PN Issue 97 / Winter 2014 Physiology News

Physiology on the go

Sleep disturbance alters autonomic balance to the heart

Secrets of life from beyond the grave

#Biobakes Contents

Welcome to the Winter 2014 edition of Physiology News

Introduction Features

05 Editorial 21 Human metabolism and obesity: the influence of exercise 25 Exercise: more than just a role in energy balance Physiology 2015 28 Sleep disturbance alters autonomic balance to the heart 6 - 8 July 2015 News in brief 30 The mighty protein: Insulin-like growth factor type 1 34 Secrets of life from beyond the grave Motorpoint Arena Cardi 06 #Biobakes Mary Ann Street, Cardi , United Kingdom, CF10 2EQ LifeSci TRC Registration Opens 07 Student-led ‘Physiology Challenge’ for Biology Week at the University of Leeds 1 January 2015 Physiology Feed Membership Abstract Submission 08 Policy Focus 36 Great textbooks of physiology 1 March - 31 March 2015 38 An affiliate’s view on networking and mentoring www.physiology2015.org 40 Physiology to pedagogy In depth 42 ETRIS: facilitating research and training in in vivo physiology

10 Cambridge physiology scores a century 43 The Benevolent Fund 12 Physiology on the go 44 Obituary: Alex Livingston Physiology News Editor 14 A tribute to Bernhard Frankenhaeuser 1915-1994 46 Journal updates Mike Collis We welcome feedback on our membership magazine, or letters and suggestions for Editorial Board articles for publication, including book reviews, from Physiological Society Members. Siobhan Dennis Please email [email protected] (Eli Lilly UK) Meetings & events Michael Evans Physiology News is one of the benefits of membership of The Physiological Society, along with (Keele University) reduced registration rates for our high-profile events, free online access to The Physiological 16 Forthcoming events Sarah Hall Meeting notes: Obesity – a physiological perspective Society’s leading journals, The Journal of Physiology and Experimental Physiology, and travel (Cardiff University) grants to attend scientific meetings. Membership of The Physiological Society offers you access Jamie McPhee 17 Meeting notes: Special symposium for Dr Robert Banks to the largest network of physiologists in Europe. (Manchester Metropolitan University) 18 Young Life Scientists’ Symposium 2014 Join now to support your career in physiology: David Miller (Glasgow University) 19 Meeting notes: International lecture 2014 Visit www.physoc.org/membership or call 0207 269 5728. Keith Siew 20 We know where we are going but how do we get there? (University of Cambridge) Membership Fees for 2015 FEES Managing Editor Scan to view PN online Membership category Direct Debit Non-Direct Debit Helen Burgess MCIPR Member £75 £95 Media & Communications Officer Helga Groll Ordinary Retired Member – – [email protected] Affiliate £17 £22 YOUTUBE LOGO SPECS Associate £38 £48 PRINT on light backgrounds on dark backgrounds standard standard main red gradient bottom www.physoc.org PMS 1795C PMS 1815C C0 M96 Y90 K2 C13 M96 Y81 K54 Undergraduate – £15

white black WHITE BLACK no gradients no gradients C0 M0 Y0 K0 C100 M100 Y100 K100 @ThePhySoc Opinions expressed in articles and letters submitted by, or commissioned from, Members, Affiliates or outside bodies are not necessarily those of The Physiological Society. /physoc watermark watermark © 2014 The Physiological Society ISSN 1476-7996 (Print) ISSN 2041-6512 (Online) The Physiological Society Cover image credits: is registered in England as a company limited by guarantee: No 323575. Registered office: Hodgkin Huxley House, /company/The-Physiological-Society 30 Farringdon Lane, London EC1R 3AW. Registered Charity: No 211585. stacked logo (for sharing only) stacked logo (for sharing only) 2014 Biobakes entrants: Jonathan Lawson, Lucy Sandhu, Ava Wixey, Andrew Bullough, Aimee Wilkinson, Ciara Gavin, Alidia Newlan, Alexandra Newman, /physoctv Abigayle Driscoll, Jordan Beasley, Asmita Mandal, Beth Goodenough, Helen Mason, Jemima Cook, Charlotte Reed, Stover School (pupils of), Lydia Roberts, ‘The Physiological Society’ and the Physiological Society logo are trademarks belonging to The Physiological Society Monica Taylor and Sharon Lyons. and are registered in the UK and in the EU Community respectively. Designed, produced and printed by Lavenham Press Ltd. 3 Editorial

I have been lucky to have had the support of an area of research in a more ‘digestible’ form Mike Collis a very hard working and enthusiastic editorial than is typical in a research paper or review. Editor, Physiology News board. The board have a range of Feedback from members indicates that these backgrounds, expertise and experience types of accessible scientific articles are much (including chairs of two Society committees) appreciated and are often useful as teaching and broadly reflect the membership. Together aids. Physiology News is of course not a This is my final editorial forPhysiology News we have introduced a wide range of articles: peer- reviewed scientific journal and (PN), as I am standing down as Editor at the Science features and updates, the clinical consequently we ensure that science based end of this year. When I took over as editor in application of physiological research, articles do not contain unpublished (un- Public 2012, I posed the question, ‘Why should discussions on ethics, science policy and reviewed) data. A delicate balance has to be members pick up Physiology News to read research funding. We have published articles struck between making physiological research when they have a pile of scientific papers to on the activities of members, laboratory more accessible and oversimplification. I hope plough through?’ I also mused about the role profiles, book reviews and, sadly, obituaries. that, as a board, we have got the balance of a quarterly hard copy magazine in an era A major innovation has been themed issues, right more often than not. The value of these Engagement where information can be transmitted almost which have featured Education, Imaging, The science based articles would be increased if immediately through electronic media. After Pharmaceutical Industry and most recently they could be searched easily online and I am acting as editor of PN for the last three years, Obesity. I am particularly proud of PN 91, pleased to say that there are plans to I am reassured that the magazine is being which was produced to coincide with The introduce a new platform for the archive to read widely by members of The Society (84% Society hosting the IUPS 2013 meeting and facilitate this in 2015. Grants according to the recent membership survey). included articles from many sister societies Interestingly, about 70% prefer to read the from around the world. There are many people who I want to thank hard copy, so even in a digital age, there is still for their support for PN over the last 3 years: a need for a paper magazine. A new format and design for PN was the other members of the editorial board introduced in 2012. The standardised format (Siobhan Dennis, Mike Evans, Sarah Hall, 2015 A further question I have asked myself is, of contents has been well-received with the Jamie McPhee, David Miller and Keith Siew), ‘What is the unique selling point of PN’? Is it majority of members considering it a more the publications staff of The Society and of primarily a means by which The Society enjoyable read than previously. The original course all those who have contributed articles trustees and associated committees re-design of the magazine received mixed to the magazine. I am sure that Physiology Funding of up to £5000 available for activities communicate with the members? Or is it a comments from members and the board. We News will go from strength to strength under vehicle for The Society office to keep all feel that ‘content is king’ and that the the leadership of a new editor and wish all members informed of past and new simpler design we have now adopted provides involved success with this important discussing physiology with public audiences ventures? Is it primarily a publication that a modern look and feel, without publication. highlights new and interesting physiological compromising the content or gravitas of science? Or a publication that reports on Physiology News. Identifying compelling members’ activities – a way for The Society cover images for each issue, which encourage Deadline: 15 February 2015 to promote itself to non-members? In truth the casual reader to pick up the magazine, has PN is all of these, but integrating such a wide been a challenge. We would welcome relevant range of content from different sources images from members of The Society that needs good team work and a clear alignment would fulfil this important function. of responsibility and authority. Fundamentally PN is (and should remain) a magazine for This edition (PN 97) contains the usual members, written and directed by members, diverse mix of articles. Scientific features with the expert help of Society staff. written by members are included that present For further information please visit our website: www.physoc.org/public-engagement-grants

5 News in brief Physiology Feed votes were cast and the winner, 11-year-old Abigayle Driscoll, was announced at 5pm on Physiology Friday. Bringing you snippets of the latest #Biobakes intriguing research The student at Colchester County High School for Girls took the Biobakes crown with Sugar linked to memory As part of the activities for Physiology Friday her stunning lungs cake, and will receive a (part of Biology Week), The Society launched £50 Amazon voucher. Runners-up included a problems and brain inflammation its inaugural Bio-bodies baking competition. model of the human brain, and a birthday in adolescent rats Members of the public were challenged to cake in the form of a cell. A diet high in sugar impaired hippocampal- celebrate the human body by making a dependent spatial learning and memory in ‘biological bake’ and sending a picture of their Abigayle’s win was announced on Facebook adolescent but not adult rats. This research ‘edible cells, organs and physiological delights’ and Twitter on Friday and has since been indicates that consumption of added sugars to The Society via social media with the retweeted over 300 times, including a negatively affects hippocampal function, hashtag #biobakes. retweet from Scientific American. metabolic outcomes and neuroinflammation Colchester County High School for Girls also when consumed in excess during the With over 270 entries, the competition sold all their biobakes to raise funds for the adolescent period of development. certainly sparked the imagination of the Tom Bowdidge Foundation, a local young DOI: 10.1002/hipo.22368 public. With such a large number of cakes, persons’ cancer charity. Abigayle’s ‘Lungs’ cake took the Biobakes crown during Biology Week 2014 the top eleven entries were shortlisted Mood food – omega 3 before being put to a public vote. Over 4,000 Many congratulations to Abigayle! supplements beneficial in treatment of depression Two studies showed that omega 3 supplementation prevents detrimental chronic stress-induced emotional and The Physiological Society joins the Life Science Teaching neuronal impairments by impeding Student-led ‘Physiology Challenge’ for hypothalamic–pituitary–adrenal (HPA) axis Resource Community hyperactivity, as well as depression in Biology Week at the University of Leeds hepatitis C patients receiving IFN-α therapy. DOI: 10.1038/tp.2014.77

Physiology Friday, the annual event supported within the scientific community, but also into by The Physiological Society as a finale for the public eye. The week ended in a social Researchers watch dynamic ‘Biology Week’, aims to engage with science quiz, and, aside of anything else, outsmarting motion of HIV as it readies an in a novel way. This year, the challenge was some of our lecturers was great fun!’ attack set by Dr Charlotte Haigh, an associate Researchers at Weill Cornell Medical professor in Human Physiology at the Chris Salmon, a third year student, elected to College have developed technologies that For several years, Society members have can be used in their entirety or adapted to and share resources with each other. A set of University of Leeds, and James Croft, a final use peak flow meters to inform the public allow investigators, for the first time, to developed many digital teaching resources specific requirements. In essence, if you need FAQs for submission of teaching resources will year Human Physiology student; to ‘design about obstructive disorders such as asthma, watch what they call the ‘dance’ of HIV but we have not been able to find a mechanism to deliver a new teaching activity, we would be available via The Society’s website over the and run a fun and engaging stall for the local and the effects of smoking, in line with the proteins on the virus’s surface, which may for evaluating, managing, updating and strongly recommend you explore the LifeSciTRC next few months. Leeds public at Leeds Central Library’. NHS’s Stoptober campaign. He said, ‘It was a contribute to how it infects human distributing them. It became obvious very to investigate what is already available in your challenge trying to communicate principles immune cells. quickly that the Life Science Teaching subject area. This can save you time and give Furthermore, we are also looking for Teams of six, which each contained learned in lectures to the public in a fun and DOI: 10.1126/science.1254426 Resource Community (LifeSciTRC) is the you new ideas for activities. interested members to act as referees for undergraduate BSc Human Physiology easy to understand way, but we think the answer to this problem. submissions to the LifeSciTRC. If you are students from each year, engaged the public visitors to our stand were left feeling inspired.’ Members of the partner organisations can interested, please contact Angela Breslin at with a range of physiology themed stands: Liquid DNA behind virus attacks The LifeSciTRC is a dynamic digital repository also submit their own teaching resources for [email protected] Alzheimer’s disease and neuro-degeneration, Jordan Appleyard, a second year student, Researchers found that bacteriophages and managed by the American Physiological evaluation and review by The Society - if cardio-pulmonary health, diabetes, and the designed a mountain range with the peak flow herpes virus can convert their DNA from Society (APS) which provides teachers and accepted, they will be uploaded for all to use. In the meantime, please take the time to science of hangovers. Rose Bavage, Outreach readings of famous athletes, singers, the solid to fluid form, and so inject DNA into the lecturers with a comprehensive and diverse If you have any particularly useful resources, register as a member of the LifeSciTRC, which Officer for the Faculty of Biological Sciences, average person and smokers to allow people cells of their victims. The phase transition range of teaching aids aimed at students at we would encourage you to submit them so is free, and explore the repository to find out said of the event, ‘It always amazes me how to compare their peak flow readings with for the studied herpes virus is temperature- different stages of their education. that they will benefit the whole community. which activities might be useful for your much undergraduates want to get involved in those of celebrities. He found the Physiology dependent and takes place at 37°C. teaching, outreach or public engagement these activities and how much effort they put Challenge ‘a great way to make friends with DOI: 10.1038/nchembio.1628 Marsha Lakes Matyas, APS Director of Contributions from Society members will be activities. into these events. We will certainly be other Physiology and Biomedical Science Education Programs, says, ‘We are excited to marked with The Society’s logo, thereby working with more undergraduates on public students in different years, and a way to How rabies ‘hijacks’ neurons to welcome The Physiological Society as the establishing a community for members to use http://www.lifescitrc.org/ events like this in the future.’ engage with members of academic staff newest LifeSciTRC partner, and look forward outside lectures.’ attack the brain to collaborating in other activities as well.’ Students evaluated the success of their Researchers discovered that the rabies efforts and were marked on the quality of This outreach activity was a great success and virus ‘hijack’ the ‘train’ transporting cell Other partner organisations include the their presentations, impact of their projects introduced undergraduate students to public components along a neuron and drive it Human Anatomy and Physiology Society, the and the effectiveness of their engagement engagement on behalf of both our institution straight into the spinal cord. Once in the Society for Developmental Biology, the strategy. The activities culminated in a social and The Physiological Society. We look spinal cord, the virus catches the first American Association of Anatomists, and the quiz within the students’ union bar, and marks forward to running the Physiology Challenge available train to the brain, where it wreaks Genetics Society of America. from both the outreach project and quiz were again in 2015. havoc before speeding through the rest of used to select a winning team. James Croft the body, shutting it down organ by organ. As a part of this community, Society members commented, ‘There is a University-wide drive DOI: 10.1371/journal.ppat.1004348 can access a range of teaching resources that to promote our research findings not only continues overlea

Physiology News / Winter 2014 / Issue 97 7 Physiology Feed Policy Focus

Bringing you snippets of the latest While politicians were enjoying summer recess, The Society’s policy work was intriguing research at full speed.

Making sure antibiotics work as Engaging with Parliamentarians they should Following the launch of the Engaging with New insight about the structure of Parliamentarians Scheme at the House of Lords in mitoribosomes (mitochondrial ribosomes), June, we were delighted to welcome around 30 and their different use of transfer RNA will Society members to Hodgkin Huxley House in lead the way in improving effectiveness of September for the Engaging with Parliamentarians antibiotics. training day. DOI: 10.1038/nature13895 DOI: 10.1038/nature12890 The day was designed to provide information on the policy-making process, encourage members to think about policy development, and provide Basel scientists are bringing cells an opportunity to explore how policy issues are on the fast track communicated by The Society. This was the first Engaging Parliamentarians at H3 Recent research gave novel insights into time The Society has run such an event and a the regulating signalling pathways in time number of lessons were learned. In 2015 the Policy Committee will be developing new policy and space in order to facilitate migration of positions on the key issues that were identified at the meeting as core concerns for The Society cells only in one direction. This could help and its members. The Committee is also keen to ensure that the communication of ongoing to find new targets and approaches to fight policy work is improved, with opportunities for members to help shape policy positions. cancer metastasis and inflammation. DOI: 10.1016/j.devcel.2014.07.022 The Health of Physiology

Cold exposure prompts body to The Health of Physiology review is a major project being led by the President and the Chief convert white fat to calorie- Executive of The Society. It is reviewing physiology as a scientific, medical and educational burning beige fat discipline in the UK and Ireland, looking at data across a range of metrics including student numbers, research funding and publication data. In September separate stakeholder meetings Exposure to cold temperatures can convert were held with members and external organisations to gauge opinion. white fat tissue from the thighs and belly Enjoy great rates on your event at to beige fat that burns calories for heat, Interestingly there was much similarity in the discussions, including – the teaching and but this biological response is hampered in learning of physiology in schools and universities; academic research and ties with industry; obese people. and concern for the profile of physiology and The Society. One of the recommendations for Hodgkin Huxley House DOI: 10.1210/jc.2014-2440 the future was for The Society to be more externally focused, with the external stakeholders encouraging greater collaboration. Hodgkin Huxley House (H3) is the HQ of The Physiological Society Hunger games: how the brain The Society is currently gathering the views of industry and will also be seeking student and a modern and versatile Central London venue for the scientific ‘browns’ fat to aid weight loss opinion. The findings from all the key stakeholders will be incorporated into the final report community. Researchers at Yale School of Medicine and will help shape the future strategy for The Society. The report will be launched in 2015. have uncovered a molecular process in the H3 is equipped with the latest AV technology and communications brain known to control eating that Letter to the Prime Minister transforms white fat into brown fat. This systems, including high-speed Wi-Fi for all visitors, and video and process affects how much energy we burn On 12 August The Society wrote to the Prime Minister in response to comments made by telephone conference facilities. and how much weight we can lose. Norman Baker MP, the Home Office Minister with responsibility for animal research. He was DOI: 10.1016/j.cell.2014.09.010 quoted in the media as saying he wanted ‘to see an end to all animal testing’. Our letter strongly urged the Government to understand the clear and vital need for the continued use The Bernard Katz auditorium can accommodate up to 68 people for Dinosaurs neither warm-blooded of animals in research, impressing on them the need to provide clear, consistent and theatre-style events, and 100 for receptions. Our Starling, Sherrington balanced messages on the issue. nor cold-blooded and Hill meeting rooms can be configured in a variety of ways for Metabolic analysis suggests dinosaurs could We received a response from Mr Baker explaining that he had not called for a ban on all use meetings of up to 26 people. regulate body temperature, but only to a of animals in scientific procedures and instead he looked forward to the day, ‘in the far–off point. Researchers compiled a database of future, when science has developed techniques that make use of animals redundant’. growth rates in 381 animal species, including Whether your event is promoting the latest developments in scientific research, science policy, education, technology, governance or the 21 dinosaurs and compared the speed of Section 24 reforms growth rate for each animal with energy public understanding of science, look no further for the best service use. They found that mammals grew ten In June The Society responded to a Home Office consultation on proposed changes to Section and most competitive pricing around. times faster than reptiles and had metabolic 24 of the Animals (Scientific Procedures) Act. At the time of writing The Home Office has yet rates that were ten times faster. But rather to formally announce what changes will be made to Section 24; once they do we will than being ectotherm, dinosaurs were communicate these through The Society’s usual channels. found to be mesotherm (able to adjust to a metabolically favourable temperature). If you would like to know more about or contribute to the policy work The Physiological Society performs on behalf of its members please email Ed Hayes – [email protected] DOI: 10.1126/science.1253143

