A5027930827- Nutrition and Health in Aging
- Muscle Physiology and Disorders
- Adipose Tissue and Metabolism
- Muscle metabolism and nutrition
- Sports Performance and Training
- GDF15 and Related Biomarkers
- RNA modifications and cancer
- MicroRNA in disease regulation
- Body Composition Measurement Techniques
- Obesity, Physical Activity, Diet
- Metabolomics and Mass Spectrometry Studies
- Cancer-related molecular mechanisms research
- Diet and metabolism studies
- Adipokines, Inflammation, and Metabolic Diseases
- Physical Activity and Health
- Genetics and Physical Performance
- Health and Lifestyle Studies
- Vitamin D Research Studies
- Body Contouring and Surgery
- Circular RNAs in diseases
- RNA Research and Splicing
- Immune Response and Inflammation
- Cardiovascular and exercise physiology
- Exercise and Physiological Responses
- Sports Analytics and Performance
Edinburgh Napier University
2023-2025
University of Stirling
2015-2024
Roslin Institute
2017
University of Edinburgh
2004-2017
Edinburgh Royal Infirmary
2012-2015
Genomics England
2015
University of the Highlands and Islands
2015
MRC Centre for Regenerative Medicine
2012
Medical Research Council
2012
University of Birmingham
2012
MicroRNAs (miRNA), small noncoding RNA molecules, may regulate protein synthesis, while resistance exercise training (RT) is an efficient strategy for stimulating muscle synthesis in vivo. However, RT increases mass, with a very wide range of effectiveness humans. We therefore determined the expression level 21 abundant miRNAs to determine whether variation these was able explain RT-induced gains mass. Vastus lateralis biopsies were obtained from top and bottom ∼20% responders 56 young men...
Skeletal muscle insulin resistance (IR) is considered a critical component of type II diabetes, yet to date IR has evaded characterization at the global gene expression level in humans. MicroRNAs (miRNAs) are fine-scale rheostats protein-coding product abundance. The relative importance and mode action miRNAs human complex diseases remains be fully elucidated. We produce map coding non-coding RNAs with aim identifying novel disease biomarkers. profiled >47,000 mRNA sequences >500 using...
Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases older age. We take a transcriptomics approach to build first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years age in good health. One hundred and fifty probe-sets form an accurate classifier young versus muscle this healthy performed consistently independent cohorts muscle,...
Abstract Alternatively activated macrophages (AAMΦ) are found in abundance during chronic Th2 inflammatory responses to metazoan parasites. Important roles for these being defined, particularly the context of Th2-mediated pathology and fibrosis. However, a full understanding requirements alternative activation, at innate level, is lacking. We present evidence that activation by cytokines IL-4 IL-13 an rapid response tissue injury takes place even absence infectious agent. This early does not...
ABSTRACT Ym1 and Fizz1 are secreted proteins that have been identified in a variety of Th2-mediated inflammatory settings. We originally found as highly expressed macrophage genes Brugia malayi infection model. Here, we show their expression is generalized feature nematode they induced at the site with both tissue Litomosoides sigmodontis gastrointestinal Nippostrongylus brasiliensis . At sites N. , also observed induction other chitinase Fizz family members (ChaFFs): acidic mammalian...
The molecular pathways that are activated and contribute to physiological remodeling of skeletal muscle in response endurance exercise have not been fully characterized. We previously reported ∼800 gene transcripts regulated following 6 wk supervised training young sedentary males, referred as the training-responsive transcriptome (TRT) (Timmons JA et al. J Appl Physiol 108: 1487-1496, 2010). Here we utilized this database together with data on biological variation adaptation aerobic both...
Cancer cachexia is a multi-organ tissue wasting syndrome that contributes to morbidity and mortality in many cancer patients. Skeletal muscle loss represents an established key feature yet there no molecular understanding of the disease process. In fact, postulated regulators originate largely from pre-clinical models it unclear how these translate clinical environment.Rectus abdominis biopsies were obtained 65 upper gastrointestinal (UGI) patients during open surgery RNA profiling was...
Serious and underappreciated sources of bias mean that extreme caution should be applied when using or interpreting functional enrichment analysis to validate findings from global RNA- protein-expression analyses.
