Author Archives: The Physiological Society

About The Physiological Society

The Physiological Society brings together over 3,500 scientists from over 60 countries. Since its foundation in 1876, its Members have made significant contributions to our knowledge of biological systems and the treatment of disease. We promote physiology and support those working in the field by organising world-class scientific meetings, offering grants for research, collaboration and international travel, and by publishing the latest developments in our leading scientific journals, The Journal of Physiology, Experimental Physiology and Physiological Reports.

Supporting breathing in muscular dystrophy

By David P Burns and Ken D O’Halloran, Department of Physiology, University College Cork, Ireland

The respiratory system plays a very important role in maintaining oxygen levels within our blood. The supply of oxygen to our body is necessary to allow the cells in our body to make and use energy (a process called metabolism).

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Respiratory muscle from mdx mice displays signs of muscle damage. When dystrophin is absent from muscle, muscle fibres become damaged during normal cycles of muscle contraction and relaxation. Over time, damaged muscle becomes replaced by fat cells and there is an accumulation of connective tissue resulting in further muscle weakness and hardening of the tissue.

The respiratory system is an integrated organ system that relies on input from our central nervous system (brain and spinal cord). Motor nerves project from our central nervous system and send electrical signals, called action potentials, to our respiratory muscles. These signals activate our respiratory muscles, including the diaphragm (the main pump muscle of breathing) and intercostal muscles, resulting in contraction of these important muscles. The diaphragm and external intercostal muscles contract during inspiration, allowing a negative pressure to be generated within the respiratory system. This negative inspiratory pressure draws air from the atmosphere into our lungs. In our lungs, oxygen that has entered from the atmosphere enters our blood and is transported around our body to our cells. The same system is crucial for the excretion of carbon dioxide, a by-product of cellular metabolism, during expiration.

Poor performance or weakness of our respiratory muscles can result in impaired respiratory function, limiting how much air enters and leaves our lungs. Respiratory muscle weakness can occur due to a loss of muscle mass, such as in cancer cachexia and age-related sarcopenia.

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Recording of the electrical activity of diaphragm muscle (electromyogram) in an anaesthetised mouse.

Breathing with neuromuscular disease

Researchers at University College Cork in Ireland are focusing on respiratory muscles and how they are controlled by the central nervous system in neuromuscular diseases such as muscular dystrophy. Duchenne muscular dystrophy (DMD) is a genetic disease that causes severe muscle weakness in boys. The diaphragm has reduced strength in DMD due to the absence of an important structural protein found in muscle, called dystrophin. As boys with DMD grow older they have difficulty with their breathing. Initially, this occurs during sleep with the development of sleep-disordered breathing and later problems also present during wakefulness.

Studies led by researchers David Burns and Ken O’Halloran aim to understand the effects of a weakened diaphragm (due to a lack of dystrophin) on respiratory system performance in animal models of muscular dystrophy. Currently, the group is trying to understand ways in which the body can compensate for a mechanically weakened diaphragm muscle, with the aim of enhancing or at least protecting these compensatory mechanisms that support normal breathing.

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Healthy diaphragm muscle is composed of a blend of different types of muscle fibres (shown above as blue, red, black and green muscle fibres). Each muscle fibre type has its own unique characteristics. The blue muscle fibres (Type I) can generate small amounts of force when they contract and are resistant to fatigue. The green fibres (Type IIB) can generate large forces such as those required during coughing or clearing of our airways. Type IIB are not resistant to fatigue. Top left traces show diaphragm electromyogram activity. Bottom right shows diaphragm muscle contractions in response to increasing stimulation frequency.

New research published by the group in The Journal of Physiology (1) has revealed that the capacity of the respiratory system to increase breathing when challenged is preserved in an animal model of muscular dystrophy, the mdx mouse. This is an interesting finding given the diaphragm muscle of mdx mice can generate only half the force of a non-diseased diaphragm.

Compensation to support breathing

To understand how mdx mice can breathe at levels similar to the control group of mice, the group measured the inspiratory pressure generated by the system during normal and near maximal breathing. In order to examine how the central nervous system controls weakened respiratory muscles, the group measured the electrical signals in the diaphragm and intercostal muscles (which were sent along motor nerves from the central nervous system). These unique studies have revealed that although the diaphragm muscle of mdx mice is weakened and displays less electrical activity than the control group of mice, the mdx mice can generate inspiratory pressures similar to control mice. These novel findings reveal a form of compensation that supports breathing in young mdx mice.

