A5045412197- Birth, Development, and Health
- Epigenetics and DNA Methylation
- Nutrition and Health in Aging
- Adipose Tissue and Metabolism
- Gestational Diabetes Research and Management
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Folate and B Vitamins Research
- Advanced biosensing and bioanalysis techniques
- Neonatal Respiratory Health Research
- SARS-CoV-2 detection and testing
- Pregnancy and preeclampsia studies
- Metabolism, Diabetes, and Cancer
- Muscle Physiology and Disorders
- Biosensors and Analytical Detection
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Animal Genetics and Reproduction
- Adolescent and Pediatric Healthcare
- Human Health and Disease
- Urological Disorders and Treatments
- Identity, Memory, and Therapy
- Dietary Effects on Health
- Plant Genetic and Mutation Studies
- Obesity and Health Practices
University of Southampton
2014-2024
University Hospital Southampton NHS Foundation Trust
2017-2024
NIHR Southampton Biomedical Research Centre
2017-2024
National Institute for Health Research
2019-2023
Institute of Developmental Physiology
2017
Faculty (United Kingdom)
2015
Health and Human Development (2HD) Research Network
2015
Southampton General Hospital
2010
Cambridge University Press
2010
New York University Press
2010
Fixed genomic variation explains only a small proportion of the risk adiposity. In animal models, maternal diet alters offspring body composition, accompanied by epigenetic changes in metabolic control genes. Little is known about whether such processes operate humans.Using Sequenom MassARRAY we measured methylation status 68 CpGs 5' from five candidate genes umbilical cord tissue DNA healthy neonates. Methylation varied greatly at particular CpGs: for 31 with median ≥5% and 5-95% range...
The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related wasting weakness termed sarcopenia, which directly impacts physical autonomy survival. Here, we compare genome-wide transcriptional changes sarcopenia versus age-matched controls biopsies from 119 older men Singapore, Hertfordshire UK Jamaica. Individuals with reproducibly demonstrate a prominent signature mitochondrial bioenergetic...
Abstract Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD + ) levels are hallmarks of skeletal muscle ageing sarcopenia 1–3 , but it is unclear whether these defects result from local changes or can be mediated by systemic dietary cues. Here we report a functional link between circulating the natural alkaloid trigonelline, which structurally related to nicotinic acid 4 NAD health in multiple species. In humans, serum trigonelline reduced with correlate positively...
Background Higher maternal plasma glucose (PG) concentrations, even below gestational diabetes mellitus (GDM) thresholds, are associated with adverse offspring outcomes, DNA methylation proposed as a mediating mechanism. Here, we examined the relationships between dysglycaemia at 24 to 28 weeks’ gestation and in neonates whether dietary physical activity intervention pregnant women obesity modified signatures dysglycaemia. Methods findings We investigated 557 women, recruited 2009 2014 from...
ABSTRACT Maternal vitamin D deficiency has been associated with reduced offspring bone mineral accrual. Retinoid-X receptor-alpha (RXRA) is an essential cofactor in the action of 1,25-dihydroxyvitamin (1,25[OH]2-vitamin D), and RXRA methylation umbilical cord DNA later adiposity. We tested hypothesis that collected at birth skeletal development, assessed by dual-energy X-ray absorptiometry, a population-based mother-offspring cohort (Southampton Women's Survey). Relationships between...
Childhood obesity is a major public health issue. Here we investigated whether differential DNA methylation was associated with childhood obesity. We studied profiles in whole blood from 78 obese children (mean BMI Z-score: 2.6) and 71 age- sex-matched controls 0.1). samples control groups were pooled analyzed using the Infinium HumanMethylation450 BeadChip array. Comparison of between subjects revealed 129 differentially methylated CpG (DMCpG) loci 80 unique genes that had greater than 10%...
Rapid, high throughput diagnostics are a valuable tool, allowing the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in populations so as to identify and isolate people with asymptomatic symptomatic infections. Reagent shortages restricted access testing solutions have limited effectiveness conventional assays such quantitative RT-PCR (RT-qPCR), particularly throughout first months disease 2019 pandemic. We investigated use LamPORE, where loop-mediated isothermal...
Abstract Small noncoding RNAs (sncRNAs) are implicated in age‐associated pathologies, including sarcopenia and insulin resistance (IR). As potential circulating biomarkers, most studies have focussed on microRNAs (miRNAs), one class of sncRNA. This study characterized the wider sncRNA transcriptome older individuals associations with IR. expression miRNAs, transfer (tRNAs), tRNA‐associated fragments (tRFs), piwi‐interacting (piRNAs) was measured serum from 21 healthy sarcopenic Hertfordshire...
