A5037874382- Cardiac electrophysiology and arrhythmias
- Corneal surgery and disorders
- Cardiomyopathy and Myosin Studies
- Proteoglycans and glycosaminoglycans research
- Ion channel regulation and function
- Mitochondrial Function and Pathology
- Ocular Surface and Contact Lens
- Cardiovascular Function and Risk Factors
- Protease and Inhibitor Mechanisms
- Connective tissue disorders research
- Corneal Surgery and Treatments
- Endoplasmic Reticulum Stress and Disease
- Cardiac Imaging and Diagnostics
- Collagen: Extraction and Characterization
- ATP Synthase and ATPases Research
- Force Microscopy Techniques and Applications
- Neuroscience and Neural Engineering
- Atrial Fibrillation Management and Outcomes
- Electron and X-Ray Spectroscopy Techniques
- RNA and protein synthesis mechanisms
- Proteins in Food Systems
- Tissue Engineering and Regenerative Medicine
- RNA modifications and cancer
- Cardiac Arrhythmias and Treatments
- Advanced Electron Microscopy Techniques and Applications
University of Manchester
2015-2025
Manchester Academic Health Science Centre
2019-2024
Cardiff University
2006-2016
Cardiovascular Institute Hospital
2015
Cardiovascular Research Center
2015
Manchester University
2014
The organization of the transverse-tubular (t-t) system and relationship to sarcoplasmic reticulum (SR) underpins cardiac excitation-contraction coupling. architecture SR, with t-ts, is not well characterized at whole-cell level. Furthermore, little known regarding changes SR ultrastructure in heart failure.The aim this study was unravel interspecies differences commonalities between t-t networks within myocytes, as modifications that occur failure, using a novel high-resolution...
Significance The cornea is a specialized connective tissue assembled as remarkably ordered array of superimposed collagenous lamellae, and their component collagen fibrils, essential for optical transparency. Surprisingly, the mechanisms involved in deposition this unique structure are still not fully understood. Here we have used correlative microscopy techniques, including innovative methods serial block face scanning electron microscopy, to observe sequence corneal matrix formation...
Intracellular calcium cycling is a vital component of cardiac excitation-contraction coupling. The key structures responsible for controlling dynamics are the cell membrane (comprising surface sarcolemma and transverse-tubules), intracellular store (the sarcoplasmic reticulum), co-localisation these two to form dyads within which calcium-induced-calcium-release occurs. organisation tightly controls dynamics. In this study, we present computational model in three-dimensions (3-D),...
Obesity-induced lipid overload in cardiomyocytes contributes to profound oxidative stress and cardiomyopathy, culminating heart failure. In this study, we investigate a novel mechanism whereby lipids accumulate cardiomyocytes, seek the relevant treatment strategies. P21-activated kinase 3 (PAK3) was elevated obese human myocardium, murine hearts upon diet- or fatty acid–induced stress, respectively. Mice with cardiac-specific overexpression of PAK3 were more susceptible development cardiac...
BACKGROUND: Morbidity and mortality of heart failure with preserved ejection fraction (HFpEF) is increased in metabolic disorders. However, options for preventing treating these prevalent outcomes are limited. Intramyocardial lipotoxicity contributes to cardiac dysfunction. Here, we investigate the mechanisms underlying endoplasmic reticulum degradation enhancing EDEM2 (endoplasmic degradation–enhancing alpha-mannosidase–like protein 2) regulation lipid homeostasis assess strategies that...
Background Heart failure is a common secondary complication following myocardial infarction ( MI ), characterized by impaired cardiac contraction and t‐tubule (t‐t) loss. However, post‐ nano‐scale morphological changes to the remaining t‐ts are poorly understood. Method Results We utilized porcine model of , using nonlethal microembolization method generate controlled microinfarcts. Using serial block face scanning electron microscopy, we report that after mild left‐ventricular dysfunction...
The role of Decorin in organising the extracellular matrix was examined normal human corneas and from patients with Congenital Stromal Corneal Dystrophy (CSCD). In CSCD, corneal clouding occurs due to a truncating mutation (c.967delT) decorin (DCN) gene. Normal protein truncated one were reconstructed silico using homology modelling techniques explore structural changes diseased protein. CSCD specimens also 3-D electron tomography Small Angle X-ray diffraction (SAXS), image...