Retaining the capacity to generate peak inspiratory pressure during the course of aging and in disease states such as DMD is essential during periods of increased demand on our respiratory systems. Current studies by Burns and O’Halloran aim to understand the specific mechanisms responsible for this compensatory support in young mdx mice and to determine if this compensation is preserved or lost over the course of this progressive disease. Therapeutic and rehabilitative strategies that promote compensatory support of breathing in muscular dystrophy may provide support for maintaining respiratory function in patients as the disease progresses.

References:

  1. Burns DP, Murphy KH, Lucking EF, O’Halloran KD (2019) Inspiratory pressure-generating capacity is preserved during ventilator and non-ventilatory behaviours in young dystrophic mdx mice despite profound diaphragm muscle weakness. The Journal of Physiology 597(3):831-848.

Treating autism spectrum disorders by targeting connections in the brain

By David A. Menassa, @DavidMenassa1, University of Southampton, Neuroscience Theme Lead of The Physiological Society

The United Kingdom has seen a rise in the number of people diagnosed with autism spectrum disorders (ASDs). More recently, some trusts in Northern Ireland have reported a three-fold increase in diagnoses since 2011. Some cases of ASD are linked to a genetic mutation but most of the time, we do not actually know why they occur.

ASD is an umbrella term for disorders characterised by impairments in social interaction and language acquisition, sensory and motor problems and stereotypical behaviours of variable severity according to the Diagnostic and Statistical Manual of Mental Disorders.

Multiple studies report that the physiology and structure of synapses (the gaps between our neurons) are affected in ASDs (1, 2) and that addressing these changes could offer clues for therapy.

The genetic mutations giving rise to different ASDs are predominantly involved in synaptic function. A large-scale analysis of 2000 human brains from individuals with ASDs, schizophrenia and bipolar disorder showed that genes involved in controlling the release of neurotransmitters into the synapse are least active in ASDs (3, 4).

An attempt using the CRISPR/Cas9 gene editing method in a genetic form of ASD known as Fragile-X syndrome (FXS) showed some promise (5). When the researchers turned on a gene that is turned off in this condition, this changed the cells derived from affected individuals from diseased to normal.

Because the number of synapses in ASD post-mortem brains is altered (1), microglia (the brain’s resident immune cells) are thought to be directly involved (as these cells can determine whether synapses stick around) (6-8). Minocycline, which inhibits these microglia, has been used in trials on FXS individuals with promising outcomes including improvements in language, attention and focus as well as an alleviation of core symptoms (9, 10). Furthermore, novel approaches involving inducing microglia to self-destruct (11) or shielding synapses from microglia (12) are being explored. At least in terms of symptom alleviation, addressing synaptic dysfunction and microglia seem to be promising avenues for treatment.

Environmental factors such as changes during pregnancy could contribute to ASD such as the transfer of maternal antibodies against fetal synapses (13) or maternal immune activation (14) or lack of oxygen to the mum or the baby (15). Ways to reduce the risk of injury to the brain with low oxygen in the mum for example have involved delivering antioxidants to the placenta (16). Furthermore, in the early life of the newborn when low oxygen is detected, inhalation of xenon gas combined with cooling also seem to provide promising results that improve neurological outcome (17).

The impact of altered brain development extends beyond the individual influencing their family, carers and the healthcare system. More funding is needed to support this research in order to elucidate the underlying physiology and identify effective treatments.

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This figure illustrates how connections can occur in the ASD brain. Neurons in various colours (black, green and blue) make connections with each other through synapses and some connections are interrupted. Microglia (pink) are near the synapses which we can see in the highlighted squares: in a) a part of the neuron called a dendrite with very few dots on it means there are less synapses than in b) where there are more black dots on the dendrite which means more synapses. These changes represent what we tend to see in post-mortem brain tissue in ASD. Microglia are thought to be involved here by either not clearing away black dots in which case we get more synapses (e.g. typical autism) or by overclearing in which case we have less synapses (e.g. Rett’s syndrome). ASD is otherwise known as a disorder of how connections are established in the brain or a connectivity disorder.

