Publications

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

If you are publishing research which has had funding and / or support from the NIHR Cambridge Biomedical Research Centre, please complete this form

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Publication: Nature Communications

Sungsam Gong, Francesca Gaccioli, Justyna Dopierala, Ulla Sovio, Emma Cook, Pieter-Jan Volders, Lennart Martens, Paul D. W. Kirk, Sylvia Richardson, Gordon C. S. Smith & D. Stephen Charnock-Jones 

11 May 2021


Summary

The placenta is understudied and is commonly omitted from large-scale “-omic” analyses, this study enables tissue-wide comparison of transcriptome analyses, looking at identification placentally-related adverse pregnancy outcomes such as fetal growth restriction (FGR) and preeclimisia (PE).

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Publication: bioRxiv

Conde C Domínguez, T Gomes, LB Jarvis, C Xu, SK Howlett, DB Rainbow, O Suchanek, HW King, L Mamanova, K Polanski, N Huang, E Fasouli, KT Mahbubani, M Prete, L Campos, HS Mousa, EJ Needham, S Pritchard, T Li, R Elmentaite, J Park, DK Menon, OA Bayraktar, LK James, KB Meyer, MR Clatworthy, K Saeb-Parsy, JL Jones, SA Teichmann

28 April 2021


Summary

Despite their crucial role in health and disease, researchers knowledge of immune cells within human tissues, in contrast to those circulating in the blood, remains limited. Researchers surveyed the immune compartment of lymphoid and non-lymphoid tissues of six adult donors by single-cell RNA sequencing, including alpha beta T-cell receptor, gamma delta TCR and B-cell receptor variable regions.

To aid systematic cell type identification researchers developed CellTypist, a tool for automated and accurate cell type annotation. Using this approach combined with manual curation, researchers determined the tissue distribution of finely phenotyped immune cell types and cell states.

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Publication: Science

Josephine M. Bryant,  Karen P. Brown,  Sophie Burbaud,  Isobel Everall,  Juan M. Belardinelli, Daniela Rodriguez-Rincon,  Dorothy M. Grogono,  Chelsea M. Peterson,  Deepshikha Verma,  Ieuan E. Evans,  Christopher Ruis,  Aaron Weimann,  Divya Arora,  Sony Malhotra,  Bridget Bannerman, Charlotte Passemar,  Kerra Templeton,  Gordon MacGregor, Kasim Jiwa,  Andrew J. Fisher,  Tom L. Blundell,  Diane J. Ordway,  Mary Jackson, Julian Parkhill, R. Andres Floto

30 April 2021


Summary:

Researchers have been able to track how a multi-drug resistant organism is able to evolve and spread widely among cystic fibrosis patients – showing that it can evolve rapidly within an individual during chronic infection. The researchers say their findings highlight the need to treat patients with Mycobacterium abscessus infection immediately, counter to current medical practice.

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Publication: Nature Communications

Wittemans LBL, Lotta LA, Oliver-Williams C, Stewart ID, Surendran P, Karthikeyan S, et al.

5 March 2019

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Publication: Diabetes Care

Vissers LET, Sluijs I, van der Schouw YT, Forouhi NG, Imamura F, Burgess S, et al.

6 February 2019


Eating healthily on a daily basis is a major step to prevent development of type 2 diabetes. Higher intake of dairy products has been associated with a lower risk of diabetes in a meta-analysis of observational studies. Yogurt and cheese intake particularly were associated with lower diabetes risk, whereas milk intake was not, with substantial heterogeneity for most dairy products.

However, potential confounding and reverse causation cannot be excluded. Owing to these limitations, the causal role of dairy products in diabetes prevention remains debatable.

The relationship between dairy products and risk of diabetes could be investigated by applying a Mendelian randomization (MR) approach, using genetic variability in the MCM6 gene associated with lactase persistence (LP) in adults as an instrumental variable (IV).

Lactase is necessary to break down the sugars that are found in dairy products, i.e., lactose. Single nucleotide polymorphisms (SNPs) in the MCM6 region have been associated with LP (6). rs4988235 (LCT-12910C>T) has been associated with LP in European populations and has been associated with a higher intake of milk in European cohorts, albeit not in all.