Spotted some interesting research? Interested in these or any other policy related issues? Please contact us via [email protected] Send it to us at [email protected]

Physiology News / Winter 2014 / Issue 97 www.hodgkinhuxleyhouse.com In depth

Cambridge physiology scores a century – 100 years of The Physiological Laboratory, University of Cambridge

studies of high altitude physiology, pioneered Sue Jones by Sir Joseph Barcroft, continued by Sir Bryan & Roger Keynes Matthews, and still a strong area of research in the Department of PDN. Chris Huang Sir Colin Blakemore delivers the Centenary Lecture Department of Physiology, reviewed the innovative work of past nerve Development & Neuroscience, and muscle physiologists, including AV Hill, University of Cambridge, UK Lord Adrian, Sir Alan Hodgkin and Sir Andrew Huxley. Chris also reminded us that Roger Tsien joined The Physiological Laboratory as a PhD student of Richard Adrian and then Physiology took off in Cambridge when continued as a Research Fellow. Martin Michael Foster arrived there in 1870. He had Johnson gave a moving account of the a remarkable influence, inspiring students and scientific, medical and social impact of Sir co-founding both the Physiological Society Robert Edwards’s research in the field of and The Journal of Physiology. As his Reproductive Physiology. Guests then visited Cambridge School flourished, it needed to interactive displays, where demonstrations, house an increasing number of talented real experiments and a range of physiological students and young researchers, including measurements were in action. Around 40 future Nobel laureates AV Hill (1922), volunteers designed and ran the displays, Measuring action potential conduction at FG Hopkins (1929), CS Sherrington (1932), including graduate students, postdocs, the Hodgkin–Huxley display ED Adrian (1932) and HH Dale (1936). When academic staff and support staff from PDN, two disused coal cellars had been pressed and there was much-appreciated help from into service as labs, it was clear that a new our colleagues at Anglia Ruskin University. building was urgently needed. The Worshipful Sir Colin Blakemore closed the afternoon’s Company of Drapers provided funding for a events with a Centenary Lecture – a personal References At the Barcroft display, Sixth Form students contemplate Sixth Form students track the sensory-guided movements of flies fine new home, designed under the careful account of his experience as a young Langley JN (1883). The arrangement of the physiology at the top of the world using high speed cameras eye of Foster’s protégé, John Newport neurophysiologist in The Physiological sympathetic nervous system, based chiefly on Langley, and the Physiological Laboratory Laboratory. Through his anecdotes and observations upon pilo-motor nerves. opened in full ceremony in 1914. One reminiscences we were reminded of further J Physiol 15, 176–248. hundred years later, in September 2014, the achievements in the one hundred year Department of Physiology, Development and history of the building. Guests and volunteers Barcroft J (1914). The Respiratory Functions of the Neuroscience (PDN) hosted a series of then had the opportunity to mingle and Blood. Cambridge University Press. events to celebrate the Centenary. Our aim ‘network’ at dinner in the Great Hall of Matthews BHC (1945). Effects of high altitude on was to give insight and inspiration to a wide Trinity College. man. Br Med J 2, 75–78. audience about what physiology is, what it has achieved and contributed in the past, and By all accounts the occasion was informative Hill AV (1910). The heat produced in contracture and what it continues to contribute today. and enjoyable, and served as a positive muscular tone. J Physiol 40, 389–403. reminder of the past and continuing The opening event took place on 2 importance of physiology. Our volunteers, in Adrian ED (1926). The impulses produced by sensory September 2014 with over a hundred invited their distinctive green Centenary T-shirts, nerve endings. J Physiol 61, 49–72. guests: colleagues from across the University ran their interactive displays enthusiastically Hodgkin AL & Huxley AF (I952). A quantitative of Cambridge, including the Vice-Chancellor; on three more afternoons in September for description of membrane current and its application physiologists from nearby Universities and local GCSE students and interested members to conduction and excitation in nerve. from funding agencies, scientific journals and of the public. Further information about the J Physiol 117, 500–544. Societies; family members of our alumni; Centenary events can be found at http:// local Sixth Form students, and the Mayor of www.pdn.cam.ac.uk/centenary/index.shtml. Tsien RV (1981). A non-disruptive technique for Cambridge. After a welcome from our Head loading calcium buffers and indicators into cells. Nature 290, 527–528. of Department, Bill Harris, we heard from The events were supported by the Roger Keynes about Foster’s inspirational Department of PDN, the Wellcome Trust Edwards RG, Bavister BD & Steptoe PC (1969). Early teaching and Langley’s quest to understand Institutional Strategic Support Fund, The stages of fertilization in vitro of human oocytes all aspects of autonomic nervous system Physiological Society, Trinity College, matured in vitro. Nature 221, 632–635. Guests at the dinner in Trinity College Great Hall All photographs courteousy of Adrian Newman function, then from Andrew Murray about Cambridge and St John’s College, Cambridge.

Physiology News / Winter 2014 / Issue 97 11 In depth

Physiology on the go

Physiology is one of the health sciences that Mobility for a medical device can come in must. Lastly, and perhaps most importantly, However, an important feature of implantable Proper functioning of such technologies Vadim Alexeenko embraced the use of computers as soon as different forms. At its simplest it takes the an efficient and compact power source is devices that has not been mentioned is that requires permanent network connectivity and University of Surrey, UK they became available, and has heavily relied shape of an external device connected by essential to supply the implant. they have the ability to collect data and relay this might have had an influence on the on digital equipment ever since. As sensors to a patient, like a Holter heart rate it to external data storage centres for further paradigm shift in the design of mobile technology progressed, digital devices grew in monitor or glucose monitor. More complex Some of these tasks were solved by analysis by healthcare professionals. The networks. The development of all previous Anna Shumitskaya capability and shrank in size and weight, technologies that can augment or replace microfluidics technologies – tiny liquid pumps increased capabilities of portable electronics standards of mobile communication ultimately becoming portable and connected, physiological functions include implantable with the smallest of them being less than a make it even possible to perform a limited technologies was aimed primarily at increasing Independent telecommunications at first via wired networks. A recent boom in prosthetic devices: pacemakers, defibrillators, few cubic millimetres. Others were addressed data analysis on the implantable or wearable the data transfer rate as the most important journalist mobile communications has enabled portable cochlear implants, sacral neuromodulators by development of biosensors: for example, it device. This can restrict the uploaded data to parameter, and loss of service in some devices to stay online and maintain the link and drug pumps. Such implants do not is now possible to detect blood glucose just those segments that report deviations locations was treated as a valid trade-off for with data processing centres virtually anytime restrict patient movement and can content using optical methods (Ozana et al. from the normal state and enabling the device high data transfer rates in the neighbouring and anywhere. This change has not yet substantially increase their quality of life. But 2014). A highly competitive to alert medical services and carers of places. The upcoming standard of fifth- affected the health sciences, but it is the these implantable digital devices overcome telecommunications market has helped to potentially dangerous situations. A review generation mobile network (5G) is expected to wave of change that seems to be on its way. quite a few technological challenges. First, shrink the size of portable electronic devices, analysing continuous cardiac monitoring be adopted in early the 2020s and, according there is a requirement for compact and hugely increased the capacity of their devices, piloted in France, indicated a to Professor Rahim Tafazolli, the head of the Physiology, as the science of body function, energy-efficient computers, sporting high batteries, and introduced wireless charging four-times quicker intervention response 5G Innovation Centre in the UK, the new has always needed to record the tissue or precision analogue-to-digital and digital-to- technology to the mass market. Application compared with conventional monitoring standard will focus mostly on availability of ‘Physiology, as the organ response to stimuli, and almost till the analogue converters to interface the implant. of the same technologies to implantable strategies (Maillard et al. 2014). digital services, with the ultimate aim of the end of the last century every physiology Secondly, an appropriate set of sensors is devices has brought similar benefits of total elimination of ‘bad reception areas’. science of body laboratory had an extensive collection of needed to read the relevant physiological decreased size and power consumption; The progress of telecommunications has function, has always chart recorders and paper rolls used for information. The list of such parameters wireless charging is now available for devices made the link between an implantable device Other important features of 5G devices will analogue data collection and storage. Even might be long: electric potentials, blood or that are implanted several centimetres deep and a remote data centre much more feasible include increased energy efficiency, reduced needed to record the now, if you go through the laboratory other liquid pressure, oxygen and glucose (Ho et al. 2014). than was previously possible. During the last delays and latencies, and better management cupboards, very likely you will find one or two concentration; this list is by no means decade, considerable effort has been of portable device resources. tissue or organ such ‘fossilised’ devices. Most likely they are exhaustive. Thirdly, if the implantable device directed towards the development of preserved purely for sentimental reasons, is intended for drug delivery, methods to facilitate data exchange It is still too early to make any assumptions on response to stimuli’ while the ‘real science’ went fully digital long then a pump is a between stationary and mobile digital a final shape of the 5G standard, but one can ago. The major driving forces were the devices – machine-to-machine now make some informed guesses as to the prospect of easy access to huge volumes of technology (M2M). Originally possible uses of its features: mobile phones data, the power of numerical data analysis conceived for automation and used as portable remote cardiac monitoring and the ability to automate the experiment. instrumentation, now it also covers base stations is just one of them. The exciting various telematics applications, and possibilities for other futuristic medical The determination to use computers was so buzzwords such as ‘connected gadgets may emerge very soon. And one of strong that the first electronic devices, used revolution’ or ‘internet of things’ the key things to make it happen is a tight to control experiments or treat the became a commonplace in the collaboration of telecommunication scientists patient, were bulky, consequently limiting telecommunications world. and health scientists. the subject’s movements to the immediate vicinity of the apparatus (Fogt et al. 1978). However, the ultimate aim of life sciences is not References to gather physiological data or cure a patient who is tethered by Fogt EJ, Dodd LM, Jenning EM & Maillard N, Perrotton F, Delage E, Gourraud JB, wires and tubes to a computer, Clemens AH (1978). Development and Lande G, Solnon A, Probst V, Grimandi G & but to help them have as evaluation of a glucose analyzer for a Clouet J (2014). Cardiac remote monitoring normal a life as possible, and glucose controlled insulin infusion system in France. Arch Cardiovasc Dis 107, 253–260. this means mobility. (Biostator). Clin Chem 24, 1366–1372. Ozana N, Arbel N, Beiderman Y, Mico V, Sanz M, Ho JS, Yeh AJ, Neofytou E, Kim S, Tanabe Y, Garcia J, Anand A, Javidi B, Epstein Y & Patlolla B, Beygui RE & Poon AS (2014). Zalevsky Z (2014). Improved noncontact Wireless power transfer to deep-tissue optical sensor for detection of glucose microimplants. Proc Natl Acad Sci U S A concentration and indication of dehydration 111, 7974–7979. level. Biomed Opt Express 22, 1926–1940.

Physiology News / Winter 2014 / Issue 97 13 In depth

A tribute to Bernhard Frankenhaeuser 1915 – 1994

Bernhard Frankenhaeuser was born in 1915 mechanism of nerve impulse conduction. experimental data and advanced Jan Lännergren in the small town of Borgå in the south of Their voltage clamp experiments had programming. Karolinska Institutet, Sweden Finland where his father was an architect. He revealed the voltage- and time-dependency went to school in Borgå and then started to of the Na+ and K+ conductance in the axon One aim at the onset of the voltage-clamp study medicine in Helsinki in 1934. Late in membrane; the ’H-H’ equations gave a experiments on the node was to try to 1939 the Soviet Union attacked Finland and quantitative description of the mechanism resolve ’quanta’ in the recorded ionic the so-called Winter War started. Bernhard underlying the nerve impulse. Still, it was not currents. The node is especially suitable for was called into the Finnish army and served known how the opening of the ion channels this approach because of the very restricted as military doctor both in the Winter War and in the axon membrane came about. membrane area. Bernhard did not quite reach in the so-called Continuation War (1941-44). Frankenhaeuser and Hodgkin decided to test his goal, but his method of noise analysis was Very much later, he told dramatic stories the hypothesis that Ca2+ acts as a ’plug in the of a pioneering kind. about narrow escapes from the advancing hole’ that controls the conductance. This idea enemy. When the war was over, Bernhard originated from the knowledge that the Ca2+ Bernhard had a position as researcher at the finished his studies and obtained his medical concentration of the external medium Swedish Medical Research Council between degree in Helsinki in 1946. In that year he influenced excitability. Voltage clamp 1963 and 1965, was Professor in Physiology ‘Bernhard was one of also met Marianne von Wright and they experiments were again performed on the at the University of Umeå 1965–67, and married after having known each other for squid giant axon at the Marine Biological succeeded Granit as Professor in the pioneers in just a few months. Marianne later became a Laboratory in Plymouth. They found that Neurophysiology at the Karolinska Institutet computer simulation of world authority in stress research. They had changes in Ca2+ concentration shifted the and as Director of the Nobel Institute for their only child, a daughter named Carola, in voltage dependency of the ion conductances Neurophysiology in 1967 until his retirement biological processes and 1949. She is married (Lidén) and is now a – as predicted by the hypothesis – but the in 1981. A characteristic of Bernard as a Professor of Occupational and Environmental effect was not large enough. Nevertheless, scientist was his aim at perfection. He could managed, together with Dermatology at the Karolinska Institutet. the findings about the Ca mechanism were of spend many weeks, even months, at refining great importance and this paper has been a technique: it was all or nothing – he would Andrew Huxley, to By 1939, Bernhard had already come into highly cited. never engage in mediocre science. Bernhard contact with Ragnar Granit, then Professor in is author of 49 publications listed in PubMed recreate a nodal action Physiology at the University of Helsinki. After Hodgkin and Huxley had clarified the and contributed to at least equally as many the war, Granit helped Bernhard to go to mechanism of impulse generation in squid as supervisor. For him it was natural to share eutrophication and the risk of lack of oxygen large steel engraving and, from the steel potential using his Oxford. There he met William Rushton who axons. But vertebrate myelinated nerve his vast knowledge generously and to work in the Baltic, as well as the use of pesticides block, a limited number of prints were made. made a deep impression on him, as did the fibres have a different structure. Huxley and with the manuscripts of pupils and colleagues. such as DDT and PCB. Bernhard was in fact The artist has been playing a little when experimental data and whole British School of Physiology. In Oxford, Stämpfli had shown that impulse propagation one of the pioneers in environmental science, drawing the voltage clamp circuit and it is up advanced programming’ Bernhard undertook the experimental work in myelinated fibres is saltatory. But which I remember Bernhard as extremely which is now such a hot topic. to the reader to discover the error that was the foundation of his doctoral ionic currents underlie the nerve impulse at knowledgeable about electronics: from the - no prizes given! thesis, which he defended in Stockholm in the node? In order to answer this, a method beginning in the laboratory he constructed Bernhard was not only generous with his 1949. Bernhard had been in contact with was required that allowed voltage clamp of his own equipment – very much the British knowledge in mathematics and electronics, Granit during the years after the war and the isolated nerve fibre. After several false style. He also designed a large part of the but also generous outside the lab. Many of us moved to Stockholm (with Marianne) in starts, and when Bernhard was near despair, electronic equipment for other people in the remember his summer parties at his house in 1946. Granit had already moved to Sweden he finally managed to get the method to department. He was very generous with his Saltsjöbaden, southwest of Stockholm, close References in 1940 and set up a laboratory at the old work. Using negative feedback, the knowledge and put together a lab to the water, where the whole department Dodge FA & Frankenhaeuser B (1958). Membrane Karolinska Institutet. In 1946, Granit was longitudinal currents could be controlled and programme for us beginners to increase was invited. Not far from his house, his currents in isolated frog nerve fibre under voltage offered a chair at the new Karolinska and his the membrane potential recorded. This was our understanding of the mysteries of beloved Dulcibella, a relatively big sailing clamp conditions. J Physiol 143, 76–90. own institute, which he accepted. Bernhard decisive for allowing control of the electronics. Bernhard had many collaborators boat, was moored. Some of us PhD students joined Granit at the new Nobel Institute for membrane potential with yet another (post-docs) from other countries as well as a were recruited as crew onboard Dulcibella Frankenhaeuser B (1963). A quantitative description Neurophysiology in 1947. feed-back amplifier and obtaining a voltage- number of Swedish PhD students (including and sailed with Bernhard in the Åland of potassium currents in myelinated nerve fibres of clamp system. With the new method in hand, myself) of which he took very good care. archipelago where he tried (with mixed results) Xenopus laevis. J Physiol 169, 424–430. Between 1950 and 1952, Bernhard worked Bernhard made a thorough analysis of the to teach us navigation and seamanship. on accommodation in single nerve fibres of nodal ionic currents and discovered many Questions about the threat to the Frankenhaeuser B & Huxley AF (1963). The action the frog. He was also interested in the similarities with the squid axon membrane, environment were something that engaged The starting point of this portrait of Bernhard potential in the myelinated nerve fibre computed on mechanism of saltatory conduction in but also some interesting differences. Bernhard at an early stage. He was an ardent was a photo-collage, made by some of his the basis of voltage clamp data. myelinated nerve fibres. In 1952 Bernhard Bernhard was one of the pioneers in (and very well-informed) opponent of nuclear pupils just before his retirement. The collage J Physiol 171, 302–315. met Alan Hodgkin at a meeting in Cold Spring computer simulation of biological processes power and was politically active in the debate was given to Arne Wallhorn, a well-known Harbor. Hodgkin and Huxley had just and managed, together with Andrew Huxley, in Sweden which raged in the 1970s. He was engraver and famous for his miniature published their famous papers on the to recreate a nodal action potential using his also very concerned about phosphate engravings for postage stamps. He made a

