A5058879323- Atrial Fibrillation Management and Outcomes
- Ultrasound and Hyperthermia Applications
- Cardiac Imaging and Diagnostics
- Cardiomyopathy and Myosin Studies
- Ultrasound Imaging and Elastography
- Neuroscience and Neural Engineering
- Cardiac Valve Diseases and Treatments
- Cardiac Arrhythmias and Treatments
- COVID-19 and healthcare impacts
- Advanced Fluorescence Microscopy Techniques
- Cardiac Structural Anomalies and Repair
- Cardiovascular and Diving-Related Complications
- Photoreceptor and optogenetics research
- Cardiovascular Function and Risk Factors
- Cardiovascular Effects of Exercise
- Cardiac pacing and defibrillation studies
- Cardiac, Anesthesia and Surgical Outcomes
- Coronary Interventions and Diagnostics
- Mitochondrial Function and Pathology
- Bacterial Genetics and Biotechnology
- Photoacoustic and Ultrasonic Imaging
- Viral Infections and Immunology Research
- Cardiac electrophysiology and arrhythmias
- Infective Endocarditis Diagnosis and Management
- Ion channel regulation and function
Novo Nordisk (Denmark)
2025
Manchester Royal Infirmary
2020-2024
Oxford University Hospitals NHS Trust
2017-2023
University of Oxford
1971-2023
Manchester University NHS Foundation Trust
2020-2023
Henry Royce Institute
2020-2023
University of Manchester
2020-2023
Manchester Academic Health Science Centre
2020-2023
Health Sciences Centre
2022
Sana Biotechnology (United States)
2022
Abstract Luminescence imaging has gained attention as a promising bio-imaging modality in situations where fluorescence cannot be applied. However, wider application to multicolour and dynamic is limited by the lack of bright luminescent proteins with emissions across visible spectrum. Here we report five new spectral variants protein, enhanced Nano-lantern (eNL), made concatenation brightest luciferase, NanoLuc, various colour hues fluorescent proteins. eNLs allow five-colour live-cell...
The intratumor microenvironment generates phenotypically distinct but interconvertible malignant cell subpopulations that fuel metastatic spread and therapeutic resistance. Whether different microenvironmental cues impose invasive or therapy-resistant phenotypes via a common mechanism is unknown. In melanoma, low expression of the lineage survival oncogene microphthalmia-associated transcription factor (MITF) correlates with invasion, senescence, drug However, how MITF suppressed in vivo...
Germ-line mutations inactivating BRCA2 predispose to cancer. BRCA2-deficient cells exhibit alterations in chromosome number (aneuploidy), as well structurally aberrant chromosomes. Here, we show that deficiency impairs the completion of cell division by cytokinesis. inactivation murine embryo fibroblasts (MEFs) and HeLa targeted gene disruption or RNA interference delays prevents cleavage. Impeded separation is accompanied abnormalities myosin II organization during late stages may have a...
The membranes of plant and animal cells contain aquaporins, proteins that facilitate the transport water. In plants, aquaporins are found in vacuolar membrane (tonoplast) plasma membrane. Many mercury sensitive, AQP1, a mercury-sensitive cysteine residue (Cys-189) is present adjacent to conserved Asn-Pro-Ala motif. Here, we report molecular analysis new Arabidopsis aquaporin, delta-TIP (for tonoplast intrinsic protein), show it located tonoplast. water channel activity sensitive mercury....
Paravalvular leak (PVL) occurs in 5% to 17% of patients following surgical valve replacement. Percutaneous device closure represents an alternative repeat surgery.All UK and Ireland centers undertaking percutaneous PVL submitted data the Registry. Data were analyzed for association with death major adverse cardiovascular events (MACE) at follow-up.Three hundred eight procedures attempted 259 20 (2004-2015). Patient age was 67±13 years; 28% female. The main indications heart failure (80%)...
Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying progression are unclear. We sought to assess the extent of LGE HCM explore potential causal clinical implications.Seventy-two patients had two CMR (CMR1-CMR2) at an interval 5.7 ± 2.8 years with annual follow-up for 6.3 3.6 from CMR1. A combined endpoint heart...
The field of left atrial appendage occlusion is rapidly evolving. However, several issues remain including the limited randomized efficacy data, peri-device leak, device-related thrombus, and ongoing refinement procedural techniques. In this article, we provide a contemporary overview focusing on 4 key remaining challenges: optimization.
To investigate mitophagy in 5 patients with severe dominantly inherited optic atrophy (DOA), caused by depletion of OPA1 (a protein that is essential for mitochondrial fusion), compared healthy controls.Patients DOA (DOA plus) had peripheral neuropathy, cognitive regression, and epilepsy addition to loss vision. We quantified dermal fibroblasts, using 2 high throughput imaging systems, visualizing colocalization fragments engulfing autophagosomes.Fibroblasts from 3 biallelic OPA1(-/-)...
We report development of the first genetically encoded bioluminescent indicator for membrane voltage called LOTUS-V. Since it is bioluminescent, imaging LOTUS-V does not require external light illumination. This allows bidirectional optogenetic control cellular activity triggered by Channelrhodopsin2 and Halorhodopsin during imaging. The other advantage robustness a signal-to-background ratio (SBR) wherever expressed, even in specimens where autofluorescence from environment severely...
Thin filament hypertrophic cardiomyopathy (HCM) mutations increase myofilament Ca2+ sensitivity and alter handling buffering. The myosin inhibitor mavacamten reverses the increased contractility caused by HCM thick mutations, we here test its effect on thin where mode of action is not known. Mavacamten (250 nM) partially reversed Cardiac troponin T (cTnT) R92Q, cardiac I (cTnI) R145G in vitro ATPase assays. was also analyzed cardiomyocyte models cTnT R92Q cTnI containing cytoplasmic specific...
The bacterial cell membrane seems to have a direct role in DNA replication (Ganesan and Lederberg, 1965; Smith Hanawalt, 1967) segregation (Jacob et al., 1963; Lark, 1966). A physical connection between the has been found various bacteria by electron microscopic examination of thin sections (Ryter, 1968) sedimentation lysates through sucrose gradients 1967). influence artifacts preparation on results obtained these methods cannot be assessed with certainty.
Lipid synthesis during the cell duplication cycle of Bacillus megaterium KM and Escherichia coli was studied by glycerol incorporation both in synchronized cultures unsynchronized exponentially growing populations subsequently fractionated according to size (and age). A large transient increase rate per unit mass observed around time division, probably reflecting division septum.
Increasing numbers of genes are being implicated in Mendelian disorders and incorporated into clinical test panels. However, lack evidence supporting the gene-disease relationship can hinder interpretation. We explored utility testing 51 additional for hypertrophic cardiomyopathy (HCM), one most commonly tested disorders.Using genome sequencing data from 240 sarcomere gene negative HCM cases 6229 controls, we undertook case-control individual variant analyses to assess that have been...
Subcellular Ca2+ indicators have yet to be developed for the myofilament where disease mutation or small molecules may alter contractility through sensitivity. Here, we develop and characterize genetically encoded restricted directly visualize changes in sarcomere.To produce validate myofilament-restricted imaging probes an adenoviral transduction adult cardiomyocyte model using drugs that function (MYK-461, omecamtiv mecarbil, levosimendan) following cotransduction of 2 established...
We compared commonly used BAPTA-derived chemical Ca
Both biomedical research and clinical practice rely on complex datasets for the physiological genetic characterization of human hearts in health disease. Given complexity variety approaches recordings, there is now growing recognition need to embed computational methods cardiovascular medicine science analysis, integration prediction. This paper describes a Workshop Computational Cardiovascular Science that created an international, interdisciplinary inter-sectorial forum define next steps...