References

  1. Penzes P, Cahill ME, Jones KA, Van Leeuwen JE, Woolfrey KM. Dendritic spine pathology in neuropsychiatric disorders. Nat Neurosci. 2011;14(3):285-93.
  2. Lima Caldeira G, Peça J, Carvalho AL. New insights on synaptic dysfunction in neuropsychiatric disorders. Curr Opin Neurobiol. 2019;57:62-70.
  3. Zhu Y, Sousa AMM, Gao T, Skarica M, Li M, Santpere G, et al. Spatiotemporal transcriptomic divergence across human and macaque brain development. Science. 2018;362(6420).
  4. Gandal MJ, Zhang P, Hadjimichael E, Walker RL, Chen C, Liu S, et al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science. 2018;362(6420).
  5. Liu XS, Wu H, Krzisch M, Wu X, Graef J, Muffat J, et al. Rescue of Fragile X Syndrome Neurons by DNA Methylation Editing of the FMR1 Gene. Cell. 2018;172(5):979-92.e6.
  6. Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron. 2012;74(4):691-705.
  7. Schafer DP, Heller CT, Gunner G, Heller M, Gordon C, Hammond T, et al. Microglia contribute to circuit defects in Mecp2 null mice independent of microglia-specific loss of Mecp2 expression. Elife. 2016;5.
  8. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, et al. Synaptic pruning by microglia is necessary for normal brain development. Science. 2011;333(6048):1456-8.
  9. Utari A, Chonchaiya W, Rivera SM, Schneider A, Hagerman RJ, Faradz SM, et al. Side effects of minocycline treatment in patients with fragile X syndrome and exploration of outcome measures. Am J Intellect Dev Disabil. 2010;115(5):433-43.
  10. Paribello C, Tao L, Folino A, Berry-Kravis E, Tranfaglia M, Ethell IM, et al. Open-label add-on treatment trial of minocycline in fragile X syndrome. BMC Neurol. 2010;10:91.
  11. Kim HJ, Cho MH, Shim WH, Kim JK, Jeon EY, Kim DH, et al. Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects. Mol Psychiatry. 2017;22(11):1576-84.
  12. Lehrman EK, Wilton DK, Litvina EY, Welsh CA, Chang ST, Frouin A, et al. CD47 Protects Synapses from Excess Microglia-Mediated Pruning during Development. Neuron. 2018;100(1):120-34.e6.
  13. Coutinho E, Menassa DA, Jacobson L, West SJ, Domingos J, Moloney TC, et al. Persistent microglial activation and synaptic loss with behavioral abnormalities in mouse offspring exposed to CASPR2-antibodies in utero. Acta Neuropathol. 2017;134(4):567-83.
  14. Careaga M, Murai T, Bauman MD. Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates. Biol Psychiatry. 2017;81(5):391-401.
  15. Kolevzon A, Gross R, Reichenberg A. Prenatal and perinatal risk factors for autism: a review and integration of findings. Arch Pediatr Adolesc Med. 2007;161(4):326-33.
  16. Phillips TJ, Scott H, Menassa DA, Bignell AL, Sood A, Morton JS, et al. Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development. Sci Rep. 2017;7(1):9079.
  17. Mayor S. Xenon shows promise to prevent brain injury from lack of oxygen in newborns. BMJ. 2010;340:c2005.

Physiology 2019: Something for everyone

By Guy Bewick, University of Aberdeen, UK, Member of local organising committee

Whatever your interest in physiology, be it in research of systems (cardiovascular, respiratory, musculoskeletal, neural, etc.), tissues (epithelia, adipose etc.) or nuclear receptors, or be it in teaching, we have it covered at Physiology 2019, our Annual Conference, in Aberdeen. If the Annual Conference does not quench your thirst for knowledge, why not extend your stay in Scotland’s north-east to attend one of the five Satellite Symposia covering fatigue, obesity, cancer drug cardiotoxicity, and renal and placental physiology.