Physiology News / Winter 2014 / Issue 97 15 Meetings & events Meeting Notes Prof Tom Sears, Dr Guy Bewick and Dr Bob Banks

Something Old, Something New, Something Borrowed, Something… Else

4–5 September 2014, University of Durham, UK

Guy Berwick University of Aberdeen, UK Emeritus. First day highlights included a timely breaks around the posters displayed Rade Durbaba reminder of how proprioceptive physiology throughout the meeting. In this regard, an and anatomy relate to clinical need and attendee of particular note was Professor Northumbria University, UK rehabilitation (Something Old), plus the latest Peter Matthews, the ‘elder statesman’ of research into channel distributions responsible muscle spindle physiology, who came out of The weather was kind to the 52 delegates for repetitive firing of motoneurones and retirement to attend in recognition of Bob’s who gathered to recognise Dr Robert Banks’s muscle spindle afferents, and potential unique contribution to this area. His scientific Forthcoming events >40 year career investigating mechanical damage by chemotherapy (Something New). enthusiasm clearly undiminished, Prof 2015 2016 sensation. Speakers from Canada, Australia, There was also a group photograph. Matthews energetically and regularly USA, Europe and the UK jumped at the chance contributed insightful comments and 28 Mar–1 Apr 10–12 Apr 6–8 July 29–31 July to participate, providing a marvellous blend of The enjoyable day was rounded off perfectly questions throughout the two days. Many old reminiscence, review, and cutting-edge by the symposium meal of excellent friendships were renewed and new friendships Experimental Biology 2015 Ageing and Degeneration: A Physiology 2015 Physiology 2016 sensory neuroscience in an extremely convivial Aberdeen Angus steak in the converted forged while celebrating Bob’s extensive Boston Convention and Physiological Perspective Motorpoint Arena, The Convention Centre Dublin, atmosphere. All speakers had scientific chapel of St Hild and St Bede - truly an career as a long-time Society member and Exhibition Center, Royal College of Physicians, Cardiff, UK Republic of Ireland connections with Bob, mostly as collaborators, atmospheric, gastronomic and social success. recognising the substantial advances he and Boston, USA Edinburgh, UK www.physiology2015.org and with the attendees made for a veritable colleagues have made together. http://experimentalbiology.org www.physoc.org/ageingtopic ‘Who’s Who’ of muscle spindle research over For the second day, highlights included the /2015/home the last half-century. Talks ranged from higher burgeoning evidence for synaptic-like vesicles We are indebted to The Physiological Society motor control, through proprioception and into (Something Borrowed) as part of a system for for designating this as a Special Symposium, cellular aspects of mechanosensory function, autogenic regulation of stretch-evoked firing with associated financial support. We would encompassing humans, other mammals, via an atypical glutamate receptor that eludes also like to thank the University of Durham invertebrates and systems biology. any canonical pharmacological profile, plus Biophysical Sciences Institute, Cambridge emerging indications that general sensory Electronic Design and World Precision The research focus throughout both days was physiology principles may apply across Instruments for their kind sponsorship of the Bob’s career in muscle spindle physiology and tissues, phyla and even sensory systems event. Photographs were provided by Tom Meeting Notes relating this to mechanoreception as a whole, (Something Else...). Every talk was followed Banks (Bob’s photographer son). with talks from PhD students to Professors by lively discussion, which continued into Obesity – a physiological perspective

10–12 September 2014, St. James’ Park Newcastle upon Tyne, UK

Our first ever Topic Meeting took place at the Newcastle United Football Club, Newcastle upon Tyne. This year’s theme was Obesity: a physiological perspective. With over 200 attendees, 20 symposia and 80 poster presentations, it is safe to say that the meeting was highly successful and well attended.

The conference took us on a journey into the complex nature of obesity. Topics range from underlying the physiology of appetite control, We are looking forward to seeing you at our causes of obesity, obesity during pregnancy as well as the impact of obesity on society next Topic Meeting, on Ageing and and metabolic and cardiovascular and possible lifestyle interventions to Degeneration, which will take place on Group photograph of attendees consequences of obesity, to mechanisms challenge obesity. 10–12 April 2015 in Edinburgh.

Physiology News / Winter 2014 / Issue 97 17 Meeting Notes Meeting Notes

Young Life Scientists’ 2014 International Symposium 2014 Lecture and Pan-American

4 October 2014, Congress Kings College London, UK 2–6 August 2014, Iguassu Falls, Brazil Aisah Aubdool Professor Sue’s Brain Lab Michael Spyer Kings College London, UK Honorary member, The Physiological Society

The award of the 2014 International Lecture YLS2014 Poster Presentation session to me was both an honour and surprise. I was delighted to have the opportunity to renew old friendships in Brazil and to travel to places that I had not previously visited. These visits would allow me to learn more of how Carol Leandro and Joao Henrique with Mike Spyer at the Federal University of Paraiba physiological sciences are developing in Brazil and allow me to promote The Physiological Society. The Society was also eager for me to measure through the importance of Benedito organised in a manner similar to IUPS 2013. represent it at the PANAM 2014 Congress, Machado (Ribiero Preto) who is Brazil’s The Society also provided financial support for the first meeting that had been organised for leading physiologist and the mentor of the several UK scientists. Bene Machado and his The Young Life Scientists’ Symposium 2014 physiological societies from south, central and majority of Brazil’s young and accomplished organising committee had done a really good (YLS2014) was held at King’s College London north America. physiologists. I had a lively audience for my job and the meeting was a huge success. on October 2014, with the theme The lecture and had numerous engaging There are now plans for this to become a Physiology & Pharmacology of TRP channels. Brazil holds a very real interest for me. In the discussions. regular regional meeting. The symposium was supported by The 1970s in Birmingham Pedro Guertzenstein Physiological Society, the Biochemical Society from Sao Paulo had spent time in Sidney I then travelled to Vitoria where my hosts The next meeting will not be until after IUPS and the British Pharmacological Society in Hilton’s laboratory and around that time I had were Henrique Futuro Neto and Karla Sampaio. 2017, probably in 2019, and it is likely to be addition to King’s College London, and was also met Osvaldo Lopes from the same The Federal University has developed greatly held in Chile, which was well-represented at sponsored by various biotechnology Brazilian lab in Eric Neil’s laboratory. Whilst since my last visit and there has been a the current meeting. I was gratified that The companies. having rather different scientific views, we had growing level of support from the national Society’s contribution was appreciated to the become good friends. Pedro was followed by government. However resources are still much extent that as The Society’s representative I The symposium attracted about over a Henrique Futuro Neto who studied for his PhD less than in Sao Paulo State. However the labs was included in discussions about the future of hundred national and international early- in John Coote’s lab developing a longstanding are very active and the department was full of the meeting. The American Physiological career researchers, and held vivid discussions collaboration with Mike Gilbey that continued enthusiastic students and post-docs. I had a Society was also very well-represented and on the cutting-edge research on the Interactive workshop on ‘New Frontiers to Publishing: Publish or Perish’ by F1000 when Mike joined my Department at the Royal very full academic visit that was supplemented has and will give strong support for the physiology, pharmacology and biochemistry Free. From that beginning several young by a wonderful social programme that allowed planned continuation of the initiative. Bene of TRP channels. Additionally, YLS2014 Brazilian physiologists passed through my me to visit the countryside and get a feeling and his team gave strong evidence that even incorporated engaging workshops on the London lab and in particular Karla Sampaio for the amazing variety of vegetation. The without the financial muscle and organisational future of publications (F1000) and outreach spent a period working on vagal preganglionic hospitality was excellent and I wished that I support that is a strength of The Physiological opportunities, including Dr Julie Keeble’s neurons in London. A significant collaboration could have had longer to really understand the Society they have the ability to cope with the experience with the Mission Discovery developed between my lab and Vitoria, with changes occurring. difficulties that come with organising programme to send experiments to the the support of CAPES (the Brazilian international meetings. I hope that IUPS will International Space Station. Governments Funding Agency), the British The next part of the tour was PANAM 2014. give them the support that they need to Council and the Wellcome Trust, that Karla and her colleagues accompanied me ensure the success of IUPS 2017 by allowing Achievements were celebrated with numerous facilitated exchanges. from Vitoria, worried that alone I would have them the flexibility to limit the size and scope prizes from F1000 and the organising failed to negotiate the various airports en of the meeting to what they feel comfortable committee. The symposium was concluded This lecture tour represented my fifth visit to route. We arrived in Iguassu Falls with a day to offer. with a ‘Spicy TR(i)P’ to Masala Zone for some Brazil and began in Sao Paulo. My host at the for exploration before the meeting began. The classic activation of TRP channels. Federal University was Thiago dos Santos Falls are truly amazing and like most of the The meeting lasted for four days and I gave a Congratulations to all the winners and a huge Moreira, currently the President of the participants, I took a boat ride to the falls talk in a symposium organised by Thiago and thank you to all the judges for their time and Brazilian Physiological Society. Thiago and leaving looking like a drowned sheep. All the Dr Daniel Mulkey (USA) entitled ‘New assistance in reviewing the entries. Vagner Attunes, the treasurer of the PANAM other Brits at the meeting experienced the advances in the neural control of breathing’ Meeting and IUPS2017, gave me a good same soaking. We also visited the which was sponsored by The Journal of We’d like to thank all of the speakers introduction to their labs. They are in an neighbouring bird sanctuary. The meeting, Physiology. Experimental Physiology (Professor Susan Brain, Professor Maria international competitive department and are entitled ‘Physiology without borders’, was sponsored a further three symposia. Belvisi, Dr Scott Earley, Dr David Andersson, well funded with significant funds being attended by around 1,000 delegates of whom Dr Anthony Albert, Dr Peter Cox & Dr Eva available from Sao Paulo State. It is a major approximately 60% were students. The Following the meeting I travelled to the north Amsen) and delegates for making this YLS2014 poster and oral prize winners: T Banke, R Clarke, A Soares, C O’Leary and H Wilson centre for cardio-respiratory research, which Society’s two journals sponsored four east of Brazil. This was the first occasion that I symposium such a success. is a major interest in Brazil. This is in no small symposia within the meeting, which was have gone so far north and it was an exciting

Physiology News / Winter 2014 / Issue 97 19 Features opportunity to learn how the reforms in was impressed by the students’ and in facilitating these advances. Physiology is education and social policy initiated by the academics’ commitment to the ethos clearly playing its part! previous President of Brazil, Dr Lula, had engendered by the reforms. As in every affected physiological teaching and research. department that I visited in Brazil, the It proved to be a revealing visit. students were enthusiastic and showed genuine interest in discussion on my My first stop was in Recife where I was hosted presentation and their own research. by Carol Leandro and Joao Henrique da Silva Costa of the Federal University of My trip finished with a drive north to the town Human metabolism and obesity: the influence of exercise Pernambuco. This is a relatively poor state and of Joao Pessoa in Paraiba State. Here my visit the reforms have led to a major expansion of was hosted by Prof Valdir Braga who heads a education including the establishment of new thriving department in a recently established This article discusses the effects of physical activity and exercise universities in deprived areas. The university biotechnology institute in the Federal programmes on human metabolism and obesity. It demonstrates how has a major campus in Recife and a second University of Paraiba. This has been supported some one-hour’s drive inland. The Department by both government and state resources and exercise and physical activity are important regardless of body weight or of Physiology is situated within an Institute of seeks to develop novel drugs from the wide Public Health as well as having links to variety of plants that are unique to Brazil. The composition, and reports on a number of successful interventions including biomedical sciences. There is an emphasis on emphasis on translation does not detract from research into obesity which is a major national the keen determination to develop a strong community-based exercise programmes that have reduced body fat and problem as in most western societies. Joao basic science presence. The institute has improved health outcome markers in overweight/obese individuals. provides a physiological approach to already identified two lead compounds that understanding the relationship between will enter preclinical trials. It was clear from my obesity and cardiovascular disease. Carol is a visit to the north-east that the reforms have leading player in major international had a major impact in both socio-economic programmes studying obesity and its social terms but also in the recognition of the A small part of the majestic Iguassu Falls impact. Their labs were well-developed and I importance of higher education and research Dr Naomi Brooks The rapid and continuing rise in obesity throughout both the developed & Dr Stuart Galloway and developing world is a current critical world health issue. Increased Health & Exercise Sciences Research levels of obesity are a major challenge to public health with obesity Group, University of Stirling, UK contributing to increased cases of type 2 diabetes, cardiovascular We know where we are Recently, on the pages of this fine publication, meaningful impact. The newly launched Topic The Society’s President, Richard Vaughan- style format is off to a flying start with disease, stroke, cancer and loss of quality of life. Metabolic syndrome and going, but how do we Jones, rightly proclaimed a new age for our advanced plans now in place for the second type 2 diabetes are also key factors influencing cardiovascular disease st beloved discipline: a 21 century renaissance instalment in the series: Ageing & risk. Further, location of adipose tissue – i.e. abdominal adipose and get there? The Society’s of Physiology – the science that seeks to Degeneration – A Physiological Perspective Meetings Committee unravel the logic of life. This timely clarion call (Edinburgh, 10–12 April 2015). intra-abdominal (visceral) adipose tissue – is associated with increases in was indeed moving, for I sat up rather too the risk of cardiometabolic disease. Morbidity and mortality from quickly and toppled my over-priced coffee- However, our meetings come at a considerable shop Americano as I read his wise words. As a cost to the Society’s coffers. Newsflash: cardiometabolic disease put a great burden on individuals, families and physiologist (and as a member and elected success is expensive. As such, there is added communities and put an increased financial burden on health care systems. Trustee of The Society), I have a shared pressure on Meetings Committee to get it ‘Physical activity and responsibility for this vision. By the way, so do right and ‘on budget’. I welcome a shared you reader. However, as newly elected approach to how we, the Members, might exercise have consistently At its most simple, obesity is considered to be been consistently reported to be linked to Meetings Secretary, it dawned on me that I respond to these challenges, harnessing the been shown to improve caused by increased energy intake without increased mortality and morbidity throughout might actually have to take action. Crikey. I’m wisdom of the crowd. To that end, Meetings concomitant energy usage. However, it is not the lifespan. The recommended BMI for a an academic: I don’t have the requisite Committee is accessible to the membership in health outcomes in that simple. Environmental and behavioural healthy individual is 18.5–24.9 kg/m2; training! Surely there’s a Committee? a number of ways: through the theme leads factors including increased calorie overweight is defined as BMI of 25–29.9 kg/ who provide valuable input on many aspects of individual and group consumption and food intake (foods high in m2 and obese is defined as ≥30 kg/m2. Thankfully, we have that and much more: The the flavour of our various meetings; through sugar and fat) can influence the energy However, BMI does not take into consideration Society’s Meetings Committee. It turns out the current Meetings Committee membership; exercise programmes, imbalance. Decreases in physical activity also body composition or location of fat mass. that my role is quite straight-forward. Bring or route one, directly to me. Praise endlessly contribute, some would argue more so, to the these bright minds together so that we might flatters and it has the unfortunate albeit with varying obesity crisis. Physical inactivity and Obese individuals develop health chart the right course for The Society’s voyage consequence of maintenance of the status sedentary lifestyle are independent risk complications due to an increasing number of discovery. Our principal aim is simple: get quo. Alas, excellence is not static. The Society degrees of individual factors for metabolic disorders. Adequate and size of adipocytes (increasing fat mass). the science and setting right. Ay, there’s the must move, and be seen to move, with the physical activity is required for metabolic The increased size and number of adipocytes rub. But get it right and success follows times. Therefore, constructive criticism (to responsiveness’ health and acts to reduce risk factors leads to dysfunction and cellular stress which because The Society’s staff, members and make use of managerial parlance), or good associated with atherosclerosis and metabolic contributes to insulin resistance, increased guests deliver – time and time again. The old-fashioned, heart-felt, considered views are disorders, particularly rectifying high blood inflammation and increases in circulating lipids current construct is not without its critics but especially welcome during my tenure in the hot pressure, insulin resistance, glucose (for detailed review see Capurso & Capurso, few can argue with the large-scale success of seat of Meetings Committee. We may agree or intolerance, low HDL-cholesterol, high 2012). Obese individuals develop resistance recent ventures guided by my predecessor, disagree on method but I am sure we will share LDL-cholesterol, and high triglycerides. to the cellular effects of insulin, which Ken O’Halloran David Wyllie, and Prem Kumar before him, the same ambition for the membership. I am Physical activity in addition to reduced displays as an impaired ability of insulin to working with their respective committees. Our convinced that The Society has a wonderful sedentary time (sitting less) is therefore stimulate glucose uptake from plasma into fat Meetings Secretary, meetings are successful, not just because we sense of where we’ve been and where we want recommended in both prevention and and muscle cells. It is thought that increased The Physiological Society think they are. Rather, because you and others to go. Our meetings will define how we get treatment of these metabolic disorders. fatty acids (FAs) combined with lipid tell us so. Our meetings deliver beyond our there. It is said that the journey is as important metabolites/signalling molecules interfere important charitable object of promoting as the destination. Important too that we An increased body mass, measured by body with the insulin-signalling pathway and can physiology. The Annual Meeting has ensure we bring everyone along. mass index (BMI: mass (kg)/height (m)2), has impair the actions of insulin and contribute to

Physiology News / Winter 2014 / Issue 97 21 Table 1. Healthy Unhealthy Insulin sensitivity Definitions 6–7 mmol/L impaired fasting glucose Fasting glucose < 6 mmol/L Insulin sensitivity can be assessed by > 7 mmol/L diabetes measuring fasting blood glucose and insulin levels and/or levels after a glucose Fasting insulin 1.4–14 µIU/ml drink (oral glucose tolerance test).

