Publications

The latest list of publications from the Cambridge Biomedical Research Centre with a brief summary. 

Publication: Nature Immunology

Kylie R. James, Tomas Gomes, Rasa Elmentaite, Nitin Kumar, Emily L. Gulliver, Hamish W. King, Mark D. Stares, Bethany R. Bareham, John R. Ferdinand, Velislava N. Petrova, Krzysztof Polański, Samuel C. Forster, Lorna B. Jarvis, Ondrej Suchanek, Sarah Howlett, Louisa K. James, Joanne L. Jones, Kerstin B. Meyer, Menna R. Clatworthy, Kourosh Saeb-Parsy, Trevor D. Lawley, Sarah A. Teichmann

17 February 2020

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Summary:

This research surveyed the microbiome in different regions along the length of a healthy human colon, and in parallel surveyed the populations of immune cells.The map of the bacterial composition in the human colon showed that specific genera had preferences for colonising certain regions of the colon. B and T cells also changed along the length of the colon. This is the first survey to find out what constitutes a healthy homeostatic relationship between the microbiome in the human colon and host immune cells.

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Publication: Nature Communications

Sanne Simone Kaalund, Luca Passamonti, Kieren S. J. Allinson, Alexander G. Murley, Trevor W. Robbins, Maria Grazia Spillantini and James B. Rowe

4 February 2020


Summary:

The locus coeruleus is the major source of noradrenaline to the brain and contributes to a wide range of physiological and cognitive functions. Neurodegeneration and pathological aggregation of tau protein in the locus coeruleus are early features of progressive supranuclear palsy (PSP). It is proposed to contribute to the clinical expression of the disease, including the PSP Richardson’s syndrome. Researchers investigated whether the tau and neuronal loss are associated with clinical heterogeneity and severity in PSP.

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Publication: Nature

Duuamene Nyimanu, Richard G. Kay, Petra Sulentic, Rhoda E. Kuc, Philip Ambery, Lutz Jermutus, Frank Reimann, Fiona M. Gribble, Joseph Cheriyan, Janet J. Maguire, Anthony P. Davenport

27 December 2019

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Summary:

An LC-MS method was developed to measure Apelin in human plasma, and demonstrate apelin dosing achieved the correct concentration in volunteers. The extracts were also analysed on an LC-MS system to identify break-down products of the peptide that were produced in the body. The researchers found out that apelin is broken down from both ends of the peptide, but more so from the C-terminal. This information can be used to develop a better peptide that is stabilised against degradation, therefore improving its characteristics as a drug; and apelin-derived peptides may be potential new drugs for cardiovascular disease.

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Publication: Toxicological Pathology

Michelle Curran, Maelle Mairesse, Alba Matas-Céspedes, Bethany Bareham, Giovanni Pellegrini, Ardi Liaunardy, Edward Powell, Rebecca Sargeant, Emanuela Cuomo, Richard Stebbings, Catherine J. Betts, Kourosh Saeb-Parsy

18 December 2019

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Summary:

Immunodeficient mice which are reconstituted with a human immune system (HIS), so called ‘humanised mice’, have great potential in research, acting as a powerful tool for investigating the human immune system in different disease states and helping to improve drug development in order to minimise toxicity of novel drugs in clinical trials. However some aspects of HIS need to be improved and this research discusses current HIS platforms, their pathology and recent advances in their development to improve the quality of human immune cell reconstitution.

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Publication: Science

Tim H. H. Coorens, Taryn D. Treger, Reem Al-Saadi, Luiza Moore, Maxine G. B., Thomas J. Mitchell, Suzanne Tugnait, Christine Thevanesan, Matthew D. Young, Thomas R. W. Oliver, Minou Oostveen, Grace Collord, Patrick S. Tarpey, Alex Cagan, Yvette Hooks, Mark Brougham, Ben C. Reynolds, Giuseppe Barone, John Anderson, Mette Jorgensen, G. A. Amos Burke, Johannes Visser, James C. Nicholson, Naima Smeulders, Imran Mushtaq, Grant D. Stewart, Peter J. Campbell, David C. Wedge, Iñigo Martincorena, Dyanne Rampling, Liz Hook, Anne Y. Warren, Nicholas Coleman, Tanzina Chowdhury, Neil Sebire, Jarno Drost, Kourosh Saeb-Parsy, Michael R. Stratton, Karin Straathof, Kathy Pritchard-Jones, Sam Behjati

6 December 2019

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Summary:

Wilms tumour is the most common type of kidney cancer in childhood but it was not previously known how it arose in children’s kidneys. This research found out that both pediatric and adult kidney cancer arise in a similar way, from premalignant clonal expansions.