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The Annual Prize Lecture by Silvia Arber (Basel Biozentrum, Switzerland) will describe her elegant work elucidating the function, assembly and plasticity of motor circuits. The Hodgkin-Huxley-Katz Lecture by Stephen Traynelis (Emory University, Georgia, USA) reveals the characteristics of neuronal glutamate receptors in health and disease. In the Joan Mott Prize Lecture, Claire Hills (University of Lincoln, UK) presents important discoveries in diabetic nephropathy and kidney disease mechanisms. And, finally, the Sharpey-Schafer Lecture by endocrinologist Roger Smith (University of Newcastle, Australia), a leading expert on pathophysiology of human pregnancy, will expound on the idiosyncrasies, interactions and inner workings of the body across species but especially in humans.

A particular teaching highlight will be Dee Silverthorn, whose textbook is a staple of many physiology degree programmes, who will provide insights into best teaching practice from an international perspective.

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Aberdeen’s local representation is by Lora Heisler, recent winner of the Outstanding Scientific Achievement Award from the American Diabetes Association. She will present the Annual Public Lecture describing her work on the neural control of appetite, looking for new targets to tackle the current global epidemic of obesity.

So, please come and join these world-class speakers from across the globe and all stages of their careers who are coming to sample the renowned Scottish hospitality. We look forward to welcoming you to Aberdeen for a memorable summer scientific conference.

Attend our specialist Satellite Symposia, free to Physiology 2019 attendees

Our Satellite Symposia increase the involvement of underrepresented sub-disciplines of physiology at our flagship Annual Conference, Physiology 2019. This year, join us for one of the following five Satellite Symposia. Free to Physiology 2019 attendees, they are all held on Sunday, 7 July 2019. Keep reading for more detail about each meeting, and don’t forget to sign up when registering for Physiology 2019 on our website:
physoc.org/physiology2019/satellite-symposia

Cellular Mechanisms of Anticancer-Induced Cardiotoxicity
Organisers: Susan Currie & Margaret Cunningham from the University of Strathclyde, UK

Cardiovascular disease and cancer are the leading causes of death in the industrialised world. Anti-cancer therapies have dramatically improved over recent years with increased patient survival rates following diagnosis. Kinase inhibitors in particular have had a major impact on cancer patient survival. However, a number of these agents have been reported to cause serious adverse effects on cardiac function, leading to increased numbers of cancer patients with cardiovascular complications that can, in some cases, lead to death. The true extent of the overall risk to cancer patients is unknown, and the underlying mechanism(s) responsible for the cardiotoxic effects remain to be fully identified.

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Strategies to prevent or mitigate cardiotoxicity resulting from cancer treatment are urgently needed to ensure the best cancer care possible. Future management of anticancer-drug-related cardiotoxicity will rely on improved understanding of the cellular effects of these agents in the heart. This, combined with improved biomarker identification along with cardiac imaging for monitoring purposes, will be crucial in an overarching strategy to design effective targeted cardioprotective agents. This symposium will be a forum to bring together basic scientists, cardiologists and oncologists to present recent findings that will work towards this overall goal. Ultimately, collaboration across these disciplines will be essential for promotion of evidence-based research that can relate to clinical practice in the area of anticancer cardiotoxicity.

Fatigue as a Limitation to Performance
Organisers: Derek Ball, University of Aberdeen, UK, and Ron Maughan, University of St Andrews, UK

The complex nature of fatigue is a function of single or multiple mechanisms that result in the failure to produce or maintain the required or expected muscle force/power output. Models to explain the underlying causes of fatigue range from single cell, to organ, to whole body examples and bring together the many different aspects of physiology represented through The Physiological Society.

This symposium will discuss potential limitations to performance imposed by the cardiovascular and respiratory systems, muscle metabolism and the central nervous system and how these factors are modulated by training, environment and nutritional status. In addition, a discussion of the strategies aimed at offsetting fatigue from the perspective of training adaptation and nutritional and pharmacological intervention will be invaluable.

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Physiology of Obesity and Diabetes
Organisers: Lora Heisler, University of Aberdeen, UK, Peter Aldiss, University of Nottingham, UK, Daniel Brayson, King’s College London, UK, and Jo Lewis, University of Cambridge, UK

Obesity is an increasingly common disorder of energy homeostasis and has become a leading cause of type 2 diabetes, cardiovascular disease, human morbidity and mortality worldwide. Exciting new scientific discovery continues to propel the understanding of the molecular, cellular and neural mechanisms underlying the control of metabolic health. Dysregulation of these and other processes underpin the development and progression of obesity, type 2 diabetes and cardiovascular disease.

