An Ab Initio Description of the Mott Metal-Insulator Transition of M2_{2} Vanadium Dioxide

Using an \textit{ab initio} approach based on the GW approximation which includes strong local \textbf{k}-space correlations, the Metal-Insulator Transition of M$_2$ vanadium dioxide is broken down into its component parts and investigated. Similarly to the M$_{1}$ structure, the Peierls pairing of the M$_{2}$ structure results in bonding-antibonding splitting which stabilizes states in which the majority of the charge density resides on the Peierls chain. This is insufficient to drop all of the bonding states into the lower Hubbard band however. An antiferroelectric distortion on the neighboring vanadium chain is required to reduce the repulsion felt by the Peierls bonding states by increasing the distances between the vanadium and apical oxygen atoms, lowering the potential overlap thus reducing the charge density accumulation and thereby the electronic repulsion. The antibonding states are simultaneously pushed into the upper Hubbard band. The data indicate that sufficiently modified GW calculations are able to describe the interplay of the atomic and electronic structures occurring in Mott metal-insulator transitions.Comment: 10 Pages, 7 Figure

Transient Receptor Potential Melastatin-4 Is Involved in Hypoxia-Reoxygenation Injury in the Cardiomyocytes

<div><p>Ischemic heart disease still remains the most common cause of cardiac death. During ischemia-reperfusion (I/R), reactive oxygen species (ROS) are produced in excess in cardiac tissue, where they induce cell death. Our previous study showed that 9-phenanthrol (9-Phe), a specific inhibitor of the TRPM4 channel, preserves cardiac contractile function and protects the heart from I/R injury-related infarction in the excised rat heart. Accordingly, we hypothesized that TRPM4 channels are involved in the 9-Phe-mediated cardioprotection against ROS-induced injury. In rats, intravenous 9-Phe mitigated the development of myocardial infarction caused by the occlusion of the left anterior descending artery. Immunohistochemical analysis indicated that TRPM4 proteins are expressed in ventricular myocytes susceptible to I/R injury. Hydrogen peroxide (H₂O₂) is among the main ROS overproduced during I/R. In the cardiomyocyte cell line H9c2, pretreatment with 9-Phe prevented cell death induced by conditions mimicking I/R, namely 200 μM H₂O₂ and hypoxia-reoxygenation. Gene silencing of TRPM4 preserved the viability of H9c2 cardiomyocytes exposed to 200 μM H₂O₂. These results suggest that the cardioprotective effects of 9-Phe are mediated through the inhibition of the TRPM4 channels.</p></div

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ

Cardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Pioglitazone, the widely used thiazolidinedione, is shown to be efficient in the prevention of cardiovascular complications of T2DM. In this study, we report that pioglitazone inhibits CXCR7 expression and thus blocks chemotaxis in differentiated macrophage without perturbing cell viability or macrophage differentiation. In addition, pioglitazone-mediated CXCR7 suppression and chemotaxis inhibition occur via activating peroxisome proliferator-activated receptor γ (PPARγ) but not PPARα in differentiated macrophage. More importantly, pioglitazone therapy-induced PPARγ activation suppresses CXCR7 expression in human carotid atherosclerotic lesions. Collectively, our data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ

Immunofluorescence imaging of TRPM4 in the healthy rat heart.

<p><b>(A)</b> Adult rat heart sections were labeled with anti-TRPM4 antibodies (green) and stained with Hoechst 33342 for the nuclei (blue). The green and blue fluorescence images were overlaid with the DIC image. Staining specificity was confirmed by the lack of signal when anti-TRPM4 antibodies were preincubated with the antigenic blocking peptide (ab65597). Scale bar: 100 μm. <b>(B)</b> Double immunofluorescence showing TRPM4 (green) and SERCA2 (red) expression in ventricular cardiomyocytes. Scale bar: 20 μm. The overlaid image (left bottom) reveals alternating positions for the TRPM4 and SERCA2 proteins on the longitudinal axis of cardiomyocytes. Arrowheads indicate the intercalated disc. Fluorescence intensity profile (right bottom) confirmed the alternating expression of TRPM4 and SERCA2.</p

Knockdown of TRPM4 prevents cell death caused by H₂O₂ challenge in H9c2 cardiomyocytes.