Feeding pregnant rats a protein-restricted (PR) diet induces altered expression of candidate genes in the liver adult offspring, which can be prevented by supplementation PR with folic acid (PRF). We investigated effect maternal nutrition during pregnancy on transcriptome their male offspring. Pregnant were fed control, or PRF diets. Male offspring killed day 84. The was analysed microarray (six livers per dietary group) followed post hoc analysis relative mRNA levels and gene ontology....
We have previously demonstrated inverse associations between maternal 25(OH)-vitamin D status and perinatal DNA methylation at the retinoid-X-receptor-alpha (RXRA) locus RXRA offspring bone mass. In this study, we used an existing randomized trial to test hypothesis that gestational vitamin supplementation would lead reduced methylation. The Maternal Vitamin Osteoporosis Study (MAVIDOS) was a multicenter, double-blind, randomized, placebo-controlled of 1000 IU/day cholecalciferol or matched...
There is now increasing evidence that asthma and atopy originate in part utero, with disease risk being associated the altered epigenetic regulation of genes.To determine relationship between variations DNA methylation at birth development allergic disease, we examined status CpG loci within promoter regions Th1/2 lineage commitment genes (GATA3, IL-4, IL-4R, STAT4 TBET) umbilical cord a cohort infants from Southampton Women's Survey (n = 696) who were later assessed for asthma, atopic...
Background Early life environments induce long-term changes in neurocognitive development and behaviour. In animal models, early environmental cues affect neuropsychological phenotypes via epigenetic processes but, as yet, there is little direct evidence for such mechanisms humans. Method We examined the relation between DNA methylation at birth child outcomes two culturally diverse populations using a genome-wide analysis validation by pyrosequencing. Results Within UK Southampton Women's...
Poor intrauterine and childhood growth has been linked with the risk of osteoporosis in later life, a relationship that may part be mediated through altered epigenetic regulation genes. We previously identified region within promoter long non-coding RNA ANRIL encoded by CDKN2A locus, at which differential DNA methylation birth showed correlations offspring adiposity. Given common lineage adipocytes osteoblasts, we investigated between perinatal bone mass ages 4 6 years. Using sodium...
The early life environment may influence susceptibility to obesity and metabolic disease in later through epigenetic processes. SLC6A4 is an important mediator of serotonin bioavailability, has a key role energy balance. We tested the hypothesis that methylation gene predicts adiposity across course.
Abstract Background Amongst healthy older people, a number of correlates impaired skeletal muscle mass and function have been defined. Although the prevalence obesity is increasing markedly in this age group, information sparse about particular impacts on ageing or molecular mechanisms that underlie associated disease risk. Methods Here, we examined genome‐wide transcriptional changes using RNA sequencing biopsies from 40 community‐dwelling men Hertfordshire Sarcopenia Study with regard to...
The genes encoding nuclear receptors comprise multiple 5′untranslated exons, which give rise to several transcripts the same protein, allowing tissue-specific regulation of expression. Both human and mouse peroxisome proliferator activated receptor (PPAR) α have promoters, although their function is unknown. Here we characterised rat PPARα promoter region identified three alternative transcripts, different transcription start sites owing utilisation distinct first exons. Moreover these were...
Introduction: Rapid, high throughput diagnostics are a valuable tool, allowing the detection of SARS-CoV-2 in populations, order to identify and isolate people with asymptomatic symptomatic infections. Reagent shortages restricted access testing solutions have limited effectiveness conventional assays such as reverse transcriptase quantitative PCR (RTqPCR), particularly throughout first months pandemic. We investigated use LamPORE, where loop mediated isothermal amplification (LAMP) is...
Abstract Background While ageing is associated with increased insulin resistance (IR), the molecular mechanisms underlying IR in muscle, primary organ for glucose clearance, have yet to be elucidated older individuals. As epigenetic processes are suggested contribute development of ageing-associated diseases, we investigated whether differential DNA methylation was human muscle stem cells (myoblasts) from community-dwelling Methods We measured (Infinium HumanMethylationEPIC BeadChip)...
descriptive data on rates of total hip (THR) and knee replacement (TKR) within a large national cohort incident RA patients describe the potential influence age, sex, geographic region socio-economic status.Methods: Patients with first diagnosis between 1995 2013 were identified from Clinical Practice Research Datalink (CPRD).Those diagnoses multiple types inflammatory arthritis excluded.First occurrence subsequent primary THR TKR using validated (to hospital records) Read code lists...