This symposium will bring together breaking research advances from the basic science and clinical realms with the objective of sharing novel insights relevant to human obesity, type 2 diabetes and cardiovascular disease. Specifically, the meeting seeks to integrate existing knowledge with novel discoveries on appetite, cognitive drivers of feeding behaviour, the gut-brain axis, the neurobiology of ingestive behaviour and energy expenditure, adipogenesis and lipolysis, glucose sensing and glycaemic control, cardiovascular disease and the genetics of obesity and type 2 diabetes. Several new areas will also be addressed, including state-of-art technologies for neuroscience and physiological research, ageing, anorexia and metabolic resilience.

The primary goal of this meeting is to provide cutting-edge research related to the control of body weight and glucose homeostasis. The maintenance of stable body weight involves the biological process energy homeostasis that matches cumulative energy intake to expenditure. The discovery of critical integrative systems that underpin energy homeostasis and glucose metabolism has important implications for the future of obesity and type 2 diabetes treatment. This symposium will highlight the latest advances in the cellular and molecular mechanisms whereby brain circuits modulating physiological appetite and the cognition of food intake are integrated with systems controlling gut function and insulin sensitivity. We will explore the cross-regulation of these circuits by adiposity- and nutrient-related signals.

Renal Physiology: Recent Advances and Emerging Concepts
Organisers: Morag K Mansley and Robert W Hunter from the University of Edinburgh, UK

Renal physiology is flourishing in the UK and beyond. In recent years, physiologists have made fundamental advances: we now know the molecular basis of oedema formation in nephrotic syndrome, how renal sodium and potassium excretion can be controlled independently and how glomerular capillary permeability is regulated. We are also learning much about the influence of the kidney on whole-organism physiology, in particular blood pressure homeostasis including advances in understanding the (renal) mechanism underpinning circadian control of blood pressure.

These recent advances have not only allowed us to better understand renal physiology, but have opened up an array of potential targets for novel therapies in a range of kidney diseases and fluid-electrolyte disorders. The clinical impact of renal physiology research has been demonstrated recently where Vallon and colleagues published a series of papers showing that sodium-glucose co-transporter inhibitors (SGLT2i) can attenuate glomerular hyperfiltration in diabetic rodent models. In 2017-2018, large-scale clinical trials demonstrated that these agents can delay progression of diabetic nephropathy, meaning that – in large part because of basic renal physiology research – we now have the first new effective treatment for this common condition in 15 years. This symposium aims to bring together scientists from across the UK and beyond to discuss the latest advances in renal physiology.

The Placenta and Maternal Metabolic Regulation in Health and Disease
Organisers: Luis Sobrevia, Universidad Católica de Chile, Chile, Raheela Khan, University of Nottingham, UK and Abigail Fowden, University of Cambridge, UK

During pregnancy, many physiological changes occur in the mother, which are designed to support fetal growth and to sustain the baby during lactation. These include changes in the cardiovascular, pulmonary, immune and metabolic systems. A failure to appropriately adapt maternal physiology can lead to pregnancy complications, including abnormal birth weight, pre-eclampsia, and gestational diabetes, which can be traced to poor placental development in early pregnancy. The placenta is the place for bidirectional materno-fetal crosstalk involving transfer of metabolic substrates and epigenetic regulation, about which little is known. Amino acids, lipids, glucose and other substrates such as nucleosides and nucleotides are vital for fetal growth and maturation. However, our understanding of the physiological and pathophysiological aspects of placenta transport mechanisms and the potential consequences for fetal physiology in diseases of pregnancy is still fragile.

The overall goal of this Satellite Symposium is to explore the nature and wider biological significance of placental endocrine function in adapting maternal physiology during pregnancy to support fetal growth in both normal and compromised environments. Discussions will cover insights into regulatory epigenetic mechanisms within the placenta, placental structure and vascular/trophoblast function, contribution of the placenta to disease, placental transfer of nutrients and possible translation to the clinic, and potential consequences of human placenta pathophysiological transfer of nutrients for fetus and newborn health.

