A5080278530- Cardiac electrophysiology and arrhythmias
- Cardiovascular Function and Risk Factors
- Advanced MRI Techniques and Applications
- Advanced Neuroimaging Techniques and Applications
- Cardiac Arrhythmias and Treatments
- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Congenital heart defects research
- Pulmonary Hypertension Research and Treatments
- Ion channel regulation and function
- NMR spectroscopy and applications
- Advanced Fluorescence Microscopy Techniques
- Venous Thromboembolism Diagnosis and Management
- Mitochondrial Function and Pathology
- Functional Brain Connectivity Studies
- Cardiomyopathy and Myosin Studies
- Cardiac, Anesthesia and Surgical Outcomes
- Neonatal Respiratory Health Research
- Neurogenesis and neuroplasticity mechanisms
- Advanced Electron Microscopy Techniques and Applications
- Alzheimer's disease research and treatments
- Infant Development and Preterm Care
- Atrial Fibrillation Management and Outcomes
- Surgical site infection prevention
- Receptor Mechanisms and Signaling
University of Leeds
2011-2020
Kagawa Prefectural College of Health Sciences
2016
University of Manchester
2016
University of California, San Francisco
2016
University of Sheffield
2009
Cardiff University
2008
The human heart develops through complex mechanisms producing morphological and functional changes during gestation. We have recently demonstrated using diffusion tensor MRI that over the relatively short space of 40 days, between 100-140 days gestational age, ventricular myocardium transforms from a disorganised tissue to ordered structure characteristic mature cardiac tissue. However, genetic basis underpinning this maturation is unclear. Herein, we used RNA-Seq establish...
Nanodomains are intracellular foci which transduce signals between major cellular compartments. One of the most ubiquitous signal transducers, ryanodine receptor (RyR) calcium channel, is tightly clustered within these nanodomains. Super-resolution microscopy has previously been used to visualize RyR clusters near cell surface. A majority nanodomains located deeper cells have remained unresolved due limited imaging depths and axial resolution modalities. series enhancements made expansion...
We studied a new amyloid-beta precursor protein (App) knock-in mouse model of Alzheimer's disease (AppNL-G-F ), containing the Swedish KM670/671NL mutation, Iberian I716F mutation and Artic E693G which generates elevated levels amyloid beta (Aβ)40 Aβ42 without confounds associated with APP overexpression. This enabled us to assess changes in anxiety-related social behaviours, neural alterations potentially underlying such changes, driven specifically by Aβ accumulation. AppNL-G-F mice...
We construct the components for a family of computational models electrophysiology human foetal heart from 60 days gestational age (DGA) to full term. This requires both cell excitation that reconstruct myocyte action potentials, and datasets cardiac geometry architecture. Fast low-angle shot diffusion tensor magnetic resonance imaging (DT-MRI) hearts provides with voxel resolution approximately 100 µm. DT-MRI measures relative protons measure average intravoxel orientation, orientation any...
Right heart failure is the major cause of death in Pulmonary Artery Hypertension (PAH) patients but not a current, specific therapeutic target. Pre-clinical studies have shown that adrenoceptor blockade can improve cardiac function mechanisms action within right ventricular (RV) myocytes are unknown. We tested whether β
Heart block is associated with pulmonary hypertension, and the aim of study was to test hypothesis that heart result a change in ion channel transcriptome atrioventricular (AV) node.The most commonly used animal model monocrotaline-injected rat, used. The functional consequences monocrotaline injection were determined by echocardiography, ECG recording, electrophysiological experiments on Langendorff-perfused isolated AV node. measured quantitative PCR, biophysically detailed computer...
The developmental timeline of the human heart remains elusive. takes on its characteristic four chambered appearance by ~56 days gestational age (DGA). However, owing to complexities (both technical and logistical) exploring development in utero, we understand little how ventricular walls develop. To address this, employed diffusion tensor magnetic resonance imaging explore architecture tissue organization developing aged 95-143 DGA. We show that fractional anisotropy increases (from ~0.1...
