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Physiology 2021 Our Annual Conference Physiology 2021 Our Annual Conference 12 – 16 July 2021 Online | Worldwide #Physiology2021 Contents Prize Lectures 1 Symposia 7 Oral Communications 63 Poster Communications 195 Abstracts Experiments on animals and animal tissues It is a requirement of The Society that all vertebrates (and Octopus vulgaris) used in experiments are humanely treated and, where relevant, humanely killed. To this end authors must tick the appropriate box to confirm that: For work conducted in the UK, all procedures accorded with current UK legislation. For work conducted elsewhere, all procedures accorded with current national legislation/guidelines or, in their absence, with current local guidelines. Experiments on humans or human tissue Authors must tick the appropriate box to confirm that: All procedures accorded with the ethical standards of the relevant national, institutional or other body responsible for human research and experimentation, and with the principles of the World Medical Association’s Declaration of Helsinki. Guidelines on the Submission and Presentation of Abstracts Please note, to constitute an acceptable abstract, The Society requires the following ethical criteria to be met. To be acceptable for publication, experiments on living vertebrates and Octopus vulgaris must conform with the ethical requirements of The Society regarding relevant authorisation, as indicated in Step 2 of submission. Abstracts of Communications or Demonstrations must state the type of animal used (common name or genus, including man. Where applicable, abstracts must specify the anaesthetics used, and their doses and route of administration, for all experimental procedures (including preparative surgery, e.g. ovariectomy, decerebration, etc.). For experiments involving neuromuscular blockade, the abstract must give the type and dose, plus the methods used to monitor the adequacy of anaesthesia during blockade (or refer to a paper with these details). For the preparation of isolated tissues, including primary cultures and brain slices, the method of killing (e.g. terminal anaesthesia) is required only if scientifically relevant. In experiments where genes are expressed in Xenopus oocytes, full details of the oocyte collection are not necessary. All procedures on human subjects or human tissue must accord with the ethical requirements of The Society regarding relevant authorisation, as indicated in Step 2 of submission; authors must tick the appropriate box to indicate compliance. PL01 Teaching physiology: Past present and future James Clark1 1School of Cardiovascular Medicine and Sciences, King’s College London, London, United Kingdom Educating our expanding undergraduate student cohorts in whole body physiology is complex, and to do this effectively can sometimes be a challenge. I was awarded the Otto Hutter Physiology Teaching Prize in 2019 (pre-COVID) and my oral presentation at Physiology 2020 was going to be looking at the role of online teaching in physiology education. However, the recent global COVID-19 Pandemic has hit physiology education hard with restrictions on face-to-face on-campus teaching and instructors have had to be more and more imaginative to delivery high quality online teaching. In this presentation, therefore we will explore the challenges of physiology education with a specific focus on practical skills and human physiology looking back at our traditional approach, how we responded to the COVID-Pandemic and the ways we might be educating our students in the socially distanced future within our Institutions. PL02 Hidden clocks: circadian rhythms and the vulnerable fetus. Laura Bennet1 1The University of Auckland, Auckland, New Zealand Despite marking our age from the day of birth, our physiological journey starts 9 months before; assuming we went to full term gestation. During this time we build our existence upon the merging of two cells, growing an entire human being, the environment it lives in; the amniotic sac, and the organ of gas, nutrient and waste exchange; the placenta. An undeniably fantastic bioengineering feat, and one which provides the physiological foundation for our post-natal development to adulthood. However, our physiological journey from conception to birth can face adverse challenges, such as hypoxia and inflammation, leading to impaired development of organs and their functional control and injury, all of which has consequences for our post-natal physiology. Further, such adverse events may cause the fetus to be vulnerable to further challenges to its environment leading to death before birth, as is seen with stillbirth. To develop methods of detecting the at-risk-fetus to inform clinical decision making and targeting of perinatal treatments requires a greater understanding