explain the low baseline OCI of 4.1 in during strenuous exercise. When increase in cerebral O2 consumption the study by Fox et al. (1988), maybe strenuous exercise is carried becomes so pronounced that reflecting the anxiety provoked out with the β1/β2-adrenergic both global and regional cerebral by being placed in a scanner. In receptor antagonist propranolol, oxygenation decrease to a critical support, subjects seem to adapt the decrease in OCI is prevented level. to participating in an experiment (Larsen et al. 2008), whereas the OCI with reduced anxiety, as illustrated decreases during exercise with the

Sympathetic influence on cerebral by a reduced cerebral carbohydrate β1-adrenergic receptor antagonist metabolism ? uptake and, thus, a higher resting metoprolol (Dalsgaard, 2006). The OCI decreases not only during OCI when they visit the laboratory Thus, circulating adrenaline seems exercise. In a positron emission for the follow-up (Fig. 2). At that to stimulate cerebral carbohydrate tomography (PET)-based evaluation time, the arterial adrenaline metabolism mediated via a of brain metabolism, OCI decreased concentration is attenuated. β2-adrenergic receptor mechanism.

Figure 2. Demonstration of a β2‑adrenergic-dependent decrease in the cerebral oxygen to carbohydrate index (OCI) in response to various levels of sympathetic activity, as indicated by estimates of plasma adrenaline and noradrenaline. The continuous line indicates various exercise-induced decreases in OCI from a resting value of ~5.7 with ergometer rowing representing the extreme low value. Just after catheterization of the internal jugular vein, OCI is ~4 (▲), while for subjects participating in a training study, OCI is higher and the arterial adrenaline concentration lower, when they report to the laboratory for the follow-up (□). Adrenaline (●), but not noradrenaline (■) reduces OCI at rest and to a degree corresponding to the estimated arterial adrenaline concentration during intense exercise. In contrast propranolol, but not metoprolol, prevents the decrease in OCI during maximal ergometer cycling (○).

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How does adrenaline affect cerebral carbohydrate Parathyroid hormone-related protein metabolism? (PTHrP): a modulator of fetal growth and How adrenaline exerts its effect on cerebral metabolism remains development speculative. A decrease in OCI The role of PTHrP during embryonic development is slowly supports the idea that glycolysis being elucidated. Recent data suggest that PTHrP plays a takes place in astrocytes during key role in the regulation of placental calcium transport, intense brain activation since the fetal skeletal development and calcium homeostasis. Our carbohydrate uptake cannot be understanding of how PTHrP exerts these effects in utero has accounted for by that of O2 and adrenaline may accelerate cerebral been improved by studies using genetically modified mice glycogenolysis. The premise for in which fetal expression of PTHrP has been ablated. These this suggestion is that adrenaline investigations have provided insights into the multiple roles of released into the circulation fetal PTHrP in normal embryonic development is capable of penetrating the blood–brain barrier. In order to elucidate the role of adrenaline on In order for a baby to undergo cerebral carbohydrate uptake, we normal development and achieve its are awaiting, for example, a tissue growth potential, maintenance of an optimal in utero environment is culture evaluation of β2-adrenergic influence on glycogen turnover absolutely crucial. Epidemiological in astrocytes, thereby revealing evidence has demonstrated that whether a decrease in OCI is related babies of low birth weight, reflecting to breakdown or replenishment of possible undernourishment during the cerebral glycogen level. intrauterine life, are at increased risk of various chronic diseases including Thomas Seifert the development of osteoporosis later in life (Cooper et al. 2002). Department of Anaesthesia, The So, is there is a causal relationship Jocelyn Glazier and Mark Dilworth. Copenhagen Muscle Research between sub-optimal fetal nutrition Centre, Faculty of Health Sciences, and aberrant bone development? unidirectional maternofetal and University of Copenhagen, Denmark Observations from animal studies fetomaternal fluxes. suggest that there is. Maternal References protein restriction leads to reduced Movement of calcium across the Dalsgaard MK (2003). Brain food: The bone mineral content and bone placenta is an asymmetric process, cerebral metabolic response to exercise. with the maternofetal calcium flux Physiol News 53, 29–31. area in the offspring, with evidence of altered bone morphology and predominant, driven by active, Dalsgaard MK (2006). Fuelling cerebral structural strength (Lanham et al. transporter-mediated transfer of activity in exercising man. J Cereb Blood Flow calcium. The mechanisms involved Metab 26, 731–750. 2008). Thus, osteoporosis could be partly programmed in utero. To in maternofetal calcium flux across Fox PT, Raichle ME, Mintun MA & Dence C the epithelium of human placenta, (1988). Nonoxidative glucose consumption gain a better understanding of the during focal physiologic neural activity. biological mechanisms that link an the syncytiotrophoblast, have been Science 241, 462–464 altered fetal nutrient provision to modelled as a three-stage process Larsen TS, Rasmussen P, Overgaard M, compromised bone development (Fig. 1): calcium entry, cytosolic Secher NH & Nielsen HB (2008). Non- in utero, we first need to elucidate translocation and exit, in common selective β-adrenergic blockade prevents how fetal skeletal development with the transcellular movement of reduction of the cerebral metabolic ratio is regulated, particularly as the calcium across other epithelia such during exhaustive exercise in humans. J as the intestine and kidney. Ca2+ Physiol 586, 2807–2815. placenta must ‘adapt’ its transport function in order to meet the in maternal plasma is transported Madsen PL, Hasselbalch SG, Hagemann LP, across the maternal-facing Olsen KS, Bulow J, Holm S, Wildschiodtz G, dynamic fetal demand for calcium Paulson OB & Lassen NA (1995). Persistent and mineral provision during microvillous plasma membrane of resetting of the cerebral oxygen/glucose skeletogenesis. This demand is the syncytiotrophoblast down the uptake ratio by brain activation: evidence most acute over the last third of favourable electrochemical gradient obtained with the Kety-Schmidt technique. J through epithelial calcium channels Cereb Blood Flow Metab 15, 485–491 pregnancy when fetal deposition of calcium rises exponentially. Such an of the transient receptor potential Seifert TS, Brassard P, Jorgensen TB, Hamada vanilloid (TRPV) subfamily, with AJ, Rasmussen P, Quistorff B, Secher NH & increase in fetal calcium accretion must reflect an increased net involvement of TRPV6 implicated. Nielsen HB (2009). Cerebral non-oxidative 2+ carbohydrate consumption in humans driven calcium flux to the fetus, represented Ca is then translocated across by adrenaline. J Physiol 587, 285–293. as the difference between the the cytosol following binding to

Physiology News | No. 75 | Summer 2009 | www.physoc.org FEATURES PN 23 calcium binding proteins which help Ca2+-ATPases (PMCAs) localised to et al. 1989; Care et al. 1990). By to buffer intracellular Ca2+ whilst the BM. PMCA1 and PMCA4 isoforms contrast, infusion of hPTHrP(1–34) facilitating transcellular calcium have been demonstrated in placenta or hPTHrP(75–86)amide into the movement. The molecular identities (Strid & Powell, 2000; Bond et al. fetoplacental circulation of intact rat of the calcium binding proteins 2008). The upregulation of PMCA fetuses had no effect on placental involved in this process in human activity in BM over the last trimester calcium transport (Shaw et al.1991). placenta are not well defined, as of human pregnancy (Strid & Powell, These observations, although not several calcium binding proteins are 2000) would serve to promote fetal consistent between studies, do raise expressed. However, in rat placenta provision of calcium at a time of the possibility that PTHrP can act to great fetal demand. modulate placental calcium transport and mouse placenta, calbindin-D9K is particularly important as shown and highlight that these effects are by the marked increase in placental PMCA activity in BM can be PTHrP fragment specific. As PTHrP stimulated by physiological has the ability to act in an endocrine, expression of calbindin-D9K over the last third of pregnancy and its concentrations of PTHrP (38–94 paracrine, autocrine as well as stoichiometric relationship with amide), but not by PTHrP (1–34), intracrine manner, the question the rise in maternofetal calcium PTHrP (67–86) or PTH at comparable arises whether PTHrP produced by concentrations (Strid et al. 2002). flux (Glazier et al. 1992; Bond et al. the maternal (uterine) and/or fetal Calcium transfer into the fetal 2008). In these species, at least, (from placenta and fetal tissues) circulation of the in situ perfused placental calbindin-D expression compartments of the uteroplacental 9K placenta of parathyroidectomised may be rate-limiting to placental unit are involved in such regulation? or thyroparathyroidectomised fetal calcium transport. Ca2+ is then lambs was also stimulated by the We (Bond et al. 2008), and others transported across the fetal-facing addition of partially purified hPTHrP (Kovacs et al. 1996; Tucci et al. basal plasma membrane (BM) of or recombinant PTHrP(1–84), 1996), have explored this issue the syncytiotrophoblast against PTHrP(1–108), PTHrP(1–141), hPTHrP further by examining fetal calcium the electrochemical gradient to (75–84), hPTHrP(67–86 amide) homeostasis and placental calcium the fetus. This occurs through the and hPTHrP(75–86 amide) but not transport in mice with deletion actions of the plasma membrane by synthetic PTHrP(1–34) (Abbas of the PTHrP gene (PTHrP–/–), whereby the fetal source of PTHrP is Ca2+ eliminated. PTHrP–/– fetuses exhibit 2+ [Ca ] = chondrodysplasia characterised by 1.13 mmol/l the premature and inappropriate Ca2+ MATERNAL ossification of the developing SIDE skeleton with skeletal abnormalities apparent, such as a domed skull, Microvillous TRPV6 TRPV6 TRPV6 MaternofetalMaternofetalMaternofetal membrane short snout and mandible, and MaternofetalMaternofetalMaternofetal shortened upper and lower limbs.

CALBINDIN-D9K One intriguing feature of these animals is that despite the broad 2+ ATP Ca ADP + Pi tissue distribution of PTHrP, skeletal

Fetomaternal Fetomaternal Fetomaternal Fetomaternal morphogenesis is most notably affected whilst other tissues show no PMCA Basal membrane gross morphological abnormalities (Karaplis et al. 1994). PTHrP–/– FETAL SIDE fetuses are modestly growth- Ca2+ restricted with an ~6% reduction in fetal weight compared to their 2+ PARACELLULAR TRANSCELLULAR [Ca ] = wild-type littermates (Kovacs et al. 1.5 mmol/l 2001; Bond et al. 2008) and have a Figure 1. Schematic showing mechanisms of Ca2+ transport across the human significantly reduced blood ionised 2+ placenta (which could be applied generically to other species). Calcium enters the [Ca ] resulting in the abolition of syncytiotrophoblast across the maternal-facing microvillous plasma membrane down the fetomaternal calcium gradient a favourable electrochemical gradient via the calcium channel TRPV6. Calcium binds (Kovacs et al. 1996; Tucci et al. 1996; to the calcium binding protein (most probably calbindin-D9K) which mediates the Bond et al. 2008). Near term, they transcytosolic movement of calcium. Calcium is extruded across the fetal-facing basal have a significantly higher calcium plasma membrane by the action of PMCA. This active transport of calcium results in content than wild-type littermates a fetal ionised calcium concentration significantly higher than maternal. Calcium flux (Tucci et al. 1996; Bond et al. 2008), is highly asymmetric with the maternofetal calcium flux prevailing (bigger arrow) implying that the net flux of calcium whilst the fetomaternal flux of calcium is comparatively small (smaller arrow). TRPV6, transient receptor potential vanilloid type 6 channel; PMCA, plasma membrane across the placenta to the fetus has calcium ATPase. been increased.

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To elucidate this further, we Maternal and Fetal Health Research transport in the basal plasma membrane of measured the unidirectional Group, Research School of the human syncytiotrophoblast. J Endocrinol 175, 517–524. maternofetal clearance of calcium Clinical and Laboratory Sciences, (CaK ) across the perfused and Manchester Academic Health Strid H & Powell TL (2000). ATP-dependent mf Ca2+ transport is up-regulated during third –/– intact placenta of PTHrP fetuses Science Centre, University of trimester in human syncytiotrophoblast basal compared to wild-type at embryonic Manchester, St Mary’s Hospital, membranes. Pediatr Res 48, 58–63. day 18 (Bond et al. 2008). These Manchester, UK Tucci J, Hammond V, Senior PV, Gibson A & studies demonstrated that CaK was Beck F (1996). The role of fetal parathyroid mf References –/– hormone-related protein in transplacental significantly raised in PTHrP fetuses Abbas SK, Pickard DW, Rodda CP, Heath JA, calcium transport. J Mol Endocrinol 17, whilst calcium flux in the reverse Hammonds RG, Wood WI, Caple IW, Martin 159–164. direction, measured as unidirectional TJ & Care AD (1989). Stimulation of ovine placental calcium transport by purified natural fetoplacental clearance of calcium, and recombinant parathyroid hormone- Acknowledgements was unaffected. This stimulation of related protein (PTHrP) preparations. Q J Exp The research described in this article placental calcium transport appears Physiol 74, 549–552. was supported by a project grant from to be underscored by an upregulated Bond H, Dilworth MR, Baker B, Cowley E, the Wellcome Trust (Grant number Requena Jimenez A, Boyd RD, Husain SM, 076026/Z/04/Z). The Maternal and Fetal placental expression of calbindin-D9K (Bond et al. 2008). Our data differ Ward BS, Sibley CP & Glazier JD (2008). Health Research Group is supported Increased maternofetal calcium flux in by the Manchester Academic Health from the earlier work of others who parathyroid hormone-related protein-null Sciences Centre (MAHSC) and the NIHR showed that, when compared to a mice. J Physiol 586, 2015–2025. Manchester Biomedical Research Centre. 51 Ca marker of diffusion ( Cr-EDTA), Kmf Care AD, Abbas SK, Pickard DW, Barri M, was reduced in PTHrP–/– fetuses, Drinkhill M, Findlay JB, White IR & Caple accompanied by a decrease in IW (1990). Stimulation of ovine placental The Physiological Society placental calbindin-D expression transport of calcium and magnesium by mid- sponsors a Daphne Jackson 9K molecule fragments of human parathyroid and unaltered fetal calcium content hormone-related protein. Exp Physiol 75, Trust Fellowship (Kovacs et al. 1996). The possible 605–608. Many scientists take a career break, reasons for this have been fully Cooper C, Javaid MK, Taylor P, Walker-Bone K, for example for family reasons. debated previously (Bond et al. Dennison E & Arden N (2002). The fetal origins Returning to the lab after a few years 2008). of osteoporotic fracture. Calcif Tissue Int 70, absence can be a daunting prospect, 391–394. given the speed with which science These studies have clearly Glazier JD, Atkinson DE, Thornburg KL, Sharpe and technologies progress. Daphne demonstrated that fetal PTHrP PT, Edwards D, Boyd RD & Sibley CP (1992). Jackson was Britain’s first female 2+ plays a pivotal role in maintaining Gestational changes in Ca transport across professor of physics and a lifelong rat placenta and mRNA for calbindin9K and the hypercalcaemic status of the Ca2+-ATPase. Am J Physiol 263, R930–R935. campaigner, encouraging women fetus relative to the mother. The into engineering and science. In Karaplis AC, Luz A, Glowacki J, Bronson RT, 1985 she began a pilot scheme to excessive skeletal mineralization and Tybulewicz VL, Kronenberg HM & Mulligan RC premature calcification/ossification (1994). Lethal skeletal dysplasia from targeted return women to science engineering found in PTHrP–/– fetuses raises disruption of the parathyroid hormone-related and technology (SET) careers. the possibility of an elevated fetal peptide gene. Genes Dev 8, 277–289. The Daphne Jackson Trust (www. calcium demand. This appears to Kovacs CS, Chafe LL, Fudge NJ, Friel JK & daphnejackson.org) was set up after Manley NR (2001). PTH regulates fetal her death to continue her work. stimulate maternofetal calcium blood calcium and skeletal mineralization transport by the induction of independently of PTHrP. Endocrinology 142, The Physiological Society recognises 4983–4993. placental calbindin-D9K expression. the value of these fellowships and The stimuli that drive this response Kovacs CS, Lanske B, Hunzelman JL, Guo has agreed to co-sponsor a 2 year, are unknown, but may be J, Karaplis AC & Kronenberg HM (1996). part-time fellowship for a physiologist multifactorial (Bond et al. 2008). Parathyroid hormone-related peptide (PTHrP) who wishes to return to research regulates fetal-placental calcium transport after a career break. The widespread tissue expression through a receptor distinct from the PTH/ PTHrP receptor. Proc Natl Acad Sci U S A 93, Daphne Jackson Fellows are usually of PTHrP during fetal life strongly 15233–15238. at the PhD level and the majority implicates PTHrP as a key regulator Lanham SA, Roberts C, Perry MJ, Cooper C & of developmental processes that are women, although men can also Oreffo RO (2008). Intrauterine programming apply. Applicants must be resident influence fetal growth. In the light of bone. Part 2: alteration of skeletal structure. in the UK and have the necessary of the observations described Osteoporos Int 19, 157–167. documentation to allow them to here, the notion that PTHrP serves Shaw AJ, Mughal MZ, Maresh MJ & Sibley CP work in the UK. They should be as a linchpin in the programming (1991). Effects of two synthetic parathyroid hormone-related protein fragments on existing or past Members of The of bone development by in utero maternofetal transfer of calcium and Physiological Society and must environment is certainly worthy of magnesium and release of cyclic AMP by the meet all the Trust’s application further investigation. in-situ perfused rat placenta. J Endocrinol 129, requirements. 399–404. Mark R Dilworth Strid H, Care A, Jansson T & Powell T (2002). For full details and application forms Parathyroid hormone-related peptide (38-94) go to www.physoc.org Jocelyn D Glazier amide stimulates ATP-dependent calcium

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Calcium: it’s not just for bones! Calcium ions in the human body have diverse physiological functions. Recently, extracellular calcium ions and a G protein-coupled, calcium-sensing receptor have been shown to play a role in developmental lung physiology. By increasing our knowledge of the lung development process, we may be able to pursue novel treatments that could improve outcomes for infants born prematurely or born with developmental lung disorders Calcium is an ion with diverse roles mice, sheep and humans. The fetal When talking with friends and CaR is involved in the maintenance family, if you say that you work with of this relative hypercalcaemia, calcium ions, most automatically which lasts throughout gestation, assume that you also work with and is resolved to normocalcaemia bones. Correct this assumption to within 24 hours after birth (Kovacs tell them that you are looking at the et al. 1998). While late in gestation 2+ effects of Ca2+ on lung development the majority of Ca obtained by the From left to right: Daniela Riccardi, and their next question becomes, fetus is deposited in the developing Brenda Finney, Paul Kemp and William ‘There is calcium in the lungs?’ The skeleton, other physiological effects Wilkinson. answer to this question is, of course, of this relative hypercalcaemia number of optimally distended ‘There is calcium throughout the during development, are only terminal airway buds which contain body’. There are many processes, recently emerging. In our study the requisite cellular components from the formation of bones to the (Finney et al. 2008), we have so that the emerging fetus can shown that Ca2+ is an important, contraction of muscles and beyond, o efficiently take its first breath. that are dependent upon Ca2+. extrinsic factor which regulates several aspects of the intrinsic In embryonic rat lungs, the airway 2+ Aside from its direct actions, Ca developmental programme of the smooth muscle (ASM) lining the can act as a signalling molecule lung. basal side of the developing airway through a G protein-coupled epithelium, exhibits spontaneous receptor called the calcium- Calcium and lung development peristaltic movements which are sensing receptor (CaR). Indeed, In order to meet its primary function dependent on an intracellular our bodies maintain a constant 2+ 2+ after birth – gas exchange – the Ca (Ca i) wave originating from systemic free-ionised extracellular developing lung must undergo a a pacemaker region in the right 2+ 2+ Ca concentration ([Ca ]o) by process of branching, growth and proximal lung. This phenomenon, integrating the actions of several 2+ differentiation. These processes which is dependent upon Ca o tissues including the parathyroid are accompanied by airway influx, can be correlated with fetal gland, intestine, kidney and bone. peristalsis, stereotypic branching lung growth, that is, an increase In the adult, parathyroid CaR keeps morphogenesis and chloride in lung growth causes an increase 2+ systemic [Ca ]o at approximately secretion into a fluid-filled lumen in peristalsis, and a decrease in 2+ 1.2 mM. In the fetus, [Ca ]o is higher (Fig. 1A). Together, these events peristalsis decreases lung growth than in the mother, as reported in 2+ ensure that there is a correct (Jesudason et al. 2005). Ca i imaging

Figure 1. A, exemplar E12.5 mouse lung at time of placement into culture. Arrows indicate branching points of terminal buds, arrowheads indicate fluid-filled lumena.B , intracellular Ca2+ waves in airway smooth muscle of the developing lung are regular (top trace) and are initiated from a pacemaker region 2+ in the right proximal lung. These waves can be abolished when Ca o is removed from the bath solution, 2+ but restart when Ca o is re-introduced (bottom trace). Panel B reproduced with permission from Featherstone et al. 2005.

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Figure 2. A, CaR is detected in the E11.5 mouse lung by immunofluorescence. CaR expression (green fluorescence) is detected in both the epithelium (co-localised in cells which express the epithelial marker, E-Cadherin – red fluorescence) and the mesenchyme. Scale bar, 75 µm. B, higher magnification of red boxed area to show detail of CaR expression in both the epithelium and the mesenchyme. has revealed that regenerative, fetus may effect lung growth and grown in the presence of adult 2+ spontaneous waves (Fig. 1B, top development. [Ca ] o (1.05–1.2 mM, Fig. 3A and trace) travel via gap junctions B). Activation of the CaR with a through the ASM. Nominally Recently, we have found that the CaR specific positive allosteric modulator 2+ is expressed and active during mouse Ca o-free solution applied to of the receptor, R-568, mimics lung development (see Finney et al. 2+ cultured lung explants causes both the effects of the higher [Ca ] o 2+ 2008 and Figs 2 and 3). This receptor the Ca i signalling and peristalsis in that it too restricts the rate of to cease completely (Fig. 1B, exhibits a developmentally regulated branching morphogenesis. This bottom trace), but these processes pattern of expression which peaks CaR-dependent control of branching 2+ at the time corresponding to lung restart when Ca o is reapplied occurs through phospholipase C (Featherstone et al. 2005). Therefore, branching morphogenesis. Using and phosphotidylinositol 3-kinase both Ca2+ and Ca2+ signalling are serum-free, chemically defined signalling pathways. Additionally, o i 2+ vital components of ASM peristalsis medium containing 1.7 mM Ca o secretion of chloride into the lung 2+ and the growth of the developing (corresponding to [Ca ] o in late lumen, a vital part of forming the lung. While these studies show that gestation, fetal plasma), embryonic liquid template around which the 2+ 2+ day 12.5 mouse lungs cultured both the presence of Ca o and Ca i lung branches grow, is also affected for 48 hours undergo significantly 2+ signalling are necessary, there is by Ca o and CaR activation. Thus, no information regarding how the less branching morphogenesis chloride secretion, measured as 2+ than that achieved by explants chronically elevated [Ca ]o of the transepithelial potential difference,

2+ 2+ Figure 3. A, lung branching morphogenesis is sensitive to [Ca ]o. In the presence of low [Ca ]o (i.e. 1.05 mM, black squares) in a greater number of terminal branches, after both 24 and 48 h in culture, are 2+ seen than in the presence of the higher [Ca ]o (i.e. 1.7 mM, red circles). B, exemplar lungs from each of 2+ the culture conditions. Top panel, an E12.5 mouse lung grown in the presence of 1.05 mM Ca o for 48 h. 2+ Bottom panel, an E12.5 mouse lung grown in the presence of 1.7 mM Ca o for 48 h. C, transepithelial potential difference is used to assay epithelial Cl– secretion into the developing lung lumen. When 2+ 2+ lungs are cultured in the presence of either 1.7 mM Ca o (green bar) or 1.05 mM Ca o + 30 nM R-568 (blue bar, positive allosteric modulator of CaR) for 48 h, the transepithelial potential difference is more 2+ negative than when lungs are cultured in the presence of 1.05 mM Ca o (yellow bar) for 48 h.

