A5087947862- Neurogenetic and Muscular Disorders Research
- Congenital Anomalies and Fetal Surgery
- Veterinary Orthopedics and Neurology
- Advanced MRI Techniques and Applications
- RNA modifications and cancer
- Congenital Heart Disease Studies
- Amyotrophic Lateral Sclerosis Research
- Congenital Diaphragmatic Hernia Studies
- Muscle Physiology and Disorders
- Veterinary Oncology Research
- RNA Research and Splicing
- Spine and Intervertebral Disc Pathology
- Lysosomal Storage Disorders Research
- Congenital heart defects research
- Glycogen Storage Diseases and Myoclonus
- Parkinson's Disease Mechanisms and Treatments
- Hereditary Neurological Disorders
- Cardiovascular Function and Risk Factors
- Cardiac Imaging and Diagnostics
- Spinal Dysraphism and Malformations
- Barrier Structure and Function Studies
- Craniofacial Disorders and Treatments
- Cellular transport and secretion
- Cardiac Structural Anomalies and Repair
- Alzheimer's disease research and treatments
Mott MacDonald (United Kingdom)
2018-2025
University of Edinburgh
2018-2025
University of Glasgow
2014-2020
Centre for Human Genetics
2012-2017
University of Oxford
2012-2017
British Heart Foundation
2013-2014
Semmelweis University
1987-1991
Hospital for Sick Children
1981
Great Ormond Street Hospital
1981
SickKids Foundation
1981
Increasing energy storage capacity by elevating creatine and phosphocreatine (PCr) levels to increase ATP availability is an attractive concept for protecting against ischaemia heart failure. However, testing this hypothesis has not been possible since oral supplementation ineffectual at myocardial levels. We therefore used mice overexpressing transporter in the (CrT-OE) test first time whether elevated beneficial clinically relevant disease models of failure ischaemia/reperfusion (I/R)...
Congenital vertebral malformations are common in brachycephalic “screw‐tailed” dog breeds such as French bulldogs, English Boston terriers, and pugs. The aim of this retrospective study was to determine whether a radiographic classification scheme developed for use humans would be feasible these breeds. Inclusion criteria were hospital admission between September 2009 April 2013, neurologic examination findings available, diagnostic quality lateral ventro‐dorsal digital radiographs the...
New Findings What is the central question of this study? There an ethical imperative to optimize analgesia protocols for laboratory animals, but impeded by our inability recognize pain reliably. We examined whether Mouse Grimace Scale (MGS) provides benefits over a standard welfare scoring system identifying low level in frequently used murine surgical model myocardial infarction. main finding and its importance? Low‐level pain, responsive analgesia, was detected MGS not methods. In model,...
Creatine buffers cellular adenosine triphosphate (ATP) via the creatine kinase reaction. levels are reduced in heart failure, but their contribution to pathophysiology is unclear. Arginine:glycine amidinotransferase (AGAT) kidney catalyses both first step biosynthesis as well homoarginine (HA) synthesis. AGAT-/- mice fed a creatine-free diet have whole body creatine-deficiency. We hypothesized that would develop cardiac dysfunction and rescue by dietary imply causality.Withdrawal of provided...
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in survival motor neuron 1 (SMN1). SMN-restoring therapies have recently emerged; however, preclinical and clinical studies revealed limited therapeutic time window systemic aspects of the disease. This raises fundamental question whether SMA has presymptomatic, developmental components to pathogenesis. We addressed this combining micro-computed tomography (μCT) comparative proteomics examine pre-symptomatic changes...
In pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries, there is a tendency for each artery to be the sole supply particular region of lung. On injection into artery, however, "wash-out" contrast medium by non-opacified blood from second source sometimes seen. Alternatively, may faintly "wash-in" an adjacent lobar supplied source. "Wash-in" therefore show that duplicate exists. To assess importance these phenomena, we reviewed angiograms 50 patients...
The objectives of this study were: To investigate computer-assisted digital radiographic measurement Cobb angles in dogs with congenital thoracic vertebral malformations, to determine its intra- and inter-observer reliability association the presence neurological deficits. Medical records were reviewed (2009–2013) identify brachycephalic screw-tailed dog breeds studies column at least one malformation present. Twenty-eight included study. end vertebrae defined as cranial plate vertebra...
