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.

Kalata B1 and Kalata B2 Have a Surfactant-Like Activity in Phosphatidylethanolomine-Containing Lipid Membranes.

Abstract: Cyclotides are cyclic disulfide-rich peptides that are chemically and thermally stable and possess pharmaceutical and insecticidal properties. The activities reported for cyclotides correlate with their ability to target phosphatidylethanolamine (PE)-phospholipids and disrupt cell membranes. However, the mechanism by which this disruption occurs remains unclear. In the current study we examine the effect of the prototypic cyclotides, kalata B1 (kB1) and kalata B2 (kB2), on tethered lipid bilayer membranes (tBLMs) using swept frequency electrical impedance spectroscopy. We confirmed that kB1 and kB2 bind to bilayers only if they contain PE-phospholipids. We hypothesize that the increase in membrane conduction and capacitance observed upon addition of kB1 or kB2 is unlikely to result from ion channel like pores but is consistent with the formation of lipidic toroidal pores. This hypothesis is supported by the concentration dependence of effects of kB1 and kB2 being suggestive of a critical micelle concentration event rather than a progressive increase in conduction arising from increased channel insertion. Additionally, conduction behavior is readily reversible when the peptide is rinsed from the bilayer. Our results support a mechanism by which kB1 and kB2 bind to and disrupt PE-containing membranes by decreasing the overall membrane critical packing parameter, as would a surfactant, which then opens or increases the size of existing membrane defects. The cyclotides need not participate directly in the conductive pore but might exert their effect indirectly through altering membrane packing constraints and inducing purely lipidic conductive pores.

mRNA isoform diversity can obscure detection of miRNA-mediated control of translation

Abstract: Reporter-based studies support inhibition of translation at the level of initiation as a substantial component of the miRNA mechanism, yet recent global analyses have suggested that they predominantly act through decreasing target mRNA stability. Cells commonly coexpress several processing isoforms of an mRNA, which may also differ in their regulatory untranslated regions (UTR). In particular, cancer cells are known to express high levels of short 39 UTR isoforms that evade miRNA-mediated regulation, whereas longer 39 UTRs predominate in nontransformed cells. To test whether mRNA isoform diversity can obscure detection of miRNA-mediated control at the level of translation, we assayed the responses of 11 endogenous let-7 targets to inactivation of this miRNA in HeLa cells, an intensively studied model system. We show that translational regulation in many cases appears to be modest when measuring the composite polysome profile of all extant isoforms of a given mRNA by density ultracentrifugation. In contrast, we saw clear effects at the level of translation initiation for multiple examples when selectively profiling mRNA isoforms carrying the 59 or 39 untranslated regions that were actually permissive to let-7 action, or when let-7 and a second targeting miRNA were jointly manipulated. Altogether, these results highlight a caveat to the mechanistic interpretation of data from global miRNA target analyses in transformed cells. Importantly, they reaffirm the importance of translational control as part of the miRNA mechanism in animal cells.

Education and practice gaps on atrial fibrillation and anticoagulation: a survey of cardiovascular nurses

Abstract: Patients’ knowledge of their atrial fibrillation (AF) and anticoagulation therapy are determinants of the efficacy of thromboprophylaxis. Nurses may be well placed to provide counselling and education to patients on all aspects of anticoagulation, including self-management. It is important that nurses are well informed to provide optimal education to patients. Current practice and knowledge of cardiovascular nurses on AF and anticoagulation in the Australian and New Zealand (ANZ) context is not well reported. This study aimed to; 1) Explore the nurse’s role in clinical decision making in anticoagulation in the setting of AF; 2) Describe perceived barriers and enablers to anticoagulation in AF; 3) Investigate practice patterns in the management of anticoagulation in the ANZ setting; 4) Assess cardiovascular nurses’ knowledge of anticoagulation. A paper-based survey on current practices and knowledge of AF and anticoagulation was distributed during the Australian Cardiovascular Nursing College (ACNC) Annual Scientific Meeting, February 2014. This survey was also emailed to Cardiovascular Trials Nurses throughout New South Wales, Australia and nursing members of the Cardiac Society of Australia and New Zealand (CSANZ). There were 41/73 (56 %) respondents to the paper-based survey. A further 14 surveys were completed online via nurse members of the CSANZ, and via an investigator developed NSW cardiovascular trials nurse email distribution list. A total of 55 surveys were completed and included in analyses. Prior education levels on AF, stroke risk, anticoagulation and health behaviour modification were mixed. The CHA2DS2VASc and HAS-BLED risk stratification tools were reported to be underused by this group of clinicians. Reported key barriers to anticoagulation included; fears of patients falling, fears of poor adherence to medication taking and routine monitoring. Patient self-monitoring and self-management were reported as underutilised. ANZ cardiovascular nurses reported their key role to be counselling and advising patients on therapy regimens. Anticoagulant-drug interaction knowledge was generally poor. This study identified poor knowledge and practice in the areas of AF and anticoagulation. There is scope for improvement for cardiovascular nurses in ANZ in relation to AF and anticoagulation knowledge and practice.

Rapid Knockout and Reporter Mouse Line Generation and Breeding Colony Establishment Using EUCOMM Conditional-Ready Embryonic Stem Cells: A Case Study.

Abstract: As little as a decade ago, generation of a single knockout mouse line was an expensive and time-consuming undertaking available to relatively few researchers. The International Knockout Mouse Consortium, established in 2007, has revolutionized the use of such models by creating an open-access repository of ES cells that, through sequential breeding with first FlpE and then Cre recombinase transgenic mice, facilitates germline global or conditional deletion of almost every gene in the mouse genome. In this Case Study, we describe our experience using the repository to create mouse lines for a variety of experimental purposes. Specifically, we discuss the process of obtaining germline transmission of two EUCOMM ‘knockout-first’ gene targeted constructs and the advantages and pitfalls of using this system. We then outline our breeding strategy and the outcomes of our efforts to generate global and conditional knockouts and reporter mice for the genes of interest. Line maintenance, removal of recombinase transgenes and cryopreservation are also considered. Our approach led to the generation of heterozygous knockout mice within 6 months of commencing breeding to the founder mice. By describing our experiences with the EUCOMM ES cells and subsequent breeding steps, we hope to assist other researchers with the application of this valuable approach to generating versatile knockout mouse lines.