44 research outputs found
MAGNETOHYDRODYNAMIC EQUILIBRIUM OF HELICITY-INJECTED SPHEROMAK BY COMBINATION OF FDM AND BEM
The sustainment of the spheromak has been successfully achieved by DC helicity injection
in the FACT device at Himeji Institute of Technology. The flux conserver actually used in
the experiments has the shielding wall to prevent the plasma from being in contact with
the divertor bias coil. Equilibrium configurations of the spheromak in the flux conserver
with the shielding wall and the divertor bias coil are numerically determined by using the
combination of the finite difference and the boundary element method. Several results for
equilibrium configurations and their equilibrium quantities are presented. On the basis
of the results, the effects of the divertor bias coil on equilibrium configurations of the
helicity-injected spheromak are investigated
Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of two response elements
BACKGROUND: Synergistic transcriptional activation by different stimuli has been reported along with a diverse array of mechanisms, but the full scope of these mechanisms has yet to be elucidated. RESULTS: We present a detailed investigation of hypoxia-inducible factor (HIF) 1 dependent gene expression in endothelial cells which suggests the importance of crosstalk between the peroxisome proliferator-activated receptor (PPAR) β/δ and HIF signaling axes. A migration assay shows a synergistic interaction between these two stimuli, and we identify angiopoietin-like 4 (ANGPTL4) as a common target gene by using a combination of microarray and ChIP-seq analysis. We profile changes of histone marks at enhancers under hypoxia, PPARβ/δ agonist and dual stimulations and these suggest that the spatial proximity of two response elements is the principal cause of the synergistic transcription induction. A newly developed quantitative chromosome conformation capture assay shows the quantitative change of the frequency of proximity of the two response elements. CONCLUSIONS: To the best of our knowledge, this is the first report that two different transcription factors cooperate in transcriptional regulation in a synergistic fashion through conformational change of their common target genes
Direct evidence for pitavastatin induced chromatin structure change in the KLF4 gene in endothelial cells.
Statins exert atheroprotective effects through the induction of specific transcriptional factors in multiple organs. In endothelial cells, statin-dependent atheroprotective gene up-regulation is mediated by Kruppel-like factor (KLF) family transcription factors. To dissect the mechanism of gene regulation, we sought to determine molecular targets by performing microarray analyses of human umbilical vein endothelial cells (HUVECs) treated with pitavastatin, and KLF4 was determined to be the most highly induced gene. In addition, it was revealed that the atheroprotective genes induced with pitavastatin, such as nitric oxide synthase 3 (NOS3) and thrombomodulin (THBD), were suppressed by KLF4 knockdown. Myocyte enhancer factor-2 (MEF2) family activation is reported to be involved in pitavastatin-dependent KLF4 induction. We focused on MEF2C among the MEF2 family members and identified a novel functional MEF2C binding site 148 kb upstream of the KLF4 gene by chromatin immunoprecipitation along with deep sequencing (ChIP-seq) followed by luciferase assay. By applying whole genome and quantitative chromatin conformation analysis {chromatin interaction analysis with paired end tag sequencing (ChIA-PET), and real time chromosome conformation capture (3C) assay}, we observed that the MEF2C-bound enhancer and transcription start site (TSS) of KLF4 came into closer spatial proximity by pitavastatin treatment. 3D-Fluorescence in situ hybridization (FISH) imaging supported the conformational change in individual cells. Taken together, dynamic chromatin conformation change was shown to mediate pitavastatin-responsive gene induction in endothelial cells
Colossal Magnetoresistant Materials: The Key Role of Phase Separation
The study of the manganese oxides, widely known as manganites, that exhibit
the ``Colossal'' Magnetoresistance (CMR) effect is among the main areas of
research within the area of Strongly Correlated Electrons. After considerable
theoretical effort in recent years, mainly guided by computational and
mean-field studies of realistic models, considerable progress has been achieved
in understanding the curious properties of these compounds. These recent
studies suggest that the ground states of manganite models tend to be
intrinsically inhomogeneous due to the presence of strong tendencies toward
phase separation, typically involving ferromagnetic metallic and
antiferromagnetic charge and orbital ordered insulating domains. Calculations
of the resistivity versus temperature using mixed states lead to a good
agreement with experiments. The mixed-phase tendencies have two origins: (i)
electronic phase separation between phases with different densities that lead
to nanometer scale coexisting clusters, and (ii) disorder-induced phase
separation with percolative characteristics between equal-density phases,
driven by disorder near first-order metal-insulator transitions. The coexisting
clusters in the latter can be as large as a micrometer in size. It is argued
that a large variety of experiments reviewed in detail here contain results
compatible with the theoretical predictions. It is concluded that manganites
reveal such a wide variety of interesting physical phenomena that their
detailed study is quite important for progress in the field of Correlated
Electrons.Comment: 76 pages, 21 PNG files with figures. To appear in Physics Report
Inhibition of cardiac PERK signaling promotes peripartum cardiac dysfunction
Peripartum cardiomyopathy (PPCM) is a life-threatening heart failure occurring in the peripartum period. Although mal-angiogenesis, induced by the 16-kDa N-terminal prolactin fragment (16 K PRL), is involved in the pathogenesis, the effect of full-length prolactin (23 K PRL) is poorly understood. We transfected neonate rat cardiomyocytes with plasmids containing 23 K PRL or 16 K PRL in vitro and found that 23 K PRL, but not 16 K PRL, upregulated protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling, and hypoxia promoted this effect. During the perinatal period, cardiomyocyte-specific PERK homogenous knockout (CM-KO) mice showed PPCM phenotypes after consecutive deliveries. Downregulation of PERK or JAK/STAT signaling and upregulation of apoptosis were observed in CM-KO mouse hearts. Moreover, in bromocriptine-treated CM-KO mice, cardiac function did not improve and cardiomyocyte apoptosis was not suppressed during the peripartum period. These results demonstrate that interaction between 23 K PRL and PERK signaling is cardioprotective during the peripartum term
Downregulation of ERG and FLI1 expression in endothelial cells triggers endothelial-to-mesenchymal transition.
Endothelial cell (EC) plasticity in pathological settings has recently been recognized as a driver of disease progression. Endothelial-to-mesenchymal transition (EndMT), in which ECs acquire mesenchymal properties, has been described for a wide range of pathologies, including cancer. However, the mechanism regulating EndMT in the tumor microenvironment and the contribution of EndMT in tumor progression are not fully understood. Here, we found that combined knockdown of two ETS family transcription factors, ERG and FLI1, induces EndMT coupled with dynamic epigenetic changes in ECs. Genome-wide analyses revealed that ERG and FLI1 are critical transcriptional activators for EC-specific genes, among which microRNA-126 partially contributes to blocking the induction of EndMT. Moreover, we demonstrated that ERG and FLI1 expression is downregulated in ECs within tumors by soluble factors enriched in the tumor microenvironment. These data provide new insight into the mechanism of EndMT, functions of ERG and FLI1 in ECs, and EC behavior in pathological conditions