Physiology News | No. 75 | Summer 2009 | www.physoc.org FEATURES PN 27 is higher in the presence of 1.7 mM or BPD have a higher incidence International Society for 2+ 2+ Ca o than it is in 1.05 mM Ca o, and of respiratory illness, as well as it is increased even further upon decreased respiratory flow and Autonomic Neuroscience specific activation of the CaR by diffusion capacity later in life (Moss, (ISAN) Congress, 2009 R-568. (Fig. 3C). 2006). Symposium: These data are the first Along with the physical symptoms Advances in sympathetic 2+ demonstration that Ca o, acting detailed above, there are significant through the CaR, have long-term socio-economic impacts of junctional transmission effects on lung development. prematurity which can last for the Tuesday 1–Friday 4 September These data imply that [Ca2+] lifetime of the affected individuals. 2009, Sydney, Australia and CaR-dependent signalling In order to reduce the number of o Chairpersons: are involved in the formation and deaths and improve the outcomes Keith Brain & James Brock expansion of peripheral airways. Our for these individuals, we must first initial interpretation of these data understand normal developmental Invited Speakers: 2+ James Galligan is that CaR activation at fetal [Ca ] o lung physiology. By incorporating (approximately 1.7 mM) acts as a our new data regarding Ca2+ and William Dunn physiological brake on branching CaR signalling into the established Rohit Manchanda morphogenesis while enhancing paradigms of developmental lung chloride secretion. The physiological physiology, we may be one step significance of these opposing closer to ameliorating the suffering effects may be to ensure matching of of many infants and adults by the airway branching with expansion to development of interventions that Burnstock, Holman, Bennett, MacLachlan optimise the gas transfer interface. could promote the formation of and Brock are some of the names one might associate with both autonomic healthy lungs. junctional transmission and Australia. The importance of getting lung It is therefore fitting that ISAN2009 in development right Brenda A Finney1 Sydney should include a symposium Perturbations of the developmental William J Wilkinson1 exploring the regulation of sympathetic transmission. programme which impinge upon Paul J Kemp1 this important developmental Daniela Riccardi1,2 The symposium will explore recent balance can result in decreased and emerging issues in junctional functionality of the postnatal lung. 1School of Biosciences and 2Cardiff transmission, including presentations on Disruption of lung development Institute of Tissue Engineering and a comparison of transmission in arteries can be caused by malformations Repair (CITER), Cardiff University, UK and veins in DOCA–salt hypertension of the chest cavity, exposure (Galligan), a focus on sympathetic References junctional transmission in pressurised to toxins, inappropriate gene vessels (Dunn), and some important expression, fetal growth restrictions Featherstone NC, Jesudason EC, Connell questions related to the pharmacology of or premature birth. Premature MG, Fernig DG, Wray S, Losty PD & Burdyga gap junction inhibitors (Manchanda). birth is a significant problem which TV (2005). Spontaneous propagating inherently carries with it the risks calcium waves underpin airway peristalsis in embryonic rat lung. Am J Respir Cell Mol Biol of inadequate lung development. 33, 153–160. The inadequacies of the premature Finney BA, del Moral PM, Wilkinson WJ, lung are exacerbated by instances Cayzac S, Cole M, Warburton D, Kemp PJ & of respiratory disease such as Riccardi D (2008). Regulation of mouse lung respiratory distress syndrome (RDS) development by the extracellular calcium- or bronchopulmonary dysplasia sensing receptor, CaR. J Physiol 586, 6007– 6019. (BPD; Warburton & Bellusci, 2004). Jesudason EC, Smith NP, Connell MG, Spiller Indeed, RDS is a major cause DG, White MRH, Fernig DG & Losty PD (2005). Developing rat lung has a sided pacemaker of morbidity and mortality in region for morphogenesis-related airway So, for those of you with an interest in premature infants. In the UK for the peristalsis. Am J Respir Cell Mol Biol 32, autonomic junctions, or sandy beaches, year 2001, 58% of newborn deaths 118–127. perhaps we will meet in sunny Sydney occurring before the infant had Kovacs CS, Ho-Pao CL, Hunzelman JL, sympathetically to explore transmission. Lanske B, Fox J, Seidman JG, Seidman CE & reached 28 days old were due to The generous support of The RDS or an extremely low weight at Kronenberg HM (1998). Regulation of murine fetal–placental calcium metabolism by the Physiological Society in supporting this birth (National Office of Statistics, calcium-sensing receptor. J Clin Invest 101, symposium is gratefully acknowledged. http://www.statistics.gov.uk/pdfdir/ 2812–2820. The conference web site is: chi0303.pdf). There is also evidence Moss TMJ (2006). Respiratory consequences of www.iceaustralia.com/isan2009/ to suggest that children who are preterm birth. Clin Exp Pharmacol Physiol 33, born prematurely and suffer RDS 280–284. K Brain

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Where do we look while sleeping? The question of whether rapid eye movements during sleep are similar to those during alertness has been controversial. Recently, a precise description of eye movements and the behaviour of extraocular motoneurons during the wake–sleep cycle has shown that the oculomotor system is controlled by tonic and phasic signals that fully explain eye movements during sleep. Tonic inhibition and a complex pattern of bilateral activation–inhibition of extraocular motoneurons are responsible for the exclusive characteristics of rapid eye movements during sleep

More than 50 years ago, Aserinsky mainly at the pons, the lateral & Kleitman (1953) reported for geniculate nucleus and the occipital the first time the existence of cortex (Jeannerod et al. 1965) – and periods with fast and jerky eye sporadic muscular twitches (Chase movements during sleep, thereby & Morales, 1983), both occurring in defining a new state that has coincidence with bursts of rapid eye been named active, paradoxical, movements. These observations, or – most generally – rapid eye together with the regularity in movement (REM) sleep. The same frequency, amplitude and velocity laboratory observed that REM Javier Márquez-Ruiz (left) and Miguel of rapid eye movements recorded sleep coincided with periods of Escudero (right). in different species, pointed to the dreams with high visual content, exploration of visual scenes during possibility that rapid eye movements and in some studies the researchers dreaming. could result from automatic found a relationship between the activations not merely related with direction of eye movements and However, the recording of new visual scanning during dreaming. the subjects’ reports about what variables during REM sleep revealed they were seeing during dreaming the existence of other phasic To resolve between these two (Dement & Kleitman, 1957). Thus, phenomena such as high-amplitude possibilities, it is necessary to know eye movements during REM sleep spiky potentials – ponto-geniculo- the precise characteristics of eye were considered to be related to the occipital (PGO) waves, recorded movements and the mechanisms

Figure 1. Eye movements during the sleep–wake cycle in cats. Representative recording of left and right (in red and black, respectively) eye movements in the horizontal and vertical plane along the sleep–wake cycle. Polysomnographic recordings enabled the distinguishing of four different periods in the sleep–wake cycle (horizontal bar at the top): awake, non-REM sleep, period of transition to REM sleep, and REM sleep. A schematic representation of binocular position is presented beneath to facilitate comparison between different oculomotor behaviour during each period. During alertness, eye movements were conjugated and were characterised by fixations interrupted by saccades that moved the eye from one visual target to another. During non-REM sleep, eye movements were of low velocity and non-conjugated, leading the eyes to a mean divergent and upward position. During REM sleep, the eyes performed bursts of movements of high amplitude and velocity that were greater in the horizontal plane. During REM sleep, the right eye deviated to the left and the left eye to the right (curved arrows in horizontal eye-position traces), generating a tonic convergence. In the vertical plane, the two eyes rotated strongly downward (curved arrow in vertical eye- position traces), and all rapid eye movements in this plane were directed upward. Dotted lines in eye-position traces indicate the centre of the orbit.

Physiology News | No. 75 | Summer 2009 | www.physoc.org FEATURES PN 29 by which rapid eye movements This technique determines the exact about the nature of eye movements are generated during sleep position of the eye in the orbit even during the sleep–wake cycle, as well compared to alertness. Until now, when the eyelids are closed, and is as their relationship with the rest with very few exceptions, the an excellent tool for investigating of tonic and phase phenomena. In most popular technique used to the physiology of the oculomotor these studies, we recorded binocular record eye movements has been system. eye movements by the scleral electrooculography, a technique search-coil technique (Márquez-Ruiz that although easy to implement Regarding the motor output of the & Escudero, 2008) and the activity of during sleep, has a very low spatial oculomotor system, the movement identified motoneurons of the ABD resolution and does not yield of each eye is controlled by the nucleus (Escudero & Márquez-Ruiz, information about eye position in action of six extraocular muscles. 2008) in adult cats. the orbit or the dynamics of the Lateral and medial recti control small eye movements. This, besides eye movements exclusively in the Eye movements during alertness an almost complete absence of horizontal plane, while superior consisted of conjugated saccades recordings of neuronal activity in the and inferior recti and superior and eye fixations (Fig. 1, awake). oculomotor system during sleep, has and inferior oblique muscles are During non-REM sleep, the two resulted in a continuing confusion involved in the control of vertical and eyes slowly rotated upwards and in about the nature of eye movements torsional movements. Abducting the abducting direction, producing during sleep. and adducting movements are a tonic divergence and elevation controlled by abducens (ABD) and of the visual axis (Fig. 1, non-REM It is paradoxical that the key oculomotor nucleus, respectively. sleep). During the transition phenomenon that denominates one Internuclear interneurons in the ABD period between non-REM and of the phases of sleep is the least nucleus project to the contralateral REM sleep, rapid, low-amplitude known of all the classical signs of oculomotor nucleus, allowing monocular eye movements in REM sleep, and even more so when conjugated eye movements in the the abducting direction occurred the oculomotor system is probably horizontal plane. in coincidence with PGO waves the most-studied and best-known (Fig.1, transition). In REM sleep, motor system. In 1963, Robinson Two recent papers from our the eyes tended to maintain a introduced the scleral search-coil laboratory published in The Journal of tonic convergence and depression, technique into oculomotor research. Physiology provide important detail broken by high-frequency bursts

Figure 2. Activity of abducens motoneurons during wakefulness and rapid eye movement (REM) sleep. During wakefulness (left), abducens motoneurons showed a burst, and a tonic firing rate that was proportional to the velocity and position of the ipsilateral eye during movements in the abducting direction. During REM sleep (right), the abducens motoneuron activities were dependent on the occurrence of ponto-geniculo-occipital (PGO) waves. During triphasic PGO waves recorded at the abducens nucleus (filled arrowheads), motoneurons produced a very short burst followed by a pause in their discharge. This short burst produced a short ipsilateral movement of high velocity in the ipsilateral eye (C1). During biphasic PGO waves (open arrowheads), motoneurons paused in their firing discharge, followed by a burst and tonic discharge. This activity induced an ipsilateral movement of the ipsilateral eye (C2) which tended to maintain the position reached. By contrast, the contralateral eye tended to drift to the position it had initially before the rapid eye movement.

Physiology News | No. 75 | Summer 2009 | www.physoc.org 30 PN FEATURES of complex rapid eye movements study of motor control during sleep, No peace for monkey (Fig. 1, REM sleep). In the horizontal enabling accurate recording of the plane, each eye movement in the motor output (by the search-coil mothers burst comprised two consecutive technique) and the motor and Every parent is familiar with the feelings movements in opposite directions premotor neuronal activity inside experienced when a child throws a public

(Fig. 2, see C1 and C2 at right), the brainstem in a well-characterised tantrum, and all too often the presence which were more evident in the system. This new model could of scowling, disapproving strangers leads eye that performed the abducting throw new light on some human them to give in to the outburst. A new movements. In the vertical plane, pathologies, such as the risk of study of rhesus monkeys provides the rapid eye movements were always myocardial ischaemia or arrhythmia first evidence that a similar effect is seen upward. or narcolepsy, in which the phasic among our primate cousins (Semple et al. 2009). Bystanders affect the outcome and tonic activities during REM sleep of mother–infant interations in rhesus The activity of ABD motoneurons are relevant. during REM sleep was characterised macaques. Proc Biol Soc 276, 2257– 2262). by a tonic decrease of their mean Javier Márquez-Ruiz1 firing rate throughout this period, Miguel Escudero2 and short bursts and pauses coinciding with the occurrence of 1División de Neurociencias, PGO waves (Fig. 2, at bottom). We Universidad Pablo de Olavide, demonstrate that the decrease Sevilla, Spain in the mean firing discharge was 2Neurociencia y Comportamiento, due to an active inhibition of Facultad de Biología, Universidad de ABD motoneurons, and that the Sevilla, Sevilla, Spain occurrence of primary and secondary PGO waves induced a pattern of References simultaneous but opposed phasic Aserinsky A & Kleitman N (1953). Regularly Rhesus mothers are much more likely activation and inhibition in each occurring periods of eye motility, and to give in to their offspring’s tantrums ABD nucleus. With regard to eye concomitant phenomena, during sleep. when there are potentially aggressive Science 118, 273–274. animals nearby. Indeed, it appears that movements, during REM sleep, ABD it is the threat of violence from these Chase MH & Morales FR (1983). motoneurons failed to codify eye nearby animals that tips the balance position as during alertness, but Subthreshold excitatory activity and motoneuron discharge during REM periods in favour of the screaming infants, and continued to codify eye velocity. of active sleep. Science 221, 1195–1198. forces mothers to acquiesce to their demands. Comparisons of the characteristics Dement W & Kleitman N (1957). The of eye movements during the sleep– relation of eye movements during sleep to Stuart Semple of Roehampton University dream activity: an objective method for and his colleagues made these new wake cycle reveal the uniqueness the study of dreaming. J Exp Psychol 53, discoveries while studying a population of eye movements during sleep, 339–346. of rhesus monkeys living on Cayo and the noteworthy existence of Escudero M & Márquez-Ruiz J (2008). Santiago, an island off the coast of tonic and phasic phenomena in the Tonic inhibition and ponto-geniculo- Puerto Rico. The crying of rhesus monkey oculomotor system, not observed occipital-related activities shape abducens infants – just like that of human babies – until now. The pattern of tonic motoneuron discharge during REM sleep. J is high pitched, grating and unrelenting. Physiol 586, 3479–3491. inhibition and the phasic activations While these cries are directed at Jeannerod M, Mouret J & Jouvet M (1965). and inhibitions shown by ABD mothers, nearby animals share the pain, motoneurons coincide with those Étude de la motricité oculaire au cours de la phase paradoxale du sommeil chez le chat. and these onlookers often resort to reported in other non-oculomotor Electroencephalogr Clin Neurophysiol 18, violence to bring the earache to an end. motoneurons (Chase & Morales, 554–566. Semple and his team found that both mothers and infants were over 30 times 1983), indicating that the Márquez-Ruiz J & Escudero M (2008). Tonic more likely to receive aggression during oculomotor system – contrary to and phasic phenomena underlying eye crying bouts than when infants were what has hitherto been accepted movements during sleep in the cat. J Physiol silent. Perhaps as a result of this threat, – is not different from other motor 586, 3461–3477. mothers are more than twice as likely systems during REM sleep, indicating Robinson DA (1963). A method of measuring to give in to their bawling babies when eye movements using a scleral coil in a that all motor systems are receiving there were animals nearby that could magnetic field. IEEE Trans Biomed Electr 10, similar command signals during this turn nasty. 137–145. period, and therefore that bursts Acknowledgements The study also found that mothers are of rapid eye movement during prone to losing their cool when faced REM sleep are not directly related This research was supported by grants with screaming infants on one side and MCYT-BFU2005-01579 and BFU2008-04537/ to the scanning of images while irritated onlookers on the other: mothers dreaming. On the other hand, the BFI from the Ministerio de Educación y Ciencia and the Consejeria de Innovación, are over 400 times more likely to be oculomotor system has been found Ciencia y Empresa of the Junta de Andalucía, aggressive to their infants when they are to be an excellent model for the Spain. crying than when they are quiet.

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The peri-conceptional origins of the life-long physiological consequences of being a twin Studies in twins, both human and ovine, suggest that the fetal developmental trajectory in twins is different from that of singletons and may be reflected by altered physiology in post-natal life. The early pregnancy environment may be critical in determining both pregnancy outcome and the risk for adverse long-term health outcomes In essence, therefore, twins could The associations between reduced be considered to have constrained size at birth and a large range fetal growth in that they fail to grow of adverse health outcomes in to their genetic potential. This is adulthood are now well established also the definition of intrauterine in singletons. However, the literature growth restriction (IUGR). Do a on these associations in twins is mean gestational length decrement much less clear. This may be due of 3 weeks, and a shift to the left in part to classical methodological in distribution of birth size in twins approaches in twin studies, which matter? entail comparisons of outcomes between monozygotic and dizygotic Frank Bloomfield. The consequences of being a twin twins to separate the effects of for short- and long-term health genes versus environment. However, Pregnancy outcome in twins outcomes when the effects of the intrauterine The incidence of twin (and higher Newborn twins have a higher environment on outcome are order multifetal) pregnancies incidence of most common being studied, this separation is is increasing worldwide, largely neonatal problems, with mortality due to increased use of assisted and disability rates increased 5- to reproductive techniques and 10-fold compared with those of advancing maternal age. Twins are singletons. Much of the increased born both earlier and smaller than risk can be attributed to preterm singletons with a mean gestation birth or IUGR, with even late length of 37 weeks compared with preterm birth (birth at 34–36 weeks 40 weeks in singletons. The reduced gestation) now recognised as size at birth in twins is not only carrying significantly increased risks due to their shorter gestational for a variety of adverse outcomes, length; rather, twins have a including not only physiological different birth-size distribution parameters such as blood pressure (affecting weight, length and head and glucose tolerance, but also circumference) from singletons developmental progress and school and this persists into childhood. achievement (Morse et al. 2009).

Figure 1. A, insulin area under the curve (AUC) in response to a glucose load (left bars) and to arginine stimulation (right bars) in singleton (white bars) and twin (black bars) ovine fetuses in late gestation. *P < 0.05, **P < 0.001 vs singleton fetuses. The increased insulin response to glucose, but decreased response to arginine, is consistent with advanced pancreatic maturation as the beta cells switch from fetal sensitivity to amino acids to mature sensitivity to glucose. B, ACTH (x-axis) and 11-deoxycortisol (y-axis) responses to metyrapone in singleton (blue squares) and twin (yellow circles) ovine fetuses in late gestation. Metyrapone blocks the rate-limiting enzyme for cortisol biosynthesis, resulting in elevation in ACTH and then 11-deoxycortisol (the cortisol precursor) in response to a fall in negative feedback inhibition. Note the increased ACTH concentrations required to achieve a given 11-deoxycortisol concentration in twin fetuses, consistent with adrenal resistance to ACTH (P < 0.0001). C, corticotrophic stimulation test in adult singleton and twin sheep. The y-axis shows the decrease in ACTH AUC for every kilogram increase in birth weight. The numbers below the bars are the regression coefficients for birthweight in singletons (S), and the between twin-

pair (βB) and within twin-pair regression (βW) coefficients for birth weight in

twins. The effect size is largest, and statistically significant, forβ W, indicating that the decrease in ACTH AUC with increasing birth weight is due to factors intrinsic to each twin fetus, rather than to maternal factors affecting both fetuses.