Lipid profile Lipid profile measures various lipids in the blood including triglycerides, total ‘lifestyle interventions Total cholesterol < 5 mmol/L > 5 mmol/L cholesterol, low-density lipoprotein (LDL-)cholesterol and high-density can be more effective HDL cholesterol > 1 mmol/L < 1 mmol/L lipoprotein (HDL-)cholesterol). Increased risk of than current prescription cardiovascular disease Blood pressure is measured with a LDL cholesterol < 3 mmol/L > 3 mmol/L sphygmanometer and normal values are drugs for treating and 120/80 mmHg. Hypertension is Triglycerides < 1.7 mmol/L > 1.7 mmol/L considered to be when values are above 140 and 90 mmHg, respectively. preventing diabetes’ Figure 1. Insulin signalling normally increases GLUT4 translocation, but with insulin Blood pressure resistance this is thought to be blocked by accumulation of fatty acid metabolites such as (Healthy values are in Table 1) long-chain acylCoA (LCACoA), diacylglycerols (DAG) and ceramides. That is delivery of Systolic BP 120 mmHg > 140 mmHg fatty acids is greater than the capacity for oxidation and/or storage as triglycerides. Figure Values taken from NHS Choice simplified from Timmerset al. (2008). More detail from the original review article. Hypertension Diastolic BP 80 mmHg > 90 mmHg

insulin resistance (Fig. 1). The resistance to Skeletal muscle is an extremely important mass). Thus, there are strong associations programme of lifestyle intervention has been reported waist circumference reduced from the action of insulin results in elevated plasma metabolic tissue and uses glucose and fat as between aerobic fitness, amount of vigorous running for the last 4 years in Scotland. The baseline by 7.3cm, BMI reduced by 1.8 kg/ glucose concentration (see Table 1 for normal well as amino acids for energy production. activity, and adiposity that are important in Football Fans in Training (FFIT) is a 12-week, m2, body fat percentage by 2%, systolic BP by values). The pancreas continues to secrete Glucose is a key fuel utilised in skeletal muscle reducing cardiovascular and metabolic disease gender-sensitised weight management and 8 mmHg and diastolic BP by 5 mmHg (all insulin in an attempt to reduce blood glucose during exercise and this uptake and usage is risk markers. physical activity programme delivered to statistically significant). The alterations concentration and eventually the beta-cells independent of insulin action. Thus, individuals groups of men at Scottish Premier League reported in diet were maintained at 12 months. fail, and individuals with type 2 diabetes then who are insulin resistant, such as those with Physical activity and exercise have clubs. The programme has been led by the Significant increases in self-esteem, mental require insulin therapy. type 2 diabetes, can reduce blood glucose by consistently been shown to improve health University of Glasgow and was developed to and physical health, and quality of life were all increased use of their skeletal muscle mass. outcomes in individual and group exercise use scientific approaches to weight loss, noted after 12 weeks and remained higher The adipocytes themselves are not inactive Physical activity, particularly in the fasted programmes, albeit with varying degrees of physical activity and diet, which are delivered than baseline at 12 months. The FFIT cells but are extremely important in human state, can also reduce the pathological individual responsiveness. While there is to participants at their football clubs. The aim programme has been hugely successful at metabolism. Adipocytes secrete metabolically complications of metabolic dysfunction in consistent evidence that BMI is a predictor of of the intervention was to encourage encouraging lifestyle changes and increases in active proteins (adipokines) such as leptin, obesity by increasing oxidation of blood borne all-cause mortality, and therefore reducing individuals to make lifestyle changes to physical activity for overweight and obese adiponectin and resistin, which contribute to and intramuscular FAs, reducing the impact of BMI is of benefit health-wise, there are a reduce their risk of ill health by losing weight, men. Furthermore, the study targeted a healthy metabolism and are altered with these FAs on insulin resistance. Chronic bouts number of paradoxes to this thinking. Of becoming more physically active and population who are generally reluctant to join obesity. Alterations of adipokine secretion of contraction of skeletal muscle (e.g. particular interest is the FIT FAT phenomenon consuming a healthier diet. Individuals were exercise programmes, and there was a 90% lead to pathological consequences such as exercise training) lead to production of recently reviewed by McAuley & Blair (2011), recruited from football clubs throughout retention of individuals in the programme – a insulin resistance and increases in plasma lipid myokines and anti-inflammatory responses, which suggests obesity is not a risk factor for Scotland. After a successful pilot study (Gray key point in its ongoing success. concentration. Adipocytes also contribute to which reduce reactive oxygen species, mortality in fit individuals. The FIT FAT et al. 2013) showed that the 12-week the increased systemic inflammation noted mitochondrial dysfunction and ER stress, all phenomenon is based on evidence that obese intervention was feasible and can have a Another older success story of the positive with obesity, including increases in tumor of which contribute to reducing metabolic individuals who are fit are at no greater risk positive effect on lifestyle choices, reduced effects of exercise and lifestyle changes on necrosis factor-α, interleukin-6 and dysfunction. Interestingly, there appears to be for mortality than normal weight fit obesity and increased physical activity, the metabolic health is reported with the C-reactive protein, which are associated with a relationship between intensity and volume individuals. However, the likelihood of being project was expanded to include football clubs Diabetes Prevention Program, a large insulin resistance and CVD. In addition, the of physical activity and the cardiovascular/ fit is also related to BMI, with higher numbers throughout Scotland. randomised clinical trial involving individuals increase in circulating FAs and other lipids metabolic health outcomes. Research from of normal weight individuals being considered who were at risk for developing type 2 leads to increased storage of fat in other competitive athletes suggests that their to have higher fitness levels compared to The recent report on this study published in diabetes in the USA (Knowler et al. 2002). tissues such as triglycerides in skeletal muscle physical activity volume is conducted overweight individuals (i.e. NHANES, Duncan The Lancet (Hunt et al. 2014) details a The aim of the study was to investigate and liver. While an increase in fat storage in predominantly at low intensity (~75–80%) et al. 2010). These observations further follow-up of the 747 individuals who took whether lifestyle intervention or treatment muscle provides an important fuel source for and with very little at moderate exercise highlight the importance of exercise and part in the 12-week FFIT programme. Each with metformin (a popular drug to treat some (i.e. athletes), in others such as (~5–10%) and a larger amount at vigorous particularly moderate to vigorous exercise in week participants had one 90-minute diabetes) could prevent or delay the onset of non-active obese individuals, this has been intensity (~15–20%). Adopting these activity maintaining health, regardless of body mass session, which included combined advice on diabetes. Participants in the study were at risk further linked to insulin resistance (Fig. 1). durations/distributions can produce greater or BMI. While weight loss is important to healthy diet with physical activity. After 12 for type 2 diabetes, with BMI of ≥24 kg/m2 Indeed, the capacity to oxidise FA seems an cardiovascular and metabolic adaptations obese and overweight individuals, increasing weeks, average mass loss was 5.8 kg, waist and fasting plasma glucose of 5.3 – 6.9 mmol/L. important determinant of the impact of (Neal et al. 2013) in well-trained recreational physical activity and exercise to improve circumference reduced by 6.7 cm, BMI by 1.9 Individuals in the study were randomly caloric excess and obesity on insulin athletes, which suggests that targeting fitness is of importance to healthy outcomes kg/m2, body fat percentage by 3%, systolic assigned to one of three interventions: resistance. It is now well recognised that physical activity intensity at the light and regardless of weight loss. This is a key aspect BP by 8 mmHg and diastolic BP by 4 mmHg standard lifestyle recommendations with increasing the capacity of skeletal muscle to vigorous intensity ends of the spectrum could often missed when interpreting results of (all statistically significant). Improvements metformin (initially 850 mg once/day and oxidise lipids, through exercise induced be more beneficial for health. Vigorous exercise programmes and when planning were reported in dietary intake with reduced increased to 850 mg twice/day after 1 increases in mitochondrial volume, can activity produces health improvements such interventions for improvements in health. fatty food intake, sugary food score, and month); standard lifestyle recommendations effectively restore insulin sensitivity. This as reducing adiposity and risk markers of alcohol consumption, and increased fruit and with placebo; or an intensive programme of effect would likely be larger if both caloric cardiovascular and metabolic diseases (e.g. An excellent recent example of a successful vegetable score (all significantly different lifestyle modifications. The intensive restriction and exercise were adopted. increases aerobic capacity and reduces fat public health intervention involving a research from baseline). The 12 month follow-up programme of lifestyle modifications involved

Physiology News / Winter 2014 / Issue 97 23 Features a 16-lesson curriculum containing diet, characterised in type 2 diabetes can be exercise and behaviour modifications. The reversed (Lim et al. 2011). The project References goal was to achieve and maintain a 7% weight undertaken at Newcastle University reduction through low-calorie, low-fat diet investigated the effects of a very low energy Brooks NE, Bowes J, Gava L, January N, Esterhuizen A and engage in physical activity of moderate intake (600 kcal/day) on type 2 diabetes. & Myburgh KH (2014). Twelve weeks of community intensity for at least 150 minutes/week. The Participants had type 2 diabetes (age 49.5 ± exercise improves health parameters in women living study included 3234 individuals (average age 2.5 years) and BMI of 33.6 ± 1.2 kg/m2. in a semi-rural township in South Africa. 50.6 ±10.7 years) and the average follow-up After 1 week of energy restriction, fasting FASEB J 28:884.25. was 2.8 years. At follow-up, the placebo plasma glucose concentration normalised to group had incidence of diabetes with 11.0 5.9 mmol/L and remained stable throughout Capurso C & Capurso A (2012). From excess cases/100 person years. The group given the 8-week study. Beta-cell function and adiposity to insulin resistance: the role of free fatty acids. Vascul Pharmacol 57, 91–97. metformin had a reduced incidence of hepatic insulin sensitivity were both restored diabetes (7.8 cases/100 person years; 31% to healthy function within the 8-week study Duncan GE (2010). The ‘fit but fat’ concept revisited: lower). However, the lifestyle intervention timeframe. Average mass loss was 15 kg. population-based estimates using NHANES. Exercise: more than just a role in energy balance group had a significantly lower incidence of These data clearly demonstrate the power of Int J Behav Nutr Phys Act 24:7:47. diabetes than both the placebo and the short-term reductions in energy intake alone, metformin group (4.8 cases/100 person but exercise in combination with diet Gibala MJ, Little JP, MacDonald MJ & Hawley JA Improving our understanding of the mechanisms by which physical years; 58% lower). The results show that restriction would ensure healthy body (2012). Physiological adaptations to low-volume, individuals in the lifestyle group decreased composition changes to help retain lean mass high-intensity interval training in health and disease. exercise enhances health requires physiologists to isolate the relative energy intake by ~450 kcal/day and increased while losing fat mass. J Physiol 590.5, 1077–1084. effects of exercise per se. physical activity to the greatest degree. Thus, lifestyle interventions can be more effective In summary, increasing physical activity and Gray CM, Hunt K, Mutrie N, Anderson AS, Treweek S than current prescription drugs for treating exercise, even in individuals who are obese, & Wyke S (2013). Weight management for and preventing diabetes. can have beneficial effects on reducing risk of overweight and obese men delivered through mortality, increasing/maintaining muscle professional football clubs: a pilot randomized trial. Int J Behav Nutr Phys Act 10. Finally, there has been a lot of recent mass and improving metabolism in the face attention on short-term high-intensity of mass loss, as well as overall health and Jean-Philippe Walhin, Hunt K, Wyke S, Gray CM, Anderson AS, Brady A, Research studies investigating the impact of exercise on health often interval training (HIIT) and the benefits to wellbeing. The present article provides a very Bunn C, Donnan PT, Fenwick E, Grieve E, Leishman J, James Betts metabolic health. Skeletal muscle is highly brief overview of a number of studies Miller E, Mutrie N, Rauchhaus P, White A & Treweek S show physical activity/exercise to be beneficial. However, energy status adaptable to exercise and short-duration highlighting that provision of community (2014). A gender-sensitised weight loss and healthy & Dylan Thompson (deficit, balance, surplus) can have a profound impact on metabolism. high-intensity exercise bouts can significantly based exercise programmes and appropriate living programme for overweight and obese men improve skeletal muscle metabolism. It lifestyle interventions are feasible and can be delivered by Scottish Premier League football clubs Department for Health To understand whether exercise leads to health improvements, energy appears that the disturbance in homeostasis extremely beneficial for health outcomes in (FFIT): a pragmatic randomised controlled trial. University of Bath, UK balance needs to be carefully controlled. at exercise onset, i.e. the beginning of a HIIT obese individuals. We have recently Lancet 383, 1211–1221. session, or the high rate of utilisation of presented similar findings of a community- glucose/glycogen is fundamental for based exercise intervention in women from Knowler WC, Barrett-Connor E, Fowler SE, Hamman Numerous studies have shown that regular Some excellent studies have already started upregulation of key regulators in skeletal previously disadvantaged backgrounds in RF, Lachin JM, Walker EA & Nathan DM (2002). exercise can have beneficial effects on to unpick the relative importance of exercise Diabetes Prevention Program Research Group. muscle fat and carbohydrate metabolism. South African townships, demonstrating metabolic function and various other health in the context of an energy deficit. For Reduction in the incidence of type 2 diabetes Thus, repeated rest-to-exercise transitions, improvements in metabolic health are also with lifestyle intervention or metformin. markers. Over the last decade, there has been example, work by the CALERIE team at which occur over a short period, appear to be observed in these individuals. Our data also N Engl J Med 346, 393–403. a prolonged debate about whether the Pennington has used sophisticated designs a beneficial way to increase whole body fat demonstrate that community-based exercise effects of exercise are simply secondary to where weight reduction was achieved either metabolism. Adopting this approach in seven programmes are feasible and effective in the Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, the role of exercise in energy balance. through caloric restriction alone, or through a high intensity interval training sessions over 2 South African township setting (Brooks et al. Mathers JC & Taylor R (2011). Reversal of type 2 Whether exercise offers additional benefits combination of caloric restriction and weeks led to an increase in whole body fat 2014). diabetes: normalisation of beta cell function in compared to diet alone remains unclear – increased structured exercise. The energy oxidation during exercise by 36%, and association with decreased pancreas and liver ‘The combination of which makes it difficult to provide clear deficit elicited was matched between groups increased skeletal muscle capacity to oxidise It is clear from the details presented that triacylglycerol. Diabetologia 54, 2506–2514. guidance to the public and healthcare leading to similar changes in body mass and FAs in women (Talanian et al. 2007). This there are a variety of ways to improve short-term overfeeding professionals. If exercise is only important composition (Redman et al. 2009). While this type of exercise intervention has been metabolic health including volume and McAuley PA & Blair SN (2011). Obesity paradoxes. because of a role in energy balance then, study suggested that exercise plays an reported to have great promise for individuals intensity of exercise as well as dietary J Sports Sci 29, 773–782. and reduced physical arguably, the greatest emphasis and focus equivalent role to caloric restriction in terms with impaired metabolic responses and has modification. While it is widely acknowledged should be on adiposity as the key outcome – of energy balance, another study by the same been shown to increase fat metabolism and that exercise is beneficial, we do not yet Neal CM, Hunter AM, Brennan L, O’Sullivan A, activity had a dramatic irrespective of the route via which weight loss group showed that exercise combined with Hamilton DL, De Vito G & Galloway SD (2013). Six reduce body fat stores in obese individuals. understand the optimal approach to exercise or weight maintenance has been achieved (i.e. caloric restriction did further improve weeks of polarized training-intensity distribution impact on insulin Alternatively, sprint interval training has also interventions. Perhaps the bigger question is leads to greater physiological and performance diet or exercise). In this context, one historical metabolic function compared to caloric been shown to have similar effects on skeletal how to maintain people in exercise adaptations than a threshold model in trained sensitivity’ problem is that many exercise studies fail to restriction alone (Larson-Meyer et al. 2010). muscle metabolic adaptation in a time programmes, which tend to have a large cyclists. J Appl Physiol 114, 461–471. adequately control energy balance in order to Although understanding the contribution of efficient manner (reviewed in Gibalaet al. dropout rate. The Scottish FFIT programme unpick the relative effects of exercise per se. physical exercise during a period of energy 2012). Furthermore, Gibala et al. (2012) provides evidence that retention and longer Talanian JL, Galloway SD, Heigenhauser GJ, Bonen A, For example, if a group of individuals are deficit or energy balance is extremely helpful discuss in detail how HIIT training has been term behavioural changes are certainly Spriet LL (2007). Two weeks of high-intensity trained for several weeks during which they in the context of weight loss, it is only part of used effectively to improve cardiorespiratory possible in hard to reach groups when the aerobic interval training increases the capacity for fat lose several kilograms of adipose, it will the picture. It is likely that most individuals fitness in individuals at risk for CVD and correct approach is taken. It is clear that oxidation during exercise in women. remain unclear which physiological events intermittently experience brief periods of metabolic disease. physical activity and exercise are beneficial for J Appl Physiol 102, 1439–1447. were primary in driving any observed changes positive energy balance and experimental obese individuals with or without associated (i.e. exercise, energy balance or loss of studies focusing on the impact of exercise In addition to the positive influences of weight loss. As such, it is fundamental to Timmers S, Schrauwen P & de Vogel J (2008). adipose). To understand and isolate how and physical activity during periods of energy exercise, dietary restriction and associated incorporate a variety of exercise programmes Muscular diacylglycerol metabolism and insulin exercise exerts its effects on metabolism, it is surplus might be equally relevant. resistance. Physiol Behav 94, 242–251 mass loss remain influential in the pursuit for and use the expertise of health scientists, important to conduct studies that will tease health and reduction in obesity and exercise physiologists, behavioural change apart the effects of energy balance and One of our recent papers published in The consequential effects. A promising recent experts and nutritionists/dieticians when weight loss from exercise/physical activity, Journal of Physiology took a very different study reports evidence that the beta-cell designing and implementing an exercise while carefully controlling energy status approach with striking results (Walhin et al. dysfunction and insulin resistance programme or physical activity intervention. (Braun & Brooks, 2008). 2013). In this study, 26 healthy young men

Physiology News / Winter 2014 / Issue 97 25

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-1 -1 . . . . -1 -1 Plasma Glycaemic Response (mmol 120 min l ) PlasmaSerum Glycaemic Insulinaemic Response Response (mmol (nmol120 min.120l )min.l ) Serum Insulinaemic Response (nmol.120 min.l ) 100 150 200 250 300 350 400 100 150 200 250 300 350 400

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alone, butalsoonthebehaviour(exercise). emphasis shouldnot just focus onbodymass can have profound physiological effects. The balance andweight loss, butalsobecause it at exercise asaroute to achieve energy the evidence thatwe shouldnot just belooking Thisstudyare addsto gainingweight. actively considerable energy surplusand whilst people even inthefacephysiological function ofa that exercise haspowerful effects on J Physiol of energy imbalance inhealthy youngmen. overfeeding andreduced independent physical activity (2013). Exercise counteracts theeffects ofshort-term Walhin JP, Richardson JD, Betts JA&Thompson D weight loss. caloric restriction: implications for themaintenance of Metabolic andbehavioral compensations inresponse to DelanyJP&Ravussin E(2009). Williamson DA, deJongeL, CK, Redman Martin LM,Heilbronn LK, Am JClinNutr implicates acompensatory increase inenergy intake. expenditure ismaintained withstructured exercise and energy (2010). Nonprescribed physical activity Turner Markovitch JE, D, Betts JA&ThompsonD References Med Sci Sports ExercMed SciSports exercise: the fitness versus fatness debate. restriction& Ravussin E(2010).Caloric withorwithout CK Martin Heilbronn Redman LK, L, Larson-Meyer DE, Nutr J holidayonweight The effect oftheThanksgiving gain. D, Radley DingerMK&Fields DAHull HR, (2006). ‘exercise’ onmetabolism. controlling energy status to understand theeffects of Braun B&Brooks (2008).Critical GA importance of IRS1 5 , 29.