of the maturational changes in fetal physiology and pathophysiology. This includes the role of a key regulator of our own biology; circadian rhythms. This talk will discuss how a preterm fetus can survive a significant hypoxic insult and continue to develop to full maturity, but with evolving brain injury. It will examine how injury and/or impaired brain development may make the fetus more vulnerable to further episodes of hypoxia. The talk will then explore how we can utilise information about the temporal changes in fetal physiology and behaviour after hypoxia to develop potential clinical biomarkers to detect an adverse event and determine phases of injury. This is vital for facilitating implementation of targeted therapies and inform clinical decision making. Here, time of day is an important factor as the fetus has robust circadian and ultradian rhythms, but their nature and functional role are poorly understood. The talk will present new data about fetal cardiovascular and neurophysiological circadian and ultradian rhythms. It will detail how they change with maturation and are altered by hypoxia and inflammation. The talk will highlight the importance of the time of day when utilising fetal diagnostic and prognostic biomarkers and the implications for the timing of routine clinical assessments. Finally, the talk will end with reflection upon the challenges we face to improve our understanding about the first 9 months of our physiological journey if we are to optimise our physiological development from birth to adulthood. Acknowledgements :- The Fetal Physiology and Neuroscience Group, Department of Physiology, The University of Auckland The Health Research Council of New Zealand PL03 Regulation of blood flow at the capillary level in health and disease David Attwell1 1University Collegeg London, London, United Kingdom It is often assumed that local increases of tissue blood flow are mediated by relaxation of arteriolar smooth muscle but in many tissues, including the brain, heart, kidney and pancreas, capillary control of blood flow by contractile pericytes also occurs. In the brain, most of the adjustable resistance of the intra-cerebral vasculature is located in capillaries. I will demonstrate that neuronal activity mainly increases cerebral blood flow by dilating capillaries via pericytes, that this involves signalling via astrocytes, and that dilation of capillaries and of arterioles are mediated by different messengers. In the brain, heart and kidney, ischaemia leads to pericytes constricting, producing a long-lasting decrease of blood flow after ischaemia. Constriction of cerebral capillaries by pericytes also occurs at an early stage of Alzheimer’s Disease, when it is expected to amplify the production of amyloid beta. The SARS-CoV-2 virus causing Covid-19 binds to ACE2 on cerebral pericytes and amplifies angiotensin II - evoked pericyte constriction by decreasing ACE2 function. Thus, awareness of the possibility of pericyte-mediated capillary constriction reveals new therapeutic targets to increase blood flow in numerous pathologies. Acknowledgements :- Supported by Investigator Awards from the Wellcome Trust and European Research Council, a research grant from the Rosetrees Trust, and PhD studentships from the BBSRC, Wellcome Trust and HRH Princess Chulabhorn College of Medical Science. PL04 The gut endocrine axis in the control of metabolism Fiona Gribble1 1University of Cambridge, Cambridge, United Kingdom The gut endocrine system comprises a collection of enteroendocrine cells scattered throughout the intestinal epithelium, producing hormones that signal locally within the gut and distantly at tissues such as the brain and pancreas. In the field of diabetes and obesity, the best studied gut hormone is glucagon-like peptide-1 (GLP-1), which has been exploited therapeutically for the treatment of type 2 diabetes and obesity through the development of GLP-1 receptor agonists and DPP4 inhibitors. Our research is focussed on gaining a molecular understanding the enteroendocrine system and its involvement in the control of metabolism and food intake. Technical advances now make it possible to apply live single cell recording and transcriptomic techniques to human enteroendocrine cells using intestinal organoid models engineered by CRISPR-Cas9 to express fluorescent sensors in specific cell types of interest. Mirroring previous findings from mouse models, we have shown that human GLP-1 secreting cells utilise a variety of signalling pathways for nutrient detection, including electrogenic glucose uptake and activation of specific G-protein coupled receptors by free fatty acids and amino acids. Overall, we aim that our research will identify new drugs for type 2 diabetes and obesity that act by targeting gut endocrine
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