Physiology News | No. 75 | Summer 2009 | www.physoc.org 32 PN FEATURES not so distinct. The intrauterine Altered developmental trajectory There is good evidence that environment is affected by two in twins may be determined in periconceptional factors affect fetal components: maternal factors (e.g. early pregnancy development in animal studies. For nutritional status, body habitus, The physiological reasons behind example, we have demonstrated that ingestion of toxins), which will be the altered fetal development, moderate maternal undernutrition common to both fetuses; and factors adverse pregnancy outcomes and around the time of conception intrinsic to each fetus. Some of long-term consequences for adult in singleton-bearing ewes (a these fetal factors will be genetic, health that are associated with principally monotocous species) but others will not. For example, twin pregnancies are still poorly leads to preterm birth and altered the proportion of the placental understood. The dogma is that fetal development (Bloomfield et nutrient supply that each member reduced size at birth and gestational al. 2003). Maturation of the fetal of a monozygotic twin pair claims is length in twins are related to an hypothalamic pituitary adrenal not related to genotype. More recent inability of the mother to adequately axis (HPAA) and of the pancreas studies have addressed this issue by support more than one fetus to are advanced. In twin fetuses of including coefficients for both within term: the competition between the well-nourished ewes, pancreatic twin-pair and between twin-pair twins for nutrients results in nutrient development is also advanced factors in the statistical analyses, and demand outstripping supply, and compared with singletons (Fig. 1A; these studies have tended to find there is excessive stretch caused by Rumball et al. 2008). However, the same associations between birth two fetuses. These two factors then other aspects of fetal development weight and risk of adult disease in result in initiation of mechanisms in twin fetuses, such as the fetal twins. that lead to preterm parturition. HPAA, are delayed compared with However, the fetus is known to singletons (Fig. 1B). Ontological The question of the effect of a twin be a highly effective nutritional studies of HPAA maturation in pregnancy on outcome is not one parasite, and the signal transduction sheep demonstrate, however, that most animal experiments can mechanisms initiated by uterine that both the accelerated address. The majority of the animal stretch do not appear to be development in singletons from studies investigating the associations advanced in multiple pregnancies. In undernourished ewes and the between intrauterine environment fact, there is no evidence that twins delayed development in twins are and long-term outcomes have been are born earlier than singletons as a already present in mid-gestation performed in polytocous species result of increased uterine stretch. and that placental glucocorticoid (those that give birth to several Data from pregnancies in which the metabolism is also altered at fetuses at once). Furthermore, number of fetuses was reduced early this time. Intriguingly, in adult these species often give birth to in gestation (either spontaneously sheep born to periconceptionally young that undergo critical aspects or through intervention) show a undernourished ewes HPAA function of organ development (such as of significant association between is suppressed, whereas in adult the pancreas) postnatally, rather both gestation length and birth twin sheep it is activated, and the than before birth as in the human. weight and the original number of degree of activation is related to the Clearly, if fetuses from multifetal fetuses, rather than the number that within-twin pair coefficient for birth pregnancies are fundamentally are actually delivered, raising the weight (Fig. 1C). Thus, two different different from singleton fetuses, and intriguing possibility that factors periconceptional events both have long-term health is affected by stage in early pregnancy, perhaps even profound, but different, influences of development at birth (as is now around the time of conception, on fetal development that persist as apparent in preterm humans), such determine, at least in part, fetal altered physiology in adult life. species cannot be used to address growth trajectory and gestation these questions. length in twins. These experimental data are supported by increasing circumstantial evidence that gestation length and size at birth in human pregnancies are also associated with factors operating in the periconceptional period. For example, preterm birth in humans is associated with maternal undernutrition in early pregnancy (Rayco-Solon et al. 2005) and with exposure of the mother to severe stress such as an earthquake. Figure 2. Although twins may be discrepant in size (above), even the larger twin of Human studies also suggest that a a pair is, on average, smaller than the average singleton. Dizygotic twin pregnancies discrepancy between actual fetal are also relatively common in sheep, with a similar reduction in birth weight distribution. size and expected fetal size in the

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first trimester predicts both small- phenotypic differences (Poulsen et early pregnancy which improve for-gestational age and preterm al. 2007). pregnancy outcome. birth (Smith, 2004). Male fetuses are already larger than female fetuses in The life-long consequences of Frank H Bloomfield early human pregnancy, and some periconceptional factors, whether Liggins Institute, University of twin studies have suggested that they be the nutritional status of the Auckland, Private Bag 92019, growth trajectories of twins diverge mother or the presence of a co-twin, Auckland, New Zealand have implications for both research from those of singletons as early as References and for potential interventions. 8 weeks gestation. Bloomfield FH, Oliver MH, Hawkins P, A conundrum for research Campbell M, Phillips DJ, Gluckman PD, Challis Do the periconceptional origins design is whether fetuses from JRG & Harding JE (2003). A periconceptional of the long-term consequences of multitocous species are immune nutritional origin for noninfectious preterm being a twin matter? to developmental adaptations in birth. Science 300, 606. The periconceptional period appears response to additional (or fewer) Morse SB, Zheng H, Tang Y & Roth J (2009). Early school-age outcomes of late preterm to be one critical period during fetuses, or whether adaptations infants. Pediatrics 123, e622–e629. which pregnancy outcome can similar to those demonstrated Poulsen P, Esteller M, Vaag A & Fraga be influenced. Adverse maternal in monotocous species occur. MF (2007). The epigenetic basis of twin exposures, such as undernutrition, Clearly, the answer to this question discordance in age-related diseases. Pediatr Res and intrinsic fetal events, such as may impact on how findings in 61, 38R–42R. twin conception, both permanently animal experiments may translate Rayco-Solon P, Fulford AJ & Prentice AM alter the fetal developmental to the human situation. Further (2005). Maternal preconceptional weight and trajectory with consequences research into understanding the gestational length. Am J Obstetr Gynecol 192, 1133–1136. for post-natal physiology. The mechanisms and key signalling mechanisms mediating these effects pathways that mediate signals from Rumball CWH, Harding JE, Oliver MH & Bloomfield FH (2008). Effects of are not yet known, but accumulating the periconceptional environment twin pregnancy and periconceptional evidence suggests that epigenetic to the fetus, resulting in setting undernutrition on maternal metabolism, fetal modification of DNA and histones of developmental trajectory, is growth and glucose–insulin axis function in may play a role and that epigenomic critical. Such research may lead ovine pregnancy. J Physiol 586, 1399–1411. differences between members of to knowledge that could result in Smith GC (2004). First trimester origins 58728.09 nestle malof adfetal PHYSIO growth NEWS:58728.09 impairment. Semin nestle mal ad PHYSIO NEWS 20/4/09 13:24 Page 1 monozygotic twin pairs may explain interventions before or during very Perinatol 28, 41–50.

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Physiology News | No. 75 | Summer 2009 | www.physoc.org Advertisement_Phys-News.indd 1 15.04.2009 15:54:13 34 PN INTERVIEW

Thinking the thoughts of a cell... Austin Elliott caught up with Professor Sir Michael Berridge (below) in Manchester where he delivered the President’s Lecture on ‘Calcium signalling in health and disease’ at the Summer 2008 EPHAR (Federation of European Pharmacological Societies) meeting

Professor Sir Michael Berridge FRS (right), MB I think we’ve got most of the well-known for his work on calcium (Ca) elements. You can’t divide channels up signalling and inositol phospholipids, was into smaller bits so we’ve now essentially born in what is now Southern Rhodesia. got the basic building blocks. But I think He came to Cambridge as a PhD student we’ve just scratched the surface in most and has worked for many years there and cell types. So there’s still a lot to learn at Babraham. on how these systems are put together in specific cell types. And I really make a Austin Elliott (AE) I wanted to start by plea for looking at primary cells, because asking a very long timescale question: so much work now, in Ca and many other do we know how far back in evolution Ca signalling pathways, is done in cloned signals go, in primitive organisms? cell lines. [That] work can certainly be it is extraordinary the kinds of indicators helpful in identifying the components Michael Berridge (MB) They don’t seem that he’s produced. As you mentioned, and studying how they might operate. to be present in bacteria as such, but it’s what’s fired the revolution really, But there’s no escape from actually they go back into fungi and plants. In going hand in hand with imaging working on the primary cells. And plants it’s quite interesting because they technology. It’s been extraordinary, what there, I think, there is still an enormous have all of the same elements that you one can now see at the single cell level. amount of work to be done. We know see in mammalian cells. In addition to a lot about cardiac cells, perhaps more AE And of course, also in Cambridge, the temporal aspects that I was talking than anything else. We know almost around the same era were Rex Dawson about today, and for example in root exactly, down to the number of channels and Robin Irvine doing inositol lipid nodules, they can detect nod factors occurring in the junctional zone. That work. When I was [preparing for] this which are produced by fungi and soil. sort of detail is absent in most other interview, I looked up the mission These act on cells in the root and they cell types. I think it’s now just the long statement from the very first issue of the induce the formation of a nodule and process of going into specific cell types journal Cell Calcium, because it happened to do that they induce these regular and seeing how their systems are put about this same sort of era. One of the oscillations, absolutely beautiful, that together and how they work. things it [contained was] a summary go on for ages. So all the elements of Ca of what was then vaguely known. And signalling are certainly well established AE [That] fantastic level of detail that it said: “stimulated Ca entry in cells” in plants. we’ve now got to in certain cell types and then it said in brackets “(coupled [has] been dependent on the technical AE So both release of Ca from storage to phospholipid metabolism?)”. And advances in how one measures these pools in the cell and stimulated Ca entry, I remember this because it was the kinds of signals, which have been really they’re there? only question mark in the article. And dramatic. And of course you were there at the time that was really, as you’ve MB Yes, they are somewhat different in the early stage of this in Cambridge mentioned, regarded by many people as because plant cells are dominated by in the late 1970s and early 1980s, when a crazy idea. So what made you think… it the vacuole… so there are important some of these ideas were just being was worth running with? differences [from animal cells]. But the booted around. basic principle of having an elevation of MB Well, I think really it was reading MB Yes, I remember quite distinctly, Ca, having strict control over the spatial Bob Michell’s review in 1975 or ‘76 I started to try and grapple with this and temporal aspects, is certainly well (Mitchell, 1975). I really recommend to problem by developing Ca-sensitive in place in plants. And, of course, it’s anybody, including young students, to electrodes, which turned out to be present in insects and in worms such as read that review. It is an extraordinary, extremely difficult. And at that time, C. elegans. There is some beautiful work scholarly kind of review: he brought Roger Tsien was working with Tim Rink going on Ca signalling in C. elegans and together biochemistry, pharmacology, over in physiology and I can remember all the same elements are there as well. physiology. But the main theme of distinctly their coming over to ask me the review, really, was the fact that, AE One of the things that people who for advice on how to construct a Ca based on the pharmacology of many have been in Ca signalling… a while like electrode. I think it was the only time of these systems, some receptors were to do is look [back] at the progression I ever gave Roger Tsien any advice. activating cyclic AMP, and not Ca. of the field and say: what were the key And they arrived a few weeks later The other receptors were activating a problems over the decades? You’re to ask some more questions and I’d phosphatidyl-inositol (PI) response. And famously associated with solving the already given up on Ca electrodes. I was [those receptors] were all activating Ca. problem of how Ca is released from starting to study phosphatidyl-inositol So it was this association that he built up storage pools, in the 1980s onwards, but (PI) metabolism. They were absolutely which convinced me that it was worth you spent much of your lecture talking appalled that I’d given up on Ca pursuing. about spatio-temporal organization of electrodes to study this wacky system of signals in cells, which I guess is the 1990s the PI response, but that turned out to I then did some experiments, which until now. Do you think we’ve got wholly be a wise decision. I think Roger gave up would [take] a bit too long to relate, to the bottom of that problem, or is it on electrodes and that’s when he started but the essence was that insect salivary still not quite solved? looking at the indicators, and of course glands were very permeable to inositol.

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That was the way I was able to measure of, for example, muscle contraction. a primary cell which has a specific TRP the PI response, by measuring the release And it’s hard enough trying to do it just function associated with it. The only one of tritiated inositol from the glands in mammalian systems but one would is Orai, which isn’t a TRP channel, but upon stimulation. But then I realized then have to do it in a whole lot of other is a store-operated channel. We know that if they were losing this inositol, species. And then try and pick up what that Orai is very important in T cells. And if I stimulated them hard and washed the subtle changes were. I’m not sure, at we know that mutations in Orai lead to continuously, I might be able to deplete this stage, that it’s worth the effort, to spontaneous SCID (Severe Combined the lipid. That’s exactly what happened be honest. But in time it may well be. Immunodeficiency). So there’s a genetic and the Ca signalling then faded away. mutation in a store-operated… channel, And then when I re-fed the cells with AE Your lecture today was a tour through which is leading to a certain deficiency. inositol the Ca signal came back again. the way Ca signalling elements are That does suggest that something that And that absolutely convinced me that ‘selected’ by different cell types and their would act on TRP channels, as you Michell was right, that there was a link differentiating programme to enable suggest, may well be an interesting between the two. And then one had to them to do their different jobs. One of target to deal with. But with all these go on to try and find the link. But that the things that calcium scientists joke other TRPs, it is really amazing that it really, in my mind, put [it] on a firmer about after meetings is often: we know is hard to tie down where they actually footing, that this may well be what the PI so much about this now, but relatively work in a specific process. There’s plenty response was about. But it was Michell’s speaking, the amount of pharmacology it of information on cloned cells, but review that really got me interested. has so far generated is surprisingly small. there’s an enormous mismatch between We have the L-type calcium channel all the work that’s been done on these AE You mentioned there the system blockers, particularly for hypertension, TRP channels, [and] relating that back to that you were famous for many years but beyond that… sometimes people a specific cell type and saying ‘the liver for working on, which is the bluebottle say: you might’ve expected more has TRP 6 and it’s very important for salivary gland. Of course… invertebrate pharmacology. Do you think that’s true? doing x, y and z’. That part seems to be physiology has a classical place in Or are we going to see more, do you absent. physiology and pharmacology. But suspect, in the next 10 or 20 years? perhaps now, with the exception of AE Well part of it is almost a Catch-22 niches such as Drosophila, it seems… MB It’s an interesting question. I think because it’s hard to probe the function less prevalent than it used to be. Do the problem is that the Ca signalling without a selective inhibitor. you think the use of systems [from] system is so central to everything the comparative physiology still has a place cell does, moment-to-moment. If you MB Yes, but the technology is there to in the modern investigation? interfere with this too strongly, you do cell-specific knock outs and so on… really are in trouble. So it came as a great but it’s actually very difficult. The other MB Drosophila is still feeding… very surprise when the voltage-gated channel thing which I think is so important is interesting signalling molecules into blockers started to emerge. People plasticity of the Ca signalling system. It the general arena. Like… Orai, a store- were really surprised that the heart has an extraordinary ability to be able to operated channel that emerged from didn’t stop, and so on. There seemed to get around any imposed changes. Many screens done on Drosophila. The TRP be some degree of [tissue] selectivity of the knockout studies that have been channels emerged from Drosophila and and that may explain why they were so done, it’s just amazing how there’s just there are many other signalling systems effective. an absence of a phenotype. But if you where Drosophila has actually been very go in and look at what has happened, important in feeding in information. I think in time, if we really get to know you find it’s extraordinary, the way the The Wnt system is another example. and understand how the system is cell has been able to go back into the The people in the Drosophila field are… actually constructed, we might be toolkit, select out an alternative and put very active and… very aware of the able to start to develop more specific that in place, so that the cell looks quite importance of their molecules with and selective drugs. But it will really normal. And it is this self-assessment regard to mammalian systems. That’s be ways of subtly modulating the mechanism that I mentioned. The cell always at the end of [their] papers, as system. But when you think of how seems to know, after it’s differentiated, it were. So no, I don’t think it’s at an amazingly it’s constructed in terms of that it has to produce a certain type end. And C. elegans is coming on-stream these oscillations; they’re very delicate of calcium transient. And if you come now with [use of] genetic manipulation. beasts, these oscillatory systems. Minor in and suddenly pluck out one of [the] That too is now feeding in important tinkering and the whole thing could just components, as long as it’s got a certain information collapse. So it’s not an easy thing to do. amount of time, it can adapt in an extraordinary way. AE Do you think there’s anything special AE Yes, not an easy thing to modulate. we can learn from these evolutionary The TRP channels, which were not in These adaptations are not just replacing approaches? As more and more your lecture but have been the focus of alternative components, they can organisms are cloned, one gets to see much attention in the last 10 to 15 years, actually adapt by changing, for example, these same mechanisms, as you’ve have been touted as one of the next the downstream effector systems. So briefly alluded to, developing through generation drug targets. The rumours people have been trying to knock out evolutionary time, which is quite tell us that the drug companies are busy, some of the N-type and R-type channels fascinating. but as yet there isn’t much. Or at least that promote exocytosis in synaptic nothing much that they’re telling us. endings. What they find is that… lo and MB I think that’s going to be quite behold, they actually start altering the difficult to handle, because the only way MB I’ll go back to this business of profile of the synaptotagmins. [The cells] I can see that one might be able to do differentiation and studying specific cell actually put in new synaptotagmins, it is to really develop an understanding types. It’s hard to find an example of which increased the selectivity of the

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effector system. So even though the in the phenotype [for example] through And that’s what I’ve tried to do [Ca] signal is weaker, the end result is abuse. The system is desperately trying with my website (http://www. the same because you’ve got a more to accommodate [these changes], but in cellsignallingbiology.org), I’ve tried to sensitive effector. Now to my mind doing that it brings about other changes summarise what I feel is the current that’s the most extraordinary kind of which finally have disastrous results. state of different signalling systems in adaptation. This relates back to your And one of the results is for example different cell types. That may suggest to question about new drugs. You see you atrial arrhythmias [which are] due to some people new things to do. may be able to get something which phenotypic remodelling as well. These dampens down x, but with time the cell are the aspects we have to get to grips AE One final question. There is a rumour will get around that and put something with and it’s not easy. that circulates in the field that you nearly else in. And then you’re back to square didn’t become a physiologist at all, you one. You have got to understand the primary almost became a big game ecologist. Is cell. That’s the key point. that true, or is that just an urban legend? AE At the end of your lecture [you talked about] the linkage of human AE Yes, of course, with something like MB No, that’s true. diseases, and particularly of common atrial arrhythmias, [one is] particularly AE And this stems from your childhood? diseases like diabetes and hypertension, perhaps thinking of stretch-induced to dysfunction in the Ca signalling ones, because many dysrhythmic MB Yes, I’ve been fascinated, since I toolkit. You were stressing not so much problems result particularly from volume was a child by African wildlife. I decided direct dysfunction of single elements, overload and stretch. And of course at school that I’d like to become a which perhaps is the way that we’ve that comes back not only to primary game ranger, but when I applied to the been conditioned to think about it cells but also to in vivo models, which is department towards the end of my from genetic channel diseases, [the] something else that both physiology and school career they were a bit reluctant. channelopathies… but much more subtle pharmacology have been coming back They advised me to go into big game aspects, to do with the regulation of to, after 20 years of retreat. ecology because they thought that whole panels of proteins. Could you tell MB Absolutely, I couldn’t agree with you ecology was going to be the big thing in us something more about that? more. Africa. Of course they were right. But at that stage there was no ecology course MB This is what I referred to as as such. The only ecology courses in big phenotypic remodelling and AE You are well known as a very prolific game were run in California, and from the question is: what drives that and lucid review writer, from your the middle of Africa, that was a long remodelling? It all comes back to the fact original 1984 Nature review on inositol way away. So I ended up going to do that this system has a plasticity built into phosphates with Robin Irvine (Berridge zoology, which was the closest that I got it, which means that you can in fact bring & Irvine, 1984) onwards. With the to that. I had a most amazing lecturer, about and actually accommodate subtle proliferation of experimental papers in all Eina Bursell, a Danish insect physiologist changes in the quality of the signal. And fields, do you think reviews have become [whose] lectures just blew me away the question is: what’s driving this? more important in that respect? One hears scientists repeatedly say that they – just extraordinarily interesting. In For example, in hypertension you can struggle to keep up with the literature, fact I remember to this day, he talked trace from the fact that you have a high so reviews provide a very important about the ‘staircase phenomenon’ in salt diet then this is going to impose service to people. the heart. You had the beating heart an increase in blood pressure, and you and you applied [a hormone] and you will have water retention. That increase MB I think they are very important. But got this gradual increase in the force of in pressure then feeds back on to the there are reviews and there are reviews, contraction. And I still remember that heart, which starts trying to force the of course! If they can be really objective and being absolutely fascinated by this heart to work harder so it now produces then I think they serve an enormous ‘staircase phenomenon’. stronger signals. It achieves it’s end, by value to the field and that’s what I’ve Anyway, it’s amazing that now, through increasing the force of contraction, but always tried to do, to pull areas together my work on signalling, I now understand then you pay for that by the fact that and perhaps stick my neck out a little how that actually develops. It’s really the system is being unstable, it’s not bit. There are times, when you immerse rewarding. But that’s what took me working at it’s normal level. So then the yourself in a field, you start to get a away from the idea of being a big game cell tries to make adjustments to cope feel for what might be happening. You ecologist. And that’s what brought me to with this elevated calcium and then that almost try to think like the cell thinks, Cambridge to do a PhD with [Sir Vincent] leads to remodelling, which can have a as it were. And if you can write this Wigglesworth, on insect physiology. catastrophic effect on the heart. down clearly and perhaps just provide a way forward. I’ve always advocated So it is a very subtle process, but I think that but I know that there are lots of References the channelopathies are much simpler. people who think that one shouldn’t do Berridge MJ & Irvine RF (1984). Inositol You’ve got your mutation, you’ve this, you shouldn’t be too speculative. trisphosphate, a novel second messenger got your change, in many cases these But I’ve always thought that was the in cellular signal transduction. Nature 312, are lethal. [Other] mutations that we wrong way around. I think one should 315–321. know about are those that aren’t too be speculative, because that’s what Michell RH (1975). Inositol phospholipids serious, like the mutation in the Type I we’re about. We speculate when we and cell surface receptor function. Biochim ryanodine receptor, which only shows start doing experiments. We speculate Biophys Acta 415, 81–147. up during anaesthesia [in malignant on how we think something works and An extended audio podcast of this interview hyperthermia]...But these aren’t the then we do the experiments. There’s no is on the British Pharmacological Society’s major diseases in man. The major reason why you can’t do that in other meetings podcasts page: www.bps.ac.uk/site/ diseases are these changes which occur areas. cms/contentCategoryView.asp?category=357

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Tomorrow’s women, leader in research. Futurologist, Dr Shultz gave some fascinating insights tomorrow’s world into what we might be doing in 2030 including vertical urban greenhouses The Physiological Society, in Valerie Gladwell. and meat grown in labs. collaboration with the UK Resource Centre for Women in Science, Annette Williams, the Director of Engineering and Technology (SET), career ladder. Emily Cummins (an the UK Resource Centre, gave her have set up a pilot mentoring scheme award-winning young engineer) vision for 2030 which included the for women this year. As part of my refuted this point and believed that thought that 23% of professors in SET role to aid the process of setting she was given incorrect advice at disciplines should be women by this up this scheme, and to get a feel school, being persuaded against time. We need to ensure women have for the range of needs required by Maths and Engineering at A-level. the correct skills set to do this. As women I attended the conference Emily at 21 has already established Maggie Philbin suggested, we should held in March in London run by the herself as a well-known engineer with make sure that we all promote our UK Resource Centre for Women in the development of a sustainable strengths and our aspirations (women SET entitled ‘Tomorrow’s women, fridge (which is being used in Africa) are particularly reluctant to do this) tomorrow’s world’. The conference despite having no formal education and seek help if we have weaknesses. and the mentoring scheme are not in engineering. She is an inspiring This is where vertical networking may about women taking over the world young lady and it is the young, help. but to help retain and recruit as many bright individuals like herself that good female scientists as possible. we need to educate and keep in SET So where do we go from here? How disciplines. do we ensure we get more women Currently women make up 33.5% of at the helm of scientific excellence? all higher education students in SET Susie Uppal from The Equality and As scientists, we need to engage disciplines, and 25% of academics. Human Rights Commission discussed the public and encourage parents to As the level of seniority rises the the concrete ceiling effect that inspire their children, especially girls, percentage falls dramatically with prevents women rising to the top, to want to learn more about science. only 8% of women professors. But although sometimes it is the less We need to give the correct advice where will we be in 2030? visible constraints preventing women to ensure that a sensible path is progressing. Their research suggests followed. For emerging scientists, we In contrast to Physiological Society that pay widens in employees’ early must have a good education system. I meetings, at this conference 97% thirties, a potentially crucial point in believe that The Physiological Society of the delegates were female (as young people’s careers, but a time already plays a major role in this with might be expected) with only two when some women’s biological clock its ambassador schemes and other male speakers (The Minister of is ticking. This certainly is not the sole outreach programmes. Science, Lord Drayson, and Philip reason for the gap and efforts need Greenish). The audience was diverse to be made by employers (including If we wish to have more good female with CEOs from major companies, those in Higher Education) to ensure scientists we need to ensure that role academics, students, scientists/ that this gap narrows. Women can models are visible, especially women engineers from industry, women help themselves by networking both scientists. returning from career breaks and a horizontally and vertically, Ayo Bakare Maths clown (who made a satellite from UK Resource Centre explained, Just to test this: What famous female out of balloons). The day was as making useful contacts is crucial scientists can you name? Were they interesting and thought provoking as for progressing a career. This means born in the 20th century? we considered where SET disciplines that we should not just concentrate The UK Resource Centre for Women would be in 2030, that is 21 years so hard on the tight-rope of our in SET is an excellent wealth of time when my daughter of 10 months careers, desperately trying not to fall networks, training grants and events, will be starting on her career ladder. off, by only networking with people and links with public life positions around us in similar situations but (see www.ukrc4setwomen.org). The day was chaired by Maggie should strive hard to make links Philbin of Tomorrow’s World fame. above ourselves (not just in our own I am a Physiological Society Council She started the day off with an organisations) and start climbing Member, currently helping to set up unscientific survey using her blog to vertically up the rock face of our the Physiological Mentoring Scheme ascertain the number of women in career path. for Women with fellow co-ordinator SET at senior levels. It showed that Daniela Riccardi and Elizabeth Bell. there were relatively few making the Professor Walby also discussed the higher levels but Professor Walby economic downturn and how we Valerie Gladwell (Professor in Sociology) stated that should be prepared for recovery, with The Society are pleased that our the statistics showed it was not SET subjects high on the agenda to Mentoring Scheme has now made 10 education in schools that was the help improve the economy. We need matched mentor–mentee pairs for this sticking point but further up the to help maintain the UK as a main year.