To determine the microarchitecture of cervix using high-resolution diffusion tensor (DT) magnetic resonance imaging (MRI).Cross-sectional study.Leeds, UK.Women undergoing hysterectomy for benign pathology.Ex-vivo DT-MRI measurements were obtained a 9.4-T Bruker nuclear (NMR) spectrometer on seven fixed human cervices at hysterectomy. A deterministic fibre-tracking algorithm was used to indirectly visualise underlying fibre organisation. Inter-regional differences in tissue structure sought...
Of the many genetic mutations known to increase risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family presynaptic proteins are neurexins (NRXN), and recent mouse evidence has suggested causative role for NRXN2 in generating altered social behaviours. Autism been conceptualised as disorder atypical connectivity, yet how single-gene affect connectivity remains under-explored. To attempt address this, we have developed quantitative analysis...
We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure tested whether observed APD properties were responsible for negative mechanical in these myocytes. PAH RV provoked male Wistar by a single injection monocrotaline (MCT) compared saline-injected animals (CON). Action potentials recorded from isolated myocytes at stimulation frequencies between 1-9 Hz. waveforms 1Hz used as...
We aim to engineer a computational model of propagation during normal sinus rhythm in the foetal human heart, by modifying models for adult cardiac tissue match electrocardiogram (fECG) characteristics. The will be partially validated fECG data, and applied explore possible mechanisms arrhythmogenesis heart. Foetal electrocardiograms have been recorded pregnancy, with P- T-waves, QRS complex, identified averaging signal processing. Intervals are extracted used modify currently available...
The identification of arrhythmogenic right ventricular dysplasia (ARVD) from 12-channel standard electrocardiogram (ECG) is challenging. High density ECG data may identify lead locations and criteria with a higher sensitivity.Eighty-channel recording patients diagnosed ARVD controls were quantified by magnitude integral measures QRS T waves measure (the average silhouette width) differences in the shapes normalized cycles. channels best separability between near wall, at third intercostal...
The effect of human foetal heart geometry and anisotropy on anatomy induced drift self-termination cardiac re-entry is studied here in MRI based 2D slice 3D whole computer simulations. Isotropic anisotropic models 20 weeks gestational age obtained from 100μm voxel diffusion tensor data sets were used the fiber orientation angles DT-MRI primary eigenvectors. In a spatially homogeneous electrophysiological monodomain model with geometries, was initiated at prescribed location slice, models....
Abstract We studied two new App knock-in mice models of Alzheimer’s disease ( NL-F and NL-G-F ), which generate elevated levels Aβ 40 42 without the confounds associated with APP overexpression. This enabled us to assess changes in anxiety-related social behaviours, neural alterations potentially underlying such changes, driven specifically by accumulation. exhibited subtle deficits tasks assessing memory, but not motivation tasks. In anxiety-assessing tasks, exhibited: 1) increased...
Abstract Background Of the many genetic mutations known to increase risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family presynaptic proteins are neurexins (NRXN), and recent mouse evidence has suggested causative role for NRXN2 in generating altered social behaviours. Autism been conceptualised as disorder atypical connectivity, yet how single-gene affect connectivity remains under-explored. To attempt address this, we have developed...
Atrial and ventricular tachyarrhythmia are often sustained by re-entrant propagation, explained deterministic models. A quantitative, stochastic description of self-termination provides an alternative to the current paradigm for - that triggers a substrate, modelled parametrically heterogeneous partial differential equations data was from recordings obtained during routine clinical monitoring treatment, either noninvasively or invasively. tachycardia characterised their initiation times...
Cardiac function is impaired in severe malarial fever, and ECGs show changes associated with repolarization.These could contribute to mortality via ventricular arrhythmia.The cardiac effects be due the parasite load heart, specific cardio-toxic of or antimalarial agents.We construct a simple 1-dimensional electrophysiological model for physico-chemical clinically observed during fever: temperature, pH [ionic]plasma changes.The can quantitatively reproduce tachycardia QTc prolongation seen...