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27 Features

Sleep disturbance alters autonomic balance to the heart Sleep disturbances such as sleep apnoea can cause a chronic imbalance in the autonomic nervous system, and if left untreated, can lead to cardiovascular diseases.

Jhansi Dyavanapalli, Sleep disturbances, including obstructive sleep apnoea (OSA), are very Heather Jameson, Figure 1. Cardiac vagal neurons (CVNs), which supply the parasympathetic activity to the heart, normally receive sufficient excitatory common causes of cardiovascular diseases. For example, OSA, prevalent glutamatergic synaptic inputs to initiate and drive their activity, as well as inhibitory GABAergic and glycinergic inputs that modulate their Olga Dergacheva, in ~24% of adult males and ~9% of adult females (between 30 and 60 firing, particularly with the respiratory rhythm; see left panel. However, following chronic intermittent hypoxia–hypercapnia, a model of years of age) (Young et al. 1993), is characterized by chronic repetitive sleep apnoea, the excitatory glutamatergic activity is diminished while inhibitory GABA and glycine neurotransmission to CVNs becomes Mona Alhusayyen exaggerated (right panel). & David Mendelowitz interruptions of breathing during sleep. These episodic periods with suspensions of breathing (apnoea) cause cycles of combined hypoxia Department of Pharmacology & (low oxygen) and increases in CO levels (hypercapnia) that often brings Supporting the hypothesis that CIH impairs synaptic events, were recorded using whole significant reduction of critical parasympathetic Physiology, George Washington 2 CVN function in the brainstem, the heart rate cell voltage clamp techniques. neuronal activity to the heart. This study also the person to a lighter state of sleep or brief wakefulness to stimulate University, USA response evoked upon microinjection of provides a foundation for the development of and restore normal breathing. Left untreated, OSA may generate, and/or glutamate (Yan et al. 2008), into the nucleus Our results have shown that chronic potential therapeutic interventions to restore ambiguus, where CVNs are located, is intermittent hypoxia–hypercapnia exposure cardioprotective parasympathetic activity to maintain, many cardiovascular diseases, including hypertension, diminished by CIH. However, beyond for 4 weeks increases blood pressure to the heart in patients with OSA. arrhythmias and sudden cardiac death. alterations in glutamate receptor density little hypertensive levels and blunts cardiovascular Vivek Jain was known about how CIH impairs CVN reflexes in response to both acute hypoxia– function and what, if any, targets can be hypercapnia and CIHH. This likely occurs by Department of Medicine, One of the key consequences of OSA is a the parasympathetic activity to the heart. identified to restore cardioprotective the observed changes in the George Washington University, USA chronic imbalance in the autonomic nervous parasympathetic activity to the heart. neurotransmission to cardiac vagal neurons References system, which serves to maintain Parasympathetic cardiac vagal neurons that normally maintain a low resting heart Dyavanapalli J, Jameson H, Dergacheva O, Jain V, homeostatic cardiovascular function as well (CVNs) of the brainstem, located in nucleus The changes responsible for diminished vagal rate. Specifically, cardiac vagal neurons Alhusayyen M & Mendelowitz D (2014). as to protect against challenges and ambiguus and dorsal motor nucleus of the control of heart rate were identified by received an increased frequency of inhibitory J Physiol 592, 2799–2811. perturbations to the cardiovascular system. vagus, generate the parasympathetic activity studying the changes in blood pressure, heart (both GABA & glycinergic) and depressed Both the sympathetic and parasympathetic to the heart. The vagal descending rate and neurotransmission to CVNs evoked incidence of excitatory (glutamatergic) Gu H, Lin M, Liu J, Gozal D, Scrogin KE, Wurster R, divisions of the autonomic nervous system projections from these neurons synapse upon by acute hypoxia–hypercapnia and CIHH. The neurotransmission with CIHH. These changes Chapleau MW, Ma X & Cheng ZJ (2007). regulate neural control of the heart, with postganglionic intracardiac ganglia neurons methods have been described in detail in would act in concert to inhibit the activity of Am J Physiol Heart Circ Physiol 293, H2809–2818. parasympathetic activity dominating this located in close proximity to the heart (Dyavanapalli et al. 2014). Briefly, in vivo CVNs and diminish cardioprotective balance. A normal resting heart rate of (Mendelowitz, 1999). CVNs are intrinsically telemetry recordings of blood pressure and parasympathetic activity to the heart. These Lin M, Liu R, Gozal D, Wead WB, Chapleau MW, ~60–80 beats/minute is maintained by the silent and hence their activity is dictated by heart rate were obtained in adult rats prior to alterations of cardiorespiratory network Wurster R & Cheng ZJ (2007). tonic parasympathetic activity to the heart, the excitatory (glutamatergic) and inhibitory and during 4 weeks of CIHH exposure. CIHH function within the brainstem would Am J Physiol Heart Circ Physiol 293, H997–1006. without which heart rate would become (GABA and glycinergic) synaptic activity exposures were performed by placing the contribute to the increased heart rate, blood elevated (~100 bpm) with a higher risk of arising from other regions of the brain rats in commercial atmosphere controlled pressure and risk of adverse cardiovascular Mendelowitz D (1996). Am J Physiol 271, H2609–2614. arrhythmias. While previous work by others (Mendelowitz, 1996) (Fig. 1). chambers, exposed to repetitive cycles of 3 events that occur in patients with OSA. Mendelowitz D (1999). News Physiol Sci 14, 155–161. has focused on how OSA elicits sympathetic minutes of mild hypoxia–hypercapnia (6% O2

overactivity, the goal of the current study A functional deficit in the brainstem circuitry + 5% CO2 + 89% N2) followed by 3 minutes In addition to identifying the adverse Yan B, Soukhova-O’Hare GK, Li L, Lin Y, Gozal D, was to study and identify the mechanisms responsible for parasympathetic activity to of normoxia (21% O2 + 79% N2), repeated alterations responsible for reduced responsible for diminished cardioprotective the heart (Gu et al. 2007), especially for 10 times/h, 8 h/day, for 4 weeks during parasympathetic activity to the heart Wead WB, Wurster RD & Cheng ZJ (2008). Neuroscience 153, 709–720. parasympathetic control of heart rate in OSA. activation of CVNs (rather than anatomical or the light phase. Fluorescently labelled CVNs following CIHH, the results from this study To accomplish these goals we utilised an functional changes in peripheral innervation were visualised and identified in an in vitro would predict that patients who have OSA Young T, Palta M, Dempsey J, Skatrud J, Weber S & animal model of chronic intermittent of the heart (Lin et al. 2007; Yan et al. brainstem slice preparation obtained from and take sleep promoting medicines that Badr S (1993). N Engl J Med 328, 1230-1235. hypoxia–hypercapnia (CIHH) that mimics 2008)) is responsible for impaired adult rats exposed to either air or CIHH for 4 typically act by enhancing inhibitory OSA in humans, and examined the critical parasympathetic control of the heart with weeks. Neurotransmission to CVNs, including GABAergic neurotransmission within the CNS synaptic pathways to neurons that generate chronic intermittent hypoxia (CIH). postsynaptic inhibitory and excitatory might be at heightened risk for a more

Physiology News / Winter 2014 / Issue 97 29 Features muscle tissue,’ and a ‘generalized organ hypoplasia… including the muscles’. The essential role of IGFs in cell growth is shown by the report that fibroblasts from IGF-1 receptor knockout mice grew very slowly in culture unless they were transfected with a plasmid expressing the IGF-1 receptor. Using the opposite approach in which transgenic animals overexpressed IGF-1, Mathews et al. (1988) found that muscle and bone growth were increased approximately 30% when circulating levels of IGF-1 were 50% above control values. There was a substantial increase in weights of spleen, pancreas, brain, and kidney and an increase in DNA content of The mighty protein: insulin-like growth factor type 1 these tissues. All of these observations are consistent with the view that IGF-1 plays an essential role during normal growth and IGF-1 plays a critical role in skeletal muscle growth during development, development. In spite of the association of muscle regeneration and muscle hypertrophy in response to training. excess IGF-2 with tumours, in general it is clear that IGF-1 plays a major role in development, growth, cell differentiation, and maintenance of skeletal muscles, both in culture and in intact animals. Most, if not all of these actions are mediated by the IGF-1 Fan Ye receptor, and they are strongly modulated by Muscle atrophy and weakness are common clinical phenomena IGF binding proteins. & Stephen E Borst observed following bed rest, surgery, cast immobilization and injury or University of Florida, USA disease. The consequences of loss of muscle function are far reaching Viral-mediated IGF-1 gene transfer and include decrease of motor control and overall fitness, development Increasing blood hormone levels may be risky. Figure 1. GH/IGF-1 axis. (Courtesy of Dr H Lee Sweeney at University of Pennsylvania) of functional limitations and impairment, and long term disability. The Specifically, the long-term safety of the activation of GH/IGF-1 levels remains Figure 1: GH/IGF-1 axis recovery of muscle strength and function following injury or disease is uncertain with regard to tumour growth, as a major challenge in rehabilitation. most human solid cancers express IGF-1 Courtesy of Dr. H. Lee Sweeney at University of Pennsylvania receptors. Elevated GH levels have also been IGF-1 PBS linked to impaired glucose tolerance, injected injected The ability to manipulate muscle adaptation on the basis of its insulin-like activity, but was hypertension and fluid retention. However, and growth has great potential in clinical renamed IGF-1 when it became apparent that given the known autocrine/paracrine actions situations where functional ability and strength its growth-promoting properties were more of IGF-1, local manipulation of IGF-1 TA muscle are compromised. Administration of growth important than their insulin-like activities expression and secretion by muscle fibres may ‘Administration of hormone (GH) has been used successfully in (Rinderknecht & Humbel, 1978). not only be safer but also more effective elderly to prevent atrophy during catabolic (Fig. 1). Recent developments in genetic growth hormone has diseases or following hip fractures (Van der The IGF-1 system includes ligand IGF-1, its manipulation are appropriate for the been used successfully Lely et al. 2000). GH administration in these receptor, IGF-binding proteins (IGFBPs) and introduction of small regulatory factors, such populations resulted in increased insulin-like IGF proteases. The biological significance of as IGF-1, into tissue. The recombinant EDL muscle in elderly to increase growth factor 1 (IGF-1) levels, and increased the IGF-1 was most strikingly demonstrated adeno-associated virus (rAAV) vector system muscle mass and functional ability. IGF-1 when its expression was ‘knocked out’ by consists of rAAV inverted terminal repeats IGF-1 levels and plays a critical role in skeletal muscle growth homologous recombination techniques. (ITRs) that are necessary and sufficient for during development, muscle regeneration and Virtually every component of the IGF-1 replication and packaging of the virus. rAAV prevent atrophy during muscle hypertrophy in response to training. system (the various ligands, receptors and lacks virally encoded genes, and therefore can Several growth factors have been implicated binding proteins) has been knocked out, and be used to infect adult tissue without catabolic diseases or in directing muscle specific gene expression; the results demonstrate that the IGFs are rendering an immune response. Viral- Figure 2: Visible increases in muscle mass after virus mediated following hip fractures’ however, the hypertrophic effects of growth very important in muscle growth and mediated gene delivery of IGF-1 has been IGF-I injection into the anterior part of the mouse hindlimb. (TA= hormone have been thought to be primarily development. Indeed, a common observation shown to enable efficient transfer of IGF-1 tibial anterior, EDL= extensor digitorum longus) mediated via IGF-1. in mouse lines lacking IGF-1 (and/or its into both young and adult animals. The Figure 2. Visible increases in muscle mass after virus mediated IGF-1 injection into the receptor) is that embryonic development is rAAV-virus is introduced via direct injection anterior part of the mouse hindlimb. (TA= tibial anterior, EDL= extensor digitorum longus) IGF-1 impaired but embryos are viable. However, into a muscle compartment and endocytosed the pups die immediately after birth because by muscle cells (Fig. 2). IGF-1 was first identified in 1957. It was they cannot breathe. The central importance injecting the gene-virus package into the IGF-1, the relative rate of loss of muscle mass known by other names including sulfation of IGFs to muscle development is emphasized IGF-1 and muscle muscles of adult mice, we (Ye et al. 2013; and strength is not attenuated in virus- factors, non-suppressible insulin-like activity, by the fact that mice in which expression of Stevens-Lapsley et al. 2010) have shown injected versus control muscles. We speculate multiplication stimulating activity and myogenin has been knocked out show the Numerous in vitro studies have shown that that virally mediated gene transfer of IGF-1 that the latter is related to a decrease in somatomedins. It was initially identified on the same result; i.e. there is essentially no exposure of mammalian muscle cells to IGF-1 increases muscle size under normal loading/ IGF-1 bioactivity in the absence of basis of three unique properties: its mediation functional muscle development in the promotes myogenic proliferation and activity conditions (Fig. 3), but that this neuromuscular activity, due to alterations in of the skeletal growth-promoting actions of absence of either IGF-1 or myogenin. The differentiation as well as protein synthesis. newly established homeostasis is maintained receptor density, binding protein, or GH, its mitogenic properties, and its mimicry mice with an inactive IGF-1 gene studied by Other studies have shown that administration during cast immobilization, when postreceptor events. Allen et al. (1999) of the actions of insulin. This peptide was Powell- Braxton et al. (1993) were of IGF-1 induces an increase in muscle protein neuromuscular activity is minimal. previously postulated that the level of isolated in Zurich by Rinderknecht and Humbel ‘characterized by underdevelopment of content and reduces protein degradation. By Interestingly, despite increased expression of neuromuscular activity affects the expression

Physiology News / Winter 2014 / Issue 97 31 of the IGF-1 receptor (IGF-1R), making death, but also stimulates nerve regeneration atrophying muscles less susceptible to the in crushed or freeze-injured nerves. effects of endogenous IGF-1. Conversely, Rabinovsky et al. (2003) found that after a during hypertrophy, increased levels of sciatic nerve crush injury in transgenic mice muscle activation and loading may result in expressing the human IGF-1 transgene, there References greater IGF-1R expression. Finally, we is an increase in the number of neurofilaments demonstrate that successful gene transfer of staining the axons in muscle and an Van der Lely AJ, Lamberts SW, Jauch KW, et al. (2000 ). IGF-1 increase the muscle’s regenerating accelerated return of nerve conduction Use of human GH in elderly patients with accidental ‘One of the more capacity. Histological examination of EDL velocity. Similarly, IGF-1 increases hip fracture. Eur J Endocrinol 143, 585–592. interesting recent muscles during cast-immobilization and intramuscular nerve sprouting 10-fold when reloading showed an increased number of administered subcutaneously to normal adult A Rinderknecht E & Humbel RE (1978). The amino acid developments in the central nuclei, Pax7 and embryonic myosin in rats (Caroni & Grandes, 1990). Finally, IGF-1 sequence of human insulin-like growth factor I and IGF-1 injected muscles during reloading has also been linked to age-related alterations its structural homology with proinsulin. IGF-1 story has been (Fig. 4). The presence of central nuclei and in neuromuscular innervation (Payne et al. J Biol Chem 253, 2769–2776. Pax7 in adult myofibres is indicative of recent 2006). These data indicate that IGF-1 plays Powell-Braxton L, Hollingshead P, Warburton C, et al. the identification of a fusion of activated satellite cells to existing an important role in mature motoneuron (1993). IGF-I is required for normal embryonic myofibres. IGF-1 has multiple targets in maintenance, both in the normal state and growth in mice. Genes Dev 7, 2609–2617. unique IGF-1 isoform muscle. IGF-1 receptors are found on under conditions where motor neuronal loss is that is expressed in activated satellite cells, adult myofibres, found such as ageing and pathological A Mathews LS, Hammer RE, Behringer RR, et al. (1988). motor neurons and Schwann cells. Satellite conditions involving the central nervous Growth enhancement of transgenic mice expressing response to changes in cells, which retain their mitotic capacity, serve system. Figure 3. The efficiency of AAV gene transfer. 95–99% of EDL muscle fibres showed human insulin-like growth factor I. as the pool of myonuclei necessary for muscle expression A of reporter gene (LacZ) delivered by AAV1. Endocrinology 123, 282–2833. the loading state of enlargement. Satellite cells are mobilised in It has been shown that rAAV is retrogradely Figure 3: The efficiency of AAV gene transfer. The 95~99% of EDL muscle response to increased neuromuscular activity transported from presynaptic terminals of fibers showed expression of reporter gene (LacZ) delivered by AAV1. Ye F, Mathur S, Liu M, et al. (2013). Overexpression skeletal muscles’ (activity or loading) and injury. Following projecting neurons through the entire length of IGF-1 attenuates skeletal muscle damage and activation, the satellite cells proliferate, of the axon. Kaspar et al. (2003) took 5d Reamb/PBS 5d Reamb/IGF-1 accelerates muscle regeneration and functional differentiate and fuse with adult myofibres, advantage of the retrograde transport ability recovery after disuse. Exp Physiol 98, 1038–1052. leading to an increase in fibre size. of AAV in a mouse model of amyotrophic A lateral sclerosis and injected AAV into Stevens-Lapsley JE, Ye F, Liu M, et al. (2010). Impact of viral-mediated IGF-I gene transfer on One of the more interesting recent respiratory and motor limb muscles to directly B skeletal muscle following cast immobilization. developments in the IGF-1 story has been the target the motoneurons and test the efficacy Am J Physiol Endocrinol Metab 299, E730–740. identification of a unique IGF-1 isoform that of two neurotrophic factors, IGF-1 and glial is expressed in response to changes in the cell line-derived neurotrophic factor (GDNF). 5d Reamb/PBS 5d Reamb/IGF-1 Sheehan SM & Allen RE (1999). Skeletal muscle loading state of skeletal muscles. In both They showed that IGF-1 delays the onset of satellite cell proliferation in response to members of human beings and rats, the IGF-1 gene spans behavioural symptoms and sustains life to a the fibroblast growth factor family and hepatocyte more than 70 kilobases and consists of six greater degree than GDNF. The marked growth factor. J Cell Physiol 181, 499–506. 5d Reamb/PBS 5d Reamb/IGF-1 exons and at least five introns. Splicing is a effects of IGF-1 on onset and survival were 5d Reamb/PBS 5d Reamb/IGF-1 complex mechanism by which exons are cut accompanied by preserved morphology of Barton ER (2006). Viral expression of insulin-like B and pasted in different combinations from motoneurons. B growth factor-I isoforms promotes different pre-mRNA. In humans, alternative splicing of responses in skeletal muscle. J Appl Physiol 100, 1778–1784. IGF-1 pre-mRNA leads to the production of Conclusion three different transcripts at the 3’ end, B resulting in different E-peptides. It is the Collectively, these findings demonstrate that Rabinovsky ED, Gelir E, Gelir S, et al. (2003). Targeted expression of IGF-1 transgene to skeletal IGF-1Ec splice variant which has been most IGF-1 is a central trophic growth factor, muscle accelerates muscle and motor neuron closely associated with stretch overload and essential for muscle regeneration and C regeneration. FASEB J 17, 53–55. damage, hence its being termed ‘mechano hypertrophy, and motor neural maintenance growth factor’ (MGF). However, using a viral and regeneration. Given the role of IGF-1 in 10d Reamb/PBS 10d Reamb/IGF-1 Caroni P & Grandes P (1990). Nerve sprouting in construct and a myosin light chain (LC3f) the regeneration of nerve and muscle, it is innervated adult skeletal muscle induced by exposure promoter, Barton et al. (2006) showed that worth further investigating the therapeutic to elevated levels of insulin-like growth factors. both the MGF and IGF-1Ea gene transfer potential of overexpression of IGF-1 in C J Cell Biol 110, 1307–1317. could increase muscle IGF-1 (mature) different neuromuscular diseases. expression without increasing circulating Payne AM, Zheng Z, Messi ML, Milligan CE, Gonzalez IGF-1. It appears that skeletal muscles produce C E & Delbono O (2006). Motor neurone targeting of both a generalized tissue-type IGF-1 and the IGF-1 prevents specific force decline in ageing mouse loading-sensitive MGF isoform with differing muscle. J Physiol 570, 283–294. time courses, suggesting distinct roles for these two growth factor isoforms. Expression C Kaspar BK, Lladó J, Sherkat N, Rothstein JD & Gage FH (2003). Retrograde viral delivery of IGF-1 of both IGF-1 and MGF appears to be very 10d Reamb/PBS 10d Reamb/IGF-1 prolongs survival in a mouse ALS model. sensitive to the loading state of the muscle. 10d Reamb/PBS 10d Reamb/IGF-1 Science 301, 839–842.