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Profile: Emily Davies, participant on the BPS/Physiological Society in vivo short course Eight years ago, the British therefore nationally recognised. investigators, post-docs and PhD Pharmacological Society and The A large proportion of biomedical students within the University. Physiological Society set up Short undergraduate students do not get courses on in vivo pharmacology/ the chance to gain such skills and so Did the course reinforce your desire physiology (now known as BPS/ it was a great opportunity. to do in vivo research as a career? Physiological Society short courses The course certainly provided on integrative pharmacology and When and where did you carry out me with many opportunities and physiology) for undergraduate your short course? confirmed my intentions to pursue and postgraduate students in The week-long course took place a career in research. I decided to response to the decrease in the in June 2007 at the University of use my training and skills gained number of universities in the UK Bristol, within the Department of on the course to best advantage that offer in vivo training within Physiology and Pharmacology. Many and I selected an in vivo final year their institutions. Funding for the different research laboratories within undergraduate research project. This courses, additional to that provided the University were involved. Prior in vivo electrophysiological project by BPS and The Physiological Society, to the summer course, I attended a gave me the opportunity to present comes from the Wellcome Trust, 2 day Home Office Personal Licence work at international conferences the BBSRC and the Pharmaceutical training course and examination in including the triennial meeting of Industry and covers the cost of order to hold a Personal Licence to the International Association for the running the courses, student travel carry out experiments under the Study of Pain and the main meeting and accommodation expenses, Animals (Scientific Procedures) 1986 of The Physiological Society. I am attendance at a Home Office training Act (ASPA). now undertaking a PhD which also course (modules 1–4), and the in vivo expands on the techniques I learnt. I training course itself. Three courses Can you describe what the short believe my interest and enthusiasm are run each year, currently at King’s course entails. in pursuing an in vivo research career College London, the University of This intensive, specialised course in neuroscience has largely stemmed Bristol and the University of Glasgow. involves a mixture of lectures, from the BPS/Physoc in vivo short observation and hands-on course and the opportunities arising Emily Davies obtained a first class experimentation, in order to gain an from it. degree in Pharmacology from the understanding of the physiological University of Bristol and stayed on and pharmacological principles Why do you think that in vivo to study for her PhD in Physiology. underlying in vivo experimentation. work is important in advancing The title of her PhD is: ‘Developing I was able to learn techniques biological science? somatosensory evoked potentials in such as small animal surgery, data In vivo experiments are necessary in vivo – a translational model for pain’. acquisition and experimental design. order to investigate whole system She attended the in vivo short course physiology and pharmacology and during her undergraduate degree. Lectures were given by academia and industry representatives on the use understand interactions between different body systems and their How did you find out about the of animals in biomedical research. modification by drugs. This is not BPS/Physoc in vivo short courses? During the course we were able to carry out and have input in our own always possible using alternative I was informed about the course methods in novel research. in a lecture during the 2nd year of experiments. Participants also had my undergraduate degree at the the opportunity to observe in vivo How much of the course focused on University of Bristol. I was keen to electrophysiological experiments ethics of animal experimentation participate as I was considering a in various labs within the University and how important do you feel this career in research at the time and and get a taster of research life. is to someone planning a career in knew the course would provide me Due to the large number of staff in vivo pharmacology? with invaluable skills. The course associated with the course, and is organised and funded by BPS the small student numbers, there Both the Home Office licence training and The Physiological Society, was a great deal of expert guidance course and the in vivo short course and sponsored by a consortium and instruction. Towards the end of gave serious consideration of the of pharmaceutical companies, the week there was a dinner which ethics of animal experimentation. BBSRC and Wellcome Trust, and is allowed us to socialise with principal They emphasised the ethical

Physiology News | No. 75 | Summer 2009 | www.physoc.org REPORTS PN 39 requirements under ASPA and the Where do you see yourself in anti-research medical pedagogues. requirements of the University 5 years time and what are your As then so it is now, priority disputes of Bristol. We were also taught long-term career aims? and animal experimentation flag about seeking and using alternative I would like to stay in academia the need for continual exemplary approaches and the importance and at the moment my career aim practice. of experimental design for in vivo following my PhD is to take on a research. I believe it is crucial post-doc position and contribute for anyone embarking on an in original research to the field of vivo research career to have a neuroscience. comprehensive understanding of the legal framework relating to the use The courses are aimed at both of animals in research and the ethical undergraduates and postgraduates, considerations. with calls for nominations going out via Heads of Departments in the 4th How did the in vivo training course quarter of the year preceding the help you in choosing your PhD? course. For further details, please Gaining in vivo training at an early contact [email protected] or Tilli Tansey. stage in my research career gave [email protected] me the chance to continue in vivo Leading us through a talk peppered research during my undergraduate Judith Hall with lively anecdotes, we were privy degree and during this time I British Pharmacological Society to a treasure-chest of insights. How developed a keen interest in the wronged Bayliss countered neuroscience, in particular pain Professor Tilli Tansey anti-vivisectionists and sued them research. This is the area of research for libel – funding a scholarship in I have now decided to pursue in my Inaugural Lecture experimental biology. How UCL’s PhD. Models and mechanisms: Hill, and Beveridge of the London aspects of biomedicine at School of Economics formed the How would you compare the value Academic Assistance Council, so of the hands-on course with using UCL in the twentieth century, important during the Nazi era (and computer simulations instead? 9 March sadly still vital) bringing, amongst them, Bernard Katz to A V Hill’s Computer simulations are A ‘eureka’ moment in the group. How post-war physiologists particularly useful in reinforcing development of science is a gained from Fleming, whose ‘valve’ theory for undergraduate students beautiful thing to contemplate, (‘tube’ to those across the pond) in but the hands-on course allowed and Tilli Tansey took her audience many forms was available in ex-war me to put that theory into context. to such a time and place special department electrical equipment Although my undergraduate degree for physiology: the perception that for the amplification of the nerve’s programme widely used alternative the signals passing between nerves electrical activity. Finally we were in vitro and computer-aided may be chemical in nature. That the left to ponder which UCL scientist it education methods, for individuals place was UCL and the development was swaggering back to college from intending to undertake an in vivo published within the pages of The Tottenham Court Road with a gross research career it is important to Journal of Physiology sets the stage of condoms tucked under his arm. learn the relevant skills in order to for Tilli’s inaugural lecture that One wonders how many were used carry out productive research later in included numerous illustrations, as per the necessary chit, with the their careers. several from the Society’s archives. tips cut off. Who do you think would benefit Under her title ‘Models and Tilli is Professor of History of most from attending a short mechanisms: aspects of biomedicine Modern Medical Sciences at UCL. course? at UCL in the twentieth century’ She spent many years working as a I would definitely recommend she skillfully threaded together the neuroscientist before becoming a the course to undergraduate interactions between clinicians, historian, specializing in twentieth- students who are interested in a experimentalists, the pharmaceutical century medical sciences, especially research career as I think it would industry and the law, around physiology and pharmacology. Tilli benefit them the most, but also to her major theme ’The model has been The Physiological Society postgraduate students wishing to molecule of the twentieth century’ honorary archivist since 1990. gain new skills. There is a shortage which ‘we’ now call adrenaline. of graduates with an education Covering a century of 115 years, John Berriman involving in vivo research, and in she encapsulated the synergy at my case I found that potential work in UCL as a special place for To listen to the podcast, go to: supervisors when applying for my Biomedicine (as it is now called) www.ucl.ac.uk/histmed/downloads/ PhD really valued this training. to florish beyond the strictures of tansey_inaugural

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Forty metre man far beyond the brain’s immediate audience. leaves brain behind in Exploring in Explore Bristol After performing so brilliantly How The Physiological Society as nerve cells, all pupils had free and Bristol Neuroscience entry to science centre ‘Explore celebrated the physiology of At-Bristol’ where they could try out the BAW activities being run there the brain this spring throughout the week. Organised Found: 1 brain, 4 m across, spotted by neuroscientists from both in central Bristol on Friday 20 March Universities, these illustrated various 2009 aspects of brain science using, for example, a model man (neurobot) Would suit 40 m man or woman showing touch and pain, eyetrackers, Does this brain belong to you or and EEG. someone you know? Congratulations to the 100+ Contact: Bristol Neuroscience: neuroscientists who survived the bristol.ac.uk/neuroscience week (just!) supported by the University of Bristol’s Centre for Brain Awareness Week (BAW) – an Public Engagement and At-Bristol annual international festival of staff. neuroscience – was marked in Bristol this year thanks to a partnership And that’s not all... between The Physiological Society and the University of Bristol’s Alongside events described above, ‘Bristol Neuroscience’ (BN). With associated activities catered for 70 BN neuroscientists, 15 from the other age groups: University of the West of England, Science cafés hundreds of children and thousands Top, the giant brain was easy to spot in Bristol’s busy Millennium Square; Junior science cafés of members of the general public middle, EEG demonstrations: and below, Public lectures involved, the events run through this looking at a model brain. partnership gave a fantastic chance the year. Shoppers, tourists, office Art exhibition for Bristol’s neuroscientists to workers and commuters could not share their interests with the wider fail to miss the brain. People were Finally, a huge thank you, in community. encouraged to stop and discuss alphabetical order, to all project partners and funders: But how do you get people’s brain science with practising attention to start with? Direct neuroscientists. The event also Explore At-Bristol caught the attention of television, interaction and dialogue was at the BBSRC heart of all BAW events, but they radio and press, extending BAW would have been doomed to failure Bristol Neuroscience at the University of Bristol if no-one was aware they were taking place. MRC

Which is where a giant brain came in The Physiological Society (principal sponsor) useful. Quartet Community Foundation Giant brains and neurons with legs RCUK As ways to raise brain awareness University of Bristol’s Centre for go, a giant brain, in central Bristol, Public Engagement surrounded by 400 ‘human neurons’ was a pretty effective approach! It University of the West of England certainly didn’t leave any doubts as to what BAW is about. For a full report, video footage, and photos, please see: The role of the neurons was taken on http://tinyurl.com/bristol-baw by 5–11 year olds who had attended BAW school workshops, led by Lizzie Neurobot , a model man showing how we Anne Cooke Burns (sciencetolife.org), earlier in detect and respond to touch and pain. Bristol Neuroscience

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The annual meeting Manchester) to start the session. Professor Sibley described the of the Society placental syncytiotrophoblast’s role as a transporting epithelium and for Gynaecologic how it could respond to maternal Investigation and fetal signals to mediate the The 56th annual meeting of fetal nutrient supply. He also the Society for Gynaecologic speculated as to how the placental Investigation took place on 17–21 phenotype could be used to provide March in Glasgow. The meeting biomarkers for fetal growth. His talk was held next to the river Clyde in demonstrated how really important The speakers. the placenta is. the Scottish Exhibition Conference how the fetus may signal to the Centre, the UK’s largest conference Irene Cetin (University of Milan, placenta to optimize nutrient supply. centre, which includes a fabulous Italy) then continued by discussing If there is a mismatch between auditorium called the Armadillo. the importance of placental fat fetal nutrient supply and demand This meeting was a historic event transport for fetal development. a signal such as altered nutrients, because it was the first time that Diffusion and transport proteins glucocorticoids or IGF’s could lead to it has taken place outside of North mediate transport of the various a change in placental phenotype to America. The program included 150 fatty acids across the placenta, increase placental efficiency. Studies oral communications and over 900 and this can be affected by both in the placenta may therefore posters. There were also 15 mini placental and fetal metabolism. Dr be able to tell us about the fetal symposia, including a fascinating Cetin highlighted the importance experience of gestation and may session entitled ‘Altered placental of these processes not only in even be used to predict later health. function as a cause of altered fetal the normally growing fetus, but The placenta was also the focus growth’ which was supported by The also in fetuses from diabetic and of one of the concurrent oral Journal of Physiology. intrauterine growth restricted sessions of this meeting. This (IUGR) pregnancies. provided an opportunity for the ‘Is the placenta dying to get the new investigators to present their baby delivered?’ was a highly latest research which covered a entertaining presentation by Michael range of topics from placental Nelson (Washington University, nutrient transport to trophoblast cell USA); it is a unique ability to make signalling pathways. IUGR and placental apoptosis This meeting was indeed humorous. I was intrigued by his very informative and clearly description of the fibrin-covered The Armadillo. demonstrated the importance of clusters with apoptopic features the placenta for fetal growth and that are present within the the long term health of the baby. The placenta is the barrier between placental syncytiotrophoblast. The I am sure everyone who attended the mother and the fetus. It acts relationship between these clusters, is extremely grateful to The Journal like a lung, a gut, a kidney and is a hypoxia, apoptosis and IUGR was of Physiology for supporting this major endocrine organ regulating described using data from histology meeting. both the maternal and fetal biology. and cell culture studies. Placental function determines how effectively the available maternal Abigail Fowden (University of Jane Cleal Institute of Developmental Sciences, nutrients are transferred to the fetus Cambridge) then concluded Southampton and therefore how well the fetus this session with an overview of grows in the womb. Fetal growth is placental endocrine signalling and not just important in early life but Physiology News also throughout life, as babies who If you have enjoyed this issue of grow poorly in the womb are more Physiology News please don’t throw it likely to develop chronic diseases away. Put it in your coffee room so that including hypertension, heart others may see it too. disease, stroke and type-2 diabetes We are always looking for interesting as adults. features, meeting reports, news items and photographs. Contact Ed Sexton in Why bother understanding placental The Physiological Society Publications nutrient transfer was the question Office ([email protected]) with posed by Colin Sibley (University of The human placenta. your suggestions.

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Voice of Young of public concern at the time. From job for a non-science specialist; it this the audience raised concerns is not surprising to find that some Science Media on dealing with contentious issues, of the facts may have been ‘sexed to which all panellists emphasised up’ a little. Rebekah highlights the workshop, March the need for courage against being difficulty journalists can have when 2009 drawn into discussion on unrelated interviewing scientists, and uses topics or difficult issues, and the media-friendly scientist Trevor Cox Breaking news: body absorbs 5lb of importance of establishing in as an example of a journalist’s ideal make-up chemicals a year. Reality: advance the ‘agenda’ or ‘angle’ to science contact, explaining that a scientists suggest cosmetics may which the journalist is working. scientist who is good at digesting have cocktail effect if absorbed into complex information into sound- the blood stream. The perspective of the ‘bad guys’ bites understandable by ‘Sue’ not was put forward by a panel of How many of us have read a only makes her job easier, but helps sensationalist headline in the media broadcast and newspaper journalists, avoid misinterpretation and preserve only to despair at the scientific with local and national coverage. scientific integrity. inaccuracies being propagated to Presentations of the ‘day in a life’ Finally, both journalists and the public? Sense about Science of each journalist raised common media-relations professionals alike is a charity which works with themes emphasising the strict were keen to highlight the lack scientists to promote good science deadlines imposed upon science and evidence for the public, with journalists, the lack of science of early career scientists eager to the Voice of Young Science (VoYS) specialists in journalism, and the speak up and get involved with branch founded to aid early career impracticalities of fact checking and the media. This was echoed in the researchers stand up for science in tracking down scientists directly final message of the workshop by the public domain. involved in research detailed in Frank Swain, science writer and press releases. When challenged speaker, underlining the necessity of At a recent media workshop by the audience concerning the young scientists to be pro-active in organised by VoYS, early career ‘sensationalist’ reporting often assuming some public responsibility scientists were given the opportunity seen by the scientist as responsible for improving the media profile of to form views on how science is for turning science into ‘pseudo- science and promoting good science. portrayed and communicated in science’, freelance journalist Judith the media, and to directly question Duffy explained the plight of the Being given the opportunity to scientists and journalists on the well-intentioned science journalist interact with both scientists and ‘frontline’. Representing the ‘good when writing any newspaper article. journalists at the VoYS workshop guys’, media-savvy scientists began Science reporting is no exception brought to the attention of those the workshop with an unexpected to the rule and newspaper articles young scientists in attendance the defence of journalists, stressing the may be subject to cropping in the necessity for a better dialogue and obligation of researchers to shoulder interest of space at the last minute, understanding between science responsibility for the propagation of without consulting the author. More and the media. The battle against good science by clear presentation of surprising was the revelation that ‘pseudo-science’ can only be won the facts to journalists. Through the it is not the author, but the next when we as scientists stop viewing somewhat philosophical approach of person up in the pecking order, the media as the enemy and learn Raymond Tallis, a former life scientist the sub-editor, who is responsible to cooperate and use the power and novelist, and the enigmatic for fitting the headlines to articles. of the media to advance public enthusiasm of Trevor Cox, media This could be seen as journalists understanding and uphold scientific fellow for the Engineering and simply passing the blame; however, integrity. Physical Sciences Research Council, the comments revealed valuable it became clear that it is possible to information on the inner workings of Ellen Forty build a good relationship with the journalism nonetheless. Faculty of Life Sciences, The media and use its influence to the University of Manchester advantage of science. Insight into broadcast journalism was provided by Rebekah Crabtree The Physiological Society is sponsoring One scientist who has experienced, from the BBC, who urged the these SAS workshops: part of the first hand, the unfavourable audience to consider their research package includes a number of exposure the media can bring, or ‘story’ from the perspective of guaranteed places for Affiliates and however, is Dominic Williams, the average person on the street, younger Members to attend these very senior lecturer at the MRC Centre someone she affectionately refers to popular events. Opportunities to apply for Drug Safety Science, whose as ‘Sue’. Taking into consideration are advertised at regular intervals in research as a young scientist was that the job of a journalist is to our monthly email Newsletter. For thrust into the media spotlight due ‘sell’ a story (to both the editor further information please contact Liz to an association with a ‘hot’ topic and the reader), this is a tough Bell ([email protected]).

