Victor Chang Cardiac Research Institute

About: Victor Chang Cardiac Research Institute is a nonprofit organization based out in Sydney, New South Wales, Australia. It is known for research contribution in the topics: Mechanosensitive channels & Heart failure. The organization has 708 authors who have published 1599 publications receiving 70035 citations.

Characterization of Pitx2c expression in the mouse heart using a reporter transgene.

Abstract: To aid in detection and tracking of cells targeted by the left-right (LR) pathway in the heart throughout morphogenesis, expression from a Pitx2c-lacZ transgene (P2Ztg) was analysed in detail. β-galactosidase expression from P2Ztg was robust, allowing reliable visualisation of low-level Pitx2c expression, and was virtually entirely dependent upon NODAL signalling in the heart. P2Ztg showed expression in trabecular and septal, as well as non-trabecular, myocardium, and a strong expression bias in myocardium associated with individual endocardial cushions of the atrioventricular canal and outflow tract, which are essential for cardiac septation. Expression on the ventral surface of the outflow tract evolved to a specific stripe that could be used to track the future aorta during outflow tract spiralling and remodelling. Our data show that the P2Ztg transgene is a useful resource for detection of molecular disturbances in the LR cascade, as well as morphogenetic defects associated with other cardiac congenital disorders. Developmental Dynamics, 2011. © 2010 Wiley-Liss, Inc.

Activation of the mechanosensitive ion channel MscL by mechanical stimulation of supported Droplet-Hydrogel bilayers.

Abstract: The droplet on hydrogel bilayer (DHB) is a novel platform for investigating the function of ion channels. Advantages of this setup include tight control of all bilayer components, which is compelling for the investigation of mechanosensitive (MS) ion channels, since they are highly sensitive to their lipid environment. However, the activation of MS ion channels in planar supported lipid bilayers, such as the DHB, has not yet been established. Here we present the activation of the large conductance MS channel of E. coli, (MscL), in DHBs. By selectively stretching the droplet monolayer with nanolitre injections of buffer, we induced quantifiable DHB tension, which could be related to channel activity. The MscL activity response revealed that the droplet monolayer tension equilibrated over time, likely by insertion of lipid from solution. Our study thus establishes a method to controllably activate MS channels in DHBs and thereby advances studies of MS channels in this novel platform.

Late systolic pressure augmentation: role of left ventricular outflow patterns.

Abstract: Late systolic augmentation of the ascending aortic pressure waveform is believed to be caused by particular impedance patterns but also could be caused by particular left ventricular outflow patter...

Serum Exosome MicroRNAs Predict Multiple Sclerosis Disease Activity after Fingolimod Treatment.

Abstract: We and others have previously demonstrated the potential for circulating exosome microRNAs to aid in disease diagnosis. In this study, we sought the possible utility of serum exosome microRNAs as biomarkers for disease activity in multiple sclerosis patients in response to fingolimod therapy. We studied patients with relapsing-remitting multiple sclerosis prior to and 6 months after treatment with fingolimod. Disease activity was determined using gadolinium-enhanced magnetic resonance imaging. Serum exosome microRNAs were profiled using next-generation sequencing. Data were analysed using univariate/multivariate modelling and machine learning to determine microRNA signatures with predictive utility. Accordingly, we identified 15 individual miRNAs that were differentially expressed in serum exosomes from post-treatment patients with active versus quiescent disease. The targets of these microRNAs clustered in ontologies related to the immune and nervous systems and signal transduction. While the power of individual microRNAs to predict disease status post-fingolimod was modest (average 77%, range 65 to 91%), several combinations of 2 or 3 miRNAs were able to distinguish active from quiescent disease with greater than 90% accuracy. Further stratification of patients identified additional microRNAs associated with stable remission, and a positive response to fingolimod in patients with active disease prior to treatment. Overall, these data underscore the value of serum exosome microRNA signatures as non-invasive biomarkers of disease in multiple sclerosis and suggest they may be used to predict response to fingolimod in future clinical practice. Additionally, these data suggest that fingolimod may have mechanisms of action beyond its known functions.