Adipose tissue abundance relies partly on the factors that regulate adipogenesis, i.e. proliferation and differentiation of adipocytes. While components transcriptional program initiates adipogenesis is well-known, importance microRNAs in less well studied. We thus set out to investigate whether miRNAs would be actively modulated during obesity.Several models exist study vitro, which cell line 3T3-L1 most known, albeit not physiologically appropriate. Thus, as an alternative, we produced...
The Vitamin D receptor (VDR) has been positively associated with skeletal muscle mass, function and regeneration. Mechanistic studies have focused on the loss of receptor, in vivo whole-body knockout models demonstrating reduced myofibre size impaired development. To understand mechanistic role upregulation VDR elicits mass/health, we studied impact over-expression (OE) before exploring importance expression upon hypertrophy humans. Wistar rats underwent electrotransfer (IVE) to overexpress...
Statins, best known for their lipid-lowering actions, also possess immunomodulatory properties. Recent studies have shown a Th2-biasing effect of statins, although the underlying mechanism has not been identified. In this study, we investigated whether simvastatin can exercise Th2-promoting through modulation function dendritic cells (DCs) without direct interaction with CD4+ T cells. Exposure DCs to induced differentiation distinct subset characterized by high expression B220. These...
Abstract Purpose: The mechanisms underlying muscle wasting in patients with cancer remain poorly understood, and consequently there remains an unmet clinical need for new biomarkers treatment strategies. Experimental Design: Microarrays were used to examine the transcriptome single biopsies from healthy controls (n = 6) paired [pre-resection baseline (weight-loss 7%) 8 month post-resection follow-up (disease-free/weight-stable previous 2 months)] quadriceps of upper gastrointestinal (UGIC; n...
Low aerobic exercise capacity is a risk factor for diabetes and strong predictor of mortality, yet some individuals are "exercise-resistant" unable to improve through training. To test the hypothesis that resistance training underlies metabolic disease risk, we used selective breeding 15 generations develop rat models low high response Before training, rats selected as responders had similar capacities. However, after 8 weeks treadmill failed their capacity, whereas improved by 54%....
Abstract Background In order to grow the potential therapeutic armamentarium in cachexia domain of supportive oncology, there is a pressing need develop suitable biomarkers and drug targets. This pilot study evaluated several candidate skeletal muscle biopsies from cohort upper gastrointestinal cancer (UGIC) patients. Methods One hundred seven patients (15 weight‐stable healthy controls (HC) 92 UGIC patients) were recruited. Mean (standard deviation) weight‐loss was 8.1 (9.3%). Cachexia...
Abstract Context There is evidence demonstrating variation in insulin sensitivity across the menstrual cycle. However, to date, research has yielded inconsistent results. Objective This study investigated cycle and associations with body mass index (BMI), physical activity, cardiorespiratory fitness (CRF). Methods Data from 1906 premenopausal women NHANES cycles 1999 2006 were analyzed. Menstrual day was assessed using questionnaire responses recording days since last period. Rhythmic of...
Genome-wide association studies (GWAS), relying on hundreds of thousands individuals, have revealed >200 genomic loci linked to metabolic disease (MD). Loss insulin sensitivity (IS) is a key component MD and we hypothesized that discovery robust IS transcriptome would help reveal the underlying structure MD. Using 1,012 human skeletal muscle samples, detailed physiology tissue-optimized approach for quantification coding (>18,000) non-coding (>15,000) RNA (ncRNA), identified 332 fasting...
Key points Reduced vitamin D receptor (VDR) expression prompts skeletal muscle atrophy. Atrophy occurs through catabolic processes, namely the induction of autophagy, while anabolism remains unchanged. In response to VDR‐knockdown mitochondrial function and related gene‐set is impaired. vitro VDR knockdown induces myogenic dysregulation occurring impaired differentiation. These results highlight autonomous role has within mass regulation. Abstract Vitamin deficiency estimated affect ∼40%...
Autoimmunity is increasingly recognized as a key contributing factor in heart muscle diseases. The functional features of cardiac autoimmunity humans remain undefined because the challenge studying immune responses situ. We previously described subset c-mesenchymal epithelial transition (c-Met)-expressing (c-Met+) memory T lymphocytes that preferentially migrate to tissue mice and humans. In-depth phenotyping peripheral blood cells, including c-Met+ was undertaken groups patients with...