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.

How to test bioinformatics software

Abstract: Bioinformatics is the application of computational, mathematical and statistical techniques to solve problems in biology and medicine. Bioinformatics programs developed for computational simulation and large-scale data analysis are widely used in almost all areas of biophysics. The appropriate choice of algorithms and correct implementation of these algorithms are critical for obtaining reliable computational results. Nonetheless, it is often very difficult to systematically test these programs as it is often hard to verify the correctness of the output, and to effectively generate failure-revealing test cases. Software testing is an important process of verification and validation of scientific software, but very few studies have directly dealt with the issues of bioinformatics software testing. In this work, we review important concepts and state-of-the-art methods in the field of software testing. We also discuss recent reports on adapting and implementing software testing methodologies in the bioinformatics field, with specific examples drawn from systems biology and genomic medicine.

Cellular rescue in a zebrafish model of congenital muscular dystrophy type 1A

Abstract: Laminins comprise structural components of basement membranes, critical in the regulation of differentiation, survival and migration of a diverse range of cell types, including skeletal muscle. Mutations in one muscle enriched Laminin isoform, Laminin alpha2 (Lama2), results in the most common form of congenital muscular dystrophy, congenital muscular dystrophy type 1A (MDC1A). However, the exact cellular mechanism by which Laminin loss results in the pathological spectrum associated with MDC1A remains elusive. Here we show, via live tracking of individual muscle fibres, that dystrophic myofibres in the zebrafish model of MDC1A maintain sarcolemmal integrity and undergo dynamic remodelling behaviours post detachment, including focal sarcolemmal reattachment, cell extension and hyper-fusion with surrounding myoblasts. These observations imply the existence of a window of therapeutic opportunity, where detached cells may be "re-functionalised" prior to their delayed entry into the cell death program, a process we show can be achieved by muscle specific or systemic Laminin delivery. We further reveal that Laminin also acts as a pro-regenerative factor that stimulates muscle stem cell-mediated repair in lama2-deficient animals in vivo. The potential multi-mode of action of Laminin replacement therapy suggests it may provide a potent therapeutic axis for the treatment for MDC1A.

Perinatal angiogenesis from pre-existing coronary vessels via DLL4-NOTCH1 signalling.

Abstract: New coronary vessels are added to the heart around birth to support postnatal cardiac growth. Here we show that, in late fetal development, the embryonic coronary plexus at the inner myocardium of the ventricles expresses the angiogenic signalling factors VEGFR3 and DLL4 and generates new coronary vessels in neonates. Contrary to a previous model in which the formation of new coronary vessels in neonates from ventricular endocardial cells was proposed, we find that late fetal and neonatal ventricular endocardial cells lack angiogenic potential and do not contribute to new coronary vessels. Instead, we show using lineage-tracing as well as gain- and loss-of-function experiments that the pre-existing embryonic coronary plexus at the inner myocardium undergoes angiogenic expansion through the DLL4–NOTCH1 signalling pathway to vascularize the expanding myocardium. We also show that the pre-existing coronary plexus revascularizes the regenerating neonatal heart through a similar mechanism. These findings provide a different model of neonatal coronary angiogenesis and regeneration, potentially informing cardiovascular medicine. Lu, Wang et al. show in mice that the pre-existing embryonic coronary plexus at the inner myocardium undergoes angiogenic expansion through DLL4–NOTCH1 signalling to vascularize the expanding myocardium.