Blended learning in physiology – merging new technologies with traditional approaches

By Louise Robson, @LouisescicommDepartment of Biomedical Science, University of Sheffield, United Kingdom

Learning and teaching in physiology has undergone something of a revolution over the last 30 years, and as someone who had their very first teaching experience back in 1989 (running tutorials as a PhD student) I speak from experience! One of the biggest changes has been around digital technologies, bringing benefits and challenges to both students and staff. However, while there are challenges (e.g. information overload), for me the benefits far outweigh any challenges digital technologies generate.

I teach ion channel physiology, and aim for students to not only understand the ideas and concepts in this area, but also be able to apply these to novel experimental data. For this reason, I use data handling and interpretation exercises in my modules, i.e. students utilise mathematical approaches, interpret their data and draw on data from other sources. One thing that certainly hasn’t changed is that students struggle with mathematics, and I suspect I am not the only academic to observe a sea of white faces when I have equations on my slides!  However, my modules are very popular, despite the complex mathematics. The reason for this is my blended learning approach to teaching, matching traditional teaching with digital technologies.

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Figure 1:  Top tips for students on using lecture capture. Click here for more details: https://osf.io/edmzf/ (E, Nordmann et al, 2018).

In this approach, recorded lectures introduce calculations underpinning physiological mechanisms,  so that students can revisit to help their understanding. I have been using lecture capture for several years, and my experience is that it enhances learning. I have observed an increase in academic performance in my final year modules, and the types of questions students ask are more insightful. They utilise the captures to get to grips with the lecture content and their higher level questions are then often about the published literature. Of course if you are providing captures it is really important that students understand how to use these. Work by a cross-institutional group of academics, of which I am a member, has recently provided top tips for students and staff on using lecture capture, also presenting these in a student-friendly infographic format, Figure 1 (E, Nordmann et al 2018). his work highlights an important but often forgotten aspect of learning and teaching, share your ideas and experiences and collaborate with others.  

The best way to learn is to do, and my students complete formative data handling workbooks that reinforce lectures and provide additional guidance. This allows students to develop skills in a low risk environment, and feed-forward and improve for the assessments. Problem solving classes require students to apply their knowledge and skills, providing an opportunity for personal feedback. I also provide dynamic maths videos for them to view. Using a variety of approaches allows students to work in the way they find most beneficial (one size does not fit all in education). The final module session tests knowledge and understanding using the interactive Lecture Tools platform, allowing students to test knowledge and understanding. This blended approach provides an enhanced learning experience for the students, and is clearly appreciated by them, as they have voted me best Biomedical Science Lecturer at Sheffield several years in a row.  

Many of you reading this article may be in the early years of your academic careers, and while there is lots of advice on developing your research profile, there is often less structured support on developing learning and teaching. So here are my top tips:

  1. Get experience early on.  I started as a PhD student and continued to gain experience as a postdoctoral researcher.  
  2. Seek advice from experienced individuals.
  3. Identify the key developments in learning and teaching, and give them a go.
  4. Evaluate what you do.  Some things will work (but not everything).  Don’t forget ethical approval if you want to publish.
  5. Document innovation as you go.  In research, outputs are easy to define.  In learning and teaching, it’s not so easy!
  6. Always think about what is best for your students (note, it’s not always what they want).
  7. Share your ideas and collaborate as much as possible.  

I hope you have found this article useful, and that you have been able to identify some ideas for your learning and teaching development (if you want more information, just ask)!    

References

E, Nordmann, CE, Kuepper-Tetzel, L, Robson, S, Phillipson, GI, Lipan, P, McGeorge (2018). Lecture capture: Practical recommendations for students and lecturers (pre-publication): 10.31234/osf.io/sd7u4

Learning a research career is within my reach: Undergraduate Summer Studentship Scheme

By Sara Rayhan, University of Southampton

I received a Summer Studentship in 2017 for a project at the University of Southampton, under the supervision of Felino Cagampang. My project examined the effects of maternal obesity in pregnancy on the placenta, an organ that supplies the foetus with oxygen and nutrients, in mice. More specifically, we measured placental expression of two growth-related genes in obese pregnant mice. One gene is responsible for blood vessel formation (VGEF) and the other (RAPTOR) for the response to nutrient and insulin levels.