Monogenic diseases are well-suited paradigms for the causal analysis of disease-driving molecular patterns. Spinal muscular atrophy (SMA) is one such monogenic model, caused by mutation or deletion survival motor neuron 1 (SMN1) gene. Although several functions SMN protein have been studied, single and pathways alone do not allow identification crucial molecules. Here, we analysed systemic characteristics SMA, using proteomics, phosphoproteomics, translatomics interactomics, from two mouse...
Neuronal ceroid lipofuscinoses (NCLs) are a group of incurable lysosomal storage disorders characterized by neurodegeneration and accumulation lipopigments mainly within the neurons. We studied two littermate Chihuahua dogs presenting with progressive signs blindness, ataxia, pacing, cognitive impairment from 1 year age. Because worsening clinical signs, both were euthanized at about 2 years Postmortem examination revealed marked autofluorescent intracellular inclusions brain, characteristic...
Spinal muscular atrophy (SMA) occurs as a result of cell-ubiquitous depletion the essential survival motor neuron (SMN) protein. Characteristic disease pathology is driven by particular vulnerability ventral neurons spinal cord to decreased SMN. Perhaps not surprisingly, many other organ systems are also impacted SMN depletion. The normal kidney expresses very high levels protein, equivalent those found in nervous system and liver, dramatically lowered ~90-95% mouse models SMA. Taken...
Background Multiple studies suggest creatine mediates anti-oxidant activity in addition to its established role cellular energy metabolism. The functional significance for the heart has yet be established, but antioxidant could contribute cardioprotective effect of ischaemia/reperfusion injury. Objectives To determine whether intracellular levels influence responses acute reactive oxygen species (ROS) exposure intact beating heart. We hypothesised that mice with elevated due over-expression...
Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in naturally occurring age-associated neuropathology canine species. In aged dogs declining learned behaviour memory severity cognitive dysfunction parallels progressive build up location Aβ brain. The main aim this work was to study biological soluble oligomers isolated from an dog through investigating their interaction a cell line synthetic peptides. We report that were specifically...
Congenital insensitivity to pain (CIP) and hereditary sensory autonomic neuropathies (HSANs) are a rare group of genetic disorders causing inability feel pain. Three different associated variants have been identified in dogs: 1 Border Collies, mixed breed dogs, Spaniels Pointers.To clinically genetically characterize CIP family dogs.Two dogs from the same litter were independently presented: for evaluation painless fractures, other chronic thermal skin injuries.Physical, neurological,...
Abstract Aims Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with complex aetiology. Despite evidence of neuromuscular junction (NMJ) denervation and ‘dying‐back’ pathology in models SOD1‐dependent ALS, other genetic forms ALS limited by lack suitable animal models. TDP‐43, key mediator protein overexpressed neurons Thy1‐hTDP‐43 WT mice. We therefore aimed to comprehensively analyse NMJ this model ALS. Methods Expression TDP‐43 was assessed via western blotting....
Abstract Background Intervertebral disc herniation is widely recognized as the most common cause of myelopathy in dogs older than 2 years; however, prevalence various causes younger has not been reported. Hypothesis/Objectives To describe prevalence, clinical presentation, and etiology aged 18 months or less. Secondarily, to investigate which features were associated with each etiologies. Animals Two hundred twenty‐four less included study. Methods Retrospective review records from 4...
Abstract Background Spinal muscular atrophy (SMA) is an autosomal recessive childhood-onset neuromuscular disease with a carrier frequency of ~1:50. Mitochondrial abnormalities are widespread in patients SMA. Disease carriers for SMA (i.e., the parents SMA) viewed as asymptomatic disease. As far we aware, mitochondria have not been previously examined carriers, yet they maternally inherited, mitochondrial function has putative implications pathogenesis. Methods Fibroblast cell lines derived...
The availability of three therapies for the neuromuscular disease spinal muscular atrophy (SMA) highlights need to match patients optimal treatment. Two these treatments (nusinersen and risdiplam) target splicing