A5080626785- Adipose Tissue and Metabolism
- Muscle Physiology and Disorders
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Pancreatic function and diabetes
- Mitochondrial Function and Pathology
- CAR-T cell therapy research
- Metabolism, Diabetes, and Cancer
- Metabolism and Genetic Disorders
- Genetic Neurodegenerative Diseases
- Health Systems, Economic Evaluations, Quality of Life
- Lung Cancer Diagnosis and Treatment
- Calpain Protease Function and Regulation
- Head and Neck Cancer Studies
- Growth Hormone and Insulin-like Growth Factors
- Virus-based gene therapy research
- Biochemical Acid Research Studies
- Biomedical Ethics and Regulation
- Health, Environment, Cognitive Aging
- Genetic Associations and Epidemiology
- Peroxisome Proliferator-Activated Receptors
- Amyotrophic Lateral Sclerosis Research
- Blood properties and coagulation
- Colorectal and Anal Carcinomas
- Sulfur Compounds in Biology
- Cholangiocarcinoma and Gallbladder Cancer Studies
Data Management (Italy)
2024
University of Newcastle Australia
2021
Newcastle University
2007-2020
NIHR Newcastle Biomedical Research Centre
2018
Precision BioSciences (United States)
2016-2017
Freeman Hospital
2014
University of Glasgow
2006
Chronic fatigue syndrome (CFS) is a highly debilitating disease of unknown aetiology. Abnormalities in bioenergetic function have been cited as one possible cause for CFS. Preliminary studies were performed to investigate cellular abnormalities CFS patients. A series assays conducted using peripheral blood mononuclear cells (PBMCs) from patients and healthy controls. These experiments investigated patterns oxidative phosphorylation (OXPHOS) glycolysis. Results showed consistently lower...
Mammalian pyruvate dehydrogenase multienzyme complex (PDC) is a key metabolic assembly comprising 60-meric pentagonal dodecahedral E2 (dihydrolipoamide acetyltransferase) core attached to which are 30 decarboxylase E1 heterotetramers and 6 dihydrolipoamide E3 homodimers at maximal occupancy. Stable integration mediated by an accessory E3-binding protein (E3BP) located on each of the 12 icosahedral faces. Here, we present evidence for novel subunit organization in E3BP form subcomplexes with...
Background Post exertional muscle fatigue is a key feature in Chronic Fatigue Syndrome (CFS). Abnormalities of skeletal function have been identified some but not all patients with CFS. To try to limit potential confounders that might contribute this clinical heterogeneity, we developed novel vitro system allows comparison AMP kinase (AMPK) activation and metabolic responses exercise cultured cells from CFS control subjects. Methods Skeletal cell cultures were established 10 subjects 7...
Skeletal muscle is the key site of peripheral insulin resistance in type 2 diabetes. Insulin-stimulated glucose uptake decreased differentiated diabetic cultured myotubes, which keeping with a retained genetic/epigenetic defect action. We investigated differences gene expression during differentiation between and control cell cultures. Microarray analysis was performed using skeletal cultures established from patients family history diabetes clinical evidence marked nondiabetic subjects no...
Type 2 diabetes is characterised by an age-related decline in insulin secretion. We previously identified a 50% mitochondrial DNA (mtDNA) copy number isolated human islets. The purpose of this study was to mimic degree mtDNA depletion MIN6 cells determine whether there direct impact on Transcriptional silencing transcription factor A, TFAM, decreased levels 40% cells. This level significantly gene and translation, resulting reduced respiratory capacity ATP production. Glucose-stimulated...
Abnormalities in mitochondrial function have previously been shown chronic fatigue syndrome (CFS) patients, implying that dysfunction may contribute to the pathogenesis of disease. This study builds on previous work showing respiratory parameters are impaired whole cells from CFS patients by investigating activity individual chain complexes. Two different cell types were used these studies order assess complex locally skeletal muscle (myotubes) (n = 6) and systemically (peripheral blood...
Skeletal muscle fatigue and post-exertional malaise are key symptoms of myalgic encephalomyelitis (ME)/chronic syndrome (ME/CFS). We have previously shown that AMP-activated protein kinase (AMPK) activation glucose uptake impaired in primary human skeletal cell cultures derived from patients with ME/CFS response to electrical pulse stimulation (EPS), a method which induces contraction cells vitro. The aim the present study was assess if AMPK could be activated pharmacologically ME/CFS....
Insulin-resistant type 2 diabetic patients have been reported to impaired skeletal muscle mitochondrial respiratory function. A key question is whether decreased respiration contributes directly the insulin action. To address this, a model of cellular function was established by incubating human cell cultures with inhibitor sodium azide and examining effects on Incubation cells 50 75 microM resulted in 48 +/- 3% 56 1% decreases, respectively, compared untreated mimicking level impairment...
Abstract We report a 17‐yr‐old boy who developed microangiopathic hemolytic anemia presumed secondary to tacrolimus shortly following living‐related donor renal transplant. This was initially managed by plasmapheresis. Reinstitution of calcineurin inhibition using cyclosporine led recurrence hemolysis, so an alternative agent needed. He commenced on monthly intravenous belatacept, with no further the and subsequent stable graft function. Modulation via CTLA ‐4 offers immunosuppressive tactic...
Abstract Recent reports describing allogeneic chimeric antigen receptor (CAR) T cell therapies have generated tremendous excitement over the possibility of a universal CAR platform. We are utilizing highly engineered meganuclease designed to target (TCR) alpha chain eliminate expression TCR, preventing graft versus host disease following adoptive transfer. Meganuclease cleavage efficiency is dependent on stimulation cells prior delivery meganuclease. To determine optimal activation...
To evaluate the economic impact of MS, specifically on employment and utilization healthcare resources.
Background: Primary Sjögren’s syndrome (pSS) is a heterogeneous disease characterized by lymphocytic infiltrates to the exocrine glands, causing sicca symptoms and other manifestations. Fatigue one of most prominent symptom in pSS; up 70% suffer from chronic fatigue. has been shown be common severe patients suffering primary mitochondrial DNA (mtDNA) disease. In number diseases, copy (mtDNAcn) reported altered.Purpose: The aim study was examine if mtDNAcn altered fatigued versus non-fatigued...