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59th Annual finest senior and junior researchers. Phil Newsome (Consultant Conference of the Hepatologist, University of British Microcirculation Birmingham) emphasised that despite their clinical regenerative Society Conference, potential, adult stem cells could also 2009 contribute to the development of liver scarring/fibrosis – so not all that Having last hosted the annual BMS glistens (according to the Sun!) is meeting in 1997, the University of Malcolm Reed, University of Sheffield, gold. Birmingham was once again proud receives the BMS Clinical Lecture Award to welcome the 59th conference of from BMS President Giovanni Mann and In a move to increase the the Society to its new and splendid Andreas Gigler, Promocell. participation of clinical researchers Medical School facilities. Delegates at the BMS conferences, Malcolm When thinking of stem cells were welcomed by Ian Booth, Dean Reed (Consultant Surgeon, in the vasculature, endothelial of the Medical School, and the host University of Sheffield) was invited progenitor cells immediately come Neena Kalia, who thanked them for to give the BMS’s inaugural clinical to mind. Perhaps, therefore it was making it the most well-attended lecture. The current effectiveness of surprising to many to hear Petri and financially profitable meeting of anti-angiogenic strategies for cancer Salven’s (University of Helsinki) the Society. treatment and future developments presentation in which he provided was discussed. evidence that endothelial progenitor cells do not contribute to tumour neoangiogenesis, thus refuting data from over 50 published papers. The cat was set amongst the pigeons, but judging from the backlash, I would say the pigeons certainly had The host, Neena Kalia, welcomes their day. delegates along with Gayle Halford, PhD student Ian Holyer and postdoc Dean Kavanagh. The Conference Banquet, held at Jon Frampton (University of the Birmingham Botanical Gardens Birmingham) kick-started the and Glasshouses, was a huge designated symposium which success with the gently lit scenic this year was on ‘Stem cells in the Winners of Promocell and BMS funded gardens enjoyed by delegates, on vasculature’. His introduction poster prizes and the Moor Instruments what turned out to be a glorious provided an unbiased overview award for research conducted using evening (glorious for Brum in March on the hype and reality of stem novel technology. anyway). Conversation flowed over cell research for both the experts a slow-roasted shoulder of lamb Symposium speakers identified new and non-experts. The hype was and good wine aplenty. Live Latin regulatory factors impacting upon highlighted using tabloid articles, jazz music permeated the venue, haematopoietic stem cell (HSC) including one from the Sun (yes, that quite loudly for some, leading to trafficking, with Steffen Massberg well known scientific journal we all the inadvertent playing of Chinese (University of Munich) identifying aspire to publish in!), which only that Whispers around the dinner tables! an important role for platelets in day published a piece on how stem By the end of the evening, the old guiding stem cells to sites of vessel cells could be used to ‘enhance bums victorian ballroom was once again injury. Tsvee Lapidot (Weismann and boobs’… buzzing with enthusiastic dancers – Institute, Israel) illustrated the hopeless at salsa, though probably importance of integrating research too ‘under the influence’ to realise. from different disciplines by demonstrating how interactions I would like to use this opportunity between the nervous and immune to thank The Physiological Society systems regulated the role of HSCs in for generously providing a host defence and repair. Non-Society Symposium grant. Birmingham’s very own stem 7 of the 12 winners of the BMS student Neena Kalia assistance travel awards – are girls cell research featured extensively better in science or is it just an un- with symposium, free and poster The Medical School, University of representative photo! communications from 10 of our Birmingham

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In a house in Bracknell Gardens In the footsteps of two generations of Huxleys are giants immortalised by a blue plaque, On my way to meet a friend in Leonard Huxley, son of ‘Darwin’s Hampstead, my attention was caught bulldog’ the zoologist Thomas Henry by an English Heritage blue plaque Huxley, and his own sons Julian and that carried the word ‘physiologist’. I Aldous. Leonard was a schoolteacher stopped to take a closer look and noted and writer, notably author of Charles that the plaque commemorated Nobel Society and he succeeded Karl Pearson Darwin’s and other biographies. His prize winner Sir Henry Dale who lived as Galton Professor of Eugenics at son Aldous, also a writer, is probably at Mount Vernon House. A few months University College London in 1933. He best known as the author of Brave later whilst on a bus to work, I spotted became friends with Charles Darwin’s New World, reported to have been another blue plaque commemorating son Leonard, then President of the influenced by his brother Julian’s statistician and geneticist, RA Fisher. Eugenics Education Society. The study occupation as a biologist. The Having been born in Hampstead of eugenics flourished during the first Huxleys of Hampstead are members myself, my curiosity was aroused as half of the 20th century, when Fisher of the distinguished Huxley family, to how many other scientists had was a young man, but it lost popularity which includes the younger Huxleys’ populated this leafy London ‘village’. with the rise of Nazism. Fisher half brother, physiologist Andrew That an inordinate number of notable returned to Cambridge as Professor Huxley. Julian was an important artists, actors, poets and novelists have of Genetics in 1943. He published proponent of natural selection at a called it home is widely known, but I prolifically on both genetics and time when Darwin’s ideas were refuted decided to follow in the footsteps of statistics and died in Adelaide in 1962. as scandalous. Born in 1887, he its scientific giants, to see what else I graduated in zoology from Oxford. He could uncover. RA Fisher’s intellectual differences was a keen ornithologist, and studied with his predecessor at University avian courtship behaviour during his Back to my initial discovery of the College, generated personal enmity early career. In 1912 he moved to physiologist Sir Henry Dale, I am towards his fellow ‘Hampsteadian’, to Texas, USA, but returned to Oxford gratified to note that his blue plaque the extent that he would not publish in 1916 to take up a Fellowship in states physiologist, as his Wikipedia in the leading statistics journal, the Department of Zoology. This was page refers to him as a pharmacologist Pearson’s Biometrika. The blue plaque followed by a move to King’s College (but then Wikipedia is not always that commemorates Karl Pearson London where he took up a Chair known for its accuracy). Henry Hallett in Well Road, Hampstead, describes in Zoology. He was a co-founder of Dale was born in London in 1875 but him as a pioneer statistician. Born in the World Wildlife Fund and the first his schooling and higher education 1857 in London, he was educated at Director-General of UNESCO. Prior (physiology and zoology) occurred University College School and studied to the Second World War, Julian was in Cambridge. He went on to obtain Mathematics at Cambridge, where a prominent member of the British a medical degree and moved to he graduated as Third Wrangler in Eugenics Society and its President from University College London where he 1879. He then studied Physics in 1959–1962. A committed humanist, worked under Ernest Starling. He is Heidelberg, Germany and moved on he later revised his views and came to notable for proposing acetylcholine to the University of Berlin where he believe that race was a meaningless as a neurotransmitter, work for which attended the lectures on Darwinism by concept in biology. He died in 1975. he was awarded the Nobel Prize in the physiologist Emil du Bois-Reymond. Physiology or Medicine in 1936 jointly Back in London he was introduced It might appear from my account that with his lifelong friend Otto Loewi. to Charles Darwin’s cousin Francis early 20th century Hampstead was a In addition to his many scholarly Galton, the pioneer of eugenics hotbed of extreme right-wing idealists, publications he wrote Adventures in who became something of a hero but it must be noted that eugenics was Physiology, which was published in to him. When Galton died in 1911, not viewed in the same light then, as it 1953. A review of this book by Marthe he apportioned a part of his estate is in the post-Nazi era. Vogt can be found in Experimental to establish a Chair of Eugenics at Physiology (Vogt, 1953). Sir Henry died University College London and Pearson As an aside, and to complete my tour, in Cambridge in 1968. became its first holder. Karl Pearson I had often wondered why the road was indeed a pioneer of statistics; leading to the Hampstead campus of If you have ever wondered why the test he was instrumental in developing UCL Medical School is called Rowland statistic for the analysis of variance is linear regression and correlation and Hill Street and once again the answer F, the answer is because of Sir Ronald the latter test which bears his name, is on the blue plaque – it’s named after Aylmer Fisher, who developed it. Born was the first important effect size Sir Rowland Hill, the originator of the in London in 1890, Fisher’s childhood to be introduced into statistics. He Penny Post. was spent in a very comfortable house formulated the chi-square test and in Hampstead. He was a precocious classified probability distributions that Patricia de Winter mathematician and obtained a first in formed the basis of much of modern University College London Mathematics from Cambridge in 1922. statistical theory. Unlike his scientific Reference He became interested in genetics neighbours above, Pearson refused the Vogt M (1953). Adventures in Physiology by Sir and also in eugenics, co-founding the knighthood he was offered in 1935. He Henry Hallett Dale (reviewed in Q J Exp Physiol University of Cambridge Eugenics died in 1936. 38, 295–296).

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But! She has provided me with conclusive Aspiringate evidence that you are engaging in a It happens every Monday at around conspiracy to brainwash the British public 9am. I become paranoid and agitated into thinking that consuming half an and feel that I am being watched by Aspirin a day will prevent heart attacks an unseen evil force. Actually it’s my and strokes. I believe you to be criminal head of department. This Monday masterminds but would like to suggest a the paranoia was far worse as over couple of minor caveats that you need to the weekend I became embroiled in a consider before you go on a conspiratorial global physiological and pharmaceutical rampage. conspiracy. A health professional with Just look at this conspiracy from a three a physiology degree (‘I’ve got a 1st’ Another thing I could advise you with is a stage logical point of view. she kept saying) approached me and technique I have developed called ‘guilt announced that ‘big pharma’ and the Firstly. Recently I bought 16 Aspirin from motivated neurolinguistic programming media were engaged in a conspiracy to Tesco’s for 16p (as you had cunningly for marketing undesirable substances’ make huge amounts of money out of her forced the Chief Executive of Tesco to put (best destroy any paperwork relating to patients and the British taxpayer. As I am them on special offer) this means that this one). Using this technique you can a fan of disturbed conspiracy theories when you brainwash me to take half a exploit the understandable sympathy that I asked her for some detailed scientific tablet a day for 365 days a year, you could people have for indigenous aboriginal evidence. The evidence was in fact deeply possibly fleece me of nearly £1.83 per populations in the developing world. In disturbing. A number of scientific papers annum. essence, we invent a tribe of endangered and magazine articles had suggested that Amazonian hunter gatherers ‘the Fukawi’, half a soluble Aspirin a day was beneficial Secondly. There are approximately 60 claim that they all live to at least 100 for a wide range of ailments including million people living in the UK, if you years in age and suggest that research protection from heart attacks and strokes. exclude small children, people with demonstrates that they are immune from But! She had realised that because of the stomach ulcers and the emotionally heart attacks and strokes. Then comes the recent failure of a range of blockbuster delicate (people who think the ‘sting’; we paint a picture of an Amazonian drugs, the ‘devious bastards’ in the government is controlled by aliens, health hunter on the packet and suggest that ‘neocon controlled western drug industry’ food fanatics, vegans etc.) from this total 50p per packet will be donated to the were attempting to shore up their profit you could end up with around 50 million Cormorant Foundation (a charity founded margins by brainwashing the entire British customers. 50 million multiplied by £1.83 by the distinguished philanthropist Keith public into taking half an Aspirin a day. comes to £91.5 million. Cormorant to protect the rainforests). ‘They really are evil; that’s exactly what The beauty of this little conspiracy is they did with anti-AIDS drugs in Africa.’ And finally. Pharmaceutical sales in the that the Fukawi don’t actually exist UK in 2008 amounted to over £10 billion. and the Cormorant Foundation can be She was going to warn her patients and used to siphon 50p per packet (tax free, inform them about a natural alternative I am usually quite polite but as minus 12.5% handling fee) into your own that they could acquire easily from the conspiracies go this one sucks. You are personal offshore banking account. If by health food shop. conspiratorial neophytes and a bit dim. chance some curious anthropologist ever 91 million quid is not going to go very decides to go looking for the Fukawi, we ‘I am sure we can put a stop to this’, I far in the pharmaceutical industry is it. claim that they have been exterminated by said; ‘there are a number of unusual That’s £91 million even before you have global warming and an uncaring capitalist channels we can use’. deducted the cost of bribing a range of society (thus making us look ecologically government officials and journalists at the responsible and caring). Similar techniques After consulting the dark and hidden BBC. Being a naive innocent boy I don’t have been tried and tested to destruction corners of the internet where traumatised know what the going rate for corrupting in the banking sector over the last 10 victims of the ruling elite communicate the influential is, but using recent years and I am supremely confident that and share their pain (Lee Harvey-Oswald, events in the banking crisis by way of a we can get away with such a scheme with Sirhan Sirhan, James Earl Ray, Princess comparison it’s not going to be cheap. no danger of any criminal complications. Diana and Sarah Palin all use one site). I decided to expose their evil wrongdoings As an alternative I would like to offer If this initial conspiracy is successful by writing a letter. my services to you as a conspiracies there are a number of other conspiracies consultant: you have, for instance, been where I could offer my valuable services. particularly slow in the growing field of Dear Big Pharma, The Nelson Mandela Homeopathic Prion ‘natural’ blood thinners. Recently I looked Busting Kit is just one of a number of Recently I was approached in an at a packet of a natural blood thinning products that we could co-develop to underground car park by an informant product in a health food shop. 50 days’ fleece the general public. who for security reasons I will call ‘Reg’. supply cost £6.50. By brainwashing OK the informant was a woman, wasn’t the public into taking these instead of And just one more thing, you really do called Reg and it was a hospital, but Aspirin you could fleece an individual need to silence the informant. in 1976 I watched Deep Throat talk for nearly £47.50 a year. Multiply that to Bernstein and Woodward in All The by 50 million potential victims you end Sincerely yours Presidents Men and I suffer from serious up with £2.36 billion. Now that’s money psychological flaws. I thought that by worth defrauding. And the whole beauty Dr Keith Cormorant placing my actions into an important of this con is that when a medicine has historical context it might inflate my ego absolutely no physiological effects, PS Seriously, for a minute, the first part and sense of self importance. you get two additional competitive of the article is highly accurate. The real advantages: you don’t need animal testing scary thing is that ‘Reg’ is actually allowed And I ramble. and you never get adverse reactions. near real patients.

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Open access does more review have by no means gone quarrel is only with that segment of away) will be disastrous for the open access publishing which makes harm than good when underdeveloped world. It is often ‘read for free’ possible only at the based on a ‘pay to said that we are increasingly living expense of ‘publish for free’. in a knowledge economy and that publish’ business model while we may never have equality I thank Gesine Bottomley, Chief Librarian, Wissenschaftskolleg The traditional business model among the world’s nations in military zu Berlin, Peter Suber, Research adopted by publishers of scholarly or economic power, knowledge is one area in which we can hope for Professor of Philosophy at Earlham journals, that we may call ‘publish College and Catriona MacCallum, for free and pay to read’, leads to true equality. If there is any truth in all of this, a ‘read for free and pay Senior Editor of PLOS Biology for an inevitable disparity in access to many helpful discussions, but hasten scholarly literature. The rising costs to publish’ model would indeed be disastrous for the underdeveloped to add that this is not to imply of journals and the shrinking budgets that they necessarily agree with of libraries have only served to world as it would encourage its citizens to remain consumers all that I have said. I also thank the exacerbate this disparity. Admittedly, Wissenschaftskolleg zu Berlin for the open access movement has done (readers) of knowledge rather than become producers (authors) of providing an intellectually free and a great deal to create a near level liberating atmosphere. playing field for readers of scholarly knowledge – a form of knowledge slavery. literature. But I would argue that the Raghavendra Gadagkar segment of open access publishing, If I have to choose between the Centre for Ecological Sciences & that depends on a business model two evils, I will certainly prefer the Centre for Contemporary Studies, that we might dub ‘pay to publish ‘publish for free and pay to read’ Indian Institute of Science, and read for free’, does more harm model over the ‘pay to publish and Bangalore, 560012, India than good. read for free’ model. If I am really References Authors by no means have a level forced to choose between publish or read, I would surely choose to Brimblecombe P & Sturges K (2009). History playing field even in the traditional of atmospheric environment. Atmos Environ publishing model. The complex publish. Who would not? Fortunately, 43, 2–8. dynamics of peer review makes it there is growing evidence that a Gadagkar R (2008). Open-access more harm difficult, if not impossible, to ensure ‘publish for free and read for free’ than good in the developing world. Nature that publication of an article is model can indeed be made viable. 453, 450. merely a function of its quality and Journals published by the Indian Sandal M (2008). Future of open access could is not influenced by such extraneous Academy of Sciences (www.ias.ac.in) be online and peer-reviewed. Nature 454, 158. factors as the modishness of the and Medknow Publication and Media 1 American Scientist Open Access Forum topic, the name of the author or even Pvt. (www.medknow.com), are just Archives 2008. http://listserver.sigmaxi.org/ the address of the author. The ‘pay two of many examples. I believe that sc/wa.exe?A2=ind08&L=american-scientist- open-access-forum&F=I&P=51516 to publish and read for free’ model we just need to keep up the pressure 2 adds a significant new dimension to on those who continue to adopt American Scientist Open Access Forum Archives 2008. http://listserver.sigmaxi.org/ the unevenness of the playing field the ‘read for free’ model only at the sc/wa.exe?A2=ind08&L=american-scientist- for authors. It is often pointed out cost of ‘pay to publish’. At the very open-access-forum&F=I&P=42617 that page charges are waived for least we must prevent publishing in authors who cannot afford to pay. But such journals from becoming too it is hard to believe that a business fashionable and/or mandatory for Physiology curriculum for model which depends on payment career advancement. by authors can afford more than a medical training marginal number of such waivers. A previous abridged version of this The joint Physiological Society/ Besides, why should anyone want to piece published in Nature (Gadagkar, BPS Medical Training Working live on charity? One has also heard 2008) was misunderstood by some, Group has been working with the argument that it is not really the probably because of the somewhat Richard Dyball to produce a core 1 author but the granting agency that misleading title used by Nature Physiology Curriculum for Medical funds the research that actually pays. (Sandal, 2008) but thankfully Training. A draft is now available This argument does not wash well not everyone appears to have for comment (http://www.physoc. misunderstood me2(Brimblecombe either; if anything the playing field is org/site/cms/contentChapterView. & Sturges, 2009). I certainly have even more uneven for getting grants. asp?chapter=139) and will be no quarrel with the large segment More importantly, this will undermine presented for discussion at of open access publishing – those rather than encourage the whole the forthcoming Teaching SIG journals and other open archive genre of grant-free research. Workshop at our Main Meeting efforts that are attempting to in Dublin. For more information The new exacerbated uneven enhance the ‘read for free’ content please contact Liz Bell playing field for authors (the old without making the authors pay problems associated with the peer – indeed I welcome them all. My ([email protected])

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Animal research in tables have turned. Media headlines have avoided over-simplification started to appear on the side of and retained explicit links to the medicine: 100 years of researchers. Public engagement primary literature; indeed, many politics, protest and about the benefits of animal research, new studies have been added in this and more open policies about work edition. These frequently incorporate progress from scientists, with the support of substantive tables and informative The Story of the Research the RDS and others have started to figures with outstanding artwork. impact on opinions and help people One quibble, however, is that the Defence Society. By John to understand why animal research is referencing is not consistent. Some Illman (2008). Research necessary – a true sign of progress. figures have citations for the source, Defence Society, London. whereas for some the citations £9.95 Fiona Randall are in the accompanying text. This occasionally produces confusion as ISBN 978-0-9560008-0-4 Essentials of ecology to the source of the study. Similar For anyone doing public engagement inconsistency is also found in the on the subject, or even with an By C R Townsend, M Begon & companion website where the tables interest in it, this book provides a J L Harper (2008), 3rd edition. have sources cited but the figures do perfect overview of all the basic Blackwell Publishing, Oxford. not. This is regrettable for the authors things that are useful to know as are to be commended on continuing researchers about the broad topic £29.99 to provide such an extensive evidence of animal research. In a climate ISBN 978-1-4051-5658-5 base. where communication of our work This is the third edition of a The companion website is, by current is so important, this book makes a well-established introductory text. It standards, somewhat limited, comprehensive easy read covering is designed to be used by students although doubtless it will develop. the facts and figures which are useful undertaking a beginners’ course and Multiple-choice questions are in a debate about the use of animals to be a succinct treatment of the provided for self-testing, but these are in research. subject. In these objectives previous relatively unsophisticated in structure. This book really does follow the editions were successful, so how The authors could benefit from some ‘what it says on the tin’ policy. could the authors have improved technical advice on constructing John Illman does exactly what the on the previous text? They have such tests. One useful addition to the title says in telling the story of the managed to do so by a number of companion website would be some Research Defence Society (RDS) since innovative changes designed to example responses to the ‘challenge it was formed as the Association make the text even more usable questions’ of the review questions for the Advancement of Medicine than before. Each chapter now sections. These ‘challenge questions’ by Research (AMMR) in 1882. By sets out the key concepts to be are discursive in nature and it would describing, in digestible detail, the addressed; marginal annotations be helpful to the reader to have history of research over the past 2 provide succinct signposts of content some indication of how the authors centuries, Illman talks through the almost paragraph by paragraph; might have approached these. The changes in opinion on the subject each chapter concludes with a set other review questions are primarily of animal research since the very of review questions; and boxed text concerned with each chapter’s factual beginning. The book begins with usefully considers selected topics content and indeed should not have some history, outlining early animal in depth under the headings of the answers supplied. experiments and also some of the ‘Historical landmarks’, ‘Quantitative In summary, the authors have first anti-vivisectionist movements, aspects’ and ‘Topical ECOncerns’. undoubtedly added to the utility of followed by the set up of the AMMR Additionally, the book’s evolutionary this text. It is extremely easy to locate to counteract them. He talks of the focus, a strength of this text, has any particular topic as required, success of anti-vivisection groups been extended by a new chapter on and the pedagogical features added and of animal rights terrorism on evolutionary ecology, which provides help to make the content accessible public opinions of research in the additional material on molecular ecology. and understandable. A rather nice past. A very interesting aspect is feature is that the different sections the description of how the laws Also, this text has always been of the book are colour-coded so that have changed through history to the characterized by its readability. they can be identified with the book benefit of animals and researchers. For example, the complexity of closed. However, I suspect that the The book, although only 72 pages arguments about the meaning and pastel colours employed to do this long, is brimming with fascinating evidence for community stability is may become indistinguishable in a facts, not only about the animal explored with remarkable clarity. This well-thumbed copy. And there is no research itself, but social issues is not an isolated example – there doubt that owners of this text will use over the years including political are plenty of other difficult areas it a lot. aspects. The last few chapters of the treated in a similarly exemplary book show how, in recent years, the manner. Throughout, the authors Glenn Baggott

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A thinking approach to overall structure is described, motility and the book would have benefited is briefly discussed, and digestion of from expansion of this chapter. The physiology the major food groups is very briefly paperback version of this book retails By Ian Sabir and Juliet Usher- reviewed as is the endocrine control at £25 and I think I would recommend of digestion. Again, the purpose of that physiology students put the Smith, World Scientific some of the figures is puzzling, for money towards a more definitive text Publishing Co. Inc. pp. 232, example, Figure 37, the emulsification and give this one a miss. £25.00 of fats by bile salts. The fourth chapter deals with the respiratory system. Patricia de Winter ISBN 9789812706027 The first half of the chapter deals with The title of this slender volume rather the mechanics of respiration. In the belies its contents; I would describe latter half of the chapter, the section Max Perutz and the it as a physiology primer. If taken as concerned with gas exchange contains secret of life such, one’s expectations are more some serious errors. The equation accurately met. The book is divided given for Fick’s law is incorrect, as is A biography by Georgina Ferry. into seven chapters covering the that for the diffusion coefficient. Gas Random House, pp. 352, £25 physiology of the major systems in the exchange is driven by a difference in ISBN 9780701176952 human. The main problem is that it is partial pressure and not concentration not specialised enough to adequately as implied by the authors. It makes a Max Perutz was one of my scientific serve the needs of undergraduates simple story to say that CO2 diffuses heroes. More than half a century ago, in physiology; it is rather prescriptive 23 times faster than O2 but it is not as a final-year physics undergraduate in and there is minimal emphasis on helpful, as is done here, to confuse the Oxford, I read about the just-published experimental evidence. rate of mass transfer with the rate of DNA structure and asked my tutor diffusion, as quantified by the physical about the possibilities of applying Throughout the book, text in grey diffusion coefficient. The remainder physics to biology. My tutor, the boxes highlights clinical conditions of this chapter discusses transport of physicist Francis Price, said that he associated with malfunction, and oxygen and again oversimplifies to personally knew little about the field, suggests that it was written primarily the point of error; for example, the but he ‘believed there was a very good as an introductory text for students of authors describe a shift in the oxygen– man called Max Perutz in Cambridge’ medicine. haemoglobin dissociation curve to who did such things, and that I should the right as a Bohr effect, which, write to him. I always suspected that The Introduction is extremely brief, although not totally incorrect, fails Francis, who had been a scientific providing a skeleton overview of units to indicate that Bohr shifts leftward ‘boffin’ during the war, had come and normal values commonly used can also occur. The fifth chapter is across Max in a similar role. Shortly in medicine. I think I would prefer concerned with the circulatory system thereafter, however, I noticed a job normal ranges to normal values, or and haemodynamics. This chapter is, advertised at King’s College London, at least a statement that the values on the whole, more accurate and the at the other end of the DNA axis, and are approximate and vary. The seven figures are more pertinent than those applying there I was appointed to chapters cover the electrical properties of the preceding chapters. Flow, the JT Randall’s laboratory. I have often of cells, muscle, the digestive, cardiac cycle, cardiac output, venous wondered how things might have respiratory, and circulatory systems, return and the Starling filtration– panned out had I not seen the King’s the kidney, and lastly integrative reabsorption mechanism are discussed. advert and instead had followed physiology. I became irritated when on Francis’ advice. page 2, I noticed that ‘lose’ and ‘losing’ The penultimate chapter is concerned were misspelt as ‘loose’ and ‘loosing’. with the kidney. I think the thing that As it happened, then, I never did work This immediately put me on my guard irritated me most was the constant use with Max Perutz, but I met and talked for further spelling or grammatical of ‘filtration’ in place of ‘ultrafiltration’. to him often at scientific meetings, read errors of which I found not a few. Urine is filtered under high pressure, many of his papers, and went to hear thereby the process is ultrafiltration. him speak whenever I could. He was The first two chapters deal with the This is a shame because the chapter always ready to listen to different ideas properties of excitable cells and cover was otherwise a reasonable summary and viewpoints and was unfailingly the resting membrane potential, ion of renal function, although I would like gentle and courteous in discussion. It channels, the nerve action potential to have seen a little more here on the was therefore a pleasure to read this and its propagation, synapses and the kidney’s function in the maintenance biography, which brought alive the neuromuscular junction, myelinated of blood pressure. man himself, from his school days and unmyelinated axons, the three in post Austro-Hungarian Vienna to types of muscle, excitation–contraction I liked the concept of a final chapter his long association with the famous coupling, and intracellular calcium that deals with the interactions of Laboratory of Molecular Biology (LMB) regulation. The level is very superficial different physiological systems in in Cambridge. and the purpose of some of the figures the body. This chapter, entitled is unclear, for example, Figure 23. ‘Integrative Physiology’, explored the Georgina Ferry had already written a control of plasma pH, control of arterial splendid biography of Dorothy Hodgkin Chapter 3 covers the digestive system blood pressure and the response (another of my scientific heroes) when and is relatively straightforward. The to exercise. It is regrettably short she was asked to meet Max on his