Previous MR studies reported no association between LP-associated milk intake and diabetes. However, variation in the MCM6 gene is likely to lead to population stratification, which would introduce bias to an MR analysis, and previous MR studies did not sufficiently adjust for population substructure. Also, previous studies did not investigate whether rs4988235 was specifically associated with dairy product intake after adjusting for population substructure.

We therefore investigated whether rs4988235 associated with intake of dairy products and other foods in a pan-European study in eight countries with different dietary habits. We adjusted for genetic principal components (PCs) and study center to adjust for population substructure (16). Next, we used rs4988235 in an IV analysis to investigate whether there is a causal relationship between the LP-associated exposure and risk of diabetes.

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Publication: Sage Journals

Maria Herrero-Zazo, Rachel BerryEmma Bines, Debi BhattacharyaPhyo K. MyintVictoria L. Keevil

6 May 2021


Summary

Researchers describe how commonly medicines which block the chemical acetylcholine are prescribed to older adults admitted to hospital as an emergency and explore links between these medicines and death during or soon after hospital admission. Researchers use data collected as part of routine medical care at one university hospital to describe how often these medicines are prescribed in a large sample of older adults admitted to hospital as an emergency. They looked at the medicines patients are prescribed on admission to the hospital and also when they are later discharged.

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Publication: Nature Cancer

Xueqing Zou, Gene Ching Chiek Koh, Arjun Scott Nanda, Andrea Degasperi, Katie Urgo, Theodoros I. Roumeliotis, Chukwuma A. Agu, Cherif Badja, Sophie Momen, Jamie Young, Tauanne Dias Amarante, Lucy Side, Glen Brice, Vanesa Perez-Alonso, Daniel Rueda, Celine Gomez, Wendy Bushell, Rebecca Harris, Jyoti S. Choudhary, Genomics England Research Consortium, Josef Jiricny, William C. Skarnes & Serena Nik-Zainal

26 April 2021


Summary

A new way to identify tumours that could be sensitive to particular immunotherapies has been developed using data from thousands of NHS cancer patient samples sequenced through the 100,000 Genomes Project.  The MMRDetect clinical algorithm makes it possible to identify tumours that have ‘mismatch repair deficiencies’ and then improve the personalisation of cancer therapies to exploit those weaknesses. Read the full press release

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Publication: American Journal of Obstetrics and Gynecology

Ulla Sovio, Francesca Gaccioli, Emma Cook, Stephen Charnock-Jones, .Gordon C.S,

24 April 2021


Summary

Slowing of fetal growth and elevated maternal serum are associated with early term spontaneous labor

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Publication: Nature

Emily Stephenson, Gary Reynolds, Rachel A. Botting, Fernando J. Calero-Nieto, Michael D. Morgan, Zewen Kelvin Tuong, Karsten Bach, Waradon Sungnak, Kaylee B. Worlock, Masahiro Yoshida, Natsuhiko Kumasaka, Katarzyna Kania, Justin Engelbert, Bayanne Olabi, Jarmila Stremenova Spegarova, Nicola K. Wilson, Nicole Mende, Laura Jardine, Louis C. S. Gardner, Issac Goh, Dave Horsfall, Jim McGrath, Simone Webb, Michael W. Mather, Rik G. H. Lindeboom, Emma Dann, Ni Huang, Krzysztof Polanski, Elena Prigmore, Florian Gothe, Jonathan Scott, Rebecca P. Payne, Kenneth F. Baker, Aidan T. Hanrath, Ina C. D. Schim van der Loeff, Andrew S. Barr, Amada Sanchez-Gonzalez, Laura Bergamaschi, Federica Mescia, Josephine L. Barnes, Eliz Kilich, Angus de Wilton, Anita Saigal, Aarash Saleh, Sam M. Janes, Claire M. Smith, Nusayhah Gopee, Caroline Wilson, Paul Coupland, Jonathan M. Coxhead, Vladimir Yu Kiselev, Stijn van Dongen, Jaume Bacardit, Hamish W. King, Anthony J. Rostron, A. John Simpson, Sophie Hambleton, Elisa Laurenti, Paul A. Lyons, Kerstin B. Meyer, Marko Z. Nikolić, Christopher J. A. Duncan, Kenneth G. C. Smith, Sarah A. Teichmann, Menna R. Clatworthy, John C. Marioni, Berthold Göttgens & Muzlifah Haniffa