Both have been linked to cardiovascular disease. We also examined the effect of maternal metformin treatment in obese pregnancy on the expression levels of these genes in the placenta. Metformin is a drug used to treat gestational diabetes but its effect on the placenta and the developing foetus is unknown. Maternal high fat diet (HFD) during pregnancy reduced VEGF mRNA expression in the placenta depending on MET treatment, while placental RAPTOR expression increases with maternal HFD. These changes in gene expression could alter placental function and foetal development, and have long-term consequences on cardiometabolic health of the offspring. It further suggests that metformin should be prescribed with caution to pregnant women.

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Due to the great deal of guidance given, the project was far less daunting and the workload was more than manageable. I learnt that research is coordinated within a specific lab group, with individual each conducting their own research projects, and feeding back to the team to provide a more holistic understanding. Also, numerous different departments liaise with each other and I had the privilege of being able to attend to these meetings along with conferences held within the hospital. This showed me how a research environment is very much interdisciplinary and relies on understanding how the work presented by others may impact your own research.

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This studentship has given me the opportunity to experience what it means to be a part of a research group and the fundamental impact your work could have and this is something that has very much resonated with me. It’s allowed me to be challenged, but also to gain a greater insight and grow in confidence in my laboratory techniques. Because of this, I now realise that a research-intensive career is not beyond my reach and that it is far less intimidating than I perceived it to be. I am now in the process of considering pursuing a Masters in Biomedical Sciences, and would very much like to pursue a technical laboratory focused career, perhaps in a hospital setting.

(This article was originally published in Physiology News 110, page 43.)

Obesity: hamsters may hold the clue to beating it

Apply by 28 February for our Research Grants of up to £10,000 (over a 12 to 18-month period). This scheme supports physiologists in their first permanent academic position or returning to a permanent position after a career break, to provide support for their research or to provide seed-funding to start a new project. Gisela Helfer was a 2017 awardee of this grant, and you can read about her research below:

The global obesity crisis shows no signs of abating, and we urgently need new ways to tackle it. Consuming fewer calories and burning more energy through physical activity is a proven way to lose weight, but it’s clearly easier said than done. The problem with eating less and moving more is that people feel hungry after exercise and they have to fight the biologically programmed urge to eat. To develop effective ways to lose weight, we need a better understanding of how these biological urges work. We believe hamsters hold some clues.

Hamsters and other seasonal animals change their body and behaviour according to the time of year, such as growing a thick coat in winter or only giving birth in spring. Some seasonal animals can also adjust their appetite so that they aren’t hungry when less food is available. For example, the Siberian hamster loses almost half its body weight in time for winter, so they don’t need to eat as much to survive the winter months. Understanding the underlying physiological processes that drive this change may help us to understand our own physiology and may help us develop new treatments.

How hungry we feel is controlled by a part of the brain called the hypothalamus. The hypothalamus helps to regulate appetite and body weight, not only in seasonal animals but also in humans.

Tanycytes (meaning “long cells”) are the key cells in the hypothalamus and, amazingly, they can change size and shape depending on the season. In summer, when there is a lot of daylight and animals eat more, tanycytes are long and they reach into areas of the brain that control appetite. In winter, when days are shorter, the cells are very short and few.

These cells are important because they regulate hormones in the brain that change the seasonal physiology of animals, such as hamsters and seasonal rats.

Growth signals

We don’t fully understand how all these hormones in the hypothalamus interact to change appetite and weight loss, but our recent research has shown that growth signals could be important.

One way that growth signals are increased in the brain is through exercise. Siberian hamsters don’t hibernate; they stay active during the winter months. If hamsters have access to a running wheel, they will exercise more than usual. When they are exercising on their wheel, they gain weight and eat more. This is true especially during a time when they would normally be small and adapted for winter. Importantly, the increased body weight in exercising hamsters is not just made up of increased muscle, but also increased fat.