IGF-1 and motor neuron Figure 4. MarkersFigure of4. regeneration Markers ofin the regeneration soleus across allin experimental the soleus timepoints. across all experimental timepoints. A) Cross‐sections of The importance of IGF-1 in motor neuron the soleus muscle stained with laminin (red) + DAPI (blue) + Pax7 (green). Pax7 positive fibres (arrows) survival and motor regeneration is quickly A, cross-sections of the soleus muscle stained with laminin (red) + DAPI (blue) + Pax7 emerging. A critical role for IGF-1 in (green). Pax7at 5 positive days of fibres reloading (arrows) (5dat 5 Reamb).days of reloading Bar=12.5µm. (5d Reamb). B) Bar Light = 12.5 microscopyμm. of H&E‐stained myofibres with motoneuronal survival has been demonstrated B, light microscopycentral nucleiof H&E-stained at 10 daysmyofibres of reloading with central (10d nuclei Reamb). at 10 days Bar=50µm. of reloading C) Cross‐sections of the soleus muscle (10d Reamb). Bar10d = 50Reamb/PBSμm. C, cross-sections of the10d soleus Reamb/IGF-1 muscle stained with monoclonal during embryonic and early postnatal life, as stained with monoclonal antibody against embryonic myosin isoform (green) at 10 days of reloading. well as in spinal cord pathology. In vivo studies antibody against embryonic myosin isoform (green) at 10 days of reloading. Bar = 12.5μm. Bar=12.5µm. show that IGF-1 not only inhibits neuronal cell Figure 4. Markers of regeneration in the soleus across all experimental timepoints. A) Cross‐sections of the10d soleus Reamb/PBS muscle stained with10d laminin Reamb/IGF-1 (red) + DAPI (blue) + Pax7 (green). Pax7 positive fibres (arrows) Physiology News / Winter 2014 / Issue 97 at 5 days of reloading (5d Reamb). Bar=12.5µm. B) 1Light microscopy of H&E‐stained myofibres with 33 Figurecentral 4. nuclei Markers at 10 of days regeneration of reloading in the(10d soleus Reamb). across Bar=50µm. all experimental C) Cross‐sections timepoints. of the A) soleusCross‐ sectionsmuscle of thestained soleus with muscle monoclonal stained antibody with laminin against (red) embryonic + DAPI (blue) myosin + Pax7 isoform (green). (green) Pax7 at 10positive days offibres reloading. (arrows) atBar=12.5µm. 5 days of reloading (5d Reamb). Bar=12.5µm. B) Light microscopy of H&E‐stained myofibres with central nuclei at 10 days of reloading (10d Reamb). Bar=50µm. C) Cross‐sections of the soleus muscle stained with monoclonal antibody against embryonic1 myosin isoform (green) at 10 days of reloading. Bar=12.5µm.

1 Features that led to it. He shows that these ideas follow contribute very little to complex functions, Waddington side-lined, McClintock ignored on naturally from Popper’s conjectures and which is why the correlations between genes until the surprise Nobel Prize rescued her great refutations approach to scientific discovery. and complex diseases have been found to be a contribution. I believe he was determined to matter of large numbers of very small effects, make his lecture unanswerable. I think that many of the ‘new’ ideas can still summing up to a small overall fraction of already be found in Popper’s lecture. He was causation. The atomistic view was never going Had he been alive today, just 20 years after heard by a large and distinguished audience, so to be of much use in physiology and pathology. his death at the age of 92, he would surely why was he ignored? One possible answer to have been delighted with the discoveries that that question is that Max Perutz was in the The second way ‘in’ for Popper was his have shown just how wide that fissure has audience and he published a serious criticism appreciation of the significance of the grown. His views are now seen as not simply of the lecture, arguing that Darwin was right discovery of reverse transcription of RNA into gene-centred, but that all levels can be the Secrets of life from beyond the grave (Perutz, 1986). Actually, Popper did not so DNA2. He saw that this drives a cart and object of natural selection (Okasha, 2006). much argue that Darwin was wrong, as that horses through the Central Dogma of The rivers of experimental evidence from his theory was incomplete. The central molecular biology and was deeply suspicious epigenetics, natural genetic engineering, “The story of how humans and all living things came into existence is told problem for Perutz was the claim that of sophisticated manoeuvrings and niche theory, symbiogenesis, and much more biochemistry could not be reduced to physics redefinitions to protect the dogma from have totally changed the landscape of in two widely believed versions: the Book of Genesis and Darwin’s Origin and chemistry. He strongly opposed Popper on falsification. In his conjectures and refutations biological theory. The mighty scientific this point and said so in discussion after the view of science, it is better to acknowledge establishment that Popper faced is now a of Species. It was the philosopher Karl Popper who presented us with a lecture. The reason why Popper did not when a strong version of a theory has been much smaller conservative group of those third story, no less important.” (Niemann, 2014) immediately reply by sending his article to the refuted. The strong, original version of the who still wish to defend the standard story Royal Society for publication was that he Central Dogma was refuted. But he went against all comers. My belief is that they can entered into extensive correspondence with further than this. He saw that this could be do so only by rearranging goalposts, by Perutz and wanted to conclude the discussion one of the routes through which Lamarckian redefining the boundaries of what the Modern before finally submitting. By then Popper was processes and wholesale reorganisation of Synthesis can contain. in the ninth decade of his life. We should not genomes could occur. Again, the philosopher Denis Noble be too surprised that, despite repeated in him wanted to see this recognised, not Remember too that this is the Popper who The title of the special issue of The Journal of Physiology on 1 June requests from the Royal Society, the lecture hidden behind a web of clever re- wrote The Open Society and its Enemies, Department of Physiology, Anatomy 2014 reflected the theme of the opening of the 2013 IUPS Congress: was never published. interpretations. He has been completely opposing closed society dogmatism; the and Genetics, Oxford University, UK vindicated. Wholesale genome reorganisation, Popper who narrowly escaped the holocaust physiology moves back onto centre stage (Noble et al. 2014). How did Popper arrive at his radical position? what Shapiro, in Evolution: A View from the (he included racism as one of the disastrous The articles focus on ways in which new and often controversial His way in was his clear understanding of a 21st Century (Shapiro, 2011), calls natural social consequences of the language of phenomenon known as the Baldwin effect1. genetic engineering, has occurred many times neo-Darwinism, which he realised was largely developments in evolutionary biology have opened the door to the Organisms can choose new niches for in evolutionary history. Like Shapiro, Popper colourful metaphorical veneer); the Popper discovery of physiological functions, which play a role in determining the themselves and their descendants. Moving to appreciated the significance of the work of who advised us not to hide clear refutations of a new niche can change the course of Barbara McClintock3. scientific theory in over-sophisticated 1 In the 1986 lecture Popper writes: ‘My variations in inherited characteristics on which natural selection may act. evolution even with no mutations whatsoever. manipulations of the goalposts through problem is exactly the same as that of This is known as Lamarckian heresy, which the founders of Modern That choice is a physiological characteristic of With two such fundamental breaks with the endless redefinitions. Dogmatism in all its my forerunners, such as Baldwin, who the phenotype, not a change in DNA. So how standard theory under his belt, what – if forms, and most particularly in science, was felt that the activities ... of individual Synthesis (neo-Darwinism or Synthetic Theory of Evolution) sought to can it change the course of evolution? The anything – was missing in his 1986 lecture? his enemy. organisms have played a far more exclude. But did we really have to wait until 2014 for all that to happen? answer is surprisingly simple. In a wild important role in the history of evolution population, in which individual genomes are Actually, quite a lot. As John Maynard Smith than Darwinists have as a rule admitted.’ not identical to the combination of alleles in also recognised in Evolutionary Genetics I suspect he meant ‘neo-Darwinists’ A recent book by Niemann (2014) shows that themselves are the source of the creative the adventurous organisms, discovering new (1998), where he wrote ‘it [Lamarckism] is rather than ‘Darwinists’. Darwin admitted if history had taken a slightly different turn processes in evolution, not random mutations niches will be favoured. This is an evolution of not so obviously false as is sometimes made References the role of organisms and their emotions, three decades ago the answer might well have in DNA. Popper suggested Darwinism was not the genome by combinatorial selection, not out’. The mechanisms known to twentieth and he accepted Lamarckian inheritance. been ‘no’. On 12 June 1986, the great logician so much wrong, but seriously incomplete. He selection of new random mutations. It is not century biologists were very few and could be Niemann HJ (2014). Karl Popper and the Two New and philosopher of science, Karl Popper, gave also stated that biochemistry (and so a fortiori surprising that a logician like Popper should regarded as the rare exceptions that any Secrets of Life. Mohr Siebeck, Tübingen. 2 In a 1973 text reproduced by Niemann, the first Medawar Lecture in honour of the physiology) could not be reduced to physics have immediately understood the immense theory might cope with, by claiming that such Popper writes, ‘There is however a Nobel laureate Peter Medawar. Popper was and chemistry. significance of this fact. To illustrate his processes were not of any great consequence. Noble D (2011). Neo-Darwinism, the Modern mechanism [he then describes well known for his magisterial Logic of hypothesis, he even invented an imaginary Popper’s strength was his logical foresight. He Synthesis, and Selfish Genes: are they of use in physiology? J Physiol 589, 1007–1015. transcription of RNA into DNA]. If this is Scientific Discovery and The Open Society and Many of the points made in the recent special world, in which there was no competition for could, philosophically speaking, smell a taken as established it means that it is its Enemies. Very few people know that he issue of J Physiol were therefore made nearly survival, no ‘selfish genes’. The organisms consequence from miles away. He took his Noble D, Jablonka E, Joyner MJ, MüllerGB & Omholt possible that enzymes exist in all cells was also deeply involved with a group of 30 years ago. So why did I and the other 35 would still evolve. Of course, the world in own refutation theory very seriously indeed, SW (2014). Evolution evolves: physiology returns to which can re-translate RNA into DNA.’ scientists, including JBS Haldane, Joseph authors in the special issue not know this? which such evolution could occur would have but not in a pernickety way. Reverse centre stage. J Physiol 592, 2237–2244. Later in the same text he writes, ‘It would Needham and Conrad Waddington, with The answer is that, despite 8 years of patient to be effectively infinite in size to transcription, however one looks at it, was a constitute a break with current dogma.’ discussions dating from 1936 on the then waiting, the written manuscript was not accommodate all the organisms that have ever fissure that could grow into a chasm, as it has. Okasha S (2006). Evolution and the Levels of ‘new’ subject of molecular biology, its submitted to the Royal Society before Popper’s lived. However, this was just a thought The Baldwin effect should be rampant. All Selection. OUP, Oxford. 3 Barbara McClintock (1902–1992) was implications for evolutionary theory and the death in 1994. Worse still, his documents experiment, which found agreement with the organisms, even bacteria, have what he called an American geneticist who won the Perutz M (1986). A new view of Darwinism. formulation of the Modern Synthesis. remain archived and closed until 2029. British developmental biologist and geneticist, ‘real activity’, meaning goal-directed 1983 Nobel Prize in Physiology or New Scientist, 2 October 1986, 36–38. Connoisseurs of history will not be surprised Conrad Waddington. Why then do selfish gene behaviour that distinguishes them from purely Medicine for her discovery of genetic by the fact that the title of Popper’s lecture Hans-Joachim Niemann has, however, worked theorists ignore it? They do so by taking an physical and chemical processes in nature. This st transposition, or the ability of genes to Shapiro J (2011). Evolution: A view from the 21 was ‘A new interpretation of Darwinism’. It with the executors to repeal the classification atomistic gene-centred view. As Popper saw, was his fundamental disagreement with Century. FT Press, London. change position on the chromosome was given in the presence of Sir Peter and obtained a copy of Popper’s lecture it is the insistence on just one atomistic Perutz. No wonder he wished to refine his (http://profiles.nlm.nih.gov/LL/). Medawar, Max Perutz and other key figures; article, which is now published for the first approach that is the problem. Physiologists lecture before it was published. Think of a Smith JM (1998). Evolutionary Genetics. OUP, Oxford. it must have shocked his audience. time in English (Nieman, 2014). It should be today will readily see Popper’s point. It is 90-year-old man, each year flashing by, required reading for anyone interested in the combinations of genes, or rather combinatorial focusing on what he saw as a discovery of He proposed a radical interpretation of fundamental rethinking of evolutionary interactions between large numbers of their great significance. He knew also that the great Darwinism, essentially rejecting the Modern biology. Niemann is a lucid and enthusiastic products, RNAs and proteins, that are majority of the scientific establishment was Synthesis, by proposing that organisms expositor of Popper’s lecture and of the ideas important functionally. Most single genes against him. Lamarck had been rubbished,

