Deletion of Cardiac miR-17-92 Cluster Increases Ischemia/ Reperfusion Injury via PTEN Upregulation

The miR-17- 92 cluster is necessary for cell proliferation and development of the cardiovascular system. Deletion of this cluster leads to death in neonatal mice. The role of this cluster still needs to be defined following ischemia and reperfusion. Methods and Results: Adult male mice were injected with Tamoxifen- was to induce inducible cardiac-specific miR-17- 92-deficient (miR-17- 92-def: MCM:TG:miR-17- 92 flox/flox ) and wild type (WT: MCM:NTG:miR-17-92 flox/flox ) mice were subjected to 30 minutes of myocardial ischemia via left anterior descending coronary artery ligation followed by reperfusion for 24 hours. Post I/R survival (48%) and ejection fraction were reduced, while myocardial infarct size enlarged in miR-17- 92-deficient mice as compared to WT mice (survival: 71%). Necrosis (trypan blue staining) and apoptosis (TUNEL assay) both were higher in adult cardiomyocytes isolated from miR-17- 92-deficient mice as compared to WT mice subjected to simulated ischemia/reoxygenation with a concomitant reduction of mitochondrial membrane potential (JC1 staining). The electron transport chain was compromised through dysregulation of glutamate+malate as complex I substrate and malate dehydrogenase in the hearts of miR-17- 92-deficient mice compared to WT. After 4 hours of reperfusion, PTEN expression, a downstream target of miR-20A, increased, while phosphorylation of AKT reduced in the hearts of miR-17- 92-deficient mice in comparison to WT. The induced knockdown of cardiac miR-17- 92 increases myocardial I/R injury by ceasing suppression of PTEN, leading to decreased concentrations of AKT and mitochondrial dysfunction. These results suggest that innovative therapeutic strategies can focus on genetic upregulation of miR-17- 92 in patients with coronary artery disease

Particle Production at CBM in a Thermal Model Approach

The Compressed Baryonic Matter (CBM) experiment planned at Facility for Antiproton and Ion Research (FAIR) will provide a major scientific effort for exploring the properties of strongly interacting matter in the high baryon density regime. One of the important goal behind such experiment is to precisely determine the equation of state (EOS) for the strongly interacting matter at extreme baryon density. In this paper, we have used a thermal model EOS incorporating excluded volume description for the hot and dense hadron gas (HG). We then predict different particle ratios and the total multiplicity of various hadrons in the CBM energy range i.e. from $10$ A GeV to $40$ A GeV lab energies, which corresponds to $4.43$ A GeV and $8.71$ A GeV center-of-mass energies. Our main emphasis is to estimate the strange particles enhancement as well as increase in the net baryon density in CBM experiment. We have also compared our results with the results obtained from various other theoretical approaches existing in the literature such as hadron string dynamics (HSD) model and ultra-relativistic quantum molecular dynamics (UrQMD) etc.Comment: 16 pages, 8 figure

Optimisation of a Brownian dynamics algorithm for semidilute polymer solutions

Simulating the static and dynamic properties of semidilute polymer solutions with Brownian dynamics (BD) requires the computation of a large system of polymer chains coupled to one another through excluded-volume and hydrodynamic interactions. In the presence of periodic boundary conditions, long-ranged hydrodynamic interactions are frequently summed with the Ewald summation technique. By performing detailed simulations that shed light on the influence of several tuning parameters involved both in the Ewald summation method, and in the efficient treatment of Brownian forces, we develop a BD algorithm in which the computational cost scales as O(N^{1.8}), where N is the number of monomers in the simulation box. We show that Beenakker's original implementation of the Ewald sum, which is only valid for systems without bead overlap, can be modified so that \theta-solutions can be simulated by switching off excluded-volume interactions. A comparison of the predictions of the radius of gyration, the end-to-end vector, and the self-diffusion coefficient by BD, at a range of concentrations, with the hybrid Lattice Boltzmann/Molecular Dynamics (LB/MD) method shows excellent agreement between the two methods. In contrast to the situation for dilute solutions, the LB/MD method is shown to be significantly more computationally efficient than the current implementation of BD for simulating semidilute solutions. We argue however that further optimisations should be possible.Comment: 17 pages, 8 figures, revised version to appear in Physical Review E (2012