<p><b>(A)</b> Quantitative RT-PCR confirming the gene silencing of TRPM4. siNEG, cells transfected with control siRNA; siTRPM4, cells transfected with TRPM4-targeting siRNA. n = 5 for each group. <b>(B)</b> Confirmation of suppressed TRPM4 protein expression by immunocytochemistry 48 h after siRNA transfection. Green, anti-TRPM4, Blue, Hoechst 33342 dye (nuclei). The fluorescent images were overlaid with DIC images of the cultures. <b>(C)</b> Confirmation of suppressed TRPM4 protein expression by Western blot 24 h after siRNA transfection. <b>(D)</b> Impact of gene silencing on the loss of viability induced by 200 μM H₂O₂. Cell viability was measured by the MTT assay. n = 5 for each group. <b>(E)</b> Impact of TRPM4 knockdown on the hypoxia/reoxygenation (H/R) challenge. Cell viability was measured by the MTT assay. n = 6 for each group. Statistical analysis was performed using Dunnett’s test as post hoc. *: <i>p</i> < 0.05, **: <i>p</i> < 0.01, N.S.: <i>p</i> > 0.05.</p

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ

Cardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Pioglitazone, the widely used thiazolidinedione, is shown to be efficient in the prevention of cardiovascular complications of T2DM. In this study, we report that pioglitazone inhibits CXCR7 expression and thus blocks chemotaxis in differentiated macrophage without perturbing cell viability or macrophage differentiation. In addition, pioglitazone-mediated CXCR7 suppression and chemotaxis inhibition occur via activating peroxisome proliferator-activated receptor γ (PPARγ) but not PPARα in differentiated macrophage. More importantly, pioglitazone therapy-induced PPARγ activation suppresses CXCR7 expression in human carotid atherosclerotic lesions. Collectively, our data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ

Cardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Pioglitazone, the widely used thiazolidinedione, is shown to be efficient in the prevention of cardiovascular complications of T2DM. In this study, we report that pioglitazone inhibits CXCR7 expression and thus blocks chemotaxis in differentiated macrophage without perturbing cell viability or macrophage differentiation. In addition, pioglitazone-mediated CXCR7 suppression and chemotaxis inhibition occur via activating peroxisome proliferator-activated receptor γ (PPARγ) but not PPARα in differentiated macrophage. More importantly, pioglitazone therapy-induced PPARγ activation suppresses CXCR7 expression in human carotid atherosclerotic lesions. Collectively, our data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ

Impact of 9-Phe on the size of myocardial infarction.

<p>Rats received a bolus injection of DMSO (control) or 9-Phe before (preconditioning) or after (postconditioning) ischemia during an ischemia/reperfusion (I/R) protocol. <b>(A)</b> Impact on the percentage of area at risk (AAR) caused by I/R. <b>(B)</b> Impact on the percent infarct size over AAR. A fixed detection threshold for infarcted area was arbitrarily set, and used throughout the analysis. Only 9-Phe preconditioning significantly reduced the percent infarcted size, compared to DMSO (n = 5–6; <i>p</i> < 0.01). <b>(C)</b> Typical TTC-stained heart slices after preconditioning with DMSO or 9-Phe. The blue region indicates cardiac tissue that received normal blood flow, whereas the red region indicates ischemic tissue due to LAD occlusion. The light red region encircled by a dotted line indicates the infarcted tissue.</p

Protective effect of 9-Phe against hypoxia-reperfusion-induced death in H9c2 cardiomyocytes.

<p>Cultures of H9c2 cells, incubated with DMSO or 9-Phe (10 or 20 μM), were subjected to hypoxia-reperfusion (H/R; 4 h anoxia followed by 1 h reoxygenation). Viability was measured by the MTT assay, and absorbance was normalized to that of the normoxic condition. The presence of 9-Phe (≥10 μM) completely prevented the damage caused by H/R (n = 3 for each condition). Dunnett’s post hoc test was performed. * <i>p</i> < 0.05, N.S.: <i>p</i> > 0.05.</p

Expression of neurabin and spinophilin in the mouse brain at 4 and 12 months of age.

<p>Total brain lysates were subjected to western blot. Neurabin, spinophilin, PP1γ and tubulin (loading control) were detected by respective antibodies. (A) representative westerns. (B) Quantification of expression levels of neurabin, spinophilin and PP1γ in the WT mouse brain at different ages. Data are presented as mean ± SEM. n = 3 for each group.</p