We know that the hamsters interpret the length of day properly in winter, or, at least, in a simulated winter day (the lights being on for a shorter duration), because they still have a white winter coat despite being overweight. We now understand that in hamsters the exercise-stimulated weight gain has to do with hormones that usually regulate growth, because when we block these hormones the weight gain can be reversed.

When people take up exercise, they sometimes gain weight, and this may be similar to what happens in hamsters when appetite is increased to make up for the increased energy being burned during exercise. This doesn’t mean that people shouldn’t exercise during the winter, because we don’t naturally lose weight like Siberian hamsters, but it does explain why, for some people, taking up exercise might make them feel hungrier and so they might need extra help to lose weight.

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We need to find ways to overcome appetite. Lucky Business/Shutterstock.com

What we have learned from studying hamsters so far has already given us plenty of ideas about which cells and systems we need to look at in humans to understand how weight regulation works. This will create new opportunities to identify possible targets for anti-obesity drugs and maybe even tell us how to avoid obesity in the first place.

By Gisela Helfer@gi_helfer and Rebecca Dumbell

(This blog was originally published on The Conversation.)

Life at the Limits: Register now for our extreme environmental physiology conference

By Mike Tipton, @ProfMikeTiptonExtreme Environments Laboratory, Department of Sport and Exercise Science, Portsmouth University

“Ecology”, from the Greek “oikos” meaning home or place to live, is the branch of biology that deals with the relationships of organisms and their physical surroundings. It encompasses the impact of animals on their environment, and the environment on animals. Both sides of the ecology coin are becoming increasingly important and linked.

On one side we are careering, largely unfettered, towards the man-made abyss of the end game of global warming; we are threatening our direct descendants, but at a rate and distance that doesn’t provoke us to action.

On the other side, only 15% of the surface of our planet is not water, desert, ice or mountain. For a tropical, low altitude, air-breathing human, this means most of planet Earth represents an extreme environment, defined as a place where it is difficult to survive. The link between the two is, of course, that global warming will make our planet even more extreme with flooding, erosion, heat waves, cold snaps and desertification.

group of climbers on rope on glacier

Perhaps, therefore, there is no better time for The Physiological Society to plan a specialist conference on Extreme Environmental Physiology (EEP) on 2-4 September.

From origins where EEP research was largely undertaken for occupational groups such as miners and the military, as well as those attempting expeditions to remote parts of the globe, EEP has now become much more “mainstream.” The greatest number of submissions and publications in the journals of The Physiological Society come from the areas of “environmental” and “exercise” physiology; both of which have extreme environmental components.

EEP research continues to examine the responses of humans to environmental stressors such as heat, cold and altitude; these remain important areas in themselves with, for example, at least 1000 people dying from drowning every day around the planet. But EEP research is now also providing insights into a wide range of other conditions such as: responses to hypoxia on intensive care (“survivor phenotypes”); ageing; peripheral vascular disease; osteoporosis; and debilitation caused in critical care patients by bed rest.

STS-116_spacewalk_1.jpg

In addition, as we take greater and greater control of our environment through technology, it is becoming increasingly apparent that we need to challenge our homeostatic mechanisms in order to remain functional. At one time we did this naturally by exercise and exposure to the natural world, now we have to employ thermal therapies for a wide range of physiological and mental health pathologies, from microvascular function through autonomic function to depression.

The specialist conference at Portsmouth in September will reflect all of the above, with sessions on cold, heat, hypo- and hyperbaric physiology, micro-gravity and cross-adaptation. To remind us what an eclectic discipline physiology is, each session will include short keynotes on physiology, pathophysiology and comparative physiology, as well as plenty of time for free communications. Finally, it seems appropriate that we should “flip the coin” and spend some time on what the environment might have in store for us if we continue to damage it.

Our exciting keynote speakers include:

References

  1. Martin & McKenna (2017). High Altitude Research and its Relevance to Critical Illness. ICU Management & Practice 17(2): 103-105.
  2. Tipton MJ (2015). GL Brown Lecture: “Extreme Threats” Environmental extremes: origins, consequences and amelioration. Experimental Physiology. doi: 10.1113/EP085362.
  3. Tipton, M. J. (2018) Humans: a homeothermic animal that needs perturbation? Experimental Physiology. https://doi.org/10.1113/EP087450.