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.

What can the geographic distribution of mtDNA haplotypes tell us about the invasion of New Zealand by house mice Mus musculus

Abstract: We mapped the distribution and diversity of mitochondrial D-loop haplotypes among 502 New Zealand house mice (Mus musculus). By widespread sampling from 74 sites, we identified 14 new haplotypes. We used Bayesian phylogenetic reconstructions to estimate the genetic relationships between the New Zealand representatives of Mus musculus domesticus (all six known clades) and M. m. castaneus (clade HG2), and mice from other locales. We defined four distinct geographic regions of New Zealand with differing haplotype diversity indices. Our Results suggest (a) two independent pre-1840 invasions by mice of different origin (domesticus clade E and castaneus clade HG2) at opposite ends of the country; (b) multiple later invasions by domesticus clades E and F accompanying the post-1840 development of New Zealand port facilities in the central regions, plus limited local incursions by domesticus clades A, B, C and D1; (c) a separate invasion of Chatham I. by castaneus clade HG2; (d) previously undescribed New Zealand haplotypes, potentially the products of localised indigenous mutation, and (e) hybridisation between different lineages.

"Force-From-Lipids" mechanosensation in Corynebacterium glutamicum.

Abstract: Since the mechanosensitive channel MscCG has been identified as the major glutamate efflux system in Corynebacterium glutamicum, studies of mechanotransduction processes in this bacterium have helped to unpuzzle a long-unresolved mystery of glutamate efflux that has been utilised for industrial monosodium glutamate production. The patch clamp recording from C. glutamicum giant spheroplasts revealed the existence of three types of mechanosensitive (MS) channels in the cell membrane of this bacterium. The experiments demonstrated that the MS channels could be activated by membrane tension, indicating that the channel gating by mechanical force followed the "Force-From-Lipids (FFL)" principle characteristic of ion channels inherently sensitive to transbilayer pressure profile changes in the mechanically stressed membrane bilayer. Mechanical properties of the C. glutamicum membrane are characteristics of very soft membranes, which in the C. glutamicum membrane are due to negatively charged lipids as its exclusive constituents. Given that membrane lipids are significantly altered during the fermentation process in the monosodium glutamate production, MS channels seem to respond to changes in force transmission through the membrane bilayer due to membrane lipid dynamics. In this review, we describe the recent results describing corynebacterial FFL-dependent mechanosensation originating from the particular lipid composition of the C. glutamicum membrane and unique structure of MscCG-type channels.

Redox activation of JNK2α2 mediates thyroid hormone-stimulated proliferation of neonatal murine cardiomyocytes

Abstract: Mitochondria-generated reactive oxygen species (mROS) are frequently associated with DNA damage and cell cycle arrest, but physiological increases in mROS serve to regulate specific cell functions. T3 is a major regulator of mROS, including hydrogen peroxide (H2O2). Here we show that exogenous thyroid hormone (T3) administration increases cardiomyocyte numbers in neonatal murine hearts. The mechanism involves signaling by mitochondria-generated H2O2 (mH2O2) acting via the redox sensor, peroxiredoxin-1, a thiol peroxidase with high reactivity towards H2O2 that activates c-Jun N-terminal kinase-2α2 (JNK2α2). JNK2α2, a relatively rare member of the JNK family of mitogen-activated protein kinases (MAPK), phosphorylates c-Jun, a component of the activator protein 1 (AP-1) early response transcription factor, resulting in enhanced insulin-like growth factor 1 (IGF-1) expression and activation of proliferative ERK1/2 signaling. This non-canonical mechanism of MAPK activation couples T3 actions on mitochondria to cell cycle activation. Although T3 is regarded as a maturation factor for cardiomyocytes, these studies identify a novel redox pathway that is permissive for T3-mediated cardiomyocyte proliferation—this because of the expression of a pro-proliferative JNK isoform that results in growth factor elaboration and ERK1/2 cell cycle activation.

Absence of systemic oxidative stress and increased CSF prostaglandin F2α in progressive MS.

Abstract: Objective: We aimed to investigate the role of oxidative stress in the progression of multiple sclerosis (MS). Methods: We determined by liquid chromatography–tandem mass spectrometry nonenzymatic (F 2 -isoprostanes) and enzymatic oxidation products of arachidonic acid (prostaglandin F 2α [PGF 2α ]) in plasma and CSF of 45 controls (other neurologic disease [OND] with no signs of inflammation) and 62 patients with MS. Oxidation products were correlated with disease severity and validated biomarkers of inflammation (chemokine ligand 13; matrix metalloproteinase-9; osteopontin) and axonal damage (neurofilament light protein). Results: Compared with OND controls, plasma concentrations of F 2 -isoprostanes and PGF 2α were significantly lower in patients with progressive disease, and decreased with increasing disability score (Expanded Disability Status Scale). In contrast, CSF concentrations of PGF 2α , but not F 2 -isoprostanes, were significantly higher in patients with progressive disease than OND controls ( p 2α in CSF increased with disease severity ( p = 0.044) and patient age ( p = 0.022), although this increase could not be explained by age. CSF PGF 2α decreased with natalizumab and methylprednisolone treatment and was unaffected by the use of nonsteroidal anti-inflammatory drug in secondary progressive MS. CSF PGF 2α did not associate with validated CSF markers of inflammation and axonal damage that themselves did not associate with the Expanded Disability Status Scale. Conclusions: Our data suggest that MS progression is associated with low systemic oxidative activity. This may contribute to immune dysregulation with CNS inflammation accompanied by increased local cyclooxygenase-dependent lipid oxidation.

Candidate disease gene prediction using Gentrepid: application to a genome-wide association study on coronary artery disease

Abstract: Current single-locus-based analyses and candidate disease gene prediction methodologies used in genome-wide association studies (GWAS) do not capitalize on the wealth of the underlying genetic data, nor functional data available from molecular biology. Here, we analyzed GWAS data from the Wellcome Trust Case Control Consortium (WTCCC) on coronary artery disease (CAD). Gentrepid uses a multiple-locus-based approach, drawing on protein pathway- or domain-based data to make predictions. Known disease genes may be used as additional information (seeded method) or predictions can be based entirely on GWAS single nucleotide polymorphisms (SNPs) (ab initio method). We looked in detail at specific predictions made by Gentrepid for CAD and compared these with known genetic data and the scientific literature. Gentrepid was able to extract known disease genes from the candidate search space and predict plausible novel disease genes from both known and novel WTCCC-implicated loci. The disease gene candidates are consistent with known biological information. The results demonstrate that this computational approach is feasible and a valuable discovery tool for geneticists.