JP2 (junctophilin-2) is believed to hold the transverse tubular and jSR (junctional sarcoplasmic reticulum) membranes in a precise geometry that facilitates excitation-contraction coupling cardiomyocytes. We have expressed purified human shown using electron microscopy protein forms elongated structures ~15 nm long 2 wide. Employing lipid-binding assays quartz crystal microbalance with dissipation we determined selective for PS (phosphatidylserine), Kd value of ~0.5 μM, N-terminal domain...
BACKGROUND: Transverse (t)-tubules drive the rapid and synchronous Ca 2+ rise in cardiac myocytes. The virtual complete atrial t-tubule loss heart failure (HF) decreases release. It is unknown if or how t-tubules can be restored this affects systolic . METHODS: HF was induced sheep by ventricular pacing recovered following termination of pacing. Serial block-face scanning electron microscopy confocal imaging were used to study ultrastructure. Function assessed using patch clamp, , imaging....
Deficiencies in enzymes involved proteoglycan (PG) turnover underlie a number of rare mucopolysaccharidoses (MPS), investigations which can considerably aid understanding the roles PGs corneal matrix biology. Here, authors analyze novel pathologic changes MPS VII (Sly syndrome) to determine nature PG-collagen associations stromal ultrastructure.Transmission electron microscopy and tomography were used investigate architectures interactions cornea obtained at keratoplasty from 22-year-old man...
Efficient mitochondrial function is required in tissues with high energy demand such as the heart, and dysfunction associated cardiovascular disease. Expression of proteins tightly regulated response to internal external stimuli. Here we identify a novel mechanism regulating content function, through BUD23-dependent ribosome generation. BUD23 was for maturation, normal 18S/28S stoichiometry modulated translation transcripts human A549 cells. Deletion Bud23 murine cardiomyocytes reduced...
Defining the structural changes involved in myosin cross-bridge cycle on actin active muscle by X-ray diffraction will involve recording of whole two dimensional (2D) pattern from a time-resolved manner. Bony fish is most highly ordered vertebrate striated to study. With partial sarcomere length (SL) control we show that equatorial A-band (10) and (11) reflections, along with (10)/(11) intensity ratio tension, are much more rapid than without such control. Times 50% change SL were 19.5...
Excitation-contraction coupling in vertebrate hearts is underpinned by calcium (Ca2+) release from Ca2+ units (CRUs). CRUs are formed clusters of channels called ryanodine receptors on the sarcoplasmic reticulum (SR) within cardiomyocyte. Distances between influence diffusion Ca2+, thus influencing rate and strength excitation-contraction coupling. Avian myocytes lack T-tubules, surface (peripheral couplings, PCs), must diffuse to internal CRU sites corbular SR (cSR) during centripetal...
Cardiac myocytes rely on transverse (t)-tubules to facilitate a rapid rise in calcium throughout the cell. However, despite their importance triggering synchronous Ca2+ release, t-tubules are highly labile structures. They develop postnatally, increase density during exercise training and lost diseases such as heart failure (HF). In majority of settings, an absence decreases function. Here we show that reduced t-tubule due immature t-tubules, newborn atrium is specialised maintain release....
The highly organized transverse tubule (t-tubule) network facilitates cardiac excitation-contraction coupling and synchronous myocyte contraction. In failure secondary to myocardial infarction (MI), changes in the structure organization of t-tubules result impaired contractility. However, there is still little knowledge on regional variation t-tubule remodelling post-MI. Here, we investigate post-MI infarct border remote regions, using serial block face scanning electron microscopy (SBF-SEM)...
<p dir="ltr"><b>Abstract</b></p><p dir="ltr">Obesity-induced lipid overload in cardiomyocytes contributes to profound oxidative stress and cardiomyopathy, culminating heart failure. In this study, we investigate a novel mechanism whereby lipids accumulate seek the relevant treatment strategies. <a href="" target="_blank">P21-activated kinase 3 (PAK3) was elevated obese human myocardium, murine hearts upon diet- or fatty acid-induced stress, respectively....