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Publication: QJM: An International Journal of Medicine

R El-Damanawi, M Lee, T Harris, L B Cowley, S Bond, H Pavey, R N Sandford, I B Wilkinson, F E Karet Frankl, T F Hiemstra

30 October 2019
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Summary:

Vasopressin is a hormone that is made by the body to conserve water in states of dehydration. In Polycystic Kidney disease (PKD) this hormone accelerates cyst growth and kidney damage, making it the fourth leading global cause of kidney failure.  High water intake reduces blood levels of vasopressin, and may slow cyst growth and disease progression similarly to currently available vasopressin blockers.  However, the feasibility, safety and sustaintability of this therapeutic strategy remains unknown.

In this randomised controlled trial, patients with PKD were randomised to either high water intake (HW) or Ad libitum water intake (AW) over an 8-week period.  The primary outcome was to determine if the HW group could maintain dilute urine, and the AW group could keep their urine more concentrated over an 8-week follow up period.  We used a self-management strategy and smartphone applications to promote compliance.

Researchers found that high water intake is feasible, sustainable and safe, and can be started early in the disease course prior to the onset of irreversible kidney damage; while the use of smartphone applications to record home-monitoring of urine dipstick tests promoted adherence, driving a difference in urine results between the groups. A definitive global randomised controlled trial of high versus normal water intake is possible and will be the next stage of this work.

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Publication: Molecular Psychiatry

Varun Warrier, Simon Baron-Cohen

29 October 2019


Summary:

People with a higher genetic likelihood of autism are more likely to report higher childhood maltreatment, self-harm and suicidal thoughts. Following on from a previous study, researchers looked at the genetic likelihood for autism in 100,000 people. They found those with a higher number of genetic varients associated with autism were more likely to report maltreatment and self-harm.

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Publication: Nature

Henry Lee-Six, Sigurgeir Olafsson, Peter Ellis, Robert J. Osborne, Mathijs A. Sanders, Luiza Moore, Nikitas Georgakopoulos, Franco Torrente, Ayesha Noorani, Martin Goddard, Philip Robinson, Tim H. H. Coorens, Laura O’Neill, Christopher Alder, Jingwei Wang, Rebecca C. Fitzgerald, Matthias Zilbauer, Nicholas Coleman, Kourosh Saeb-Parsy, Inigo Martincorena, Peter J. Campbell & Michael R. Stratton

23 October 2019

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This was a study of early changes in human colorectal tissue that could lead to adenomas/carconomas. These are rare outcomes even after a substantially increased mutational burden has been placed on the tissue, but it is important to study the earliest stages of colorectal carcinogenesis.

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Publication: Nature Communications

Andrea I. Luppi1, Michael M. Craig, Ioannis Pappas, Paola Finoia, Guy B. Williams, Judith Allanson, John D. Pickard, Adrian M. Owen, Lorina Naci, David K. Menon & Emmanuel A. Stamatakis 

10 October 2019


Summary:

Researchers used functional Magnetic Resonance Imaging (fMRI) to scan the brains of healthy volunteers and brain injured patients who had been awake but no signs of awareness or in a minimally conscious state, to understand what happens to the brain when consciousness is lost.

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Publication: Nature Metabolism

Jack L. Martin, Ana S. H. Costa, Anja V. Gruszczyk, Timothy E. Beach, Fay M. Allen, Hiran A. Prag, Elizabeth C. Hinchy, Krishnaa Mahbubani, Mazin Hamed, Laura Tronci, Efterpi Nikitopoulou, Andrew M. James, Thomas Krieg, Alan J. Robinson, Margaret M. Huang, Stuart T. Caldwell, Angela Logan, Laura Pala, Richard C. Hartley, Christian Frezza, Kourosh Saeb-Parsy, Michael P. Murphy

30 September 2019

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Summary:

During retrieval of kidneys for transplant, there is inevitably a period of time when the organ is without blood flow but still warm (warm ischaemia). A human kidney cannot sustain this for long. During warm ischaemia, a metabolite called succinate builds up. When blood flow is restored, then counter-intuitively, the kidney tissue is damaged with the arrival of oxygenated blood. A drug was tested that ameliorates this damage. This research shows how the function and life span of a transplanted organ can be improved.

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Publication: Nature

Bashford-Rogers, R.J.M., Bergamaschi, L., McKinney, E.F., Pombal, D.C., Mescia, F., Lee, J.C., Thomas, D.C., Flint, S.M., Kellam, P., Jayne, D.R.W., Lyons P.A. and Smith, K.G.C.

25 September 2019

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Publication: The Proceedings of the National Academy of Sciences (PNAS)

Laurence S. C. Lok, Thomas W. Dennison, Krishnaa M. Mahbubani, Kourosh Saeb-Parsy, Edwin R. Chilvers, Menna R. Clatworthy

17 September 2019

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Summary:

Neutrophils are circulating phagocytes that are recruited to tissues after infection/injury. They have been confirmed as present in lymph nodes in healthy tissue, contrary to the classical view. This suggests a novel role for neutrophils in homeostatic immune surveillance.

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