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death-bed and agreed to write this English suspicion of someone from a scientific fraud, but probably with book. Working from accumulated different background, one wonders? some factual background in his own letters and papers, and from interviews Again, it was interesting to read further experience) before I read Jim Watson’s with Max’s friends and colleagues, she on that even a Prince Nobel of science justly famous The Double Helix. Both has given us a very valuable portrait of could have his paper to a leading read as detective stories (as Crick Max and a vivid account of his life. journal rejected because of a single remarked about Watson’s book), so catty comment by an ignorant and perhaps this ‘detective element’ is Born in 1914, Max was already working anonymous referee; I had supposed the essence of successful scientific in Cambridge at the outbreak of the that this treatment was reserved for biography. It is not easy to achieve war and was interned as an enemy lesser mortals like myself – or perhaps this, though, and more often than alien, first on the Isle of Man and later I could allude to TS Eliot’s Prufrock not we are left with the style of Royal in Canada. This much I had known, but and call those of us below the Princes Society or National Academy of Science the details of the military foul-up that ‘attendant Lords’! obituaries – worthy accounts of the constituted the internment process science but with the personality of the surprised me. We were lucky that Max An outstanding achievement of Max’s scientist not very apparent. I hasten was not lost to UK science, either to career was the establishment of the to add that this is not true of Georgina US academe or on the Atlantic to a LMB, which was set up by the MRC Ferry’s biographies of Hodgkin or passing U-boat. Later, released after under Max as an unobtrusive chairman Perutz, either – or both – of which the efforts of friends and colleagues, rather than as titular Director. This was would grace the bookshelf of anyone he worked on the Habakkuk project, not their usual modus operandi, but interested in the greats of 20th century a Churchillian enthusiasm for possible it was his own idea. He succeeded in British biological science. floating airfields of ice for which Max’s running the Laboratory, encouraging Austrian skiing and mountain-ice and facilitating first-class science and Gerald Elliott experiences were ideal. The project keeping an array of scientific prima is also covered in the biographies of donnas happy, all with a light touch Solly Zuckerman and Desmond (JD) and without a large number of boring Membrane transport Bernal (more heroes!) but the detail ‘administrative’ meetings. Would that in flux: the ambiguous given here is fascinating. As a one-time all departmental chairmen had the National Service Junior Officer, I could character and conviction to do likewise. interface between readily visualize Louis Mountbatten It was probably in the same vein that channels and pumps drawing his revolver at a demonstration he rejected the offer of a knighthood, in Canada to illustrate the resilience of because the title would tend to set Philosophical Transactions of the modified ice that Max and his team him apart from his laboratory peers. The Royal Society B Biological had produced – and narrowly failing It is good that he later accepted an Sciences. Vol 364, No. 1514. to wound himself and an American appointment to the much more Admiral with bullet ricochets. distinguished Order of Merit. pp. 143–276. Max continued to do good science until The publication reports on a Royal The long struggle that Max had to Society Discussion Meeting held in understand the structure and the he died from cancer in 2002. He also continued to write about science itself, 2008, that focused on the overlap molecular operation of haemoglobin, in function between channels and with its victories and setbacks, is very sometimes targeted for laymen; this was another side of his multifaceted transporters. Proteins are present in well described; Ferry has a talent for cell membranes to facilitate the flux of making complicated scientific concepts scientific genius. I highly commend Ferry’s book to anyone who is ions and a variety of other molecules vivid and clear. Max was awarded the across the cell membrane. Given the 1962 Nobel Prize for Chemistry for interested in the life of one of the great scientific gentlemen. central role that trans-membrane this work, jointly with John Kendrew flux of molecules has on the normal for myoglobin. That was also the I had intended to close this review functioning of all cells, these proteins UK’s scientific ‘annus mirabilis’ when by posing the problem of who in fact are a subject of intensive study. Of Watson, Crick and Wilkins were reads scientific biographies, even ones particular interest is the pathology awarded the Medicine and Physiology as excellent as this. While I was reading that can result from the malfunction of prize for DNA. All five are pictured the book I was upstaged by Georgina these proteins. before the Nobel banquet together Ferry herself, in a very perceptive with the Laureate for Literature, John article in Nature (‘A scientist’s life for These membrane proteins have Steinbeck. Steinbeck was obviously me’; Nature 2008, 455, 871–872). She traditionally been divided into two no scientist, but coincidentally is the begins by quoting Peter Medawar’s separate classes: ion channels and author of one of the best literary remark that ‘the lives of academics, membrane transporters of which portrayals of a practical scientist, ‘Doc’ considered as Lives, almost always the voltage gated sodium channel in Cannery Row. make dull reading’. The article is well and the sodium pump, respectively, worth a read; Ferry surveys the field are two well-known examples. The Historical vignettes occur throughout and its problems very well and it would distinction between these two classes the book. Despite his scientific be superfluous to do so again. are that the ion channels are pores distinctions, Max was not made an in the membrane across which ions Honorary Fellow of Peterhouse until For myself, I remember reading move down their electrochemical after he was a Nobel Laureate. Was this CP Snow’s novel The Search (about gradient, whereas transporters have

Physiology News | No. 75 | Summer 2009 | www.physoc.org 50 PN BOOK REVIEWS/MISCELLANEA a more complex mechanism where The Journal in initially used in the Aberdeen substrates bind to the transporter Office of the then Quarterly Journal with the resulting conformational jeopardy? of Experimental Physiology would change in the protein resulting In his Short History of The Physiological helpfully suggest alternatives to in translocation of the substrate Society 1926–1976 WF Bynum unfamiliar words. It once enlivened across the membrane followed by includes extracts from the minutes a manuscript by substituting ‘erotic’ release from the transporter. There for ‘aortic’. is accumulating evidence that such of the Editorial Board of The Journal rigid distinctions between the two of Physiology. Some indicate the Editorial imagination classes of membrane proteins must problems encountered by The Journal be reassessed. It is known that the during and after the Second World The abstracts submitted to the 1993 class of sodium-coupled amino acid War. The Report for 1940 says ‘No IUPS Congress in Glasgow – over transporters can conduct small ions in difficulties have so far arisen between 3500 of them – raised some alarming the presence of the substrate, thus it the Editorial Board and H.M. Board of images, including the rotation of appears to function as both a channel Censors; and the Editors regard the subjects on a barbecue. A bit of and a transporter. It is hypothesized acceptance of their guarantee that lateral thinking conjured up a human that membrane transporters may have a paper entitled “The electric organ centifuge. A few years ago the evolved into channels via the loss of a of the torpedo” contained no matter same process was applied to ‘renal gating mechanism, and more tenuously which might be used by the enemy laundry’; this led via ‘washing’ and that channels may have evolved into towards a more effective prosecution ‘cleansing’ to clearance. Recent light transporters by the addition of gating of its naval warfare, as a telling relief includes ‘immunocreativity’, mechanisms. symbol of mutual confidence and ‘neuromoral’ and ‘europeptides’. understanding.’ Bynum speculates In this volume leading researchers Ann Silver in the field focus on examples of that ‘Perhaps the Censor would membrane transport proteins have been more concerned had he (ABC proteins, neurotransmitter noticed that one of the authors of Physiology at the transporters, CLC proteins and the this particular paper (W. Feldberg) Nobels sodium pump) that most clearly was born in Hamburg.’ In 1948 when illustrate the ‘ambiguous interface’ paper supplies were still limited Although the Physiology or Medicine between channels and transporters. EN Wilmer suggested ‘that anyone 2008 Nobel Prize went to medical exceeding the current average discoveries, specifically in virology, Angus Brown length of eleven pages per paper was one holder of a PhD in Physiology behaving antisocially.’ was a 2008 Nobel winner. This was, as most readers will know, Roger Bynum W F (1976). A short history of the Tsien of UC San Diego, joint winner Physiological Society 1926–1976. J Physiol of the Chemistry Prize for his work At a glance 263, 23–72. on Green Fluorescent Protein. The Wiley-Blackwell At a glance Ann Silver series for medical students breaks http://nobelprize.org/nobel_prizes/ complex subjects into short, chemistry/laureates/2008/press.html easily digested topics. Each topic Secretarial substitution Roger Tsien is well known to is presented as a double-page Before the advent of word processors physiologists not just for his spread with a clear, easy-to-follow most would-be authors were very work with GFP, but also for his diagram supported by succinct reliant on secretarial help. Typists did development of dyes like Fura-2, explanatory text. The range of wonders with appalling handwriting among many other seminal titles, by authors who are experts but those with no scientific contributions to working out in their field so guaranteeing background sometimes produced optical methods for observing and authoritative and accurate interesting statements. In one perturbing cell signalling. coverage of the contemporary Babraham draft, the author likened curriculum, covers basic sciences lung compliance to the behaviour “Graduate students are the through to clinical specialties. of a balloon in a string bag; in the pluripotent stem cells of biology. The 2nd edition of Physiology at typescript, balloon became baboon. [University] Faculty are…well, a glance, by Jeremy Ward and A messy comma in one of my own basically terminally differentiated… Roger Linden, provides a concise drafts meant the phrase ‘but Ho, the only options left for them are introduction and revision text Paddle & Freeman (1965) reported apoptosis and necrosis.” 2008 for physiology, applicable to all . .’ was rendered rather more Nobel Laureate Roger Tsien speaking dramatically as ‘ but Ho! Paddle & introductory physiology courses. at UC Berkeley in March 2001. Quote Freeman (1965) reported . .’. from the Berkeley Science Review. For information on the complete At a glance series visit: Some of the developing technology http://sciencereview. www.blackwellmedstudent.com had interesting foibles. The optical berkeley.edu/articles. character recognition software php?issue=1&article=backpage

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100 years ago in J Physiol The period over which the reflexes can be observed well extends in my experience A mammalian spinal to ten hours and even longer.” preparation C. S. Sherrington (1909). The rest of the paper consists of examples of the reflex activity recorded. As the J Physiol 38, 375–383. passage above suggests, Sherrington’s The June 1909 issue of The Journal of spinal cord preparations became Physiology contains a paper by one of a mainstay of teaching reflexes in the most revered of all the physiologists physiology departments. The methods of the late 19th and early 20th century, were described in his highly influential Sir Charles Scott Sherrington OM FRS laboratory manual Mammalian Physiology (1857–1952). Sherrington’s status reflexes the contraction of muscles (1919) which was still in use into the among his own scientific contemporaries promoting the movement involved 1970s (see e.g. Maynard, 2009). is attested by his near one hundred a simultaneous relaxation of those Sherrington, who wrote prolifically, nominations for the Nobel Prize, which opposing it.” penned a number of articles expounding he finally won in 1932, together with his Adding: his views on scientific education. He was a friend Edgar Adrian. The nominators, who “The term negative feed-back was committed believer in learning physiology can be viewed on the Nobel Foundation’s invented much later but Sherrington had as a hands-on practical science: website, spanned 30 years (1902–32), long ago established its importance for and included many other Nobel Laureates. “Paradoxical though it may sound, the nervous system.” Another indication of Sherrington’s the more skilfully a demonstration experiment is performed the less from it scientific stature comes from the tone of The 1913 paper is, as its title indicates, do some students learn.” his many obituaries. The one in the Journal a description of an isolated spinal cord of Neurophysiology begins: preparation. Sherrington was in his (from the Preface to Mammalian “The Journal records with deepest mid-50s but still a virtuoso experimenter, Physiology). He also argued that the sheer regret the death... of Sir Charles working alone or with the assistance of a wonder of science was best imparted by Scott Sherrington who, almost single- skilled personal technician, George Cox, those with experience of doing research handed, crystallized the special field of whom he himself had taught (see e.g. themselves. Neurophysiology which this journal aims Tansey, 2008). As a student, Sherrington Sherrington’s writings, though lucid, to foster.” had trained initially for the exams of the College of Surgeons, and had later can appear a bit wordy to a modern All physiology undergraduates, and most been both an anatomy demonstrator eye, especially on less straightforwardly medical students, still hear Sherrington’s and a teacher of histology. His skills in scientific matters (he produced name in the context of spinal reflexes, to dissection technique and knowledge of philosophical writings and even poetry). the elucidation of which he devoted much anatomy were central to his life’s work of But Sherrington could add the occasional of his working life. Sherrington eventually mapping neural pathways. Sherrington touch of self-deprecation to his insight. became Waynflete Professor of Physiology begins the paper: Responding to some visitors to Oxford in Oxford, where both the physiology in the 1920s on what he saw as the building and the street it stands on bear “A difficulty often felt by those studying challenges for scientific education, he his name. However, his key period of spinal functions in [higher] animals... made the following remark, just as apt productivity as a scientist was the 18 is the want of a preparation which [is] 80+ years on: years he spent in Liverpool between 1895 reliable, resistant… and obtained easily, “After some hundreds of years of and 1913, when he published 19 of his 40 and without great expense of time. After experience we think that we have learned J Physiol papers. Here is Adrian, writing in some experience I find the procedure here in Oxford how to teach what is 1957 on the centenary of Sherrington’s described below yields a preparation known. But now with the undeniable birth: fulfilling [this]. The procedure was first devised two years ago for purposes of upsurge of scientific research, we cannot “It was when [Sherrington] held the enquiries into spinal reflexes; experience continue to rely on the mere fact that we chair of Physiology at Liverpool that he of its advantages in that work has led to have learned how to teach what is known. was at the height of his powers as an its introduction into general use in the We must learn to teach the best attitude investigator... it was in that period that Laboratory. Many purposes other than to what is not yet known.” he gave a new aspect to the study of the the study of spinal reactions are well nervous system by the precise analysis of served by it. In consequence of its success Austin Elliott its performance” (Adrian, 1957). here, directors of other Laboratories… References have adopted its employment in their Adrian ED (1957). Sir Charles Scott Adrian also gives a neat summary of the laboratories, and find [it] reliable and Sherrington, OM, 1857–1952. Notes Rec R Soc key early discoveries: valuable. Examples of the preparation Lond 12, 211–215. were demonstrated at the Physiological “One [of Sherrington’s Liverpool “Sir Charles Scott Sherrington, O.M., 1857– Society’s meeting in this Laboratory in 1952” (1952). J Neurophysiol 15, 167–190. discoveries] was the... proof that at least December of last year. a third of those [nerve fibres] which Maynard RL (2009). Memorable technicians. Physiology News 74 (Spring 2009), 55–56. enter a muscle are not efferent fibres The... whole procedure [of setting up the producing motor effects, but are afferent preparation] occupies about six minutes… Tansey EM (2008). Working with C. S. from sense organs within the muscle, Sherrington, 1918–24. Notes Rec R Soc Lond signalling tension and movement to the The preparation affords exceptional 62, 123–130. central nervous system. The other was his facilities for investigating reflexes Sherrington was elected to The Physiological demonstration that even in the simplest employing the skeletal musculature... Society at the tenth Annual Meeting in 1885.

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UK’s leading biology organisations agree to Society of Biology The forthcoming integration of the unification Institute of Biology and the Biosciences Federation offers a unique opportunity to create the leading organisation for biology in the UK. Our mission is to create a single unified voice for UK of the membership demonstrates biology, representing the discipline significant confidence in the work and its practitioners. We will champion undertaken by many during the discoveries in biology and support past few years to bring about this their translation to health, economic, unification. The Society of Biology social and environmental benefit, will have a sufficient critical mass promote understanding, learning and communication in biology, to enable it to speak with authority develop partnerships within the UK over the breadth of topics covered and overseas, and provide the widest by modern biology, and we look possible support to our membership. forward to working closely with Lord Our goals are to build upon and Drayson’s team.’ develop the strengths of both IoB and BSF, and seize new opportunities to Martin J Humphries, Chair of the broaden our range of influence and Biochemical Society, said ‘I welcome scale of activities. this decision because it will facilitate Members of the UK’s two leading greater cooperation between the The Institute of Biology (IoB) is an biology organisations, the learned societies that represent UK independent and charitable body Institute of Biology (IoB) and the Biology. The resultant synergies charged by Royal Charter to represent Biosciences Federation (BSF), have from these interactions will UK biologists and biology. It has around 12 000 individual members voted overwhelmingly in favour improve the ways in which learned and over 50 specialist learned societies of unification to form a single societies represent their members, ‘affiliated’ to it. The Institute’s organisation, the Society of Biology. whether they are based in the UK or elsewhere in the world. Mission is to promote biology and the This positive development takes biological sciences, to foster the public the IoB and BSF a step closer to A clear majority of IoB members understanding of the life sciences the creation of an organisation voted in favour of the move at the generally, to serve the needs of its that combines the expertise of the Institute’s 60th Annual General members, to enhance the status of the learned societies and other biology Meeting. Raymond Dwek, who will biology profession, and to represent its organisations with the professional be the last President of the IoB, members and the biology profession skills of the IoB and its individual said how pleased he was that the as a whole to government and other bodies in the UK and abroad. members. members had put the best interests The Government’s Chief Scientific of their science first. ‘The Institute’s The Biosciences Federation (BSF) is Adviser, John Beddington, said ‘I proud and productive 60 year history a single authority representing the am delighted to hear this news. will make a valuable contribution UK’s biological expertise, providing The Life Sciences have suffered in to the development of the new independent opinion to inform the past through fragmentation. body in the years ahead.’ Member public policy and promoting the The future health and wealth of organisations of the Biosciences advancement of the biosciences. The BSF is actively working to influence this nation will depend increasingly Federation voted without objection policy and strategy in biology-based on progress made in the biological at their Annual General Meeting. research – including funding and the sciences, and it is excellent that the The forthcoming integration of interface with other disciplines – and in scientists involved are now all pulling the Institute of Biology and the school and university teaching. The BSF together.’ Biosciences Federation offers a is also concerned about the translation of research into benefits for society, The move towards creation of the unique opportunity to create the and about the impact of legislation Society of Biology coincides with leading organisation for biology in and regulations on the ability of those Lord Drayson’s establishment of a the UK. For more information, see: www.newbio.info working in teaching and research team, within the Department for to deliver effectively. Member Innovation, Universities and Skills, Contacts societies, of which there are 45 plus which will carefully monitor the UK’s 9 Associate Members, cover the full standing in biotechnology and its Alan Malcolm Institute of Biology range of biosciences from physiology applications. Dame Nancy Rothwell, and neuroscience, biochemistry and Chair of the Interim Council of the Emma Southern microbiology, to ecology, taxonomy Society of Biology, said ‘The vote Biosciences Federation and environmental science.

