Inhibition of mTOR Signaling Protects Against Myocardial Reperfusion Injury, Acute Myocardial Infarction

Acute myocardial infarction (AMI) is the leading cause of death worldwide. Currently, the best method of treating cardiac ischemia is early reperfusion which, itself, induces myocardial damage. The mTOR complex is a key regulator of cardioprotection against cell stressors. We hypothesized that reperfusion therapy with Rapamycin, a potent mTOR inhibitor, would reduce infarct size in adult mouse hearts. Rapamycin was administered at the onset of reperfusion following 30 min in situ LAD ligation. After 24 hours of reperfusion, myocardial infarct size and apoptosis were significantly reduced in rapamycin-treated mice compared to control. Rapamycin inhibited pro-apoptotic protein Bax and phosphorylation of ribosomal protein S6 (target of mTORC1), while it induced phosphorylation of AKT (target of mTORC2). Rapamycin also induced phosphorylation of ERK, while significantly reduced phosphorylation of p38. Thus, our study shows that reperfusion therapy with Rapamycin provides cardioprotection through induction of the phosphorylation of Akt and ERK

Reperfusion Therapy with Rapamycin Attenuates Myocardial Infarction through Activation of AKT and ERK

Prompt coronary reperfusion is the gold standard for minimizing injury following acute myocardial infarction. Rapamycin, mammalian target of Rapamycin (mTOR) inhibitor, exerts preconditioning-like cardioprotective effects against ischemia/reperfusion (I/R) injury. We hypothesized that Rapamycin, given at the onset of reperfusion, reduces myocardial infarct size through modulation of mTOR complexes. Adult C57 male mice were subjected to 30 min of myocardial ischemia followed by reperfusion for 1 hour/24 hours. Rapamycin (0.25 mg/kg) or DMSO (7.5%) was injected intracardially at the onset of reperfusion. Post-I/R survival (87%) and cardiac function (fractional shortening, FS: 28.63±3.01%) were improved in Rapamycin-treated mice compared to DMSO (survival: 63%, FS: 17.4±2.6%). Rapamycin caused significant reduction in myocardial infarct size (IS: 26.2±2.2%) and apoptosis (2.87±0.64%) as compared to DMSO-treated mice (IS: 47.0±2.3%; apoptosis: 7.39±0.81%). Rapamycin induced phosphorylation of AKT S473 (target of mTORC2) but abolished ribosomal protein S6 phosphorylation (target of mTORC1) after I/R. Rapamycin induced phosphorylation of ERK1/2 but inhibited p38 phosphorylation. Infarct-limiting effect of Rapamycin was abolished with ERK inhibitor, PD98059. Rapamycin also attenuated Bax and increased Bcl-2/Bax ratio. These results suggest that reperfusion therapy with Rapamycin protects the heart against I/R injury by selective activation of mTORC2 and ERK with concurrent inhibition of mTORC1 and p38

Quark-hadron duality in electron scattering

The duality between partonic and hadronic descriptions of physical phenomena is one of the most remarkable features of strong interaction physics. A classic example of this is in electron-nucleon scattering, in which low-energy cross sections, when averaged over appropriate energy intervals, are found to exhibit the scaling behavior expected from perturbative QCD. We present a comprehensive review of data on structure functions in the resonance region, from which the global and local aspects of duality are quantified, including its flavor, spin and nuclear medium dependence. To interpret the experimental findings, we discuss various theoretical approaches which have been developed to understand the microscopic origins of quark-hadron duality in QCD. Examples from other reactions are used to place duality in a broader context, and future experimental and theoretical challenges are identified.Comment: 198 pages, 80 figures, to appear in Physics Report

Long-acting PDE5 Inhibitor Tadalafil prevents early doxorubicin induced left ventricle diastolic dysfunction in juvenile mice: Potential role of cytoskeletal proteins

The chemotherapeutic use of doxorubicin (Dox) is hindered due to the development of irreversible cardiotoxicity. Specifically, childhood cancer survivors are at greater risk of Dox-induced cardiovascular complications. Because of the potent cardioprotective effect of phosphodiesterase 5 (PDE5) inhibitors, we examined the effect of long-acting PDE5 inhibitor, Tadalafil (Tada) against Dox-cardiotoxicity in juvenile mice. C57BL/6 mice (6 weeks old) were treated with Dox (20 mg/kg, IV) and/or Tada (10 mg/kg/daily for 14 days; PO). Cardiac function was assessed by echocardiography following 5 and 10 weeks post treatment. The expression of cardiac proteins was examined by Western blot analysis. Dox treatment caused diastolic dysfunction in juvenile mice indicated by increasing the E/E’ (early diastolic myocardial velocity to early tissue Doppler velocity) ratio as compared to control at both 5 and 10 weeks post-treatment. Co-treatment of Tada and Dox preserved left ventricular (LV) diastolic function with reduction of E/E’. Dox treatment decreased the expression of SERCA2 and desmin in the LV, however, only desmin loss was prevented with Tada. Also, Dox treatment increased the expression of myosin heavy chain (MHCβ), which was reduced by Tada. We propose that Tada could be a promising new therapy for improving cardiac function in survivors of childhood cancer.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Interactive Model of Santa Fe Indian School Campus for Community Planning and Education

The Santa Fe Indian School is looking for new means to remember the past and imagine the future. - We developed a framework for a 3D model and digital archive for the past campus of SFIS and a 3D model for planning purposes. We recommend giving the students the opportunity to further their education in technologies and methods used to continue these projects