Physiology News / Winter 2014 / Issue 97 35 Membership

Great textbooks of physiology

The first article in this short series PN( 94, ‘haphazard’, it seems unlikely that any commented that the book had ‘one great Medical Physiology Bob Maynard Spring 2014, p. 9) started with the remarks: physiologist has ever read more. In addition to defect as a textbook, namely, that medical Vernon B Mountcastle ‘The age of great textbooks of physiology this almost unimaginable labour, he ran an students find it extremely difficult to read.’ A Department of Health seems to have passed. Those splendid excellent research group, established and damning comment, but softened by her ‘Mountcastle’, as the book was usually known, References London, UK thousand page volumes that used to inform maintained his position as a leading authority praise for the work as a reference book for was the largest of the great textbooks of Ruch TC & Patton HD (1965). Physiology and and perhaps intimidate, have – like battleships on the physiology of the eye and teachers of physiology. physiology of the 1970s period. Two large biophysics, 19th edn. W B Saunders. – disappeared. But actually, we can still learn a cerebrospinal fluid and as the doyen of volumes, 1858 pages plus an index – a long th lot from these books. In this article, I am membrane physiology. The range of subjects The 14 edition contains contributions of book – Medical Physiology, like the other Davson HA (1970). Textbook of General Physiology, discussing just a few of the ‘greats’ from 40 covered in depth in his book is most outstanding quality. M de Burgh Daly’s 500 or books considered in this series, had a long 4th edn, two volumes. J & A Churchill. years ago.’ In that article, I revisited Ruch and impressive. From the mechanics of flagella, so pages on blood, the circulatory and history. It appeared in 1918 and was edited Patton’s Physiology and Biophysics. Now I turn DNA, the molecular biology of connective respiratory systems (with contributions by for many years by Philip Bard from Johns Starling EH (1912). Principles of Human Physiology, st to three more examples of Great Textbooks. tissue, diffusion processes, electrophysiology, Davson), and D H Smyth’s account of the gut Hopkins University. The 14th and final edition 1 edn. photosynthesis, the gut, the kidney, cardiac are excellent pieces of work. Davson appeared in 1980: 1999 pages plus 72 pages Starling EH (1968). Principles of Human Physiology, General Physiology muscle – the list is endless. And all in faultless, contributed extensively: 558 pages on the of index. One volume was devoted to the ed. Davson H and Eggleton G, 14th edn, 1668 pages. Hugh Davson flowing English. CNS and special senses in addition to the nervous system (and muscle); the other to J & A Churchill, London. Introduction and sections on tissue fluids and the remainder of the subject. Rather Hugh Davson (1909–1996) probably knew Davson’s General Physiology was a unique the CSF. Davson told me that he had written confusingly, the order of the volumes was Mountcastle VB (ed) (1968). Medical Physiology. as much as any one person could know about book. It contains much information of classical the section on the CNS after having been let reversed between the 12th and 14th editions. 12th edn. CV Mosby Company, Saint Louis. general physiology or biophysics. His General importance and anybody who thinks he or she down by a distinguished neuro-physiologist. Physiology appeared as a single volume in has a new idea in membrane physiology would Although the CNS was not Davson’s special The approach taken by all contributors Killick EM (1957). Experimental Physiology 42, 145. 1951 and in its final two-volume form in be well advised to read Davson before area of interest, he excelled in a fluent and involved a great deal of detail. Illustrations 1970. By then, it had become a standard applying for a grant. But more valuable exhaustive style, dealing with the anatomy as were adequate but not prolific and the work and few professional physiologists perhaps than the scientific information is the well as the physiology. impression received by the beginner was one lacked a copy. It is an extraordinary book. opportunity to meet Davson. Nobody will of long passages of rather solid text. This was Davson’s approach to physiology and his write, and certainly nobody will be paid whilst Rushton’s chapter, ‘Nerve Fibres’, is still worth off-putting to some; to others the depth of unusually fluent prose style are well shown in writing this sort of book again. reading today. He wrote in a classical style treatment was rewarding and the standard of the preface to the first edition. He points out introducing striking analogies ‘Like ships the work was clearly a long way beyond that that advances in general physiology depended Principles of Human Physiology anchored to their buoys, the K+ ions cannot of ‘ordinary’ textbooks of medical physiology. on the recruiting of scientists trained in Ernest Starling drift away but all swing on their moorings in non-biological subjects (his own training was one direction with the set of the tide.’ The series of chapters, which seemed to be in chemistry) and noted the difficulties under According to Sir Charles Lovatt Evans, Starling particularly good were those on sensation which those trained only in the biological dictated much of the first edition ofPrinciples But as sales dropped, Davson deplored the contributed by Mountcastle himself. His work sciences must labour. His honesty is of Human Physiology (PHP). Perhaps the text decision to drop the book and responded in on the organisation of the cerebral cortex in transparent. How many authors would thank might have been shortened, but as it stands, it style with a new book that he wrote with columns of neurones was well known of their employers, in his case the Medical links us immediately with Starling: brilliant, Malcolm Segal: An Introduction to Physiology. course and his expertise glowed in these Research Council, for having ‘...silently impatient and busy. Starling’s pupil Charles This ran to five volumes, the first two chapters. But not all the CNS chapters were acquiesced in the theft of so many hours, Lovatt Evans took over after Starling’s death providing an admirable introduction to the up to date, indeed several had not been devoted to this book, which might perhaps in 1927 and the book changed. More details, subject, the latter three providing more detail revised at all from the earlier edition of the have been better employed in original references and historical introductions to along the lines of PHP. Volume 3 is devoted to book. research…’? sections were added. Lovatt Evans wrote (not the control of the major systems. Davson’s edited) all the editions up to the 12th in 1956, preface, in which he distinguishes sharply ‘Mountcastle’ was the largest textbook of How did he write such a book? By spending and then handed over to Hugh Davson and between an Introduction and a Synopsis, is physiology available in the 1960s. It provided thousands and eventually tens of thousands Grace Eggleton who, as editors and contributors, worth reading. But even at five volumes the a detailed account of those aspects of of hours, reading and summarising the results produced two more – the last appearing in book remained incomplete and no further physiology useful to medical students and to of original papers in the library of the Royal 1968. Again, the book changed. No longer a editions have appeared. doctors. But it was long! It lacked the punch Society of Medicine. His approach was single author work, it now comprised a series of Ruch and Patton’s Physiology and straightforward: he read only original papers of eight ‘books’ or monographs, each Principles of Human Physiology was a great Biophysics and the 1980 edition was the last. (he deliberately eschewed reviews and contributed by an expert. It is the final, 14th reference book. In its time, there was hardly a Students no longer read such long books: the monographs); he collated the results and edition which is considered here. fact likely to be needed by a student of loss is theirs. sources onto filing cards and typed up his physiology that could not be found between findings in the evenings. He set out to read Even in 1968, PHP looked more like a its covers. It remains a splendid account of everything relevant to his subject and reference book than a textbook for students. classical physiology and contains valuable although he described his approach as E M Killick, in reviewing the 12th edition, information.

Physiology News / Winter 2014 / Issue 97 37 Membership Top tips for conferences • Look at the programme carefully in advance. Often there are interesting sessions on allied subjects that you may miss. If there is an interesting session or lecture maybe spend a short An affiliate’s view on networking and mentoring time in advance looking at some background to the area or the speaker • Ask questions - don’t leave it to the person next to you, do it yourself. I turn up at the registration desk for Physiology There’s no such thing as a silly Fiona Hatch 2012 in Edinburgh and I escape into my Networking in action at Physiology 2014 question, only the one that you didn’t delegation bag and mobile phone as a Types of mentoring ask, and therefore never got answered. University of Surrey, UK distraction from the disturbing truth – I do not • Do go and talk to the speaker Mentoring The mentor is typically know anyone. This is the same for many other afterwards. Ask about their work, talk senior and may or may not be within your affiliates year on year. Though two years on, about your work when relevant, but field but regardless, they will still have after diving into the society quiz night and an don’t turn it into a sales pitch. Explain the experience and support you require. awkward piano performance at ‘Physoc’s Got why you are interested in speaking to Ensure your expectations of a mentor are Talent’ on that very same first intimidating day them and how their insight might help realistic. Keep in mind what your aims of the conference, the thought, ‘I do not know you, or broaden your knowledge. anyone’ could not be further from the truth. are; in this way a mentor could help guide you through your chosen career path. • However shy you are, you have to Currently as Affiliate Representative to Council make yourself talk to people. At a of The Physiological Society and a member of Peer Mentoring You’ll gain different poster, in the lunch queue, at meal the Policy and Education and Outreach perspectives/experience from a peer times. Wherever you go and whatever Committees, I know both Physoc staff and along with it being less intimidating for you do, you will have to be able to countless members and affiliates. In this time I you to bring your problems to them, they speak to people with confidence. have presented seven scientific posters, given sometimes offer frank advice that a you off I’ve provided you some top tips, as Sue also recommends getting on Google and Generally most people, no matter how one oral presentation, won two poster prizes and senior mentor might not. Furthermore discussed and agreed upon by our panel of looking at hints and tips for ‘networking for senior, are pleased to spend a few played a role in the policymaking and physiology this is mutually beneficial to both parties mentors and mentees (see Box 2). people who hate to network’. So next time, minutes to speak with you about a education and outreach agendas. But this is not as its reciprocal nature allows one to be do not hesitate in approaching someone, particular area that you wish clarified about me blowing my own trumpet; instead I’m both mentor and mentee. On the outside, you would assume I’m an plaster a smile on your face, proffer a solid or explained. writing to explain as an affiliate that to start outgoing people’s person, willing to engage hand shake and introduce yourself – the first off with, everyone is in the same boat and it is and debate topics on a peer level with time is always the hardest. • If you’re at a meeting with your friends very daunting trying to keep that boat afloat. It is false to think that once you have acquired prominent scientists on a council of trustees – leave them and go find new people Fiona at the Registration Desk at said mentor (see Box 1), life suddenly and not be easily intimidated. But this is far Occasionally the link between networking and to talk to. Have in mind to make new Physiology 2014 As part of the Education and Outreach becomes easier. ‘Mentors are not knights on from the truth; this ‘personality’ is a skill that I mentoring is unclear. You do not require a colleagues and acquaintances – extend Committee I took upon myself (with the help white chargers, they are personal trainers who have developed over time, through all the shy lasso and a contract detailing your relationship your group. You never know who those of Keith Siew) to revamp the Mentoring show you the route, act as a guide, but you and awkward encounters, through the ‘out of with your mentor, ensuring they’re tied to you new people also might know. scheme and help integrate affiliates into The have to do the work’, said Lucy Donaldson. my league’ conversations and seemingly in every way possible. Although I have • Try not to drink too much – at the Society. The aim was to provide interested This is a similar ethos to networking; relying intimidating physiologists. Portraying previously been allocated a mentor, I have social events always be alert and ready affiliates with advice on how to get the most on others to introduce you to their contacts is self-confidence is a mask that many people been supported more by those around me to network. out of a conference and the benefits of the best and simplest route, but sometimes use, but after a while, it will be simple and that have not been rubber stamped as my having a mentor. The revamp consisted of this is just not possible, and in some cases you easy to put on; then before you know it, ‘mentor’. They are interviewers I’ve met after • Don’t start a conversation with a two parts; firstly the Early Career Social (ECS) have to just bite the bullet and throw yourself everyone will believe it’s your natural a failed post-doc interview, Physoc ‘what’s in it for me?’ mentality. Instead which at P14 was held in the Albert pub in into the crowd. Conferences are one of the personality and you’re a gifted networker. Committee Chairs who have listened to my of thinking someone can help you out, Westminster. With over 50 affiliate attendees best places to network, be it to find your next Furthermore I would like to debunk the problems and proffered wisdom and try reaching out with curiosity. it was a successful meet and greet social. collaboration, future employer or potential pedestal phenomenon where senior, principal encouragement, and fellow PhDs and Contact interesting people and see Secondly I organised the Networking and mentor. It is a mistake to believe that the investigators are unapproachable ‘god-like’ post-docs that have echoed my thoughts and where the relationship goes down the Mentoring workshop – a pilot workshop that I communication of your poster or oral physiologists. It is important to remember provided frank advice. This would not be line. hope to build upon in the future. This involved presentation is the only benefit; remember to they were once in the same situation as you; possible without networking: by removing my • Once you obtain an email address to a a panel of mentors – Sue Wray (University of take advantage of the social events and talk the majority of physiologists are amicable head from my delegate bag, putting my phone key contact, follow it up within a Liverpool), Chris Fry (University of Bristol), to new people. Contacts are always important people and many have egos regarding their own away and walking up to a fellow physiologist. fortnight of the meeting regarding Lucy Donaldson (University of Nottingham) for career progression through academia; work and would love to have an intellectual your discussion at the conference. and Jeremy Ward (King’s College London). All therefore attend as many presentations as discussion with you. To quote Sue Wray, ‘You But regardless of any achievements, I continue of them are successful physiologists, with possible, broaden your knowledge and push have to learn to force yourself to flick that to have the same problems as every other • Many physiologists know each other experience in being a mentee and a mentor, yourself to ask questions. Set yourself goals switch that turns you into Ms or Mr affiliate: where will my next job be? who has personally. This is useful when and were able to provide us with a lively for the conference, mark abstracts and talks Congeniality. Go into that room, smile and grants/funding? and the pressures, problems introducing yourself to a new senior discussion and overall top tips. Alongside the that are of key interest ahead of time and start a conversation. Usually the cringe- and writer’s block associated with papers. contact; sharing who you work with mentor panel, were two mentees, Keith Siew make a note of the people you may want to making horror subsides and you realise you Nevertheless, I am fortunate enough to have (now or previously) may be your (University of Cambridge), who is completing approach – a welcome reception or dinner are simply having a conversation and before mentor figures I can go to for advice and biggest opener. his PhD thesis currently, and me, coming to event is perfect for this. This becomes you know it, you could be enjoying it, not just support, and ultimately this is what helps me the end of my first post-doctorate position. significantly easier with practice, but to start surviving it.’ keep my boat afloat.

Physiology News / Winter 2014 / Issue 97 39 Membership So we have a context whereby we have in the easily gained through a focus on research). putative pedagogue. As a prime example, The recent past seen a massive expansion in Upon taking up my first academic position I Physiological Society itself offers not only the student numbers, a future where this expansion was quickly thrust into the development of a annual Otto Hutter Physiology Teaching Prize may further increase and a government intent new degree programme important for the (the exceptional recipient in 2013 being Dr on rebalancing the role of teaching relative to sustainable future of my School. It was Dave Lewis from the University of Leeds) but research in part by making student satisfaction necessary therefore for my immediate focus also the David Jordan Teaching Grants to one of universities’ key performance indicators. to be on the development and subsequent enable those who focus on learning and What mechanisms are there in place that administration of a coherent new learning teaching to undertake a pedagogical research might help lecturers to manage these complex programme. This, of course, severely project. Similarly, the HEA, in conjunction with and multi-faceted challenges? restricted my opportunities to develop a the Society of Biology, has offered the HE laboratory-based research programme in the Bioscience Teacher of the Year Award (of which Physiology to pedagogy Academics’ possible response crucial early years of my academic tenure. I am this year’s unworthy recipient!). There are equivalent prizes and awards offered by many Most universities now require new academics of the other STEM disciplines and all seek to to enrol on postgraduate certificate in elevate the role of learning and teaching in UK education-type courses. These tend to give universities. It has to be pointed out, however, laboratory-based courses will be the subject UK universities has not had the attention that rather generic instruction in the fundamentals that the research in this area is ambivalent on Nicholas Freestone of particular stresses and strains? The it deserves. Many of us currently teaching of learning and teaching and are received with the awarding of prizes as a driver of general University of Kingston, UK massification of the HE system invariably physiology were probably not formally varying degrees of enthusiasm by the improvements in teaching and subsequent means that time available for research is also qualified to teach when we entered academic participants. More recently many institutions quantifiable gains in student learning. severely constrained so we may have to life. In my case, my research experience of have aligned elements of their career concentrate on the learning and teaching and spending days alone in a darkened room progression criteria to the revised United Nevertheless, it is probably likely that given administrative aspects of our roles, whether staring at fluorescently labelled cardiac cells Kingdom Professional Standards Framework our current circumstances, universities will be we want to or not. down a microscope probably made me (UKPSF) launched by the Higher Education forced to more explicitly address the learning poorly suited to teach Introductory Academy (HEA) in 2011. This framework needs of their students. This would best be Up to the present, the state has allowed large Physiology to large cohorts of eager first year seeks to benchmark ‘success within HE Teaching in the laboratory done by rewarding academics’ engagement increases in the number of students feeding undergraduates. I am sure this is similar to the teaching and learning support’ (HEA, 2014). with their learners and the processes of through the university system with no experience of many other colleagues. The possibility of progression in the university learning. I believe, therefore, that it is corresponding increase in state funding to However, the lifting of the cap on student system by evidencing strengths in learning and However, despite the frustrations that this incumbent upon us academics to grapple with manage these greater numbers of students. numbers and the introduction of student fees teaching underpinned by the UKPSF has situation caused, it gradually dawned on me the pedagogical elements of our roles to This may be thought to be a serious detractor has been driven, in part, to elevate the role of encouraged many colleagues to seek Higher that all of the basic elements of a research ensure that, even in these uncertain times, of teaching quality. It has, however, at least learning and teaching at universities and to Education Academy (HEA) recognition linked area were readily available. I had become student learning is placed at the forefront of had the effect of drawing attention to the make student satisfaction with their to the various dimensions of the UKPSF. To aid increasingly interested, due to my prolonged our academic practice. pedagogical responses needed to cope with educational provision key determinants of colleagues in this process, all of the HEA and close contact with undergraduate the new stresses imposed upon the HE university performance measures. events in the coming academic year (15 in students, in how they learned and negotiated system. Since the Dearing Report (1997), total nationally) will be explicitly mapped to their way through their degree programmes. the professionalisation of university teaching In responding to this challenge the HE sector the UKPSF. Getting to know my learners as individuals has been a much cited aspiration in the UK has, so far, paid lip service to the concept of opened up a vast array of interesting personal References HE sector. the professionalisation of university teaching At different stages of one’s career, one can circumstances, experiences and learning styles (Cashmore et al. 2013). It is still undoubtedly apply to become an Associate Fellow, Fellow, that I found increasingly fascinating. How Cashmore A, Cane C & Cane R (2013). Rebalancing Receiving ‘Most Helpful Male Lecturer’ promotion in the HE sector: is teaching excellence ‘Effective teaching and learning is essential if true that career progression for colleagues Senior Fellow or Principal Fellow of the HEA. could I develop this interest in the process of award from the Kingston university being rewarded? http://www.heacademy.ac.uk/ pharmacy students’ association in 2012 we are to promote excellence and opportunity across the sector is more straightforward Whilst this scheme has been promoted by the learning into a fruitful area of research? assets/documents/resources/publications/HEA_ in higher education. High quality teaching must when it is concentrated on the research arm of HEA, many individual institutions are also now Reward_Publication_RebalancingPromotion.pdf be recognised and rewarded, and best practice their practice. Career progression for those able to award their own fellowships accredited Here, again I was very fortunate to, almost Background context shared’ (my italics). colleagues focusing on the learning and by the HEA. There is also the facility to obtain accidentally, come into contact with the Dearing R (1997). The Dearing Report: Higher teaching aspects of their practice is not so recognition online (by logging in to the Biosciences special interest group of the HEA. Education in the learning society http://www. For UK physiologists working as lecturers in The above quote was contained in the UK simple. Thus it remains the case that there are MyAcademy section of the HEA website) This provided a very supportive, collegial and educationengland.org.uk/documents/dearing1997/ universities, research in that discipline is Government’s 2003 White Paper The Future very few pedagogical professors in the STEM making the application process quicker and collaborative environment in which to gain dearing1997.html probably what defines them in terms of their of Higher Education. However, it is not readily subjects in UK universities and even fewer in easier. One would then be able to demonstrate exposure to, and experience of, the application Higher Education Quality Council (1994). Learning professional roles and expertise. However, we apparent that teaching in the university the discipline of physiology. Continuing Professional Development (CPD) of qualitative social science research methods from audit, cited in Gibbs G (1995). How can are living in changing times and along with sector has been rewarded in the way by participating in events, developing learning in pursuit of knowledge about the nature of promoting excellent teachers promote excellent being skilled at the practice of our discipline envisaged. More recently Willett’s report for This may be due to the fact that, as the Higher tools or undertaking pedagogical research. It learning in our UK HE context. I quickly came teaching? Innovations in Education and Teaching many of us must also transmit physiological the Social Market Foundation (Robbins Education Quality Council stated, ‘at least part may be the case in the future that, by to realise that such research was not so International 32, 74–81 knowledge and expertise to our students, who revisited: Bigger and Better Higher Education, of [the] problem might be that universities benchmarking one’s role against the UKPSF and dissimilar from our quantitative laboratory- will be the next generation of physiologists, as 2013) explicitly places the student in the had not adequately addressed the issue of HEA Fellowships, one may more easily based physiological research, i.e. find an White Paper (2003). The Future of Higher Education. well as to the public who need a better role of consumer of goods and services what makes up quality in teaching’. Therefore, delineate a career path characterised by an interesting research question, use the most www.educationengland.org.uk/documents/ understanding of physiology. Life as a provided by the HE system. All of the costs the reluctance of UK universities to promote emphasis on the pedagogy of physiology. appropriate method to investigate that pdfs/2003-white-paper-higher-ed.pdf physiology academic has shifted from one of a degree are now placed onto the academics through their teaching ability alone question, obtain data, analyse the data and Willetts D (2013). Robbins revisited: Bigger and rooted purely in the discipline to one which prospective student. In this context, may reside in the fact that objective criteria to My own story then disseminate it at conferences and/or in Better Higher Education. A report for the Social must engage with the pedagogical aspects of emphasis on high ‘quality’ teaching rather compare the ‘excellence’ of different papers (here The Physiological Society Market Foundation. http://www.smf.co.uk/ that discipline for the benefit of our student than discipline-specific research would seem academics’ teaching are absent. This fact My own career progression in a post-1992, deserves a special mention for continuing to wp-content/uploads/2013/10/Publication-Robbins- learners. This dispositional shift experienced to be even more of an imperative for UK contrasts markedly with the promotion path multi-faculty civic university which sponsor an Education and Teaching Theme at Revisited-Bigger-and-Better-Higher-Education- by many of us will only be accentuated in the universities. In particular Willetts wanted to for research-orientated academics where wholeheartedly endorses a Widening its annual Main Meeting). David-Willetts.pdf future as the cap on student numbers is lifted ‘strengthen the incentives to focus on objective criteria for progression are explicit, Participation ethos, has indeed been helped by the government in 2015. How is the teaching’ as he deemed that the pendulum transparent and adhered to (publication rather than hindered by a focus on the learning Apart from career progression and promotion physiology academic to respond to these had swung too far in favour of rewarding outputs, grants received, PhD completions, etc.). and teaching aspects of my role (this might be (which as pointed out previously are not pressures and drivers at a personal level as excellence in research (Willetts, 2013). This places the learning and teaching specialist expected given that it is not a research- necessarily rewards for engagement with well as at an institutional level where at a significant disadvantage for advancement intensive university but even here it has been pedagogy) there are many prizes awarded for increasing student numbers on expensive Even now, the role of learning and teaching in within the UK HE sector. the case in the past that promotion was more teaching excellence that may motivate the