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Society update – from we need to build our technical and One further topic of discussion in public relations expertise to do this. the Executive Committee has been whether we should seek to share the Chief Executive Increasing our ambition in all areas accommodation with other learned In past years The Society has planned of current activity its activities on a year-by-year basis as societies. The Biochemical Society, This includes education, external the Society for Experimental Biology our income (which comes primarily affairs, meetings and publications, from our publishing activities) could and The British Ecological Society as well as international activity and have been seeking a building for not be predicted very far ahead. The new areas, such as translation of movement towards open access joint purchase and occupation. basic research through to clinical These three societies have recently publishing for scientific manuscripts advances. We should continually was (and still is) regarded as a major made an offer for a building that be looking for ways to increase the could accommodate a number of potential threat to our income. scope and range of our activities, If libraries and individuals stop other societies and The Physiological while maintaining our focus on the Society was approached to see subscribing to our Journals, because pivotal importance of physiology. they are made available for free at if we wished to participate. This A range of specific proposals were proposal was discussed extensively the time of publication, the resulting made by the Chairs of all The Society loss of income could ultimately but, in addition to some practical Committees as to how they could difficulties, the Executive Committee threaten our existence as a Society in increase their activities and gain its current form! thought that our strategy should be maximum value from them. to share with societies with more I am pleased to say that this Increasing our sphere of influence commonality of membership and particular threat has been To meet the challenges facing us, scientific interests. This does not, ameliorated (for a number of years it was felt to be essential that we of course, rule out the possibility into the future) by The Society engage with a broader range of of The Society co-habitating with signing a publishing agreement with people: clinical colleagues, teachers, other groups consistent with our Wiley-Blackwell that guarantees pharmaceutical companies, and the long-term strategy for expanding it a healthy publishing income, relevant research councils as well as our sphere of influence as discussed irrespective of Journal sales. So as continuing to broaden our appeal to above. long as the credit crunch doesn’t younger scientists (undergraduates, push Wiley-Blackwell out of business, postgraduates and post-docs) Mike Collis The Society can plan ahead, based studying physiology. Furthermore, on a platform of financial security. we should continue to develop For Society Noticeboard, see p. 64. our links with other like-minded Recently, the Executive Committee societies, and to increase our of Council held its first brain- political and international influence. storming meeting to consider its E-newsletter for long-term vision for the future of The Communication Members Society. These discussions will be It was agreed that The Society needs continued and developed with the to ensure that communication with You will have noticed that we have full Council during the year. colleagues is clear and transparent. recently introduced an e-newsletter This has become harder as for our Members. This started Some key features that emerged traditional physiology departments out as a monthly communication from these preliminary discussions have disappeared, but also becomes and we are considering a move were: more important if the disappearance to fortnightly editions based of departments is not to result in on feedback on its value. The Modernisation of The Society the disappearance of the discipline. newsletter is a brief screen shot We need to continue to be forward Without excellent communication it reminder of deadlines that are looking and developing our will be difficult to engage properly approaching and points readers to science to reinforce the position with physiologists, and thus to the relevant section of the website of physiology as the integrative ensure the future of the discipline. for detailed information. We hope bioscience (from molecule to Many routes were discussed to that by using this regular ‘alerting’ whole body). But we must also achieve this – email, web surveys service we can reduce the number maintain the excellence traditionally and the website; communication of emails sent to Members as we associated with The Society, so via departmental Society all suffer from email overload these that it is seen as the leading light representatives, SIG convenors and days. We welcome any feedback on in the discipline. Continuing the HoDs groups; the magazine and the newsletter and its frequency modernisation of communication of newsletter (see box) and building and general feedback on the way society information and of scientific on the opportunities afforded by The Society communicates with advances to our members and to attendance and advertising at our its membership. Please email the outside world is essential and meetings. comments to [email protected]

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Membership activities considered to be a valuable service International capacity and are always positively received – 2009 has already been a busy year, raising self-awareness and providing building in science with The Society’s membership the knowledge and skill to write an activities geared up to recruiting effective CV. and technology. new members, particularly in the Undergraduate Associate category. The potential role of Originally launched in 2007, the learned societies student membership category was introduced in recognition of In the last few years, the global the need to encourage budding development agenda has moved physiologists, welcome them to forward to embrace the importance the community and facilitate their of science, technology and innovation career. We hope our activities will in helping to address the crucial development issues facing the world raise awareness of The Society today, including climate change, and enhance our already diverse health, infrastructure development, membership of over 2600 Members. University of Leeds. the building of sustainable livelihoods and the elimination of poverty. Science The Membership Services team has The promotional visits are also a been actively recruiting through and scientists are now seen to be great opportunity to find out a little integral to this global effort, and it is visits to universities around the UK bit more about what current and recognised that a key aim has to be and Ireland, providing an information potential Members of The Society to develop local scientific capacity point to potential members as well are interested in, in terms of Member in developing countries to enable as career support to our student benefits. Taking feedback on board, them to address pressing local issues members. The purpose of our visits travel grant funding for students has and build sustainable economies. to undergraduates is to talk about been launched this year, enabling Local solutions are needed for local The Society, benefits of membership, students to apply for up to £100 a problems. This can only be achieved resources we offer students and year for support to attend meetings by supporting effective grassroots how to get together to develop a and conferences. We will continue initiatives, tying these closely to real student society under the umbrella to develop resources and benefits for local needs, and embedding them of The Physiological Society. If all our membership categories. in supportive governmental science requested by students and society policy and funding frameworks. representatives, an additional Universities we visited in early Learned societies of every discipline careers session in the form of a 2009 included King’s College are in a unique position to contribute CV workshop is also organised. London, University of Leeds, Trinity to this agenda. Such societies are Although most universities have College Dublin and the University quite different from the many other careers services providing this of Westminster. The Physiological ways in which science is organised, support, the workshops are Society, through individual whether through government funding undergraduate societies, can help agencies, universities or science-based support the career development of industries. In essence they are ‘clubs physiologists and we are very much of scientists’, whose raison d’être looking forward to hearing from is to capacity build their respective Members who would like to arrange disciplines, and in some cases they for us to visit their institution this have been doing this very successfully year. for centuries. As clubs, they are often not overly hierarchical, and Trinity College If you would like to arrange a visit are naturally organised as extended Dublin. or discuss the opportunities of networks of scientists with strong links establishing an undergraduate at grass-roots level. Many of the older society, please feel free to contact ones, founded centuries or decades me on: ago to serve their immediate scientific communities, have naturally extended +44 020 7269 5726 or email at towards having an international [email protected] membership, and have been quietly supporting budding scientists in the For more information on developing world before the main Society activities please visit: international aid agencies saw the www.physoc.org importance of this. Such programmes have not been developed by Irrum Magre sometimes remote policy makers, but have the advantage of having been

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Since 2007, The Physiological forthcoming meeting at the RAS, or to Society has reviewed this topic. A discuss this further, please contact me concept paper is now available which at [email protected] looks at the evolving international development agenda supporting Liz Bell capacity building in science and (this article was first published in CaSE technology in developing countries. It Newsletter) reviews some current developments The joint meeting of the learned societies in major players such as the World on capacity building will take place at the Bank and the Department for Royal Astronomical Society in London on International Development, and 2nd June, and a report on it will appear in a Apparatus arriving at a physics teacher outlines how learned societies might later issue of Physiology News. training workshop in Rwanda funded by be able to effectively contribute the Institute of Physics. to the development of long-term, The new invisible college: sustainable, grass-roots, research driven by the expressed needs of their and teaching communities in their how globalisation memberships. disciplines in developing countries is changing the that are closely networked with Learned societies have the potential their international colleagues. Our landscape for scientific to help in capacity building at many research indicates that this could help levels. As well as being able to directly collaboration tackle many of the capacity building respond to local scientists needs problems being encountered by The Royal Society Science and develop initiatives at grass-roots international development agencies, Policy Centre Policy Lab, level, they also often have relevant by providing long-term, stable experience of advising on science 3 March 2009 professional networks underpinning policy at governmental level. Learned their research programme and other The Royal Society has recently societies and their members know initiatives. re-organised its science policy activities how to set up and run scientific and seems to be doing lots of new journals (many of which are still closely The Physiological Society is developing and exciting stuff. As part of this they connected to the societies that created an example of a programme of have been organising a new monthly them), work with the publishing support, initially focused on Africa, series of science policy labs. This was industry, run events on topical which might be developed for the first one I had attended, and I research issues, provide networking physiology, a fundamental discipline was thrilled to discover how closely and career development support, that underpins medicine and it complemented our independent train students, work with schools bioscience. Support for this, and thoughts on how learned societies its related biomedical disciplines, and universities to encourage young should get more involved in capacity is vital in helping developing people to study and take up careers in country scientists tackle local health building for international development. science, and engage with the media issues. However, we believe that and the general public on crucial issues The key note speaker was Caroline the programme principles being Wagner from George Washington of public concern. The Royal Society developed are equally applicable to University’s Center for International conducted a survey of some current learned societies across the entire capacity building initiatives in learned spectrum of the natural, engineering Science and Technology Policy. She and social sciences, addressing other talked about her recently published vital issues to developing countries book ‘The New Invisible College’ which such as environment, climate change, Calestous Juma has described as a agriculture, energy, civil society etc. ‘forceful assault on the traditional We are currently working with a edifice of science policy’. Her basic Biosciences Federation (BSF) Working thesis was that we need to recognise Group on Capacity Building to how science has developed over the co-ordinate parallel new initiatives centuries if we are to tackle science from its member societies. The policy issues effectively. Science has Physiological Society and the BSF are got so complicated that it is returning also working with societies outside to its 17th century roots of invisible the biosciences area, including the colleges i.e. informal networks of Francis Gatete, training another teacher Institute of Physics (IOP) and the Royal to use the optics apparatus in Rwandan Astronomical Society (RAS), to develop scientists. This is now the biggest force School. new models and explore the issue with at global level and a network systems policy makers and funders. We will model is needed for its governance. societies in 2007. This indicated that be holding a joint meeting for learned In the 17th to 19th centuries, learned societies and other professional because of lack of funding, many of societies at the RAS in the summer to brainstorm how we might take this associations drove scientific their international capacity building agenda forwards. development on a networking programmes, though successful, have model. Then in the 20th century the remained small. Their potential is far If you would like a copy of our concept principal driver became scientific from being realised! paper, more information on the nationalism, with governments

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funding and organising ‘Big Science’ to Members based in the UK with an unprecedented degree. However, experience of working in Africa, Exciting pupils ICTs have now created distributed and Members based in Africa. I look networks of people working together forward to hearing from you at: about biology in a dynamic way. It is these large, [email protected] When academics, researchers and informal networks that are now really undergraduate students work together driving science, and governments Liz Bell on schools outreach programmes, have very little influence on the there is potential for everyone to social interactions involved. These The Otto Hutter benefit. Fiona Wyllie, Innovation and self-organising, grassroots networks Engagement Officer at Cardiff University need support and encouragement, Physiology Teaching School of Biosciences, explains some particularly in developing countries Prize of the initiatives she has introduced where the model used in international Over the past few years, The to encourage scientists at every stage of their career to excite primary and development has tended to be to try to Physiological Society has taken steps secondary school pupils about biology replicate the formal structures of ‘Big to raise the profile of physiology and the possibility of studying the Science’ without sufficient attention to teaching. We are now pleased to biosciences further, and to help bridge the needs of the supporting networks. announce the launch of the ‘Otto the gap between school and university. Scientists in developing countries Hutter Physiology Teaching Prize’ – a need help to get linked into the real vehicle for The Society to recognize scientific system of networks. an individual’s contribution to The discussion gave me a wonderful teaching undergraduate physiology. opportunity to flag how we were We are proud that Otto Hutter has already thinking about this, and agreed to lend his name to The that we and other learned societies, Society’s new prize. Otto began his were very well placed to provide the career in the 1940s as a scientific necessary support to such networks. technician at the Burroughs & Our club of scientists model worked Wellcome labs in Kent, before very well in the early stages of completing a BSc and PhD at UCL. developing science in the West, and is As well as having a successful now poised, if we can get appropriate research career, Otto has helped funding, to repeat the feat in helping Exciting experiences in the lab are spread physiology education to a developing countries grow their SET high on the list of things young people wider world, both internationally capacities. I was also given another enjoy about science and are frequently and through teaching innovation. opportunity to follow this up in a cited as the aspect that switches them subsequent Royal Society event on the At Glasgow, he pioneered on to further study. So, much of our 25 March where the Nobel Laureate perhaps the first, fully integrated secondary schools’ engagement work Harold Varmus, advisor to President electrophysiological lab for junior centres on inviting groups to 1-day Obama, was talking about ‘restoring teaching. He is also a virtuoso of workshops which not only illustrate science to its rightful place’. In talking small group teaching, famous for the work of research groups at Cardiff about how supporting science in every throwing the blackboard chalk as University, but are also very practically respect was a priority in addressing the an inducement to do some of the orientated. One such workshop, ‘Using global credit crunch, climate change board-work yourself! killer genes to fight cancer’, represents a research interest of Richard issues etc, he didn’t mention support The new prize will be officially for scientific capacity building in Clarkson, RCUK Fellow in the School launched at Physiology 2009 in international development. So I asked of Biosciences. Pupils learn about this Dublin, with a nomination deadline him whether this would be a priority project by participating in activities of 30 September 2009; the recipient under the new regime, bearing in analogous to those undertaken of the prize will be notified by mind its vital importance in helping on a daily basis by scientists in Dr the end of 2009 and will receive developing countries address their own Clarkson’s group. The pupils separate £1000 in prize money (£500 of and subsequently visualise DNA and global needs. He agreed that it fragments by gel electrophoresis, should be. which should be used for teaching resources) . then genetically transform bacterial So these two meetings left me feeling cells to give colonies which fluoresce We hope this prize, and Otto optimistic that the science policy green. They examine sections of tissue Hutter’s example as an enthusiastic agenda may now be moving in our under the microscope to discover how physiology teacher, will encourage direction, and that over the next few genes can be investigated as potential years we may be able to leverage continued development and therapeutic agents. Both postgraduate some funding to support networks excellence in teaching. For more and undergraduate students are of scientists in developing countries. information about the Otto Hutter heavily involved in providing advice However, it is early days yet. Physiology Teaching Prize, please and assistance during the practical visit our website at www.physoc.org/ sessions and we have found that this To help take this forward, I am teachingprize or contact creates a good informal atmosphere looking to make contact both with [email protected]. which encourages visiting pupils to

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chat to the students about courses capture the innate scientific fascination and university life. This workshop of 10/11 year olds by inviting five or has also addressed the problem that six local schools (around 240 pupils practical work, although ‘hands-on’, is over 2 days) to the University for a too often ‘minds-off’. We are currently day of engaging workshops and small running an alternative form of this ‘lectures’. This year we had over 12 workshop as part of a Royal Society workshops on offer, ranging from Partnership Grant (http://royalsociety. several with live organisms (toads, org), which involves pupils having to frogs, springtails, earthworms and design and then implement their own various pond invertebrates) through experimental plan. We have run one of to one showing why snot becomes these workshops so far and found that, green and another which involves with some help, pupils designed good scraping off pupils’ own cheek cells and insightful plans and were extremely viewing them under the microscope. eager and motivated to engage in their Undergraduate students were very own experiments. also involved in running their own workshops, either going with ideas These workshops have several aims: to a fancy buzzer system, which ensured and materials provided for them or, in improve achievement at the end of AS fair play and entertaining sound effects one case, designing and implementing year exams, to encourage subsequent throughout the quiz! their own ideas on the brain. Smoking retention in A level biology and to awareness was highlighted through encourage further study. Another Two years ago we created a new and an interactive play performed by initiative aimed even more directly at compulsory ‘Biology in Society’ module myself and undergraduate students, addressing the problem of poor exam for all Final Year undergraduates in which uses brightly coloured organ achievement has been the creation the School of Biosciences. As well as tunics to illustrate the health dangers of the first annual ‘South East Wales introducing students to the nature of cigarettes and a theme of athletic Biology Challenge’ this year. I got and importance of public engagement performance to show other problems together with three local biology across all sectors of bioscience with being persuaded to smoke. teachers and a scientist from a local employment, the module also deals bioscience company, GE Healthcare, with issues associated with a range to compile an inter-schools AS of controversial bioscientific topics. revision quiz representing ‘real-life’ Optional coursework introduced this research and commercial applications, year gave interested students the interspersed with rounds based on opportunity to not only learn more TV shows. A team of undergraduate about one such topic, that of stem students bravely formed an ‘eggheads’ cell research, but to also run their team, which all of the competing own ethical discussion session with schools delighted in subsequently GCSE classes in local schools. Training beating on the evening of the quiz! for this session provided students One of my rounds illustrated well a with materials aimed to inform and typical biomedical research group and stimulate discussion amongst the We hope to build on the experiences interests – the varied composition pupils and ideas on how to facilitate and successes of the last year and of the team, the reasons for doing the session and effectively work as increase the overall number and the research, many cutting edge a team. Specific sessions were then the variety of practically-orientated techniques, subsequent conclusions set up, available students organised workshops on offer to schools. I find and benefits for society. The other into teams of four or five and a car that when our researchers learn that I round emphasised the connection hired for the trip, which did not can provide audiences, venues, advice of our research with the everyday involve any accompanying University and/or ideas on how to engage pupils world – how understanding more staff. The sessions helped to improve with their research and substantial about how protease enzymes work students’ communication, teamwork assistance with applying for outside can help to enhance the taste and and time-management skills and also funds, that they often become very texture of cheese, lead to better and provided teachers, who have seen this keen on getting involved. In addition, more environmentally friendly washing topic only very recently introduced into we hope to involve undergraduate detergents and potentially get away the curriculum, with relevant ideas. students in as great a number of from burning fossil fuels. The teachers activities as possible, not only to ensured that the questions were very It is well recognised that children go provide role models to the visiting curricularly orientated and that their through their primary school years pupils but also to emphasise the pupils were motivated to begin early with a generally high interest and importance of engaging with outside revision in the hope that they could enthusiasm for science, but it is often audiences and to give them some of bring glory to their particular school a time when this positive approach is the skills required to do this well. and take home the coveted challenge not sufficiently built upon, especially if trophy, bought with a £1000 Special the knowledge and confidence of the Fiona Wyllie Merit Award from the Rolls-Royce teachers involved are inadequate. For Innovation and Engagement Officer, Science Prize. This money also funded some years now, we have attempted to Cardiff University

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The Discovery Zone at experiences. It is amazing how staff This comment from an eminent members managed to make intra- professor who helped to run a Leeds – an explosion and intermolecular bonding relevant station summed up the feelings of and understandable by making goo all the staff when he reported ‘This of science – the message being re-enforced was a really great occasion, it was Picture a sports hall filled with 24 beautifully by practical fun. There gratifying how many children said science stations, manned by over is nothing like the opportunity to they really enjoyed the experiments 70 research staff (PhD students blow things up to interest children – isolating DNA was ‘cool’ – and right up to Professors) from the whilst others really enjoyed learning several said they wanted to be University of Leeds; a sea of colour about the exquisite sensitivity of scientists when they grew up!’ and unusual objects, awash with the tips of our fingers, enabling us enthusiastic chatter and anticipation. to read Braille and identify objects, Crayfish in tanks are limbering up just based on touch. In the year of for races. Academics are pumping a celebration of evolution, pupils up airbeds to balance children on. learned about adaptations of plants Twelve foot models of neurones, to enable survival by changing ways made from ropes, balls and funnels of seed dispersion. are being tested. Plants are everywhere, forming small jungle areas interspersed with bats, insects and… spectrophotometers! The doors open and 120 school children Overall, a success for schools, the arrive, looking around in eager University and most importantly, expectation at all the impending science, thanks to The Physiological activities. The children are efficiently Society. assigned to their stations, the staff await the onslaught, the noise levels Sue Deuchars increase and the fun begins! This is Academic co-ordinator and the Discovery Zone at the University pipe-cleaner neurone constructor of Leeds! extraordinaire The extremely positive feedback Institute of Membrane and Systems from university staff, accompanying Biology, University of Leeds, Leeds teachers and most importantly the pupils, illustrates the importance of The outreach grant scheme is open running such events at university to all Members and Affiliates of The Society who would like to communicate and the rich and varied rewards. the excitement of physiology to young Through funding from The scientists and the wider community. Physiological Society and BBSRC, For more information, please visit our transport was provided to the event, website or email [email protected] making it accessible to all schools, This 2 day event, kindly sponsored in regardless of socioeconomic status. New international grant part by The Physiological Society’s Many children were therefore new outreach scheme, enabled schemes experiencing a university setting The Society has launched three new grant nearly 500 school children aged 8–14 and staff for the first time. One schemes to support research and teaching to experience science phenomena child described the event as a in international physiology. International first hand. Using models, live ‘wonderland’ whilst another school Junior Research Grant – intended to animals, machines, fact sheets and reported that pupils had gone back support junior researchers overseas brain power, the pupils encountered to school buzzing so that others (outstanding physiologists at senior postgraduate or post-doctoral level) and the evolution of ant colonies, LEGO who had not attended organised a proteins, the wonders of saliva, real replaces the Junior Fellowship scheme. delegation to the headteacher to International Senior Research Grant – brains, skeletons, maths problems, demand to be taken! intended to support senior researchers insect defence systems and the overseas, and replaces the Centres of importance of a healthy heart. Excellence scheme. The David Jordan They extracted DNA from fruit and International Teaching Fellowship – thought about its role in humans, aimed at teachers/learning support staff then made DNA bracelets. They to give them an opportunity to visit an experienced different kinds of institution of their choice in order to develop or acquire teaching methods of energy and its uses. Each station benefit to the teaching of physiology. provided some simple take-home For more information of the three new messages, learnt through hands-on schemes please visit www.physoc.org.