20 April 2020


Summary

A UK-wide study has identified differences in people’s immune responses to COVID-19, depending on whether they have no symptoms or more serious reactions to the virus. Read the full story

 

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Publication: Nutrition Bulletin

Hengist A, Perkin O, Gonzalez JT, Betts JA, Hewison M, Manolopoulos KN, Jones KS, et al.

3 February 2019


Vitamin D is lipophilic and accumulates substantially in adipose tissue. Even without supplementation, the amount of vitamin D in the adipose of a typical adult is equivalent to several months of the daily reference nutrient intake (RNI).

Paradoxically, despite the large amounts of vitamin D located in adipose tissue, individuals with obesity are often vitamin D deficient according to consensus measures of vitamin D status (serum 25-hydroxyvitamin D concentrations).

Thus, it appears that vitamin D can become ‘trapped’ in adipose tissue, potentially due to insufficient lipolytic stimulation and/or due to tissue dysfunction/adaptation resulting from adipose expansion.

Emerging evidence suggests that exercise may mobilise vitamin D from adipose (even in the absence of weight loss). If exercise helps to mobilise vitamin D from adipose tissue, then this could have important ramifications for practitioners and policymakers regarding the management of low circulating levels of vitamin D, as well as chronically low levels of physical activity, obesity and associated health conditions.

This perspective led us to design a study to examine the impact of exercise on vitamin D status, vitamin D turnover and adipose tissue vitamin D content (the VitaDEx project). The VitaDEx project will determine whether increasing physical activity (via exercise) represents a potentially useful strategy to mobilise vitamin D from adipose tissue.

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Publication: BMC Medicine

Khalatbari-Soltani S, Imamura F, Brage S, De Lucia Rolfe E, Griffin SJ, Wareham NJ, et al.

24 January 2019


The risk of hepatic steatosis may be reduced through changes to dietary intakes, but evidence is sparse, especially for dietary patterns including the Mediterranean diet. Here the researchers investigated the association between adherence to the Mediterranean diet and prevalence of hepatic steatosis.

Cross-sectional analysis of data from two population-based adult cohorts: the Fenland Study (England, n = 9645, 2005–2015) and CoLaus Study (Switzerland, n = 3957, 2009–2013).

Habitual diet was assessed using cohort-specific food frequency questionnaires. Mediterranean diet scores (MDSs) were calculated in three ways based on adherence to the Mediterranean dietary pyramid, dietary cut-points derived from a published review, and cohort-specific tertiles of dietary consumption.

Hepatic steatosis was assessed by abdominal ultrasound and fatty liver index (FLI) in Fenland and by FLI and non-alcoholic fatty liver disease (NAFLD) score in CoLaus. FLI includes body mass index (BMI), waist circumference, gamma-glutamyl transferase, and triglyceride; NAFLD includes diabetes, fasting insulin level, fasting aspartate-aminotransferase (AST), and AST/alanine transaminase ratio. Associations were assessed using Poisson regression.

In Fenland, the prevalence of hepatic steatosis was 23.9% and 27.1% based on ultrasound and FLI, respectively, and in CoLaus, 25.3% and 25.7% based on FLI and NAFLD score, respectively.

In Fenland, higher adherence to pyramid-based MDS was associated with lower prevalence of hepatic steatosis assessed by ultrasound. This association was attenuated after adjustment for body mass index (BMI). Associations of similar magnitude were found for hepatic steatosis assessed by FLI in Fenland and in CoLaus, and these were also attenuated after adjustment for BMI. Findings were similar when the other two MDS definitions were used.

Greater adherence to the Mediterranean diet was associated with lower prevalence of hepatic steatosis, largely explained by adiposity. These findings suggest that an intervention promoting a Mediterranean diet may reduce the risk of hepatic steatosis.

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