Physiology News / Winter 2014 / Issue 97 41 Membership

ETRIS: facilitating research and training in in vivo physiology Do you know about the Benevolent Fund?

However, the use of animals for training is into 13 categories spanning the entire Who can apply? How much money is there? Dave Lewis contentious. They should only be used, if spectrum of resources required by practising Thelma Lovick absolutely necessary, and only during the final in vivo scientists including animal welfare and Anyone can apply but applications usually The Ben Fund is a very small charity, so School of Biomedical Sciences stages of training. For example, after the husbandry, ethics and the 3Rs, experimental Benevolent Fund Chair come from members of The Society who awards are relatively modest. In recent years University of Leeds, UK observation of similar studies, viewing or and statistical design, and surgical procedures. have identified a needy cause. This is not grants have ranged from £200 to £2000. utilising electronic resources, and practising ETRIS is free to use, and no log-in or necessarily another Society member; the only The beauty of the Fund is that we can the setting of experimental preparations registration is required. Individual resources criterion is that they have contributed to the respond very quickly. In an emergency, even The transposition of EU Directive 2010/63/EU using cadavers. Electronic resources are can be located using the search function or advancement of physiology in its broadest a relatively small sum can make a significant in UK law has introduced new training and increasingly being used in the early stages of clicking on a resource category. sense. So this might be another scientist or a difference to people’s lives. competency requirements for scientists this process to supplement hands-on member of their family, or a member of working under the Animals (Scientific experience. Whilst many excellent The plan is for ETRIS to be a living repository technical or domestic support staff in your Some examples of awards: Procedures) Act 1986. Both the Directive e-resources have been developed, significant of resources, which grows and expands over institution who contributes to the and the amended Act explicitly state that numbers are locked behind the websites of time. However, this will only happen with the advancement of physiology in an indirect Health and carer support including assistance staff must be ‘adequately educated and institutions, commercial or professional help of the community. Therefore if you have way. We rely on members to identify a towards specialist wheelchairs, home trained’ and ‘that they shall be supervised in organisations, only available to members or any e-learning or training resources, including, deserving case and alert us. adaptations, mobility equipment and respite the performance of their task until they have subscribers. Those that are freely available are but not restricted to, videos, podcasts, care (including welfare breaks). demonstrated the requisite competence’. often unknown to the community. guidance notes, software or educational The Benevolent Fund of The Physiological Who decides on awards? In addition to initial Home Office accredited protocols that you are willing to share or Society (the Ben Fund) is a charity within The Short-term financial assistance in the form modular training, there is now also a In response to this problem, ETRIS know of any relevant resources on open Society, which was established by Trust Deed There is a small committee of elected of grants and donations when you are facing requirement, throughout a researcher’s (Educational and Training Resources in in vivo access websites, please contact Dave Lewis at in 1976 ‘for the purpose of assisting trustees comprising the Chair, three Society exceptional financial difficulties including career, for them to receive continued Sciences, www.etris.leeds.ac.uk) was [email protected]. Resources do not have to Members of The Physiological Society (‘The members and two ex officio members (the funeral arrangements, medical treatment, on-the-job training, to participate in other developed. ETRIS is a website which provides fall within existing categories; resources in Society’) and staff and former staff (who by Society’s President and Treasurer). The grants for re-training and childcare continuous professional development direct links to free, open access, or open other areas not currently covered are also the nature of their employment can be committee meets formally once a year; in the arrangements. activities, and to have a reassessments of educational e-resources which deliver training required. Likewise, please use ETRIS; share the considered to have contributed to the past this has been immediately before the their competencies at regular intervals. or facilitate research in in vivo physiology and site with your colleagues, link to it from your advancement of physiology) employed at AGM, usually to coincide with the main What is excluded? ‘Training for the acquisition, maintenance or pharmacology. In addition to a direct web link institutional or company Biomedical Services teaching, research and industrial summer meeting. However, most business improvement of vocational skills’ is a to individual resources, each is accompanied or Home Office websites. Your feedback on establishments who are in necessitous throughout the year is conducted by email. We cannot fund applications for travel to permissible purpose under the amended Act by a descriptive paragraph which outlines the site or individual resources would also be circumstances and their dependants’. All applications are treated in confidence and meetings, student fees or stipends, seminars and therefore all researchers (not just what is in the resource, its provenance, appreciated. considered on a case-by-case basis. or meetings. This is outside the remit of the practising microvascular surgeons) can now copyright or access restrictions and What does this dry legal statement Trust and there simply isn’t enough money, use research animals in their training, as well suggested usage or audience. All resources ETRIS was developed through the award of a mean in real life? Who administers the Fund? however worthy the cause. as in the development and maintenance of are vetted to ensure compliance with the University of Leeds Teaching Fellowship to their technical competencies. Animals (Scientific Procedures) Act and best Dave Lewis. The support of the University for What it means is that there is a relatively The Ben Fund is a separate Trust from The practice in the 3Rs. Resources are grouped this project is gratefully acknowledged. small pot of money that can be called on to Physiological Society. However, it is help anyone associated with Physiology. The administered by The Society’s officers. Our beauty of the Fund is its simplicity and rapid expenses are therefore very low. Find further information about the Ben response. Fund and make a donation on the Fund’s website www.physoc.org/benfund Where does the money come from? How does the Fund work? The Fund relies from donations from Society The Ben Fund works within a formal members. Typically this is in the form of framework but in an informal rapid response one- off or regular donations. As we are a mode. There is no formal application form. charity you can Gift Aid your donation, which Applicants simply email one of the trustees or increases its value to the Fund by 25%, as we The Society’s office and make a case for can claim the tax back. A small amount of support. The request is then emailed to the money is also generated by events like raffles. trustees who confer, again usually by email. A Retired and Honorary Members of The Society, decision is normally reached within a few days. who no longer have to pay a membership fee, sometimes donate their subscription to the Fund, which is much appreciated.

43 Membership

Obituary:

Alex Livingston 1930 – 2014 The Journal of Physiology publishes important advances in our knowledge of physiology that increase our Physiology in 1962. He continued his course chapters. Alex’s passion was scientific to complete a veterinary medical degree, research for the benefit of animals, but he still B Vet Med, and MRCVS in 1964. He then managed to run a small farm with a herd of understanding of how our bodies function in health and disease. moved to Bristol to study for a PhD with Dr K Charolais–Hereford crossbreed cows. Lederis in CNS pharmacology, which he completed in 1968. His later research focused In his younger days Alex was a keen rock Reasons to publish in The Journal of Physiology: on the action of chemical messengers in the climber, exploring cliffs throughout the UK brain areas involved in pain perception and but particularly active on the limestone of how drugs that can alter these actions affect Clifton and Cheddar Gorge as well as the sea The most highly cited Physiology journal the way animals respond to pain. His concern cliffs of Cornwall. (>47,000 total cites per year) for the welfare of animals made him aware of how little was understood about an animal’s Alex will be remembered forever for his sense behaviour associated with pain, which he felt of humour, his love for his family and for his Sustained excellence: Authors include 37 was different to humans. animals. He was a great story teller. He took Nobel Prize winners in Physiology or Medicine great pride in his family and all the students Alex became lecturer, then senior lecturer he taught and mentored over the years. His and 5 Nobel Prize winners in Chemistry and then in 1991 acting head of Pharmacology later years were spent continuing his Alex Livingston BSc BVetMed PhD FRCVS Dip in Bristol. In 1992 he moved to Canada to academic research, attending auctions and World-class Editorial Board, including three ECVPT, a prominent figure in veterinary take up the position of Dean at the Western acquiring antiques. He is survived by his wife medicine and science, died of a heart attack College of Veterinary Medicine at the of 38 years, Sue, and sons Alex, Andy, Ian, Nobel Prize winners after a short illness in June 2014, 10 days University of Saskatchewan making an daughter Kate, and grandchildren Ellie, short of his 74th birthday. important contribution to training of students Stephanie and Adam. No page or submission charges in veterinary medicine and to their position in Alex was recognised for his leadership and Canadian society. He retired from the No page or figure limits research advances in the areas of animal pain, deanship in 2002 and took up a faculty John H Coote animal welfare and pharmacology of analgesics. position until finally retiring in 2007. He had a Compliant with open access mandates including He was awarded the Merial Grand Prize for distinguished career becoming a Fellow of the Professor Emeritus Outstanding Research in Animal Pain in 2001. Royal College of Veterinary Surgeons (FRCVS) School of Clinical and Experimental NIH and RCUK in 1993 and Diplomat of the European Medicine Two reviewer reports and first decision in Alex grew up in Luton during the Second College of Veterinary Pharmacology and University of Birmingham, UK World War. Here he spent much time with his Toxicology in 1999. Throughout his deanship <4 weeks Granddad who had a collection of shacks Alex was still involved with graduate research, where he kept ferrets, dogs, chickens and teaching and mentoring of clinical residents. Immediate ‘In Press’ publication upon acceptance other animals until he sold them. This Alex was also active in the scientific experience no doubt led Alex to a love of community as board member on the Canadian Articles published ahead of issue publication in animals and a desire to study veterinary Council for Animal Care and Editor-in-Chief medicine at university. for Research in Veterinary Science. During his <6 weeks career he supervised 15 PhD students and He gained a place at the Royal College of contributed to scientific knowledge with over Every issue made free after 12 months Veterinary Medicine in the University of 100 publications in internationally recognized London, where he intercalated a BSc in peer-reviewed journals, and over 20 book Over 5.7 million full-text downloads in 2013 2013 Impact Factor®: 4.544 Ranks in the top ten of all citation metrics in the physiology category

Notices and full obituaries can be found on The Society website at www.physoc.org/obituary-notices

jp.physoc.org 14-68160 / MITM026189

Physiology News / Winter 2014 / Issue 97 Journal updates

We usually expect to be asked about submission requirements, policies, cost and speed of publication, but the audience here were Experimental far more interested in reading our content. This is probably because many of the delegates were clinicians who need to keep up-to-date with advances in cardiovascular research, but are Physiology unlikely to look to us as a potential publishing option. Despite this, we are looking forward to building up a relationship with this new David Paterson made community of readers in the coming years. Connections Have you got an ORCID ID?

Honorary Fellow of RSNZ Experimental Physiology has been making Connections by An ORCID ID provides you with a persistent digital identifier that identifying a sequence of three related articles (each one citing the distinguishes you from every other researcher and, through The Journal at Neuroscience 2014 next). The author of the middle article outlines their article’s integration in key research workflows such as manuscript and principal novel findings and traces how they were influenced by the grant submission, supports automated linkages between you and As ever, The Journal of Physiology had a stand at the Society for previous article and how they have contributed to the following your professional activities, ensuring that your work is recognised. Neuroscience’s annual meeting, this year held in Washington, DC. It article. The author speculates on where that might lead in future was another great opportunity to engage with our growing pool of research and places the article in a wider context in a style that Authors can now provide their ORCID IDs with their submissions to neuroscience authors. The Journal of Physiology compiled a makes the subject accessible to a broader readership. The Society’s (and many other) journals and although this is not Neuroscience virtual issue, which featured recently published, compulsory, we would encourage you to do so. ORCID is an open, high-quality research papers and review articles. The selected papers You can find more information at http://ep.physoc.org/cgi/ non-profit, community-based effort to provide a registry of demonstrated the broad scope of our neuroscience content, ranging collection/connections unique researcher identifiers and a transparent method of linking from research at a cellular and molecular level, to cognitive and research activities and outputs to these identifiers. For more behavioural work, as well as studies on the neurobiology of disease. information or to register for an ID go to http://orcid.org/about New EP Editor

New Editors for The Journal Professor L Ashley Blackshaw from Queen Mary Editor-in-Chief David Paterson and Production Manager from January 2015 University of London joins EP as a new editor. Jonathan Goodchild, at the ESC Congress. His research focuses on gastrointestinal sensory We are very pleased to announce that the following people will be mechanisms in a range of disease indications joining the Editorial Board as Reviewing Editors in January 2015: Physiological Reports We are delighted to announce that Professor David Paterson, including pain, obesity and reflux disease. Editor-in-Chief of The Journal of Physiology, has been elected as an • David J Adams (RMIT University, Australia) – neuroscience and Honorary Fellow of the Royal Society of New Zealand (RSNZ). membrane physiology. • Greg Funk (University of Alberta, Canada) and Frank L. Powell GL Brown Lecture 2014 (UCSD, USA) – respiration. The Journal at the ESC Congress • Anne McArdle (University of Liverpool, UK), Troy Hornberger The 2014 GL Brown Lecture by David Eisner Calcium in the heart: (University of Wisconsin – Madison, USA) and Bettina from physiology to disease has been published (October issue) Barcelona, host to this year’s European Society of Cardiology Mittendorfer (Washington University in St Louis, USA) - exercise and is also available on Youtube: https://www.youtube.com/ Congress, greeted us with warm sunshine and a variety of exciting physiology and muscle. watch?v=VXSJkq5Dk8o comestibles. Despite the laid back ‘mañana’ attitude that we often associate with the Spanish, the meeting at Fira Gran Via was well organised and went very smoothly.

In 2013, we attended the AHA Scientific Sessions meeting, but this year we chose to target the ESC meeting as we felt that the programme was more suited to our focus on basic research. LET OUR NEW VITAMIN D ASSAY BE YOUR This was the first time in recent years that we had attended a major international meeting in Europe and the demographic of the attendees was strikingly different to that of the US meetings that usually form our conference schedule. There were very Virtual Issues few people from North America, but many from South America, Eastern Europe and Asia. Of the 300 or so people that we spoke To coincide with Obesity: A Physiological Perspective, held in to, over 75 countries were represented – a pretty impressive Newcastle on 10–12 September, Physiological Reports produced a statistic! 1 2 3 4 5 virtual issue entitled New Insights in Energy: Homeostasis, Fat and Obesity. Associate Editors Julian Davis and Gareth Leng Although aware that we were targeting a new audience, we were selected articles on this subject published in the last year. There still surprised that many people had not heard of The Journal of was another virtual issue to coincide with the annual meeting of Physiology. We were therefore pleased to be able to educate them the Society for Neuroscience in November, with articles selected on the long and interesting history of The Journal and The Society, Add sample Incubate Wash Read Results by Gareth Leng. These displayed the range of Neuroscience topics and highlight some of the key papers in the field of cardiovascular that Physiological Reports has attracted, and also reflected those physiology that had been published in The Journal. We had virtual aspects that give the journal a distinctive identity and rationale, issues highlighting both classic and new cardiovascular papers and namely negative findings, the application of computational historical information listing our Nobel Prize-winning authors and modelling, and making maximally accessible original data of seminal works. The 2013 special issue dedicated to arrhythmia Randox Laboratories Limited, 55 Diamond Road, Crumlin, County Antrim, BT29 4QY, United Kingdom potential secondary use. was also promoted and was very well-received. T +44 (0) 28 9442 2413 F +44 (0) 28 9445 2912 E [email protected] I www.randox.com

AV1557 - Research Ad - Physiology(2).indd 1 25/07/2014 14:51

Physiology News / Winter 2014 / Issue 97 47 Ageing & Degeneration: A Physiological Perspective

10-12 April 2015 Royal College of Physicians Edinburgh, UK

www.physoc.org/ageingtopic 2015: Understanding Ageing