Physiology News | No. 75 | Summer 2009 | www.physoc.org EDUCATION PN 59

Hot topics meeting of research will be increasingly Do we need more important. in pharmacology and The RAE has also had impacts multiskilled scientists physiology 2009 beyond funding on HEIs. A classic and engineers to example has been on the research/ The ‘hot topics’ addressed at teaching divide in departments, manage economic The Joint Meeting of the British where HEIs have tended to link kudos recovery and change? Pharmacological Society and The to success in research rather than Physiological Society, 26–27 March teaching. Ideally research should At the Parliamentary and Scientific 2009 at the University of Warwick inform teaching and encourage the Committee Meeting on 12 March included some feedback from the next generation, but too often the 2009, Lord Drayson, the Minister of recent Research Assessment Exercise ‘stars’ have zero or very low teaching State for Science and Innovation, (RAE), managing the research and commitments. Ideally all staff should said that the answer to this question teaching divide and how to improve be able to contribute to all areas of was a resounding yes. He described National Student Survey (NSS) a department’s work, with better scores. The presenters were Jeremy his own background as an engineer use being made of support staff, and a businessman, propelled into Pearson (KCL), Ian Kitchen (Surrey), delegating to them to make their Graeme Henderson (Bristol), Clive this arena through the support work more interesting. Post grads of a joint ESRC/SERC funded PhD Orchard (Bristol), Mike Spyer (UCL), and post docs should also be used studentship in the 1980s. The social Paul Hubbard (HEFCE) and Ian more to help their CVs and broaden science elements of his engineering McFadzean (KCL). their education. Innovation in degree training helped him to put teaching should be encouraged, and The RAE requires a great deal of his work into a broader context, effort from all concerned, yet its professional rewards should perhaps be made contingent on teaching as and set him up for his subsequent output tends to result in very little success in commercialising shift in money actually distributed well as research. It should always be remembered that universities are science. In his view, SET is vital for to universities. Submissions showed rebalancing the economy post the that translational research from the not research institutes even if they Credit Crunch. Investment needs lab bench into clinical practice is are research led – financial viability to be maintained in both pure rarely evident in a single research actually comes from teaching. and applied research. We need to centre – it takes several centres National Student Survey scores develop a society literate in SET, and working in collaboration. Four year are also more of an issue for HEIs will need to produce graduates PhD programmes were valuable, and departments in the context of the capable of working well with longer-term funding (programme general quality assurance framework grant level or above) tended to for higher education. Students are people from other disciplines to correlate well with output quality. increasingly using them to help drive innovation. It could be a great Some panels did check the ISI choose an HEI. Attention to issues opportunity to get the excellent SET citations for papers submitted, and affecting an institution’s score graduates previously lost to the City found it to be a useful guide to paper were highlighted, for example, back into universities! The question quality. an increase in security in HEIs can about increased flexibility in degree make it very difficult for students provision sparked off a lot of debate The RAE will be succeeded by the to access staff and visit research on resourcing implications. Research Excellence Framework labs; reductions in small group (REF). It is hoped that the new sessions notably in practical work; This meeting rather focused on system will involve less work for and increasing assessment burdens the potential contributions from Higher Education Institutes (HEIs) on staff resulting in too little the physical and engineering and will involve bibliometric analysis individual feedback. Feedback can sciences, but the Technology and other indicators. Hopefully it be improved in a cost-effective Strategy Board did highlight the will be an improvement on the RAE manner by such strategies as using need for new treatments to tackle system of examining self-selected student peer assessment, debriefing chronic diseases in an increasingly outputs which can over-value the surgeries on exam papers etc. An ageing population. This gave me average research quality of an HEI. issue highlighted in the discussion the opportunity to highlight the HEFCE are trying to move towards was that departments are dealing importance of the biomedical assessing institutions rather than with increasingly unrealistic student sciences in many different areas individuals. Elements of peer expectations; students need the relating to the economy, and to ask review will be kept to support the differences between universities them to keep developments in e.g. other analyses, with assessments and sixth form colleges explained to Systems Biology in mind. from special groups feeding into a them early on. smaller number of expert panels. Liz Bell The economic and social benefits Liz Bell

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Early Career Author’s The Journal of Annual Review Prize Prize Physiology Editor-in- Lecture Are you eligible to compete for the Chief Elect appointed The 2009 Annual Review Prize Experimental Physiology Early Career Lecture has been awarded to a Author’s Prize 2009? Journal of Physiology Editor, Stephen The Experimental Physiology Early G Waxman of Yale University. Steve’s Career Author’s Prize is being lecture is entitled Fire, fantoms and introduced to reward early career fugu: sodium channels from squid authors who publish outstanding to clinic, and will be published in research papers in Experimental The Journal later in the year. Since Physiology which best meet the receiving the award from The journal’s remit of translation and Society, Steve has also been awarded integration. See http://ep.physoc.org/ the US Department of Veterans misc/ifora.shtml#policy Affair’s William S Middleton Award for Outstanding Achievement in The first prize, sponsored jointly by Biomedical Research, the VA’s The Physiological Society and the highest scientific honour. publishers, Wiley-Blackwell, will be $1000, There will be a runner’s up Both awards recognize Steve’s prize of $500 . The Physiological Society is delighted significant research achievements to announce that Michael Rennie in physiology and pathology Entries will be judged by the journal’s (Professor of Clinical Physiology at relating to spinal cord injury, Editorial Board and the results will be the University of Nottingham) has multiple sclerosis and painful nerve published in Experimental Physiology been appointed as Editor-in-Chief injuries. Steve trained as both a and Physiology News early in 2010. Elect for The Journal of Physiology. neurologist and a neuroscientist The winners will be invited to a formal presentation at Physiology Mike Rennie is internationally known and his research builds upon the 2010 The Society’s main meeting in for his work in human metabolism, ‘molecular revolution’, to develop Manchester 28 June –2 July. especially protein metabolism and new therapeutic strategies that will the mechanisms of growth and restore functions such as sensation Entries are invited from scientists adaptation to physical activity/ and the ability to walk after spinal who are either the first or last author inactivity, disease and ageing. He cord, nerve and brain injury. His of a research article published has a long history of publishing research was the first to show the in Experimental Physiology in high impact papers in The Journal of changes in molecules within nerve 2009. Authors will be asked if they Physiology. Mike has a deep interest cells that permit remissions – are eligible to enter when their paper and involvement in all aspects of recovery of previously lost functions is accepted for publication. We hope physiology and has served on The such as vision and motor control to offer a similar prize to early career Journal’s Editorial Board (1996–2003) – in multiple sclerosis, and he has authors of papers published in 2010. and on the MRC Physiological identified key molecules that are Applicants must have received Medicine and Infections Board responsible for pain after nerve their research degree (MD, PhD or Grants Committee. He also has an injury and spinal cord injury. equivalent) less than 6 years before illustrious history of service to The In his role as Editor of The Journal of submitting the paper. In the case of Physiological Society, having been a Physiology, Steve has contributed to candidates who have both a MD and Trustee and a member of a number the launch of Clinical Perspectives, PhD the date of the most recently of Society committees including, as The Journal’s initiative to link the awarded degree should be used. chair, the Committee of Heads of basic science reported in its research Department of Physiology for the papers to clinical treatments. The Cardiac Physiome UK. He was the Professor Sir George Journal of Physiology congratulates Lindor Brown Prize Lecturer of The Steve on his awards. Themed Issue Physiological Society in 2004. The May 2009 issue (94:5) of Mike will take over as Editor-in-Chief The Annual Review Prize Lecture Experimental Physiology is a Cardiac of The Journal when William Large will be delivered on Thursday 9 July, Physiome themed issue organised by finishes his tenure in the post on 1800–1900, at Physiology 2009 in Nic Smith, Peter Hunter and David 30 June 2010. Dublin. Paterson.

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world-leading experts. In the first models are needed that incorporate ever published dialogue on the both the kidney and the brain topic, Drs Montani and Vliet, and Drs control systems. So the question of Osborn, Averina and Fink share their whether it is the kidney or the brain opinions with us and criticise each that has a firmer grip on the reins others theories. Their frank exchange for controlling blood pressure may of views provides an interesting and have to wait for a mathematician to informative summary of the latest answer. research into how blood pressure is controlled. Read this Exchange of Views free online: http://ep.physoc.org/ The problem of high blood pressure content/94/4.toc has reached pandemic proportions, causing premature death through The Journal of Physiology heart attacks, strokes and kidney Symposia 2009 disease in a third of the UK population. For decades, scientists Novel insights into oestrogen have battled at length over its cause actions yet still cannot agree; is the kidney Wednesday 8 July 2009 or the brain to blame? In addition to providing a snapshot At The Physiological Society Annual of current cardiac physiome When blood pressure increases, Meeting, Dublin, Republic of work, the articles converge on the kidneys respond by extracting Ireland. three themes that are central to extra water and salts into the urine, the translation and integration causing blood volume –and hence Dynamic aspects of functioning focus of Experimental Physiology, pressure – to fall. But special nerve membrane proteins specifically: the application of pathways mean the brain can also Friday 31 July 2009 (10:00–12:30) modelling tools across spatial regulate urine production and hence scales; facilitating the re-use and At IUPS, Kyoto, Japan. influence blood pressure. So which application of mathematical models organ is really in charge? Montani Physiological regulation linked in experimental contexts; and the and Vliet argue that controlling with physical activity and health translation of modelling work for blood volume is the key, as the understanding human physiology Friday 31 July 2009 (10:00–16:30) kidney automatically makes more and pathophysiological function. At IUPS, Kyoto, Japan. urine as blood pressure increases. See: http://ep.physoc.org/ However, Osborn and colleagues Advances and hold-ups in the content/94/5.toc remind us that the cardiovascular study of structure, function and system is controlled by multiple regulation of Cys-loop ligand- mechanisms including the automatic gated ion channels Exchange of Views part of the nervous system, which Friday 16 October 2009 Is it really only our kidneys that directly controls the kidney. They At Neuroscience 2009, Chicago, control blood pressure? also update us on a plethora of new findings supporting a role of the USA. The April 2009 issue of Experimental nervous system in controlling blood For full details of these, and other Physiology hosts a lively debate pressure long term. Both groups symposia visit http://jp.physoc.org between two groups of acknowledge that new mathematical Prize Lectures 2009 The following Prize Lectures will be delivered in 2009:

Annual Public Lecture Stephen O’Rahilly Physiology 2009, Dublin, Wednesday 8 July, 18.15–19.15 Annual Review Stephen Waxman Physiology 2009, Dublin, Thursday 7 July, 18.00–19.00 Bayliss–Starling Gero Miesenboeck Physiology 2009, Dublin, Wednesday 8 July, 12.15–13.00 Biller Gavin Stewart Newcastle Themed Meeting, September GL Brown Mark Boyett Various (see the website for schedule) Hodgkin–Huxley–Katz Eric Kandel Physiology 2009, Dublin, Thursday 9 July, 12.15–13.00 Michael de Burgh Daly Colin Nurse Physiology 2009, Dublin, Friday 10 July, 12.15–13.00 Paton Diethelm Richter Physiology 2009, Dublin,Tuesday 7 July, 17.30–18.30

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New journal websites Look and feel – completely Looking to the future, the upgrade The Journal of Physiology and revamped design, incorporating ensures our content will work with a Experimental Physiology are hosted Society branding together with new, wide variety of Web 2.0 applications, through HighWire, a non-profit more intuitive, site navigation. feeds, widgets, and web services division of Stanford University and expanded branding. It also gives Libraries. We are pleased to end users the possibility of features announce that our journal sites have such as social networking, forums, now been upgraded to HighWire’s and a number of content delivery new Web 2.0 platform. options through mobile platforms. The upgrade makes our content Whereas Web 1.0 sites merely more accessible, and more portable published content for a visitor to than ever, allowing us to move view, Web 2.0 aims to facilitate information to where the user is and communication, participation will enable our readers to take the and collaboration between sites, latest scientific research with them. between users and sites, and between users themselves. The new We hope you enjoy the new features platform infrastructure is designed The Journal of Physiology new homepage. this platform brings, and invite you to cooperate with emerging web to send us your comments and services and technologies and feedback at: also to anticipate future website http://jp.physoc.org/feedback developments.

Some of our new features include: The Journal of Physiology (http://jp.physoc.org) Abstract preview – mouse-over the Experimental Physiology table of contents and search results (http://ep.physoc.org) page for an instant pop-up preview of the article abstract, without Liam McKay leaving the page. Experimental Physiology new homepage. IT & Communications Manager Figure expansion in place – figure and table thumbnails can be The new user interface is a flexible New staff member in the enlarged from within the article. three-column design that places Publications Office many features at your service Tag-along navigation – the without taking attention away Laura Buck, a recent MPhil graduate navigation box follows alongside as from the substantive page content. in Biological Anthropology from you scroll down the article page. Features most closely associated the University of Cambridge, will with the page content are placed be working with Ann Watson in Feature hideaway – author closest to it. A major goal of the new the Distribution Office within the affiliations, related links and design is to keep you in context as Publications Office in Cambridge, other article enhancements can you conduct your research. taking manuscripts through the be expanded or hidden. Article review process. enhancement preferences are remembered when the user next visits the site.

Popular-articles list – a list of the Most Viewed and Most Cited articles is readily available.

Related-articles search – from within an article, users can click to search for articles by author, keyword, or subject classification.

Easier scanning and reading – better positioning of the title and abstract, improved text fonts and formatting, plus quick previous/next Laura replaces Ed Sexton, who has links to scan by article section make taken on much of the work of Linda it fast to scan an article online. New Table of Contents design. Rimmer.

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the effect of venoms of a scorpion Hans Meves were also studied on Na+ currents. In 1925–2008 other experiments, Ca2+ currents and + Hans Meves was born on 13 September the effect of 4-aminopyridine on K 1925 in Berlin. After school and military currents were investigated. This work, service on the eastern front from partly done with younger colleagues, 1943 to 1945, he read medicine at the Hans Meves, Kiel appeared mainly in The Journal of University of Marburg. He received his 1968. Physiology. During this period, he and his wife enjoyed entertaining at their doctor’s degree in 1951 and started his the perfused axon technique, a method scientific career with Hans Lullies whom house. They fed many of the young, whose results had added strong support and usually very hungry, people who he followed to the recently founded to the ionic theory and paved the way Saar University in Homburg and later came to Plymouth, among them Peter for Hodgkin’s Nobel Prize in Physiology McNaughton and Roger Tsien. to Kiel. During these years with Lullies, or Medicine in 1963. who himself had made impedance In 1980, Meves returned to Germany as measurements in nerve before the war, In the 1963 season, Hodgkin and the successor of R Stämpfli in the Chair he published seven full-length papers Meves were joined by Knox Chandler of Physiology at Homburg and became mainly on the effect of carbon dioxide for further studies of low ionic strength active in a Sonderforschungsbereich and hydrogen on nerve and muscle and of ionic selectivity of the sodium on membranes. He continued studies fibres. channel using the voltage-clamp on the sodium channel using the frog method. Meves and Chandler had In 1957 he went to Stockholm for node of Ranvier instead of the squid one more season in Plymouth in 1965 giant axon. He remained the classical 6 months to work with B Frankenhäuser (see Knox Chandler’s piece). For these who had been a close co-worker of electrophysiologist, however, working studies, Stämpfli generously gave Meves alone or with only one co-worker at his Alan Hodgkin. There he investigated leave for Plymouth and helped to obtain 2+ ‘stand’. the effect of Mg ions on isolated financial support. The time at Plymouth single nerve fibres and also had long was always followed by 1 or 2 months In 1990, he retired but continued to discussions with Frankenhäuser about in Cambridge, where the data were do experiments, now with an analysis the dramatic advances in membrane evaluated and manuscripts written. of the effects of lipid mediators such physiology initiated by the ionic theory. The Meveses enjoyed their stays there, as prostaglandins on neuroblastoma x in the ancient city with its college After Meves returned to Kiel, he glioma hybrid cells. For this work, which traditions, where they were received continued to work with myelinated was published in a number of papers in with remarkable hospitality by the nerve fibres and started an analysis various journals, he learned the patch Hodgkins and Keyneses. Occasionally I of after-potentials, for which the ionic clamp technique. His successors, first myself joined the Meveses for dinner at theory provided testable predictions. In A Konnerth and then J Rettig, kindly the French restaurant in Hills Road and the autumn of 1959, he spent 2 months provided space and help in various on visits to London. with R Stämpfli, who by then was the ways. For some time he also enjoyed financial help from the DFG. Professor of Physiology in Homburg. In 1967, Meves was appointed full Together they perfected the technique Professor of Physiology in Kiel. Three Twice in the early 90s he collaborated of dissecting single nerve fibres. This years later, however, he left his Chair with RD Keynes at the Station collaboration was the start of a close in protest against the turbulence at Biologique in Roscoff (France) which friendship that lasted until Stämpfli’s the German universities which severely he enjoyed greatly. Throughout his death in 2002. In 1961, Meves joined disrupted scientific life. Although he scientific career, he was always an Stämpfli’s lab in Homburg where he had two attractive offers in the States, enthusiastic experimenter. remained until 1967. he eagerly accepted the invitation to join the staff of the Marine Biological Hans Meves became a Member of The Stämpfli had established valuable Association, first as Principal and later Physiological Society in 1965 and was international connections that were as Senior Principal Scientific Officer. He a member of the Editorial Board of The sorely missed in Germany after the spent 10 happy and scientifically fruitful Journal of Physiology from 1975 to 1984. war. Among the many foreign visitors years there, exempt from administrative to Homburg was Richard Keynes who and teaching obligations. Hans Meves’s interest went beyond recommended Hans Meves to Alan science. He was an avid reader of Hodgkin. A short visit to Cambridge Hans Meves’ research was concerned literature – both classic and modern – followed and he became one of the few with the selectivity (structure) and the and he loved the arts and the theatre. foreign co-workers of Alan Hodgkin activation/inactivation mechanisms He was a great walker and each year at the Marine Biological Laboratory in (gating) of ion channels, along the lines would spend time among the lakes and Plymouth. Exciting experiments were developed in Hodgkin and Huxley’s mountains of the Engadine in Sils Maria. done late into the night. Collaborating famous four 1952 publications. with ‘the great man’ (Peter Baker’s Many experiments were carried out Towards the end of his life, during the name for him) was certainly the most on voltage-clamped perfused squid illness which he bore with great courage important experience in his scientific giant axons where the properties and fortitude, when he could no longer life. During the Plymouth season in of Na currents could be compared go to the lab, Meves continued working 1962, Hodgkin, Baker and Meves with the asymmetrical displacement at home. His last paper The arachidonic explored the effects of low ionic currents that are thought to arise from acid and ion channels was an update strength on action potentials. They used the voltage sensors of Na+ channels; of his pioneering review from 1994; it

Physiology News | No. 75 | Summer 2009 | www.physoc.org 64 PN OBITUARIES/NOTICEBOARD appeared online on 16 June 2008 in the Society Noticeboard British Journal of Pharmacology. Hans Meves died on 25 September 2008. For Upcoming deadlines for 53 years he was married to Dorothea Scientific Meetings – 2009 Altmeyer. For a comprehensive overview visit the Hans-Christoph Lüttgau website Ruhr-University, Bochum Festschrift Symposium in honour of John A Russell Knox Chandler adds: Hans Meves and Knox Chandler, University of Edinburgh (1 July) Plymouth 1964 (photo by Peter Baker). Hans Meves and I first worked together possible reasons but never imagined Physiology 2009 – University College at the Laboratory of the Marine that the Prize would be announced the Dublin, RoI (7–10 July) Biological Association in Plymouth following week. For updates visit http://www. during the 1963 squid season, when we physiology2009.org/ set out to study the selectivity of the Hans and I had a second squid season Muscle physiology: function and Na channel and effects of low internal in 1965 when we studied Na currents dysfunction ionic strength in voltage-clamped in perfused axons without K in the internally perfused squid giant axons. internal and external solutions. After Young Physiologists’ Symposia, Dublin The experimental schedule started with that, we never had the opportunity (7 July) the 3–4 pm arrival of iced mantles from to collaborate again. Hans visited us Integrative pharmacology and freshly caught squid. After the nerve once in New Haven, in the late 1960s physiology: translating “omics” into bundles containing the giant axons as I recall. Several times after that, functional and clinical applications had been removed, we would go to after Hans had been made Professor in 7th James Black Conference – the common room for afternoon tea Homburg, my wife Caroline and I visited with other squid workers, if any, and Joint Meeting with The British Hans and Dorothy in Homburg, once Pharmacological Society (1–3 Sept) various staff members of the laboratory. with two of our teenage daughters. Experiments would begin after tea Hans and Dorothy always showed us Epithelia & Membrane Transport and go on until all (or almost all) the great hospitality in Homburg and we Themed Meeting nerves had been used, sometimes have fond memories of the wonderful University of Newcastle, UK (6–8 Sept) past midnight. By the time the last times we had together. Abstract submission and registration experiment was finished and the film opens on 22 June developed (photographs of voltage and The Society notes with regret the current records on an oscilloscope), the death of Pierre Dejours and Phillip Joint International Meeting with the local restaurants would be closed and Poole-Wilson. A full appreciation of Society of General Physiologists Hans would take me to his flat where Phillip Poole-Wilson will hopefully Basic biology and disease of muscle Dorothy would prepare supper for us at appear in the next issue. Woods Hole, MA, USA (9–13 Sept) whatever time we arrived. I was always Ion channels and receptors in cell grateful to Dorothy for her delicious Noticeboard impromptu meals. physiology Non-Society meetings Young Physiologists’ Symposia, The next day we would examine the Bone Research Society/British Society Leicester (23–24 Sept) films from the previous day, do rough for Matrix Biology Joint Meeting analysis, and discuss what to do next. University College London, UK An Introductory Workshop on 14–16 June 2009, www.bsmb.ac.uk/ Human and clinical physiological It was clear that Hans loved doing brs/ experiments. He was always full of techniques SEB Annual Main Meeting 2009 King’s College London and Imperial energy, in good spirits, and ready, even SECC, Glasgow, UK. 28 June–1 July at 2 am, to start a new experiment and 2009, www.sebiology.org College London (10–11 Dec) Registration opens 1 August carry it out with care and precision. 3rd International Symposium on He brought a lot of intelligence to the Physiology and pharmacology of Cellular & Integrative Neuroscience research and was a good teacher. I came temperature regulation Themed Meeting to like and respect him enormously. Matsue, Japan. 23–26 July 2009 http://www.med.shimane-u.ac.jp Cardiff University, UK (14–16 Dec) Since squid came only on Monday to BPS Summer Meeting Abstract submission and registration Friday, Saturdays were more relaxed. University of Edinburgh, UK opens on 28 September After analysis and various chores, Hans 8–10 July 2009, www.bps.ac.uk and I would meet Dorothy to have a Congress of the European Association 2010 good dinner in town, usually at the for Clinical Pharmacology and Physiology 2010 – University of Octagon, sometimes joined by Richard Therapeutics Edinburgh, UK, 12–15 July 2009 Manchester (30 June to 2 July) Keynes or other visiting squid workers. www.eacpt2009.org Abstract submission and registration The conversations were always lively, IUPS 2009 opens on 1 March 2010 especially after a couple of glasses Kyoto, Japan, 27 July–1 August 2009 of beer or wine, when Hans could be www.iups2009.com persuaded to tell one of his entertaining Travel Grants ISAN2009 http://www.physoc.org/grants stories. During one such dinner Dorothy, Manly Pacific Hotel, Manly Beach, I think, wondered aloud why Alan had Sydney, Australia, 1–4 September 2009 New international grant schemes: http://www.physoc.org/international not won a Nobel Prize. We talked about www.isanweb.org

Physiology News | No. 75 | Summer 2009 | www.physoc.org Themed Meeting of The Physiological Society Epithelia & Membrane Transport Including a focused symposium on Epithelial form, PowerLab : buy or rent function and environment Easy to use, easy to acquire 6-8 September 2009 Abstract PowerLab® Teaching Systems with LabTutor® and LabChart® soft ware have set the benchmarks Newcastle University, UK in quality, ease-of-use, safety and fl exibility for over 20 years. Now, we’re proud to introduce submission & another industry fi rst...the option to either buy or rent this powerful technology! Registration opens

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Development of epithelial structures Epithelia under stress Abstract submission closes Nick Wright (London, UK) Richard Boucher (North Carolina, USA) 27 July 2009 Contact us for an obligation-free demonstration. David Tosh (Bath, UK) Ole Petersen (Liverpool, UK) Diane Barber (San Francisco, USA) Marshall Montrose (Cincinnati, USA) Tel: 01865 891 623 Email: [email protected] Travel Grant deadline Web: www.adinstruments.com/buy_rent Markus Affolter (Basel, Switzerland) James M Anderson (North Carolina, USA) John Sayer (Newcastle, UK) Tomas Ganz (Los Angeles, USA) 31 July 2009 EQUIPMENT CERTIFIED FOR HUMAN CONNECTION Early-bird registration closes & Physiology and pathophysiology of epithelial Biller Prize Lecture: solute transport Gavin Stewart YPBS deadline Yuichi Sugiyama (Tokyo, Japan) UK • GERMANY • USA • BRAZIL • CHILE • INDIA • JAPAN • CHINA • MALAYSIA • NEW ZEALAND • AUSTRALIA (University College Dublin, RoI) 10 August 2009 Stephan Broer (Canberra, Australia) Peter Agre (North Carolina, USA) CELEBRATING OVER 20 YEARS OF INNOVATIONS Edith Brot-Laroche (Paris, France) Dianne Ford (Newcastle, UK) www.physoc.org/newcastle2009

ADI_InstStudent_UK_PhysioNews.indd 1 15/5/09 2:32:20 PM

0909 Newcastle Pos vPN.indd 1 12/05/2009 10:12:10 ‘Don’t look now, Mabel, but the Professor is back from the solvents cupboard’. Microscope-based histology sessions prove riveting for students and staff (from the School of Medicine Anatomy Museum).

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