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Generation of histo-anatomically representative models of the individual heart: tools and application.
This paper presents methods to build histo-anatomically detailed individualized cardiac models. The models are based on high-resolution three-dimensional anatomical and/or diffusion tensor magnetic resonance images, combined with serial histological sectioning data, and are used to investigate individualized…
Two-pore Channels (TPC2s) and Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) at Lysosomal-Sarcoplasmic Reticular Junctions Contribute to Acute and Chronic β-Adrenoceptor Signaling in the Heart.
Ca(2+)-permeable type 2 two-pore channels (TPC2) are lysosomal proteins required for nicotinic acid adenine dinucleotide phosphate (NAADP)-evoked Ca(2+) release in many diverse cell types. Here, we investigate the importance of TPC2 proteins for the physiology and pathophysiology of the heart. NAAD…
Towards high-resolution cardiac atlases: Ventricular anatomy descriptors for a standardized reference frame
Increased resolution in cardiac Magnetic Resonance Imaging (MRI) and growing interest in the effect of small structures in electrophysiology of the heart pose new challenges for cardiac atlases. In this paper we discuss the limitations of current atlas-building models when trying to incorporate cardiac small st…
Histo-anatomical structure of the living isolated rat heart in two contraction states assessed by diffusion tensor MRI.
Deformation and wall-thickening of ventricular myocardium are essential for cardiac pump function. However, insight into the histo-anatomical basis for cardiac tissue re-arrangement during contraction is limited. In this report, we describe dynamic changes in regionally prevailing cardiomyocyte (fibre) and…
Minimum Information about a Cardiac Electrophysiology Experiment (MICEE): Standardised reporting for model reproducibility, interoperability, and data sharing
Cardiac experimental electrophysiology is in need of a well-defined Minimum Information Standard for recording, annotating, and reporting experimental data. As a step towards establishing this, we present a draft standard, called Minimum Information about a Cardiac Electrophysiology Experiment (MICEE).…
Mechanism of reentry induction by a 9-V battery in rabbit ventricles.
Although the application of a 9-V battery to the epicardial surface is a simple method of ventricular fibrillation induction, the fundamental mechanisms underlying this process remain unstudied. We used a combined experimental and modelling approach to understand how the interaction of direct current (…
Uniquely identifying cell orientation and sarcomere length in the intact rodent heart with oblique plane remote focussing microscopy
© 2015 SPIE-OSA. In cardiac imaging, the spacing between sub-cellular sarcomere structures is of great importance to physiologists in understanding muscle design and performance. Making accurate measurements of the sarcomere length (SL) presents a significant imaging challenge owing to the size of the SL…
Quantitative imaging of intact cardiac tissue using remote focusing microscopy
© 2015 SPIE. Remote focussing microscopy offers many advantages when acquiring volumetric data from living tissue. The all-optical means of refocussing does not agitate the specimen by moving either the stage or imaging objective. Aberration compensated imaging extends over volumes as large as 450 μm…
Imaging cardiomyocytes in intact tissue with a remote focusing microscope
© 2015 SPIE. In cardiac imaging, the spacing between sub-cellular sarcomere structures is of great importance to physiologists in understanding muscle design and performance. Making accurate measurements of the sarcomere length (SL) presents a significant imaging challenge owing to the size of the SL…
High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with Acidic Stores (lysosomes) in the heart.
Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) stimulates calcium release from acidic stores such as lysosomes and is a highly potent calcium-mobilising second messenger. NAADP plays an important role in calcium signalling in the heart under basal conditions and following β-adrenergic stress. Ne…
Ccoffinn: Automated Wave Tracking in Cultured Cardiac Monolayers.
Cardiac arrhythmias are one of the most frequent causes of death worldwide. A popular biological model used to study arrhythmogenesis is the cultured cardiac cell monolayer, which provides a good trade-off between physiological relevance and experimental access. Excitation wave patterns are imaged usi…
Caveolae in Rabbit Ventricular Myocytes: Distribution and Dynamic Diminution after Cell Isolation.
Caveolae are signal transduction centers, yet their subcellular distribution and preservation in cardiac myocytes after cell isolation are not well documented. Here, we quantify caveolae located within 100 nm of the outer cell surface membrane in rabbit single-ventricular cardiomyocytes over 8 h post-isolation an…
Integrated Proteomics Unveils Nuclear PDE3A2 as a Regulator of Cardiac Myocyte Hypertrophy.
BACKGROUND: Signaling by cAMP is organized in multiple distinct subcellular nanodomains regulated by cAMP-hydrolyzing PDEs (phosphodiesterases). Cardiac β-adrenergic signaling has served as the prototypical system to elucidate cAMP compartmentalization. Although studies in cardiac myocytes have p…
Optimised oligonucleotide substrates to assay XPF-ERCC1 nuclease activity for the discovery of DNA repair inhibitors.
We report the design and optimisation of novel oligonucleotide substrates for a sensitive fluorescence assay for high-throughput screening and functional studies of the DNA repair enzyme, XPF-ERCC1, with a view to accelerating inhibitor and drug discovery.
Neurons derived from individual early Alzheimer's disease patients reflect their clinical vulnerability.
Establishing preclinical models of Alzheimer's disease that predict clinical outcomes remains a critically important, yet to date not fully realized, goal. Models derived from human cells offer considerable advantages over non-human models, including the potential to reflect some of the inter-individual differences t…