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A cell atlas of human thymic development defines T cell repertoire formation

Publication: Science

Jong-Eun Park, Rachel A. Botting, Cecilia Domínguez Conde, Dorin-Mirel Popescu, Marieke Lavaert, Daniel J. Kunz, Issac Goh, Emily Stephenson, Roberta Ragazzini, Elizabeth Tuck, Anna Wilbrey-Clark, Kenny Roberts, Veronika R. Kedlian, John R. Ferdinand, Xiaoling He, Simone Webb, Daniel Maunder, Niels Vandamme, Krishnaa T. Mahbubani, Krzysztof Polanski, Lira Mamanova, Liam Bolt, David Crossland, Fabrizio de Rita, Andrew Fuller, Andrew Filby, Gary Reynolds, David Dixon, Kourosh Saeb-Parsy, Steven Lisgo, Deborah Henderson, Roser Vento-Tormo, Omer A. Bayraktar, Roger A. Barker, Kerstin B. Meyer, Yvan Saeys, Paola Bonfanti,
Sam Behjati, Menna R. Clatworthy, Tom Taghon, Muzlifah Haniffa, Sarah A. Teichmann

21 February 2020

Summary:

Human thymus tissue makes T-cells for adaptive immunity and this research made a comprehensive cell atlas of thymus tissue over the course of human life, from embryo to adult thus gaining new insights into human T-cell development.

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Distinct microbial and immune niches of the human colon

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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scRNA-seq assessment of the human lung, spleen, and esophagus tissue stability after cold preservation

Publication: Genome Biology

E. Madissoon, A. Wilbrey-Clark, R. J. Miragaia, K. Saeb-Parsy, K. T. Mahbubani, N. Georgakopoulos, P. Harding, K. Polanski, N. Huang, K. Nowicki-Osuch, R. C. Fitzgerald, K. W. Loudon, J. R. Ferdinand, M. R. Clatworthy, A. Tsingene, S. van Dongen, M. Dabrowska, M. Patel,
M. J. T. Stubbington, S. A. Teichmann, O. Stegle & K. B. Meyer

31 December 2019

Summary: 

The Human Cell Atlas, which is an international collaboration to map all the cell types in the human body.

However, delays between fresh sample collection and processing may lead to poor data and difficulties in experimental design.

This study looked at the effect of cold storage on fresh healthy spleen, esophagus, and lung from donors and concluded that cold storage of tissue works well and increases the time frame for processing samples; however robust protocols are needed for tissue preservation that can be used by all the research teams involved.

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Development and validation of an LC-MS/MS method for detection and quantification of in vivo derived metabolites of [Pyr1]apelin-13 in humans

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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High water vs. ad libitum water intake for autosomal dominant polycystic kidney disease: a randomized controlled feasibility trial

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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The landscape of somatic mutation in normal colorectal epithelial cells

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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B cell receptor repertoire analysis in six immune-mediated diseases

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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TNF induces pathogenic programmed macrophage necrosis in tuberculosis through a mitochondrial-lysosomal-endoplasmic reticulum circuit..

Publication: Cell

Ramakrishnan L, Roca Soler FJ, Whitworth L, Redmond S, Jones AA.

29 August 2019

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Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses

Publication: Journal of Experimental Medicine

Spencer S, Köstel Bal S, Egner W, Lango Allen H, Raza SI, Ma CA, Gürel M, Zhang Y, Sun G, Sabroe RA, Greene D, Rae W, Shahin T, Kania K, Ardy RC, Thian M, Staples E, Pecchia-Bekkum A, Worrall WPM, Stephens J, Brown M, Tuna S, York M, Shackley F, Kerrin D, Sargur R, Condliffe A, Tipu HN, Kuehn HS, Rosenzweig SD, Turro E, Tavaré S, Thrasher AJ, Jodrell DI, Smith KGC, Boztug K, Milner JD, Thaventhiran JED.

24 June 2019

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Mitochondrial mechanisms and therapeutics in ischaemia reperfusion injury

Publication: Pediatric Nephrology

Jack L. Martin, Anja V. Gruszczyk, Timothy E. Beach, Michael P. Murphy, Kourosh Saeb-Parsy 

2 June 2018

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Acute kidney injury (AKI) is a major problem in critically unwell children, including ischaemic reperfusion (IR) injury involving mitochondria. This research proposes a variety of novel therapeutic targets as potential treaments of AKI.

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